oral presentations medicine

Overview and General Information about Oral Presentation

• Daily Presentations During Work Rounds
• The New Patient Presentation
• The Holdover Admission Presentation
• Outpatient Clinic Presentations
• The structure of presentations varies from service to service (e.g. medicine vs. surgery), amongst subspecialties, and between environments (inpatient vs. outpatient). Applying the correct style to the right setting requires that the presenter seek guidance from the listeners at the outset.
• Time available for presenting is rather short, which makes the experience more stressful.
• Individual supervisors (residents, faculty) often have their own (sometimes quirky) preferences regarding presentation styles, adding another layer of variability that the presenter has to manage.
• Students are evaluated/judged on the way in which they present, with faculty using this as one way of gauging a student’s clinical knowledge.
• Done well, presentations promote efficient, excellent care. Done poorly, they promote tedium, low morale, and inefficiency.

General Tips:

• Practice, Practice, Practice! Do this on your own, with colleagues, and/or with anyone who will listen (and offer helpful commentary) before you actually present in front of other clinicians. Speaking "on-the-fly" is difficult, as rapidly organizing and delivering information in a clear and concise fashion is not a naturally occurring skill.
• Immediately following your presentations, seek feedback from your listeners. Ask for specifics about what was done well and what could have been done better – always with an eye towards gaining information that you can apply to improve your performance the next time.
• Listen to presentations that are done well – ask yourself, “Why was it good?” Then try to incorporate those elements into your own presentations.
• Listen to presentations that go poorly – identify the specific things that made it ineffective and avoid those pitfalls when you present.
• Effective presentations require that you have thought through the case beforehand and understand the rationale for your conclusions and plan. This, in turn, requires that you have a good grasp of physiology, pathology, clinical reasoning and decision-making - pushing you to read, pay attention, and in general acquire more knowledge.
• Think about the clinical situation in which you are presenting so that you can provide a summary that is consistent with the expectations of your audience. Work rounds, for example, are clearly different from conferences and therefore mandate a different style of presentation.
• Presentations are the way in which we tell medical stories to one another. When you present, ask yourself if you’ve described the story in an accurate way. Will the listener be able to “see” the patient the same way that you do? Can they come to the correct conclusions? If not, re-calibrate.
• It's O.K. to use notes, though the oral presentation should not simply be reduced to reading the admission note – rather, it requires appropriate editing/shortening.
• In general, try to give your presentations on a particular service using the same order and style for each patient, every day. Following a specific format makes it easier for the listener to follow, as they know what’s coming and when they can expect to hear particular information. Additionally, following a standardized approach makes it easier for you to stay organized, develop a rhythm, and lessens the chance that you’ll omit elements.

Specific types of presentations

There are a number of common presentation-types, each with its own goals and formats. These include:

• Daily presentations during work rounds for patients known to a service.
• Newly admitted patients, where you were the clinician that performed the H&P.
• Newly admitted patients that were “handed off” to the team in the morning, such that the H&P was performed by others.
• Outpatient clinic presentations, covering several common situations.

Key elements of each presentation type are described below. Examples of how these would be applied to most situations are provided in italics. The formats are typical of presentations done for internal medicine services and clinics.

Note that there is an acceptable range of how oral presentations can be delivered. Ultimately, your goal is to tell the correct story, in a reasonable amount of time, so that the right care can be delivered. Nuances in the order of presentation, what to include, what to omit, etc. are relatively small points. Don’t let the pursuit of these elements distract you or create undue anxiety.

Daily presentations during work rounds of patients that you’re following:

• Organize the presenter (forces you to think things through)
• Inform the listener(s) of 24 hour events and plan moving forward
• Promote focused discussion amongst your listeners and supervisors
• Opportunity to reassess plan, adjust as indicated
• Demonstrate your knowledge and engagement in the care of the patient
• Rapid (5 min) presentation of the key facts

Key features of presentation:

• Opening one liner: Describe who the patient is, number of days in hospital, and their main clinical issue(s).
• 24-hour events: Highlighting changes in clinical status, procedures, consults, etc.
• Subjective sense from the patient about how they’re feeling, vital signs (ranges), and key physical exam findings (highlighting changes)
• Relevant labs (highlighting changes) and imaging
• Assessment and Plan : Presented by problem or organ systems(s), using as many or few as are relevant. Early on, it’s helpful to go through the main categories in your head as a way of making sure that you’re not missing any relevant areas. The broad organ system categories include (presented here head-to-toe): Neurological; Psychiatric; Cardiovascular; Pulmonary; Gastrointestinal; Renal/Genitourinary; Hematologic/Oncologic; Endocrine/Metabolic; Infectious; Tubes/lines/drains; Disposition.

Example of a daily presentation for a patient known to a team:

• Opening one liner: This is Mr. Smith, a 65 year old man, Hospital Day #3, being treated for right leg cellulitis
• MRI of the leg, negative for osteomyelitis
• Evaluation by Orthopedics, who I&D’d a superficial abscess in the calf, draining a moderate amount of pus
• Patient appears well, states leg is feeling better, less painful
• T Max 101 yesterday, T Current 98; Pulse range 60-80; BP 140s-160s/70-80s; O2 sat 98% Room Air
• Ins/Outs: 3L in (2 L NS, 1 L po)/Out 4L urine
• Right lower extremity redness now limited to calf, well within inked lines – improved compared with yesterday; bandage removed from the I&D site, and base had small amount of purulence; No evidence of fluctuance or undrained infection.
• Creatinine .8, down from 1.5 yesterday
• WBC 8.7, down from 14
• Blood cultures from admission still negative
• Gram stain of pus from yesterday’s I&D: + PMNS and GPCs; Culture pending
• MRI lower extremity as noted above – negative for osteomyelitis
• Continue Vancomycin for today
• Ortho to reassess I&D site, though looks good
• Follow-up on cultures: if MRSA, will transition to PO Doxycycline; if MSSA, will use PO Dicloxacillin
• Given AKI, will continue to hold ace-inhibitor; will likely wait until outpatient follow-up to restart
• Add back amlodipine 5mg/d today
• Hep lock IV as no need for more IVF
• Continue to hold ace-I as above
• Wound care teaching with RNs today – wife capable and willing to assist. She’ll be in this afternoon.
• Set up follow-up with PMD to reassess wound and cellulitis within 1 week

The Brand New Patient (admitted by you)

• Provide enough information so that the listeners can understand the presentation and generate an appropriate differential diagnosis.
• Present a thoughtful assessment
• Present diagnostic and therapeutic plans
• Provide opportunities for senior listeners to intervene and offer input
• Chief concern: Reason why patient presented to hospital (symptom/event and key past history in one sentence). It often includes a limited listing of their other medical conditions (e.g. diabetes, hypertension, etc.) if these elements might contribute to the reason for admission.
• The history is presented highlighting the relevant events in chronological order.
• 7 days ago, the patient began to notice vague shortness of breath.
• 5 days ago, the breathlessness worsened and they developed a cough productive of green sputum.
• 3 days ago his short of breath worsened to the point where he was winded after walking up a flight of stairs, accompanied by a vague right sided chest pain that was more pronounced with inspiration.
• Enough historical information has to be provided so that the listener can understand the reasons that lead to admission and be able to draw appropriate clinical conclusions.
• Past history that helps to shed light on the current presentation are included towards the end of the HPI and not presented later as “PMH.” This is because knowing this “past” history is actually critical to understanding the current complaint. For example, past cardiac catheterization findings and/or interventions should be presented during the HPI for a patient presenting with chest pain.
• Where relevant, the patient's baseline functional status is described, allowing the listener to understand the degree of impairment caused by the acute medical problem(s).
• It should be explicitly stated if a patient is a poor historian, confused or simply unaware of all the details related to their illness. Historical information obtained from family, friends, etc. should be described as such.
• Review of Systems (ROS): Pertinent positive and negative findings discovered during a review of systems are generally incorporated at the end of the HPI. The listener needs this information to help them put the story in appropriate perspective. Any positive responses to a more inclusive ROS that covers all of the other various organ systems are then noted. If the ROS is completely negative, it is generally acceptable to simply state, "ROS negative.”
• Other Past Medical and Surgical History (PMH/PSH): Past history that relates to the issues that lead to admission are typically mentioned in the HPI and do not have to be repeated here. That said, selective redundancy (i.e. if it’s really important) is OK. Other PMH/PSH are presented here if relevant to the current issues and/or likely to affect the patient’s hospitalization in some way. Unrelated PMH and PSH can be omitted (e.g. if the patient had their gall bladder removed 10y ago and this has no bearing on the admission, then it would be appropriate to leave it out). If the listener really wants to know peripheral details, they can read the admission note, ask the patient themselves, or inquire at the end of the presentation.
• Medications and Allergies: Typically all meds are described, as there’s high potential for adverse reactions or drug-drug interactions.
• Family History: Emphasis is placed on the identification of illnesses within the family (particularly among first degree relatives) that are known to be genetically based and therefore potentially heritable by the patient. This would include: coronary artery disease, diabetes, certain cancers and autoimmune disorders, etc. If the family history is non-contributory, it’s fine to say so.
• Social History, Habits, other → as relates to/informs the presentation or hospitalization. Includes education, work, exposures, hobbies, smoking, alcohol or other substance use/abuse.
• Sexual history if it relates to the active problems.
• Vital signs and relevant findings (or their absence) are provided. As your team develops trust in your ability to identify and report on key problems, it may become acceptable to say “Vital signs stable.”
• Note: Some listeners expect students (and other junior clinicians) to describe what they find in every organ system and will not allow the presenter to say “normal.” The only way to know what to include or omit is to ask beforehand.
• Key labs and imaging: Abnormal findings are highlighted as well as changes from baseline.
• Summary, assessment & plan(s) Presented by problem or organ systems(s), using as many or few as are relevant. Early on, it’s helpful to go through the main categories in your head as a way of making sure that you’re not missing any relevant areas. The broad organ system categories include (presented here head-to-toe): Neurological; Psychiatric; Cardiovascular; Pulmonary; Gastrointestinal; Renal/Genitourinary; Hematologic/Oncologic; Endocrine/Metabolic; Infectious; Tubes/lines/drains; Disposition.
• The assessment and plan typically concludes by mentioning appropriate prophylactic considerations (e.g. DVT prevention), code status and disposition.
• Chief Concern: Mr. H is a 50 year old male with AIDS, on HAART, with preserved CD4 count and undetectable viral load, who presents for the evaluation of fever, chills and a cough over the past 7 days.
• Until 1 week ago, he had been quite active, walking up to 2 miles a day without feeling short of breath.
• Approximately 1 week ago, he began to feel dyspneic with moderate activity.
• 3 days ago, he began to develop subjective fevers and chills along with a cough productive of red-green sputum.
• 1 day ago, he was breathless after walking up a single flight of stairs and spent most of the last 24 hours in bed.
• Diagnosed with HIV in 2000, done as a screening test when found to have gonococcal urethritis
• Was not treated with HAART at that time due to concomitant alcohol abuse and non-adherence.
• Diagnosed and treated for PJP pneumonia 2006
• Diagnosed and treated for CMV retinitis 2007
• Became sober in 2008, at which time interested in HAART. Started on Atripla, a combination pill containing: Efavirenz, Tonofovir, and Emtricitabine. He’s taken it ever since, with no adverse effects or issues with adherence. Receives care thru Dr. Smiley at the University HIV clinic.
• CD4 count 3 months ago was 400 and viral load was undetectable.
• He is homosexual though he is currently not sexually active. He has never used intravenous drugs.
• He has no history of asthma, COPD or chronic cardiac or pulmonary condition. No known liver disease. Hepatitis B and C negative. His current problem seems different to him then his past episode of PJP.
• Review of systems: negative for headache, photophobia, stiff neck, focal weakness, chest pain, abdominal pain, diarrhea, nausea, vomiting, urinary symptoms, leg swelling, or other complaints.
• Hypertension x 5 years, no other known vascular disease
• Gonorrhea as above
• Alcohol abuse above and now sober – no known liver disease
• No relevant surgeries
• Atripla, 1 po qd
• Omeprazole 20 mg, 1 PO, qd
• Lisinopril 20mg, qd
• Naprosyn 250 mg, 1-2, PO, BID PRN
• No allergies
• Both of the patient's parents are alive and well (his mother is 78 and father 80). He has 2 brothers, one 45 and the other 55, who are also healthy. There is no family history of heart disease or cancer.
• Patient works as an accountant for a large firm in San Diego. He lives alone in an apartment in the city.
• Smokes 1 pack of cigarettes per day and has done so for 20 years.
• No current alcohol use. Denies any drug use.
• Sexual History as noted above; has sex exclusively with men, last partner 6 months ago.
• Seated on a gurney in the ER, breathing through a face-mask oxygen delivery system. Breathing was labored and accessory muscles were in use. Able to speak in brief sentences, limited by shortness of breath
• Vital signs: Temp 102 F, Pulse 90, BP 150/90, Respiratory Rate 26, O2 Sat (on 40% Face Mask) 95%
• HEENT: No thrush, No adenopathy
• Lungs: Crackles and Bronchial breath sounds noted at right base. E to A changes present. No wheezing or other abnormal sounds noted over any other area of the lung. Dullness to percussion was also appreciated at the right base.
• Cardiac: JVP less than 5 cm; Rhythm was regular. Normal S1 and S2. No murmurs or extra heart sounds noted.
• Abdomen and Genital exams: normal
• Extremities: No clubbing, cyanosis or edema; distal pulses 2+ and equal bilaterally.
• Skin: no eruptions noted.
• Neurological exam: normal
• WBC 18 thousand with 10% bands;
• Normal Chem 7 and LFTs.
• Room air blood gas: pH of 7.47/ PO2 of 55/PCO2 of 30.
• Sputum gram stain remarkable for an abundance of polys along with gram positive diplococci.
• CXR remarkable for dense right lower lobe infiltrate without effusion.
• Monitored care unit, with vigilance for clinical deterioration.
• Hypertension: given significant pneumonia and unclear clinical direction, will hold lisinopril. If BP > 180 and or if clear not developing sepsis, will consider restarting.
• Low molecular weight heparin
• Code Status: Wishes to be full code full care, including intubation and ICU stay if necessary. Has good quality of life and hopes to return to that functional level. Wishes to reconsider if situation ever becomes hopeless. Older brother Tom is surrogate decision maker if the patient can’t speak for himself. Tom lives in San Diego and we have his contact info. He is aware that patient is in the hospital and plans on visiting later today or tomorrow.
• Expected duration of hospitalization unclear – will know more based on response to treatment over next 24 hours.

The holdover admission (presenting data that was generated by other physicians)

• Handoff admissions are very common and present unique challenges
• Understand the reasons why the patient was admitted
• Review key history, exam, imaging and labs to assure that they support the working diagnostic and therapeutic plans
• Does the data support the working diagnosis?
• Do the planned tests and consults make sense?
• What else should be considered (both diagnostically and therapeutically)?
• This process requires that the accepting team thoughtfully review their colleagues efforts with a critical eye – which is not disrespectful but rather constitutes one of the main jobs of the accepting team and is a cornerstone of good care *Note: At some point during the day (likely not during rounds), the team will need to verify all of the data directly with the patient.
• 8-10 minutes
• Chief concern: Reason for admission (symptom and/or event)
• Temporally presented bullets of events leading up to the admission
• Review of systems
• Relevant PMH/PSH – historical information that might affect the patient during their hospitalization.
• Meds and Allergies
• Family and Social History – focusing on information that helps to inform the current presentation.
• Habits and exposures
• Physical exam, imaging and labs that were obtained in the Emergency Department
• Assessment and plan that were generated in the Emergency Department.
• Overnight events (i.e. what happened in the Emergency Dept. and after the patient went to their hospital room)? Responses to treatments, changes in symptoms?
• How does the patient feel this morning? Key exam findings this morning (if seen)? Morning labs (if available)?
• Assessment and Plan , with attention as to whether there needs to be any changes in the working differential or treatment plan. The broad organ system categories include (presented here head-to-toe): Neurological; Psychiatric; Cardiovascular; Pulmonary; Gastrointestinal; Renal/Genitourinary; Hematologic/Oncologic; Endocrine/Metabolic; Infectious; Tubes/lines/drains; Disposition.
• Chief concern: 70 yo male who presented with 10 days of progressive shoulder pain, followed by confusion. He was brought in by his daughter, who felt that her father was no longer able to safely take care for himself.
• 10 days ago, Mr. X developed left shoulder pain, first noted a few days after lifting heavy boxes. He denies falls or direct injury to the shoulder.
• 1 week ago, presented to outside hospital ER for evaluation of left shoulder pain. Records from there were notable for his being afebrile with stable vitals. Exam notable for focal pain anteriorly on palpation, but no obvious deformity. Right shoulder had normal range of motion. Left shoulder reported as diminished range of motion but not otherwise quantified. X-ray negative. Labs remarkable for wbc 8, creat 2.2 (stable). Impression was that the pain was of musculoskeletal origin. Patient was provided with Percocet and told to see PMD in f/u
• Brought to our ER last night by his daughter. Pain in shoulder worse. Also noted to be confused and unable to care for self. Lives alone in the country, home in disarray, no food.
• ROS: negative for falls, prior joint or musculoskeletal problems, fevers, chills, cough, sob, chest pain, head ache, abdominal pain, urinary or bowel symptoms, substance abuse
• Hypertension
• Coronary artery disease, s/p LAD stent for angina 3 y ago, no symptoms since. Normal EF by echo 2 y ago
• Chronic kidney disease stage 3 with creatinine 1.8; felt to be secondary to atherosclerosis and hypertension
• aspirin 81mg qd, atorvastatin 80mg po qd, amlodipine 10 po qd, Prozac 20
• Allergies: none
• Family and Social: lives alone in a rural area of the county, in contact with children every month or so. Retired several years ago from work as truck driver. Otherwise non-contributory.
• Habits: denies alcohol or other drug use.
• Temp 98 Pulse 110 BP 100/70
• Drowsy though arousable; oriented to year but not day or date; knows he’s at a hospital for evaluation of shoulder pain, but doesn’t know the name of the hospital or city
• CV: regular rate and rhythm; normal s1 and s2; no murmurs or extra heart sounds.
• Left shoulder with generalized swelling, warmth and darker coloration compared with Right; generalized pain on palpation, very limited passive or active range of motion in all directions due to pain. Right shoulder appearance and exam normal.
• CXR: normal
• EKG: sr 100; nl intervals, no acute changes
• WBC 13; hemoglobin 14
• Na 134, k 4.6; creat 2.8 (1.8 baseline 4 m ago); bicarb 24
• LFTs and UA normal
• Vancomycin and Zosyn for now
• Orthopedics to see asap to aspirate shoulder for definitive diagnosis
• If aspiration is consistent with infection, will need to go to Operating Room for wash out.
• Urine electrolytes
• Follow-up on creatinine and obtain renal ultrasound if not improved
• Renal dosing of meds
• Strict Ins and Outs.
• follow exam
• obtain additional input from family to assure baseline is, in fact, normal
• Since admission (6 hours) no change in shoulder pain
• This morning, pleasant, easily distracted; knows he’s in the hospital, but not date or year
• T Current 101F Pulse 100 BP 140/80
• Ins and Outs: IVF Normal Saline 3L/Urine output 1.5 liters
• L shoulder with obvious swelling and warmth compared with right; no skin breaks; pain limits any active or passive range of motion to less than 10 degrees in all directions
• Labs this morning remarkable for WBC 10 (from 13), creatinine 2 (down from 2.8)
• Continue with Vancomycin and Zosyn for now
• I already paged Orthopedics this morning, who are en route for aspiration of shoulder, fluid for gram stain, cell count, culture
• If aspirate consistent with infection, then likely to the OR
• Continue IVF at 125/h, follow I/O
• Repeat creatinine later today
• Not on any nephrotoxins, meds renaly dosed
• Continue antibiotics, evaluation for primary source as above
• Discuss with family this morning to establish baseline; possible may have underlying dementia as well
• SC Heparin for DVT prophylaxis
• Code status: full code/full care.

Outpatient-based presentations

There are 4 main types of visits that commonly occur in an outpatient continuity clinic environment, each of which has its own presentation style and purpose. These include the following, each described in detail below.

• The patient who is presenting for their first visit to a primary care clinic and is entirely new to the physician.
• The patient who is returning to primary care for a scheduled follow-up visit.
• The patient who is presenting with an acute problem to a primary care clinic
• The specialty clinic evaluation (new or follow-up)

It’s worth noting that Primary care clinics (Internal Medicine, Family Medicine and Pediatrics) typically take responsibility for covering all of the patient’s issues, though the amount of energy focused on any one topic will depend on the time available, acuity, symptoms, and whether that issue is also followed by a specialty clinic.

The Brand New Primary Care Patient

Purpose of the presentation

• Accurately review all of the patient’s history as well as any new concerns that they might have.
• Identify health related problems that need additional evaluation and/or treatment
• Provide an opportunity for senior listeners to intervene and offer input

Key features of the presentation

• If this is truly their first visit, then one of the main reasons is typically to "establish care" with a new doctor.
• It might well include continuation of therapies and/or evaluations started elsewhere.
• If the patient has other specific goals (medications, referrals, etc.), then this should be stated as well. Note: There may well not be a "chief complaint."
• For a new patient, this is an opportunity to highlight the main issues that might be troubling/bothering them.
• This can include chronic disorders (e.g. diabetes, congestive heart failure, etc.) which cause ongoing symptoms (shortness of breath) and/or generate daily data (finger stick glucoses) that should be discussed.
• Sometimes, there are no specific areas that the patient wishes to discuss up-front.
• Review of systems (ROS): This is typically comprehensive, covering all organ systems. If the patient is known to have certain illnesses (e.g. diabetes), then the ROS should include the search for disorders with high prevalence (e.g. vascular disease). There should also be some consideration for including questions that are epidemiologically appropriate (e.g. based on age and sex).
• Past Medical History (PMH): All known medical conditions (in particular those requiring ongoing treatment) are listed, noting their duration and time of onset. If a condition is followed by a specialist or co-managed with other clinicians, this should be noted as well. If a problem was described in detail during the “acute” history, it doesn’t have to be re-stated here.
• Past Surgical History (PSH): All surgeries, along with the year when they were performed
• Medications and allergies: All meds, including dosage, frequency and over-the-counter preparations. Allergies (and the type of reaction) should be described.
• Social: Work, hobbies, exposures.
• Sexual activity – may include type of activity, number and sex of partner(s), partner’s health.
• Smoking, Alcohol, other drug use: including quantification of consumption, duration of use.
• Family history: Focus on heritable illness amongst first degree relatives. May also include whether patient married, in a relationship, children (and their ages).
• Physical Exam: Vital signs and relevant findings (or their absence).
• Key labs and imaging if they’re available. Also when and where they were obtained.
• Summary, assessment & plan(s) presented by organ system and/or problems. As many systems/problems as is necessary to cover all of the active issues that are relevant to that clinic. This typically concludes with a “health care maintenance” section, which covers age, sex and risk factor appropriate vaccinations and screening tests.

The Follow-up Visit to a Primary Care Clinic

• Organize the presenter (forces you to think things through).
• Accurately review any relevant interval health care events that might have occurred since the last visit.
• Identification of new symptoms or health related issues that might need additional evaluation and/or treatment
• If the patient has no concerns, then verification that health status is stable
• Review of medications
• Provide an opportunity for listeners to intervene and offer input
• Reason for the visit: Follow-up for whatever the patient’s main issues are, as well as stating when the last visit occurred *Note: There may well not be a “chief complaint,” as patients followed in continuity at any clinic may simply be returning for a visit as directed by their doctor.
• Events since the last visit: This might include emergency room visits, input from other clinicians/specialists, changes in medications, new symptoms, etc.
• Review of Systems (ROS): Depth depends on patient’s risk factors and known illnesses. If the patient has diabetes, then a vascular ROS would be done. On the other hand, if the patient is young and healthy, the ROS could be rather cursory.
• PMH, PSH, Social, Family, Habits are all OMITTED. This is because these facts are already known to the listener and actionable aspects have presumably been added to the problem list (presented at the end). That said, these elements can be restated if the patient has a new symptom or issue related to a historical problem has emerged.
• MEDS : A good idea to review these at every visit.
• Physical exam: Vital signs and pertinent findings (or absence there of) are mentioned.
• Lab and Imaging: The reason why these were done should be mentioned and any key findings mentioned, highlighting changes from baseline.
• Assessment and Plan: This is most clearly done by individually stating all of the conditions/problems that are being addressed (e.g. hypertension, hypothyroidism, depression, etc.) followed by their specific plan(s). If a new or acute issue was identified during the visit, the diagnostic and therapeutic plan for that concern should be described.

The Focused Visit to a Primary Care Clinic

• Accurately review the historical events that lead the patient to make the appointment.
• Identification of risk factors and/or other underlying medical conditions that might affect the diagnostic or therapeutic approach to the new symptom or concern.
• Generate an appropriate assessment and plan
• Allow the listener to comment

Key features of the presentation:

• Reason for the visit
• History of Present illness: Description of the sequence of symptoms and/or events that lead to the patient’s current condition.
• Review of Systems: To an appropriate depth that will allow the listener to grasp the full range of diagnostic possibilities that relate to the presenting problem.
• PMH and PSH: Stating only those elements that might relate to the presenting symptoms/issues.
• PE: Vital signs and key findings (or lack thereof)
• Labs and imaging (if done)
• Assessment and Plan: This is usually very focused and relates directly to the main presenting symptom(s) or issues.

The Specialty Clinic Visit

Specialty clinic visits focus on the health care domains covered by those physicians. For example, Cardiology clinics are interested in cardiovascular disease related symptoms, events, labs, imaging and procedures. Orthopedics clinics will focus on musculoskeletal symptoms, events, imaging and procedures. Information that is unrelated to these disciples will typically be omitted. It’s always a good idea to ask the supervising physician for guidance as to what’s expected to be covered in a particular clinic environment.

• Highlight the reason(s) for the visit
• Review key data
• Provide an opportunity for the listener(s) to comment
• 5-7 minutes
• If it’s a consult, state the main reason(s) that the patient was referred as well as who referred them.
• If it’s a return visit, state the reasons why the patient is being followed in the clinic and when the last visit took place
• If it’s for an acute issue, state up front what the issue is Note: There may well not be a “chief complaint,” as patients followed in continuity in any clinic may simply be returning for a return visit as directed
• For a new patient, this highlights the main things that might be troubling/bothering the patient.
• For a specialty clinic, the history presented typically relates to the symptoms and/or events that are pertinent to that area of care.
• Review of systems , focusing on those elements relevant to that clinic. For a cardiology patient, this will highlight a vascular ROS.
• PMH/PSH that helps to inform the current presentation (e.g. past cardiac catheterization findings/interventions for a patient with chest pain) and/or is otherwise felt to be relevant to that clinic environment.
• Meds and allergies: Typically all meds are described, as there is always the potential for adverse drug interactions.
• Social/Habits/other: as relates to/informs the presentation and/or is relevant to that clinic
• Family history: Focus is on heritable illness amongst first degree relatives
• Physical Exam: VS and relevant findings (or their absence)
• Key labs, imaging: For a cardiology clinic patient, this would include echos, catheterizations, coronary interventions, etc.
• Summary, assessment & plan(s) by organ system and/or problems. As many systems/problems as is necessary to cover all of the active issues that are relevant to that clinic.
• Reason for visit: Patient is a 67 year old male presenting for first office visit after admission for STEMI. He was referred by Dr. Goins, his PMD.
• The patient initially presented to the ER 4 weeks ago with acute CP that started 1 hour prior to his coming in. He was found to be in the midst of a STEMI with ST elevations across the precordial leads.
• Taken urgently to cath, where 95% proximal LAD lesion was stented
• EF preserved by Echo; Peak troponin 10
• In-hospital labs were remarkable for normal cbc, chem; LDL 170, hdl 42, nl lfts
• Uncomplicated hospital course, sent home after 3 days.
• Since home, he states that he feels great.
• Denies chest pain, sob, doe, pnd, edema, or other symptoms.
• No symptoms of stroke or TIA.
• No history of leg or calf pain with ambulation.
• Prior to this admission, he had a history of hypertension which was treated with lisinopril
• 40 pk yr smoking history, quit during hospitalization
• No known prior CAD or vascular disease elsewhere. No known diabetes, no family history of vascular disease; He thinks his cholesterol was always “a little high” but doesn’t know the numbers and was never treated with meds.
• History of depression, well treated with prozac
• Discharge meds included: aspirin, metoprolol 50 bid, lisinopril 10, atorvastatin 80, Plavix; in addition he takes Prozac for depression
• Taking all of them as directed.
• Patient lives with his wife; they have 2 grown children who are no longer at home
• Works as a computer programmer
• Smoking as above
• ETOH: 1 glass of wine w/dinner
• No drug use
• No known history of cardiovascular disease among 2 siblings or parents.
• Well appearing; BP 130/80, Pulse 80 regular, 97% sat on Room Air, weight 175lbs, BMI 32
• Lungs: clear to auscultation
• CV: s1 s2 no s3 s4 murmur
• No carotid bruits
• ABD: no masses
• Ext; no edema; distal pulses 2+
• Cath from 4 weeks ago: R dominant; 95% proximal LAD; 40% Cx.
• EF by TTE 1 day post PCI with mild Anterior Hypokinesis, EF 55%, no valvular disease, moderate LVH
• Labs of note from the hospital following cath: hgb 14, plt 240; creat 1, k 4.2, lfts normal, glucose 100, LDL 170, HDL 42.
• EKG today: SR at 78; nl intervals; nl axis; normal r wave progression, no q waves
• Plan: aspirin 81 indefinitely, Plavix x 1y
• Given nitroglycerine sublingual to have at home.
• Reviewed symptoms that would indicate another MI and what to do if occurred
• Plan: continue with current dosages of meds
• Chem 7 today to check k, creatinine
• Plan: Continue atorvastatin 80mg for life
• Smoking cessation: Doing well since discharge without adjuvant treatments, aware of supports.
• Plan: AAA screening ultrasound

How To Present a Patient: A Step-To-Step Guide

Last Updated on June 24, 2022 by Laura Turner

Updated and verified by Dr. Lee Burnett on March 19, 2022.

The ability to deliver oral case presentations is a core skill for any physician. Effective oral case presentations help facilitate information transfer among physicians and are essential to delivering quality patient care. Oral case presentations are also a key component of how medical students and residents are assessed during their training.

At its core, an oral case presentation functions as an argument. It is the presenter’s job to share the pertinent facts of a patient’s case with the other members of the medical care team and establish a clear diagnosis and treatment plan. Thus, the presenter should include details to support the proposed diagnosis, argue against alternative diagnoses, and exclude extraneous information. While this task may seem daunting at first, with practice, it will become easier. That said, if you are unsure if a particular detail is important to your patient’s case, it is probably best to be safe and include it.

Now, let’s go over how to present a case. While I will focus on internal medicine inpatients, the following framework can be applied to patients in any setting with slight modifications.

Oral case presentations are generally made to a medical care team, which can be composed of medical and pharmacy students, residents, pharmacists, medical attendings, and others. As the presenter, you should strive to deliver an interesting presentation that keeps your team members engaged. Here are a few things to keep in mind:

• Be confident: Speak clearly at the loudest volume appropriate to protect patient privacy, vary your tone to emphasize the most important details, and maintain eye contact with members of your team.
• Don’t fidget : Stand up straight and avoid unnecessary, distracting movements.
• Use your notes : You may glance at your notes from time to time while presenting. However, while there is no need to memorize your presentation, there is no better way to lose your team’s attention than to read your notes to them.
• Be honest: Given the importance of presentations in guiding medical care, never guess or report false information to the team. If you are unsure about a particular detail, say so.

The length of your presentation will depend on various factors, including the complexity of your patient, your audience, and your specialty. I have found that new internal medicine inpatients generally take 5-10 minutes to present. Internal medicine clerkship directors seem to agree. In a 2009 survey , they reported a range of 2-20 minutes for the ideal length of student inpatient presentations, with a median of 7 minutes.

While delivering oral case presentations is a core skill for trainees, and there have been attempts to standardize the format , expectations still vary among attending physicians. This can be a frustrating experience for trainees, and I would recommend that you clarify your attending’s expectations at the beginning of each new rotation. However, I have found that these differences are often stylistic, and content expectations are generally quite similar. Thus, developing a familiarity with the core elements of a strong oral case presentation is essential.

How to Present a Patient

You should begin every oral presentation with a brief one-liner that contains the patient’s name, age, relevant past medical history, and chief complaint. Remember that the chief complaint is why the patient sought medical care in his or her own words. An example of an effective opening is as follows: “Ms. X is a 78-year-old female with a past medical history of chronic obstructive pulmonary disease who presents to the hospital after she felt short of breath at home.”

Following the opener, elaborate on why the patient sought medical care. Describe the events that preceded the patient’s presentation in chronological order. A useful mnemonic to use when deciding what to report is OPQRST , which includes: • The Onset of the patient’s symptoms • Any Palliative or Provoking factors that make the symptoms better or worse, respectively • The Quality of his or her symptoms (how he or she describes them) • The Region of the body where the patient is experiencing his or her symptoms and (if the symptom is pain) whether the patient’s pain Radiates to another location or is well-localized • The Severity of the symptoms and any other associated Symptoms • The Time course of the symptoms (how they have changed over time and whether the patient has experienced them before) Additionally, include any other details here that may support your final diagnosis or rule out alternative diagnoses. For example, if you are concerned about a pulmonary embolism and your patient recently completed a long-distance flight, that would be worth mentioning.

The review of systems is sometimes included in the history of present illness, but it may also be separated. Given the potential breadth of the review of systems (a comprehensive list of questions that may be asked can be found here ), when presenting, only report information that is relevant to your patient’s condition.

The past medical history comes next. This should include the following information: • The patient’s medical conditions, including any that were not highlighted in the opener • Any past surgeries the patient has had and when they were performed • The timing of and reasons for past hospitalizations • Any current medications, including dosages and frequency of administration

The next section should detail the patient’s relevant family history. This should include: • Any relevant conditions that run in the patient’s family, with an emphasis on first-degree relatives

After the family history comes the social history. This section should include information about the patient’s: • Living situation • Occupation • Alcohol and tobacco use • Other substance use You may also include relevant details about the patient’s education level, recent travel history, history of animal and occupational exposures, and religious beliefs. For example, it would be worth mentioning that your anemic patient is a Jehovah’s Witness to guide medical decisions regarding blood transfusions.

Once you have finished reporting the patient’s history, you should transition to the physical exam. You should begin by reporting the patient’s vital signs, which includes the patient’s: • Temperature • Heart rate • Blood pressure • Respiratory rate • Oxygen saturation (if the patient is using supplemental oxygen, this should also be reported) Next, you should discuss the findings of your physical exam. At the minimum, this should include: • Your general impressions of the patient, including whether he or she appears “sick” or not • The results of your: • Head and neck exam • Eye exam • Respiratory exam • Cardiac exam • Abdominal exam • Extremity exam • Neurological exam Additional relevant physical examination findings may be included, as well. Quick note: resist the urge to report an exam as being “normal.” Instead, report your findings. For example, for a normal abdominal exam, you could report that “the patient’s abdomen is soft, non-tender, and non-distended, with normoactive bowel sounds.”

This section includes the results of any relevant laboratory testing, imaging, or other diagnostics that were obtained. You do not have to report the results of every test that was ordered. Before presenting, consider which results will further support your proposed diagnosis and exclude alternatives.

The emergency department (ED) course is classically reported towards the end of the presentation. However, different attendings may prefer to hear the ED course earlier, usually following the history of present illness. When unsure, report the ED course after the results of diagnostic testing. Be sure to include initial ED vital signs and any administered treatments.

You should conclude your presentation with the assessment and plan. This is the most important part of your presentation and allows you to show your team how much you really know. You should include: • A brief summary (1-2 lines) of the patient, the reason for admission, and your likely diagnosis. This should also include information regarding the patient’s clinical stability. While it can be similar to your opener, it should not be identical. An example could be: “Ms. X is a 78-year-old female with a past medical history of chronic obstructive pulmonary disease who presents with shortness of breath in the setting of an upper respiratory tract infection who is now stable on two liters of supplemental oxygen delivered via nasal cannula. Her symptoms are thought to be secondary to an acute exacerbation of chronic obstructive pulmonary disease.” • A differential diagnosis . For students, this should consist of 3-5 potential diagnoses. You should explain why you think each diagnosis is or is not the final diagnosis. Be sure to rule out potentially life-threatening conditions (unless you think your patient has one). For our fictional patient, Ms. X, for example, you could explain why you think she does not have a pulmonary embolism or acute coronary syndrome. For more advanced trainees, the differential can be more limited in scope. • Your plan . On regular inpatient floors, this should include a list of the patient’s medical problems, ordered by acuity, followed by your proposed plan for each. After going through each active medical problem, be sure to mention your choice for the patient’s diet and deep vein thrombosis prophylaxis, the patient’s stated code status, and the patient’s disposition (whether you think they need to remain in the hospital). In intensive care units, you can organize the patient’s medical problems by organ system to ensure that no stone is left unturned (if there are no active issues for an organ system, you may say so).

Presenting Patients Who Have Been in the Hospital for Multiple Days

After the initial presentation, subsequent presentations can be delivered via SOAP note format as follows:

• The  Subjective  section includes details about any significant overnight events and any new complaints the patient has.
• In the  Objective  section, report your physical exam (focus on any changes since you last examined the patient) and any significant new laboratory, imaging, or other diagnostic results.
• The  Assessment  and  Plan  are typically delivered as above. For the initial patient complaint, you do not have to restate your differential diagnosis if the diagnosis is known. For new complaints, however, you should create another differential and argue for or against each diagnosis. Be sure to update your plan every day.

Presenting Patients in Different Specialties

Before you present a patient, consider your audience. Every specialty presents patients differently. In general, surgical and OB/GYN presentations tend to be much quicker (2-3 minutes), while pediatric and family medicine presentations tend to be similar in length to internal medicine presentations. Tailor your presentations accordingly.

Presenting Patients in Outpatient Settings

Outpatients may be presented similarly to inpatients. Your presentation’s focus, however, should align with your outpatient clinic’s specialty. For example, if you are working at a cardiology clinic, your presentation should be focused on your patient’s cardiac complaints.

If your patient is returning for a follow-up visit and does not have a stated chief complaint, you should say so. You may replace the history of present illness with any relevant interval history since his or her last visit.

And that’s it! Delivering oral case presentations is challenging at first, so remember to practice. In time, you will become proficient in this essential medical skill. Good luck!

Kunal Sindhu, MD, is an assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai and New York Proton Center. Dr. Sindhu specializes in treating cancers of the head, neck, and central nervous system.

2 thoughts on “How To Present a Patient: A Step-To-Step Guide”

To clarify, it should take 5-10 minutes to present (just one) new internal medicine inpatient? Or if the student had 4 patients to work up, it should take 10 minutes to present all 4 patients to the preceptor?

Good question. That’s per case, but with time you’ll become faster.

Comments are closed.

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How to prepare and deliver an effective oral presentation

• Related content
• Peer review
• Lucia Hartigan , registrar 1 ,
• Fionnuala Mone , fellow in maternal fetal medicine 1 ,
• Mary Higgins , consultant obstetrician 2
• 1 National Maternity Hospital, Dublin, Ireland
• 2 National Maternity Hospital, Dublin; Obstetrics and Gynaecology, Medicine and Medical Sciences, University College Dublin
• luciahartigan{at}hotmail.com

The success of an oral presentation lies in the speaker’s ability to transmit information to the audience. Lucia Hartigan and colleagues describe what they have learnt about delivering an effective scientific oral presentation from their own experiences, and their mistakes

The objective of an oral presentation is to portray large amounts of often complex information in a clear, bite sized fashion. Although some of the success lies in the content, the rest lies in the speaker’s skills in transmitting the information to the audience. 1

Preparation

It is important to be as well prepared as possible. Look at the venue in person, and find out the time allowed for your presentation and for questions, and the size of the audience and their backgrounds, which will allow the presentation to be pitched at the appropriate level.

See what the ambience and temperature are like and check that the format of your presentation is compatible with the available computer. This is particularly important when embedding videos. Before you begin, look at the video on stand-by and make sure the lights are dimmed and the speakers are functioning.

For visual aids, Microsoft PowerPoint or Apple Mac Keynote programmes are usual, although Prezi is increasing in popularity. Save the presentation on a USB stick, with email or cloud storage backup to avoid last minute disasters.

When preparing the presentation, start with an opening slide containing the title of the study, your name, and the date. Begin by addressing and thanking the audience and the organisation that has invited you to speak. Typically, the format includes background, study aims, methodology, results, strengths and weaknesses of the study, and conclusions.

If the study takes a lecturing format, consider including “any questions?” on a slide before you conclude, which will allow the audience to remember the take home messages. Ideally, the audience should remember three of the main points from the presentation. 2

Have a maximum of four short points per slide. If you can display something as a diagram, video, or a graph, use this instead of text and talk around it.

Animation is available in both Microsoft PowerPoint and the Apple Mac Keynote programme, and its use in presentations has been demonstrated to assist in the retention and recall of facts. 3 Do not overuse it, though, as it could make you appear unprofessional. If you show a video or diagram don’t just sit back—use a laser pointer to explain what is happening.

Rehearse your presentation in front of at least one person. Request feedback and amend accordingly. If possible, practise in the venue itself so things will not be unfamiliar on the day. If you appear comfortable, the audience will feel comfortable. Ask colleagues and seniors what questions they would ask and prepare responses to these questions.

It is important to dress appropriately, stand up straight, and project your voice towards the back of the room. Practise using a microphone, or any other presentation aids, in advance. If you don’t have your own presenting style, think of the style of inspirational scientific speakers you have seen and imitate it.

Try to present slides at the rate of around one slide a minute. If you talk too much, you will lose your audience’s attention. The slides or videos should be an adjunct to your presentation, so do not hide behind them, and be proud of the work you are presenting. You should avoid reading the wording on the slides, but instead talk around the content on them.

Maintain eye contact with the audience and remember to smile and pause after each comment, giving your nerves time to settle. Speak slowly and concisely, highlighting key points.

Do not assume that the audience is completely familiar with the topic you are passionate about, but don’t patronise them either. Use every presentation as an opportunity to teach, even your seniors. The information you are presenting may be new to them, but it is always important to know your audience’s background. You can then ensure you do not patronise world experts.

To maintain the audience’s attention, vary the tone and inflection of your voice. If appropriate, use humour, though you should run any comments or jokes past others beforehand and make sure they are culturally appropriate. Check every now and again that the audience is following and offer them the opportunity to ask questions.

Finishing up is the most important part, as this is when you send your take home message with the audience. Slow down, even though time is important at this stage. Conclude with the three key points from the study and leave the slide up for a further few seconds. Do not ramble on. Give the audience a chance to digest the presentation. Conclude by acknowledging those who assisted you in the study, and thank the audience and organisation. If you are presenting in North America, it is usual practice to conclude with an image of the team. If you wish to show references, insert a text box on the appropriate slide with the primary author, year, and paper, although this is not always required.

Answering questions can often feel like the most daunting part, but don’t look upon this as negative. Assume that the audience has listened and is interested in your research. Listen carefully, and if you are unsure about what someone is saying, ask for the question to be rephrased. Thank the audience member for asking the question and keep responses brief and concise. If you are unsure of the answer you can say that the questioner has raised an interesting point that you will have to investigate further. Have someone in the audience who will write down the questions for you, and remember that this is effectively free peer review.

Be proud of your achievements and try to do justice to the work that you and the rest of your group have done. You deserve to be up on that stage, so show off what you have achieved.

Competing interests: We have read and understood the BMJ Group policy on declaration of interests and declare the following interests: None.

• ↵ Rovira A, Auger C, Naidich TP. How to prepare an oral presentation and a conference. Radiologica 2013 ; 55 (suppl 1): 2 -7S. OpenUrl
• ↵ Bourne PE. Ten simple rules for making good oral presentations. PLos Comput Biol 2007 ; 3 : e77 . OpenUrl PubMed
• ↵ Naqvi SH, Mobasher F, Afzal MA, Umair M, Kohli AN, Bukhari MH. Effectiveness of teaching methods in a medical institute: perceptions of medical students to teaching aids. J Pak Med Assoc 2013 ; 63 : 859 -64. OpenUrl

Posters & Oral Presentations

Good scientific research involves a sound methodology and a novel idea that can be tested simply and repeatedly to give valid, trustworthy results. However, even the most clinically significant research is useless if it is not communicated successfully. Scientific ideas are novel, sometimes simple in theory, but most always complex in technique. These attributes of research make it necessary to use all available means of presentation. The most common media for scientists to communicate with the general public is primary journal articles. However, posters and oral presentations are also affective because they allow scientists to be in direct contact with their audience. This provides both parties an opportunity to ask pertinent questions to add clarity to the work being presented.

A poster is an exciting way for scientists to present their research. It, just as a primary research article, includes all aspects of the scientific method. A title that is brief, but specific, an abstract, an introduction, material and methods, results, and a conclusion are some headings that can appear on a poster. Also, references and acknowledgments are sometimes are included. A poster is different from a written manuscript or an oral presentation because it is mostly graphical. As such, it is important to design a poster that is visually pleasing by focusing on charts, graphs, and pictures and minimizing lengthy introductions and discussions. Highlighting all significant information with the use of bullets is essential because if further explanation is needed the audience will simply ask for it.

Oral presentations are yet another avenue for scientists to share their findings with the world. Although it can be challenging to present years of works within fifteen minutes, oral presentations can be a rewarding experience because you are the only one front of an audience whose attention you know have. Of course this emphasizes the need to speak clearly and concisely with choice words that engross the audience. Again, just as with written manuscript and posters the format of oral presentations can also vary, but essentially it must include logical, easy-to-understand events that are presented in a matter with respect to the scientific method.

Electronic Resources

Poster Presentation http://www.ncsu.edu/project/posters

This is an excellent site that covers all aspects of a poster presentation from creating a poster to presenting one. It also provides several examples with critiques for each sample. Lastly, it has a quick reference page with helpful tips for delivering a successful poster presentation.

Oral Presentation http://www.kumc.edu/SAH/OTEd/jradel/Preparing_talks/103.html

This site is cited by the NIH and is quite useful when designing an oral presentation. It addresses all aspects of a scientific talk from planning and preparing to practicing and presenting. It is brief and easy to follow with helpful tips on how to prepare for the question/answer session.

Document Resources  

Scientific Poster: Tips, Significance, Design, Templates and Presentation

This document provides tips and temples for designing a poster presentation. It also discusses the significance of a poster presentation and includes a section that gives advice on how to present successfully.

Oral Presentations: Tips, Significance, Design, Guidelines & Presentation

This document provides tips and guidelines for designing an oral presentation. It also discusses the significance of an oral presentation and includes a section that gives advice on how to present successfully.

Tools for the Patient Presentation

The formal patient presentation.

• Posing the Clinical Question
• Searching the Medical Literature for EBM

Sources & Further Reading

First Aid for the Wards

Lingard L, Haber RJ.  Teaching and learning communications in medicine: a rhetorical approach .  Academic Medicine. 74(5):507-510 1999 May.

Lingard L, Haber RJ.  What do we mean by "relevance"? A clinical and rhetorical definition with implications for teaching and learning the case-presentation format . Academic Medicine. 74(10):S124-S127.

The Oral Presentation (A Practical Guide to Clinical Medicine, UCSD School of Medicine)  http://meded.ucsd.edu/clinicalmed/oral.htm

"Classically, the formal oral presentation is given in 7 minutes or less. Although it follows the same format as a written report, it is not simply regurgitation. A great presentation requires style as much as substance; your delivery must be succinct and smooth. No time should be wasted on superfluous information; one can read about such matters later in your admit note. Ideally, your presentation should be formulated so that your audience can anticipate your assessment and plan; that is, each piece of information should clue the listener into your thinking process and your most likely diagnosis."  [ Le, et al, p. 15 ]

Types of Patient Presentations

New Patient

New patients get the traditional H&P with assessment and plan.  Give the chief complaint and a brief and pertinent HPI.  Next give important PMH, PSH, etc.  The ROS is often left out, as anything important was in the HPI.  The PE is reviewed.  Only give pertinent positives and negatives.  The assessment and plan should include what you think is wrong and, briefly, why.  Then, state what you plan to do for the patient, including labs.  Be sure to know why things are being done: you will be asked.

The follow-up presentation differs from the presentation of a new patient.  It is an abridged presentation, perhaps referencing major patient issues that have been previously presented, but focusing on new information about these issues and/or what has changed. Give the patient’s name, age, date of admission, briefly review the present illness, physical examination and admitting diagnosis.  Then report any new finding, laboratory tests, diagnostic procedures and changes in medications.

The attending physician will ask the patient’s permission to have the medical student present their case.  After making the proper introductions the attending will let the patient know they may offer input or ask questions at any point.  When presenting at bedside the student should try to involve the patient.

Preparing for the Presentation

There are four things you must consider before you do your oral presentation

• Occasion (setting and circumstances)

Ask yourself what do you want the presentation to do

• Present a new patient to your preceptor : the amount of detail will be determined by your preceptor.  It is also likely to reflect your development and experience, with less detail being required as you progress.
• Present your patient at working or teaching rounds : the amount of detail will be determined by the customs of the group. The focus of the presentation will be influenced by the learning objectives of working responsibilities of the group.
• Request a consultant’s advice on a clinical problem : the presentation will be focused on the clinical question being posed to the consultant.
• Persuade others about a diagnosis and plan : a shorter presentation which highlights the pertinent positives and negatives that are germane to the diagnosis and/or plan being suggested.
• Enlist cooperation required for patient care : a short presentation focusing on the impact your audience can have in addressing the patient’s issues.

Preparation

• Patient evaluation : history, physical examination, review of tests, studies, procedures, and consultants’ recommendations.
• Selected reading : reference texts; to build a foundational understanding.
• Literature search : for further elucidation of any key references from selected reading, and to bring your understanding up to date, since reference text information is typically three to seven years old.
• Write-up : for oral presentation, just succinct notes to serve as a reminder or reference, since you’re not going to be reading your presentation.

Knowledge (Be prepared to answer questions about the following)

• Pathophysiology
• Complications
• Differential diagnosis
• Course of conditions
• Diagnostic tests
• Medications
• Essential Evidence Plus

Template for Oral Presentations

Chief Complaint (CC)

The opening statement should give an overview of the patient, age, sex, reason for visit and the duration of the complaint. Give marital status, race, or occupation if relevant.  If your patient has a history of a major medical problem that bears strongly on the understanding of the present illness, include it.  For ongoing care, give a one sentence recap of the history.

History of Present Illness (HPI)

This will be very similar to your written HPI. Present the most important problem first. If there is more than one problem, treat each separately. Present the information chronologically.  Cover one system before going onto the next. Characterize the chief complaint – quality, severity, location, duration, progression, and include pertinent negatives. Items from the ROS that are unrelated to the present problem may be mentioned in passing unless you are doing a very formal presentation. When you do your first patient presentation you may be expected to go into detail.  For ongoing care, present any new complaints.

Review of Systems (ROS)

Most of the ROS is incorporated at the end of the HPI. Items that are unrelated to the present problem may be briefly mentioned.  For ongoing care, present only if new complaints.  

Past Medical History (PMH)

Discuss other past medical history that bears directly on the current medical problem.  For ongoing care, have the information available to respond to questions.

Past Surgical History

Provide names of procedures, approximate dates, indications, any relevant findings or complications, and pathology reports, if applicable.  For ongoing care, have the information available to respond to questions.

Allergies/Medications

Present all current medications along with dosage, route and frequency. For the follow-up presentation just give any changes in medication.  For ongoing care, note any changes.

Smoking and Alcohol (and any other substance abuse)

Note frequency and duration. For ongoing care, have the information available to respond to questions.

Social/Work History

Home, environment, work status and sexual history.  For ongoing care, have the information available to respond to questions.

Family History Note particular family history of genetically based diseases.  For ongoing care, have the information available to respond to questions.

Physical Exam/Labs/Other Tests

Include all significant abnormal findings and any normal findings that contribute to the diagnosis. Give a brief, general description of the patient including physical appearance. Then describe vital signs touching on each major system. Try to find out in advance how thorough you need to be for your presentation. There are times when you will be expected to give more detail on each physical finding, labs and other test results.  For ongoing care, mention only further positive findings and relevant negative findings.

Assessment and Plan

Give a summary of the important aspects of the history, physical exam and formulate the differential diagnosis. Make sure to read up on the patient’s case by doing a search of the literature. 

• Include only the most essential facts; but be ready to answer ANY questions about all aspects of your patient.
• Keep your presentation lively.
• Do not read the presentation!
• Expect your listeners to ask questions.
• Follow the order of the written case report.
• Keep in mind the limitation of your listeners.
• Beware of jumping back and forth between descriptions of separate problems.
• Use the presentation to build your case.
• Your reasoning process should help the listener consider a differential diagnosis.
• Present the patient as well as the illness .
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PBL Information Resources and Tools for the First Year: Oral Presentation Resources

• Clinical Resources
• Background Info Resources
• Drug Info Resources
• Current Case
• PBL Case Archive
• Search Tips & Tutorials
• APA Examples
• Numbered Style Example
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• Reference : Normal Lab Values
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• Write-Ups: Word & PowerPoint Tips

Books Worth Checking Out

Have a resource to share or need something more?   Let Karen know .

Oral Presentations

Dr. Konop's Tips

The oral case presentation requires a bit of effort and benefits from repeated practice. You may have questions about what to include and the following resources will help you keep in mind the salient points to cover.  Some presentations will be brief - when fewer points will be covered - and some will be longer - where you can cover all of the key points.  

• Dr. Goldberg's Tips Don't forget the tips at the end.
• Michigan's State's PBL List (concise) A list with brief details on some points.
• Cornell's Tips for 3rd Year A bit specific to the wards, but some good guidelines to use.
• Drexel's Tip (lots of detail) Including examples, mnemonics & common mistakes. They advise, "an oral case presentation is NOT a simple recitation of your write-up. It is a concise, edited presentation of the most essential information."

Dr. Gates Tip

Dr. Gates found a great form to use as a reminder of what to cover.  For those of you that like notes, this will work well, and those of you who just want some structure, it will provide that.

• Oral Presentation as PDF A fill in the blanks form.
• Oral Presentation as Word file A fill in the blanks form where you can enter the patient info.

Quick Reminder:

Don't bury the lead!  

In other words, state up front the Chief Complaint .  Knowing that will give your listeners the chance to put all the pieces of info that you have to say together in a way that helps them.

For an Alternative Perspective

• BMJ Article on How to Present a Case A bit more detailed (good for clerkship maybe?) but some good tips. Requires a free account to BMJ Student.
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• Last Updated: Jul 17, 2024 10:04 AM
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Evaluating Oral Case Presentations Using a Checklist

How do senior student-evaluators compare with faculty.

Kakar, Seema P. MD; Catalanotti, Jillian S. MD, MPH; Flory, Andrea L. MD; Simmens, Samuel J. PhD; Lewis, Karen L. PhD; Mintz, Matthew L. MD; Haywood, Yolanda C. MD; Blatt, Benjamin C. MD

Dr. Kakar is assistant professor, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Dr. Catalanotti is assistant professor, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Dr. Flory is assistant professor, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Dr. Simmens is research professor, Department of Epidemiology and Biostatistics, The George Washington University School of Public Health and Health Services, Washington, DC.

Dr. Lewis is director of administration, Clinical Learning and Simulation Skills (CLASS) Center, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Dr. Mintz is associate professor, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Dr. Haywood is assistant dean for student and curricular affairs, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Dr. Blatt is professor, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Funding/Support: None.

Other disclosures: None.

Ethical approval: This study was approved by the institutional review board of The George Washington University.

Previous presentations: The abstract of an earlier version of this article was presented at the May 2011 Northeastern Group on Educational Affairs meeting, Washington, DC, and at the November 2011 Research in Medical Education Conference, Denver, Colorado.

Correspondence should be addressed to Dr. Kakar, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2150 Pennsylvania Ave., NW, Washington, DC 20037; e-mail: [email protected] .

Purpose 

Previous studies have shown student-evaluators to be reliable assessors of some clinical skills, but this model has not been studied for oral case presentations (OCPs). The purpose of this study was to examine the validity of student-evaluators in assessing OCP by comparing them with faculty.

Method 

In 2010, the authors developed a dichotomous checklist. They trained 30 fourth-year medical students (student-evaluators) to use it to assess 170 second-year medical students’ OCPs in real time during a year-end objective structured clinical examination. Ten faculty physicians then scored videos of a random sample of these OCPs. After discarding items with poor faculty reliability, the authors assessed agreement between faculty and student-evaluators on 18 individual items, total scores, and pass/fail decisions.

Results 

The total score correlation between student-evaluators and faculty was 0.84 ( P < .001) and was somewhat better than the faculty–faculty intraclass correlation ( r = 0.71). Using a 70% pass/fail cutoff, faculty and student-evaluator agreement was 74% (Kappa = 0.46; 95% CI, 0.20–0.72). Overall, student-evaluator scores were more lenient than faculty scores (72% versus 56% pass rates; P = .03).

Conclusions 

Senior student-evaluators were able to reliably assess second-year medical students’ OCP skills. The results support the use of student-evaluators for peer assessment of OCPs in low-stakes settings, but evidence of leniency compared with faculty assessment suggests caution in using student-evaluators in high-stakes settings. Extending peer assessment to OCPs provides a practical approach for low-resource evaluation of this essential skill.

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Developing and implementing universal guidelines for oral patient presentation skills

Affiliation.

• 1 Section of General Internal Medicine, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. [email protected]
• PMID: 16042523
• DOI: 10.1207/s15328015tlm1703_11

Background: Oral case presentations are important for patient care and clinical education. Previously published attempts to improve oral presentation skills have been labor intensive and have focused primarily on medical students.

Description: We created a multifaceted intervention to improve oral case presentations of medical students and internal medicine residents. Our intervention included a written handout with detailed instructions, pocket cards, model presentations, and multiple teaching sessions. The intervention was developed by consensus, supported by the department of medicine and endorsed by key faculty within the department. In addition to soliciting feedback from students and residents, we evaluated our intervention with prospectively acquired ratings of student oral case presentation skills recorded on a standardized evaluation for the internal medicine clerkship.

Evaluation: Students, residents, and faculty gave positive feedback, although they noted some practical obstacles to effective oral case presentations. After dissemination of the guidelines, 44% of students (42/96) were rated as "excellent" in oral presentation skills on standardized evaluations of the internal medicine clerkship, compared to 30% in the previous academic year (33/111; odds ratio [OR]=1.8, 95% confidence interval=1.04-3.3; p=.036).

Conclusion: A multifaceted intervention improved medical student oral case presentation skills. Although participants noted barriers that need further attention, we demonstrated modest improvement in student performance.

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Presenting Patients

• First Online: 14 July 2024

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Patient presentations are an essential part of patient care and the medical education process. They are a method to summarize a patient’s presenting illness, medical history, physical examination findings, diagnostic test results, and treatment plan. Patient presentations also provide learners with a platform to discuss their assessment of the patients and demonstrate medical knowledge and critical thinking skills to their peers and instructors. Effective communication skills are crucial to conveying complex medical information to patients, colleagues, and other healthcare professionals. Presentations help students develop their communication skills by allowing them to articulate their thoughts in a clear, concise, and organized manner. They also enable students to receive feedback from their peers and instructors, which can help them to refine their presentation skills and gain a deeper understanding of the clinical scenario.

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Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM, SUBCOMMITTEE ON SCREENING AND MANAGEMENT OF HIGH BLOOD PRESSURE IN CHILDREN. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904. https://doi.org/10.1542/peds.2017-1904 . Epub 2017 Aug 21. Erratum in: Pediatrics. 2017 Nov 30; Erratum in: Pediatrics. 2018 Sep;142(3).

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Najjar, M. (2024). Presenting Patients. In: Liao, N., Mahan, J., Misra, S., Scherzer, R., Schiller, J. (eds) Pediatric Rotations. Springer, Cham. https://doi.org/10.1007/978-3-031-59873-9_5

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Oral Presentations

Saturday, june 29 2024, ageing and dementia 1, opr‐001, distressing dreams, cognitive decline, and risk of dementia: a prospective study of three population‐based cohorts, uk dementia research institute, imperial college london, london, uk.

Background and aims: Distressing dreams are associated with faster cognitive decline and increased dementia risk in people with Parkinson's disease (PD). Whether distressing dreams are associated with cognitive decline and dementia in people without PD is unknown. This study investigated the association between self‐reported distressing dream frequency and the risk of cognitive decline and incident dementia in community‐dwelling men and women in the general population.

Methods: Risk of cognitive decline was evaluated in 605 middle‐aged adults from the Midlife in the United States (MIDUS) study who were followed‐up over 13 years. Cognitive decline was defined as having an annual rate of decline in global cognitive function ≥1 standard deviation faster than the mean decline rate. Risk of incident all‐cause dementia was evaluated in 2600 older adults from the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), who were followed‐up over 7 years. Distressing dream frequency was assessed in all cohorts at baseline using item 5 h of the Pittsburgh Sleep Quality Index. The association between self‐reported distressing dream frequency and later cognitive outcomes was evaluated using multivariable logistic regression.

Results: Compared with middle‐aged adults who reported having no distressing dreams at baseline, those who reported having weekly distressing dreams had a 4‐fold risk of experiencing cognitive decline (adjusted odds ratio [aOR] = 3.99; 95% CI: 1.07, 14.85). Amongst older adults, the difference in dementia risk was 2.2‐fold (aOR = 2.21; 95% CI: 1.35, 3.62).

Conclusion: Distressing dreams predict cognitive decline and all‐cause dementia in middle‐aged and older adults in the general population.

Disclosure: Nothing to disclose.

OPR‐002

Exploring family history in alzheimer's disease: evidence for x‐chromosome linked and recessively inherited risk factors, c. bernardes 1 ; r. guerreiro 2 ; j. brás 2 ; j. durães 1 ; i. baldeiras 3 ; m. lima 1 ; m. almeida 3 ; i. santana 1 ; m. tábuas‐pereira 1, 1 neurology department, coimbra university hospital centre, coimbra, portugal; 2 department of neurodegenerative science, van andel institute, grand rapids, mi , usa; 3 center for neuroscience and cell biology, coimbra, portugal.

Background and aims: Alzheimer's Disease (AD) heritability is estimated to be around 70–80%. Yet, much of it is yet to be explained. Studying transmission patterns in different populations may help to understand factors contributing to the development of AD. In this study, we aimed to analyse family history patterns in a large cohort of Portuguese AD patients.

Methods: We collected family history from patients with AD and cognitively healthy controls over 75. We compared the proportion of subjects with AD depending on their family history (to assess X‐linked and Y‐linked associated inheritance patterns) and on the parents' birthplace (as a proxy of remote consanguinity). Linear regressions to study the association of these variables with different endophenotypes were performed.

Results: We included 3073 participants, 2183 cognitively healthy controls and 890 patients with AD. Men with a mother with dementia develop AD more frequently than women with a mother with dementia. In female patients with a CSF‐supported diagnosis of AD, paternal history of dementia is associated with lower CSF total Tau, but increased CSF phosphorylated Tau. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated Tau, but higher CSF amyloid‐beta42.

Conclusion: Our study gives evidence, at a population level, of X‐linked risk factors for AD. We also add evidence to remote consanguinity as a risk factor for AD.

OPR‐003

Regulation of conditioned fear memory extinction by the orexin system in the medial prefrontal cortex, p. yi 1 ; m. lin 2 ; f. chang 3, 1 department of sport management/aletheia university, taiwan, china; 2 graduate institute of brain and mind sciences/national taiwan university, taiwan, china; 3 graduate institute of veterinary medicine/national taiwan university, taiwan, china.

Background and aims: Post‐traumatic stress disorder (PTSD) disrupts discernment of trauma‐related fear memories, causing emotional distress and sleep disruptions. The orexin system, originating from the lateral hypothalamus (LH), is implicated in fear memory recall post‐extinction. Lesions in the medial prefrontal cortex (mPFC), a LH downstream projection, hinder fear memory extinction. We proposed that the LH‐mPFC pathway crucially contributes to conditioned fear memory extinction and modulates rapid eye movement (REM) sleep, impacting memory processing.

Methods: Using chemogenetic technique, we selectively manipulated the LH‐mPFC pathway by activating or inhibiting it during extinction learning, and behavior tasks were assessed. Concurrently, electrocorticography (EEG) measured sleep–wake states under these manipulations.

Results: Extinction acquisition heightened activity in both the mPFC and LH. Activating the LH‐to‐mPFC pathway maintained elevated freezing levels during fear memory extinction, while silencing initially lowered freezing levels, decreasing rapidly. This manipulation not only affected freezing expression but also influenced the formation of the extinction engram, impacting fear memory retrieval and anxiety tasks. These findings underscore the pivotal role of the LH‐to‐mPFC pathway in extinction acquisition. Pathway augmentation induced insomnia‐like features, particularly during the light period.

Conclusion: Our results suggest that the LH‐to‐mPFC orexinergic projection regulates conditioned fear memory extinction and may disrupt REM sleep, providing insights into the intricate interplay between fear regulation, memory processing, and sleep disturbances in PTSD.

OPR‐004

Significance of plasma p‐tau217 in predicting long‐term dementia risk: insights from machine learning approaches, z. xiao 1 ; x. zhou 1 ; q. zhao 1 ; y. cao 2 ; d. ding 1, 1 institute of neurology, huashan hospital, fudan university, shanghai, china; 2 clinical epidemiology and biostatistics, department of medical sciences, faculty of medicine and health, Örebro university, Örebro, sweden.

Background and aims: The role of plasma biomarkers for predicting incident dementia in the general population is still undetermined.

Methods: A total of 1857 baseline non‐demented older adults with follow‐ups within 10 years were included from a community‐based cohort. Consensus diagnoses of dementia and Alzheimer's disease (AD) were based on clinical criteria. The Recursive Feature Elimination algorithm was used to select the important features from 90 baseline candidate predictors for developing dementia and AD prediction models. Area Under the Receiver Operating Characteristic Curve (AUC) was used to evaluate models' performance. Models were validated in the testing sets and subsets.

FIGURE 1 Illustration of the candidate variables and research process.

Results: During the follow‐up of 12,716 person‐years, 207 participants developed dementia (including 145 AD). The constructed Logistic Regression, Naive Bayes, Bagged Trees, and Random Forest models showed moderate‐to‐high AUCs predicting future dementia (AUCs = 0.709–0.808) in the testing sets. Age, neuropsychological tests, and plasma p‐tau217 were the prioritized variables in all models. The models also showed robustness in diverse subgroups.

FIGURE 2 The selected models and variable importance for predicting dementia.

FIGURE 3 Subgroup analyses of the models for predicting dementia.

Conclusion: Plasma p‐tau217, combined with age and cognitive performance, showed important values in predicting incident dementia among community older adults. In the resource‐limited settings, using these variables may be convenient and cost‐effective to identify participants with high risk of dementia in the general population.

OPR‐005

Autonomic dysfunction in rem sleep behavior disorder: heart rate variability analysis to explore neurodegeneration, m. figorilli 1 ; p. sattar 3 ; e. casaglia 1 ; m. mascia 1 ; e. facchini 2 ; g. baldazzi 3 ; n. mandas 4 ; d. pani 3 ; p. mattioli 6 ; l. giorgetti 5 ; d. arnaldi 6 ; m. puligheddu 1, 1 department of medical sciences and public health, sleep disorder research center, university of cagliari, cagliari, italy; 2 medsp lab, department of electrical and electronic engineering, university of cagliari, cagliari, italy; 3 medsp lab, department of electrical and electronic engineering, university of cagliari, cagliari, italy; department of medical sciences and public health, sleep disorder research center, university of cagliari, cagliari, italy; 4 medsp lab, department of electrical and electronic engineering, university of cagliari, cagliari, italy; the hadron academy, istituto universitario di studi superiori iuss , pavia, italy; 5 department of neuroscience, rehabilitation, ophthalmology, genetics, maternal and child health ( di‐nogmi ),clinical neurology, university of genoa, genoa, italy; 6 department of neuroscience, rehabilitation, ophthalmology, genetics, maternal and child health ( di‐nogmi ), clinical neurology, university of genoa, genoa, italy; neurophysiopathology unit, irccs ospedale policlinico san martino, genoa, italy.

Background and aims: Autonomic dysfunction is common along the alpha‐synucleinopathy continuum from prodromal stage (isolated REM sleep behavior disorder, iRBD) to overt Parkinson's disease (PD). This study aims to investigate autonomic dysregulation in iRBD, RBD‐PD and PD patients by examining sleep‐related Heart Rate Variability (HRV) parameters.

Methods: 40 iRBD (67 ± 8 y.o., 73% males), 16 PD (67 ± 10 y.o., 50% males), 30 PD‐RBD (71 ± 8 y.o., 66% males) and 24 controls (CG, 59 ± 10 y.o., 46% males) subjects were enrolled from two Italian sleep centers. A 5‐min artifact‐free ECG signal from N2, N3, and REM phases was investigated for time‐domain HRV analysis. Inter‐group significant differences have been assessed by nonparametric statistical analysis, for each sleep phase separately.

Results: When comparing iRBD and CG subjects, lower HRV parameters were observed in N2 ( p  < 0.025 for all) and REM ( p  < 0.04 for STDNN and R20) phases. iRBD showed lower HRV also when compared to PD‐RBD in N2 ( p  < 0.006, for STDNN, SDSD, RMSSD), and PD in N2 ( p  < 0.025, for STDNN, SDSD, RMSSD, pR50) and in N3 ( p  < 0.05, for STDNN, SDSD, RMSSD). Conversely, the PD group showed significant reduction when compared to the CG ( p  < 0.03), as well as a significant increase when compared to the PD‐RBD group ( p  < 0.05, R20 and pR20 in REM).

Conclusion: These findings suggest that the disrupted autonomic regulation is evident in the early alpha‐synucleinopathy stage during N2 and REM sleep, even more than in overt PD. Longitudinal studies are warranted to determine whether autonomic dysfunction in iRBD could serve as a prognostic biomarker, aiding in the prediction of alpha‐synucleinopathy subtypes development.

Cerebrovascular diseases 1

Opr‐006, nlrp3 ‐inflammasome inhibition reduces stroke induced inflammation and delays infarct growth before recanalization, department of neurology, university hospital würzburg, würzburg, germany.

Background and aims: The NLRP3‐inflammasome is a multiprotein complex regulating the activation of the innate immune system. NLRP3‐dysregulation has been implicated in various inflammatory and autoimmune diseases. In experimental ischemic stroke, NLRP3‐inhibition mitigated ischemia/reperfusion‐injury and secondary infarct growth after recanalization. In the present study, we examined whether NLRP3‐inhibition might alleviate stroke progression already under large vessel occlusion (LVO) before recanalization.

Methods: We occluded the middle cerebral artery in C57Bl/6‐mice for up to 4 hours and examined the NLRP3‐mRNA expression under LVO. In a subsequent experiment, C57Bl/6‐mice were prophylactically or therapeutically (after 1 h and 2 h of vessel occlusion) treated with the NLRP3‐inflammasome inhibitor MCC950. We then assessed stroke volumes, the NeuroScore, IL1b‐levels (immunoblot) and blood–brain‐barrier (BBB) integrity (albumin extravasation).

Results: We detected a 5–10‐fold upregulation of NLRP3‐mRNA expression already under LVO ( n  = 10/group). Its inhibition reduced stroke sizes significantly [vehicle/prophylactic/MCC950(1 h)/MCC950(2 h)‐treatment: 67.4 ± 16.4 mL/37.2 ± 10.2 mL/42.9 ± 8.4 mL/49.1 mL ± 12.1 mL] ( n  = 9/group). Consequently, the IL1b‐release decreased cortically by 20% ( n  = 9/group) while the integrity of the BBB and the NeuroScore ( n  = 9/group) improved significantly. We observed these improvements in both the prophylactic and therapeutic settings.

NLRP3 gene expression levels increase during pMCAO.

NLRP3 inhibition reduces infarct volume after prophylactic (MCC950 0 h) and delayed treatment, 1 h (MCC950 1 h) and 2 h (MCC950 2 h) post stroke onset.

Conclusion: As main finding we show that blocking of NLRP3 mitigates cerebral inflammation and infarct growth already under LVO and partly preserves the ischaemic penumbra, “buying time” before recanalization. This may have a major clinical impact in the future since infarct progression under LVO is a major caveat for an unfavourable clinical outcome despite successful recanalization.

OPR‐007

Antiplatelets in emergent carotid stenting after intravenous thrombolysis: a multicenter retrospective matched analysis, f. colò 1 ; a. alexandre 1 ; f. arba 2 ; l. scarcia 3 ; a. falcou 4 ; m. ruggiero 5 ; m. piano 6 ; a. zini 7 ; g. bigliardi 8 ; a. broccolini 1, 1 policlinico universitario agostino gemelli, rome, italy; 2 careggi university hospital, firenze, italy; 3 henri‐mondor university hospital, créteil, france; 4 clinica ospedaliero‐universitaria policlinico umberto i, rome, italy; 5 ausl romagna ‐ sede cesena, neurology, cesena, italy; 6 niguarda , neurology, milan, italy; 7 ospedale maggiore bologna, bologna, italy; 8 stroke unit, ospedale civile di baggiovara, modena, italy.

Background and aims: Mechanical thrombectomy (MT) with emergent carotid stenting (eCAS) is beneficial in patients with tandem occlusion (TO). Our aim was to address safety and efficacy of different intra‐procedural antiplatelet regimens in patients undergoing eCAS after intravenous thrombolysis (IVT) and define predictors of parenchymal hemorrhage (PH).

Methods: The databases of 17 European stroke centers were screened for consecutive patients with TO who received MT with eCAS. Intra‐procedural antiplatelet therapy was categorized in: (1) low intensity regimen, (2) high intensity regimen, and (3) high intensity regimen followed by i.v. Glycoprotein IIb/IIIa inhibitors (GPI) infusion. Propensity score matching (PSM) was used to estimate differences in outcome between treatment groups. Outcome measure included the occurrence of PH type 2 and type 1 and the 90‐day mRS score 0–2.

Results: 621 patients were collected, 48.5% received IVT. After PSM there was no significant difference between IVT and non‐IVT patients under different antiplatelet regimens concerning rates of PH type 2 and type 1. Subgroup analysis showed increased rate of PH type 2 in IVT patients receiving high intensity regimen plus GPI maintenance, but without difference in clinical outcome. In multivariate analysis, presence of atrial fibrillation (OR 4.089, 95% CI 1.759–9.508), high intensity antiplatelet regimen with GPI maintenance (OR 2.364, 95% CI 1.086–5.147) and stent thrombosis (OR 2.631, 95% CI 1.160–5.970) were predictors of PH type 2.

Conclusion: Different intra‐procedural antiplatelet regimens for eCAS are safe after IVT. Increased risk of PH type 2 is associated with use of intra‐procedural GPI maintenance in IVT patients and presence of atrial fibrillation.

OPR‐008

Stroke recurrence and overall mortality in cpap treated post‐stroke obstructive sleep apnea patients, j. suusgaard 1 ; a. west 2 ; l. ponsaing 1 ; h. iversen 2 ; p. jennum 1, 1 danish center for sleep medicine, department of clinical neurophysiology, copenhagen university hospital, rigshospitalet, denmark; 2 department of neurology, cerebrovascular research center rigshospitalet, copenhagen university hospital, rigshospitalet, denmark.

Background and aims: Obstructive sleep apnea (OSA) is strongly associated with stroke development and is identified in up to 70% of stroke patients. It is unclear whether treatment with continuous positive airway pressure (CPAP) reduces re‐stroke risk or mortality among post‐stroke patients. Previous studies examining the impact of CPAP on mortality in post‐stroke patients have either had limited follow‐up periods or involved small sample sizes.

Methods: We conducted a retrospective cohort study using data from the Danish National Patient Registry covering the period from 2003 to 2016, involving 1821 patients diagnosed with sleep‐disordered breathing (SDB) and a prior ischemic stroke or transient ischemic attack (TIA). Patients were categorized into three groups: CPAP adherent, CPAP non‐adherent and no CPAP treatment. By utilizing Cox hazard regression, we assessed the risk of recurrent stroke or TIA and overall mortality among these groups over a 5‐year follow‐up period.

Results: CPAP treatment improved survival rate in patients categorized as adherent compared to patients with no CPAP treatment (hazard ratio: 0.62; 95% CI: 0.50–0.76; p  < 0.001). This effect persisted after adjusting for age, sex, and pre‐existing comorbidities within 3 years (the Quan updated Charlson Comorbidity Index). There was no observed reduction in the risk of recurrent stroke/TIA between the CPAP groups.

Conclusion: In this large, registry‐based study, we found that CPAP‐adherence reduced the overall mortality in post‐stroke/TIA patients with SDB. CPAP treatment did not seem to affect the risk of re‐stroke/TIA during the 5 years of follow‐up.

OPR‐009

Argatroban for ischemic stroke with early neurological deterioration: a meta‐analysis of randomized controlled trials, i. barros andrade 1 ; v. morbach 2 ; v. kendi tsuchiya sano 3 ; v. maia arca 4 ; a. de oliveira macena lôbo 5 ; a. menegaz de almeida 6 ; f. cezar aquino de moraes 7 ; l. henrique geraldo 8, 1 faculdade santo agostinho de vitória da conquista, bahia, brazil; 2 feevale university, novo hamburgo, brazil; 3 federal university of acre, rio branco, brazil; 4 neurology department – hospital da clínicas ufpe , recife, brazil; 5 federal university of pernambuco, recife, brazil; 6 federal university of mato grosso, sinop, brazil; 7 federal university of para, belém, brazil; 8 department of neurology, new york university grossman school of medicine, new york, usa.

Background and aims: The presence of early neurological deterioration in acute ischemic stroke (AIS) underscores the urgent and intricate nature of managing this medical condition. Currently, argatroban is under investigation as a potential combination treatment, but there still a lack of evidence for its efficacy. Consequently, it becomes imperative to ascertain whether this compound contributes to improvement in neurological function following AIS.

Methods: We systematically searched databases (PubMed, Embase, Web of Science, and Cochrane) until January 10, 2024. Odds ratio (OR) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random‐effects model. Heterogeneity was assessed using I 2 statistics. The statistical analysis was performed using R software, version 4.3.1.

Results: A total of 9 studies and 2043 patients were included. As compared to the control group, Argatroban treated patients exhibited significantly improved NIHSS score at 7‐ and 90‐days post stroke (MD −0.8315, 95% CI −1.418 to −0.2449, p  = 0.005; MD −0.3903, 95% CI −1.9313 to 1.1506, p  = 0.62) respectively. Argatroban treatment reduced the occurrence of parenchymal hematoma (PH). There were no significant changes in the Modified Rankin Score (mRS) and symptomatic intracranial hemorrhage (sICH) occurrence in patients treated with Argatroban when compared to placebo group. Finally, patients on the placebo group had a significantly improved modified Barthel Index (mBI).

A forest plot of the change in the National Institutes of Health Stroke Scale (NIHSS) outcome of 7 days.

A forest plot of the change in the Parenchymal Hematoma (PH) outcome.

A forest plot of the modified Barthel Index (mBI) outcome.

Conclusion: Among these patients, treatment with argatroban plus drug improve NIHSS scores, most prominently at 7 days. These results demonstrate a benefit of Argatroban on reducing neurological deficits on AIS patients subject to thrombolytic therapy without increasing the risk of sICH.

Disclosure: The authors declare that they have no disclosure.

OPR‐010

Increased apnea‐hypopnea index and elevated hypoxic burden are associated with atrial fibrillation in ischemic stroke, x. yang 1 ; j. lippert 1 ; i. filchenko 1 ; s. baillieul 2 ; c. bernasconi 1 ; s. bauer‐gambelli 1 ; a. brill 3 ; d. seiffge 1 ; t. reichlin 4 ; m. arnold 1 ; m. schmidt 1 ; c. bassetti 1, 1 department of neurology, inselspital, bern university hospital, university of bern, bern, switzerland; 2 grenoble alpes university, hp2 laboratory, inserm u1300 and grenoble alpes university hospital, grenoble, france; 3 department of pulmonary medicine, allergology and clinical immunology, inselspital, bern university hospital, university of bern, bern, switzerland; 4 department of cardiology, inselspital, bern university hospital, university of bern, bern, switzerland.

Background and aims: Sleep apnea (SA) increases the risk of cardiovascular disorders (CVD). SA is highly prevalent in stroke and is associated with an increased prevalence of atrial fibrillation (AF). Which markers of SA, the apnea‐hypopnea index (AHI) or the hypoxic burden (HB), better predict AF in stroke, remains unknown.

Methods: This cross‐sectional analysis utilized data from the Bernese Sleep & Stroke Cohort, an integral component of the Swiss Stroke Registry. During acute hospitalization, patients underwent respiratory polygraphy, leading to dichotomization into AHI+/ AHI‐ groups using a 20/h threshold. Further classification into HB+/HB‐ groups occurred with the 75% percentile as the threshold. Multivariate logistic regression assessed the associations between distinct combinations of HB and AHI (HB+/AHI+, AHI+/HB‐, and HB+/AHI‐) in comparison to HB‐/AHI‐ on prevalent AF, adjusting for various confounders.

Results: In the analysis of 1010 patients (mean age 66y, 62% males), AF was diagnosed in 197 (20%) patients. HB+ was present in 254 (25%) patients, and AHI+ was present in 360 (36%) patients. The HB+/AHI+, AHI+/HB−, HB+/AHI−, and HB−/AHI− groups constituted 20%, 16%, 5%, and 59% of the total, respectively. Compared to the HB−/AHI− group, the HB+/AHI+ group was independently associated with prevalent AF (adjusted OR: 1.68; 95% CI: 1.10–2.55). No significant difference was observed in AHI+/HB− and HB+/AHI‐ groups.

FIGURE 1 Adjusted Odds Ratios for prevalent AF across distinct combinations of HB and AHI (HB+/AHI+, HB+/AHI−, and AHI+/HB−), in comparison to the baseline group HB−/AHI−

TABLE 1 Baseline characteristics between HB−/AHI−, AHI+/HB−, HB+/AHI−, AHI+/HB+ groups.

Conclusion: In stroke, an elevated HB with an increased AHI, rather than either SA measures in isolation, is associated with a higher prevalent of AF. These findings underscore the potential of both markers in enhancing risk stratification for CVD.

Disclosure: Swiss National Science Foundation grant #320030_149752.

Headache & pain 1

Opr‐011, compensated hypogonadism identified in males with cluster headache: a prospective case‐controlled study, a. petersen 1 ; d. kristensen 2 ; c. westgate 1 ; t. folkmann‐hansen 1 ; n. lund 1 ; m. barloese 3 ; m. søborg 1 ; a. snoer 1 ; t. johannsen 4 ; h. frederiksen 4 ; a. juul 4 ; r. jensen 1, 1 department of neurology, danish headache center, university of copenhagen, rigshospitalet‐glostrup , glostrup, denmark; 2 department of science and environment, roskilde university, denmark; 3 department of clinical physiology and nuclear medicine, centre for functional and diagnostic imaging and research, university of copenhagen, hvidovre hospital, hvidovre, denmark; 4 department of growth and reproduction, copenhagen university hospital ‐ rigshospitalet, copenhagen, denmark.

Background and aims: Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear.

Methods: We performed a prospective, case‐controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone‐binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age‐ and sex‐matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations.

Results: The mean fT/LH ratio was reduced by 35% (95% CI: 21%–47%, p  < 0.0001) in patients with chronic cluster headache and by 24% (95% CI: 9%–37%, p  = 0.004) in patients with episodic cluster headache compared to controls after adjusting for age, sleep duration, and use of acute medication. Androgen concentrations did not differ between bouts and remissions. Furthermore, a shared genetic risk allele, rs112572874 (located in the intron of the microtubule associated protein tau (MAPT)), between fT and cluster headache was identified.

Violin plot of free testosterone/luteinizing hormone (fT/LH) ‐ratio in serum in participants with different types of cluster headache and in healthy, sex‐ and age‐ matched controls.

Linear regression of the free testosterone/luteinizing hormone (fT/LH) ‐ratio in serum as a function of age.

Shared genetic risk variants of cluster headache and serum free testosterone concentration.

Conclusion: Our results demonstrate that the male endocrine system is altered in patients with cluster headache to a state of compensated hypogonadism, and this is not an epiphenomenon associated with sleep or the use of acute medication. Together with the identified shared genetic risk allele, this may suggest a pathophysiological link between cluster headache and fT.

OPR‐012

Cluster tics in cluster headache: a cross‐sectional and controlled study, m. carney 1 ; s. maarbjerg 1 ; m. søborg 1 ; n. lund 1 ; j. worm 1 ; l. bendtsen 1 ; r. jensen 1 ; a. petersen, department of neurology, danish headache center, university of copenhagen, rigshospitalet‐glostrup , glostrup, denmark.

Background and aims: This explorative study aimed to investigate the lifetime prevalence of cluster tics in patients with cluster headache, characterize cluster tics, including identifying possible associations to different clinical characteristics, and further investigate specific traits associated with cluster tics compared to trigeminal neuralgia.

Methods: A total of 424 patients with cluster headache were included in this controlled cross‐sectional cohort study based on a semi‐structured interview. The comparator cohort consisted of 576 patients diagnosed with trigeminal neuralgia, who had previously participated in a standardized, purpose‐built, semi‐structured interview.

Results: Cluster tics were reported in 200 out of 424 (47%) of patients with cluster headache. The odds of experiencing cluster tics were higher for males compared to females (OR: 1.93, 95% CI: 1.27–2.96, p  = 0.002), and for patients with chronic cluster headache compared to patients with episodic cluster headache (OR: 1.74, 95% CI: 1.15–2.62, p  = 0.008). We found that cluster tics presented as orbital pain in 70% of patients, and that, in comparison to trigeminal neuralgia paroxysms, the odds of a paroxysm being a cluster tic was low if the attack was triggerable (OR: 0.02, 95% CI: 0.01–0.04, p  < 2e‐16).

Odds ratios (OR) for having been diagnosed with trigeminal neuralgia (TN) prior to interview when presenting with specific attack traits, adjusted for age and sex.

Conclusion: The lifetime prevalence of cluster tics in patients with cluster headache was 47%. The cluster tics were associated with the chronic cluster headache, and in contrast to the paroxysms in TN, cluster tics were associated to male sex, often had an orbital location of pain and were non‐serial and non‐triggerable.

OPR‐013

Vascular compression in trigeminal neuralgia discloses trigeminal root somatotopic organization, g. de stefano 1 ; d. litewczuk 1 ; e. ripiccini 2 ; s. maarbjerg 3 ; g. di pietro 1 ; p. falco 1 ; c. leone 1 ; e. galosi 1 ; a. truini 1 ; g. di stefano 1, 1 department of human neuroscience, sapienza university of rome, italy; 2 advanced quantum architecture laboratory, swiss federal institute of technology of lausanne, switzerland; 3 danish headache center, rigshospitalet, glostrup, denmark.

Background and aims: In Trigeminal Neuralgia pain is localized in the distribution of one or more branches of the trigeminal nerve. A hallmark of TN is the presence of discrete skin areas able to trigger pain attacks when touched. In classical TN, trigeminal reflexes are normal but it is possible to recognize a vascular compression with morphological changes of trigeminal nerve root.

Methods: We enrolled 53 patients with clinically defined TN, normal trigeminal reflexes testing, and evidence of neurovascular compression at 3‐Tesla MRI. From MRI images we measured the polar coordinates of the impacting vessel on the trigeminal root circumference and then correlate it with pain distribution, trigger zones and latencies of the early components of the trigeminal reflexes.

Results: Pain in V1, V2 and V3 is associated, respectively, with vascular compression in the medial, superior and lateral aspect of the nerve ( p  < 0.05). Cutaneous trigger zones are associated with corresponding region of the circumference ( p  < 0.05). Increased latency of the R1 component of the blink reflex is associated with medial compression, while increased latency of the SP1 component of the masseter inhibitory reflex is associated with inferomedial compression when the reflex is evoked from the infraorbital nerve, and with lateral compression when it is evoked from the mental nerve ( p  < 0.05).

Relative frequency of location of neurovascular compression along the root circumference as derived by MRI data of TN patients with pain limited to one trigeminal division, V1 (left), V2 (middle) or V3 (right).

Relative frequency of location of neurovascular compression along the root circumference as derived by MRI data of TN patients reporting as trigger zones the forehead (left), the cheek (middle) or the jaw (right).

Mean latency of the early component of the trigeminal reflexes in patients with MRI evidence of neurovascular compression along a given zone of the trigeminal root. Reflexes were evoked from V1 (left), V2 (middle) and V3 (right).

Conclusion: Our study showing that pain distribution, trigger zones and increased latencies of the early components of the trigeminal reflexes are correlated with specific sites of neurovascular compression along trigeminal root circumference discloses its somatotopic organization.

OPR‐014

Endogenous pain control mechanisms during the migraine cycle and in chronic migraine with/without medication overuse, g. cosentino 1 ; e. antoniazzi 2 ; c. cavigioli 2 ; e. guaschino 2 ; n. ghiotto 2 ; g. sances 3 ; r. de icco 1 ; m. todisco 2 ; c. tassorelli 1, 1 irccs mondino foundation, university of pavia, italy; 2 irccs mondino foundation, pavia, italy; 3 headache science & neurorehabilitation center, pavia, italy.

Background and aims: The offset analgesia (OA) phenomenon refers to the disproportionately large decrease in the perceived pain following a slight decrease in intensity of a noxious warm stimulus. This is considered as expression of activation of the endogenous pain‐modulation system, whose dysfunction is could be involved in the pathophysiology of episodic migraine (EM) and chronic migraine (CM) with or without medication overuse (MO).

Methods: We enrolled 67 subjects with EM (in different phases of the migraine cycle), 30 patients with CM with/without MO, and 30 healthy controls. All subjects underwent an experimental paradigm consisting of 3 stimulus offset trials (OT) and 3 constant temperature trials (CT) at the level of the supraorbital region. Visual analogue scale (VAS) values were recorded during the OT and CT.

Results: Interictal EM patients and CM patients with MO did not show the OA phenomenon. A paradoxical pronociceptive facilitation during the offset trial was observed in the CM group without MO and in the preictal and ictal EM subjects. The OA phenomenon was restored in in the postictal phase. Only in patients with CM with MO we observed lack of adaptation to pain during the CT. The magnitude of VAS changes during the offset trials negatively correlated with scores at 12‐item Allodynia Symptom Checklist, migraine disability assessment (MIDAS), and depression section of the Hospital Anxiety and Depression Scale (HADS).

Conclusion: A dysfunction in the endogenous pain‐modulation system may play a role in the recurrence of migraine attacks and in the process of migraine transformation from episodic to chronic pattern.

Disclosure: none.

OPR‐015

Cortical inflammation in migraine measured with quantitative magnetic resonance imaging: a reform study, r. christensen 1 ; h. ashina 1 ; h. al‐khazali 1 ; m. pineda 2 ; r. rahmanzadeh 2 ; n. hadjikhani 3 ; c. granziera 2 ; f. amin 1 ; m. ashina 1, 1 department of neurology, danish headache center, copenhagen university hospital – rigshospitalet, copenhagen, denmark; 2 translational imaging in neurology ( think ) basel, department of biomedical engineering, faculty of medicine, university hospital basel and university of basel, basel, switzerland; 3 gillberg neuropsychiatry centre, institute of neuroscience and physiology, sahlgrenska academy, gothenburg, sweden.

Background and aims: We aimed to investigate cortical inflammation using a novel quantitative, multimodal magnetic resonance imaging (MRI) technique in adult participants with migraine compared to age‐ and gender‐matched healthy controls.

Methods: Participants underwent a single MRI session. Cortical quantitative T2 (qT2), quantitative T1 (qT1), and ADC values, considered surrogate markers of neuroinflammation, were measured in the cortical ribbon and compared between participants with migraine (with and without aura) and healthy controls. A general linear model was used with a vertex‐wise threshold of p  < 0.05 and a cluster‐wise threshold of p  < 0.05, adjusted for age and gender.

Results: A total of 296 participants with migraine (103 with aura and 180 with chronic migraine) and 155 age and gender matched healthy controls were included in the analysis. Participants with migraine had increased qT2 in the left occipital cortex compared to healthy controls ( p  < 0.0001). In participants with migraine with aura, the increased qT2 was more widespread and located bilaterally in the occipital cortices compared to healthy controls (left, p  < 0.0001; right, p  = 0.004). Exploratory analysis revealed higher ADC values within the qT2 clusters in participants with migraine with aura than in controls ( p  = 0.01). No significant differences were observed in qT1 values between the two groups.

Conclusion: Cortical inflammation is more prevalent in migraine with aura than in migraine without aura. The increased qT2 values in the occipital cortices of participants with migraine with aura are likely extracellular edema, as suggested by the concomitant ADC increase. These results support the importance of cortical inflammation in migraine pathogenesis, particularly in migraine with aura.

Visual abstract.

Disclosure: The study was funded by the Lundbeck Foundation Professor Grant (R310‐2018–3711). Funding sources had no influence on study design, patient inclusion, or data interpretation. H.A. reports personal fees from Teva, outside of the submitted work. C.G. is supported by: The University Hospital Basel (USB), as the employer of Cristina Granziera has received the following fees, which were used exclusively for research support: (i) advisory board and consultancy fees from Actelion, Novartis, Sanofi‐Genzyme, Jannsen, and F. Hoffmann‐La Roche; (ii) speaker fees from Biogen, F. Hoffmann‐La Roche, Novartis, Jannsen, and Genzyme‐Sanofi; (iii) research support by F. Hoffmann‐La Roche. F.M.A. has received personal fees from Pfizer, Teva, Lundbeck, Novartis, Eli Lilly, outside of the submitted work. M.A. is a consultant, speaker, or scientific advisor for AbbVie, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva and a primary investigator for ongoing AbbVie/Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva trials. Messoud Ashina has no ownership interest and does not own stocks of any pharmaceutical company. Messoud Ashina serves as associate editor of Cephalalgia, associate editor of the Journal of Headache and Pain, and associate editor of Brain. R.C., H.M.A., M.O‐P., R.R., and N.H. report no relevant conflicts of interest.

Motor neurone diseases 1

Opr‐016, peripherin: a novel early diagnostic and prognostic biomarker in amyotrophic lateral sclerosis, a. bombaci ; g. de marco; f. casale; g. fuda; p. salamone; g. marchese; a. calvo; a. chiò, “rita levi montalcini” department of neuroscience, university of turin, turin, italy.

Background and aims: motor neuron diseases (MND) are complex and heterogeneous neurodegenerative diseases. Biomarkers could help in early diagnosis, in defining patients' prognosis, and stratification. The most studied and promising biomarkers are neurofilaments (Nfs). A particular type of Nfs is peripherin, mainly expressed in neurons of the peripheral nervous system. There are no studies in literature led in humans evaluating peripherin in plasma.

Methods: sandwich‐ELISA was used to quantify plasma peripherin from 120 ALS MND (including 12 ALS/FTD and 10 PLS), 9 HSP, 46 MND‐mimics (including myelopathy, radiculopathy, axonal neuropathies, Hirayama disease, IBM, benign fasciculation syndrome, functional syndrome, myasthenia, post‐polio syndrome) and 38 healthy‐controls (HCs). Plasma was collected at the time of diagnosis or some months earlier. 46 ALS were evaluated longitudinally. ALSFRSr, MRC, spirometry, genetic tests, disease progression rate (PR), blood examinations, neuropsychological tests were performed. We analysed data using Kruskal–Wallis, ANCOVA and Cox regression analysis.

Results: peripherin plasma levels is different between groups ( p  < 0.0001); Bonferroni's correction shows higher levels of peripherin in MND compared to MND‐mimics and HCs. Comparing ALS with PLS and HSP peripherin resulted to be higher ( p  < 0.001). Differences are confirmed co‐variating for age and sex. ROC curve shows a good capability of peripherin to discriminate MND from MND mimics (AUC = 0.79).

Peripherin levels in MND, MND‐mimics and healthy controls.

Conclusion: peripherin plasma levels result to be increased in MND (in particular in classic ALS) compared to MND mimics since the early phases of the disease. Further multicentre studies, testing together other fluid biomarkers, are needed to better explain role of peripherin in diagnosis and prognosis in MND.

OPR‐017

Rate of change in upper and lower motor neuron burden is associated with survival and in amyotrophic lateral sclerosis, a. maranzano 1 ; f. gentile 2 ; a. doretti 1 ; e. colombo 1 ; a. wall 1 ; v. patisso 3 ; a. de lorenzo 3 ; c. gendarini 3 ; c. cinnante 4 ; c. morelli 1 ; s. messina 1 ; m. treddenti 3 ; v. silani 1 ; f. verde 1 ; n. ticozzi 1, 1 department of neurology and laboratory of neuroscience, irccs istituto auxologico italiano, milan, italy; 2 irccs ospedale san raffaele, division of genetics and cell biology, milan, italy; 3 neurology residency program, università degli studi di milano, milan, italy; 4 section of neuroradiology, department of radiology and diagnostic imaging, irccs istituto auxologico italiano, milan, italy.

Background and aims: The role of upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has been extensively studied in relation to clinical phenotype and survival. Conversely, it is not known whether the rate of change in UMN (ΔUMN) and LMN (ΔLMN) signs provides useful information on ALS evolution.

Methods: A retrospective inpatient cohort of 1000 ALS patients was evaluated. Burden of UMN and LMN signs was assessed using the Penn Upper Motor Neuron Score and Lower Motor Neuron Score, respectively. The time interval between symptom onset and first evaluation was used to quantify ΔUMN and ΔLMN values. Survival, time from symptom onset to percutaneous endoscopic gastrostomy (PEG), and to non‐invasive ventilation (NIV) were used as outcome measures. For a subset of patients, we compute the ENCALS survival model.

Results: ΔUMN and ΔLMN values are negatively associated with survival (ΔUMN: HR = 1.30; ΔLMN: HR = 4.22) time to PEG (ΔUMN: HR = 1.34; ΔLMN: HR = 4.46) and time to NIV (ΔUMN: HR = 1.23; ΔLMN: HR = 5.0). A cut‐off value of 0.195 for ΔLMN was identified to predict patients with estimated short vs. prolonged survival. ENCALS groups characterized by shorter survival were significantly associated with higher ΔUMN and ΔLMN scores when compared to those with longer survival.

Multivariate Cox regression investigating the effect of RoC in LMNS and PUMNS after adjusting for variables that are known to be associated with survival in ALS.

ROC curve illustrating the reliability of variable RoC in LMNS in predicting patients with short (survival <36 months) vs. prolonged (survival >36 months) survival.

Distribution of RoC in PUMNS (A), RoC in LMNS (B), PUMNS (C) and LMNS (D) among different ENCALS survival groups.

Conclusion: ΔUMN and ΔLMN might represent reliable clinical indexes to estimate disease evolution and survival in ALS patients. Indeed, these two measures provide distinct clinical information in addition to that derived from the total burden of UMN and LMN signs at first evaluation.

Disclosure: Alessio Maranzano, Francesco Gentile, A. Doretti, Eleonora Colombo, Aoife Wall, Mauro Treddenti, Valerio Patisso, Alberto De Lorenzo, Claudia Gendarini, Claudia Maria Cinnante, Claudia Morelli, Stefano Messina, Federico Verde report no disclosure. Vincenzo Silani received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, LiquidWeb, Srl and Novartis Pharma AG. He receives or he has received research support from the Italian Ministry of Health, AriSla, and E‐Rare Joint Translational Call. He is on. the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemproal Degeneration, European Neurology, American Journal of Neurodegenerative Disease and Frontiers in Neurology. Nicola Ticozzi received compensation for consulting services from Amylyx Pharmaceutical and Zambon Biotech SA. He received research funding from the Italian Ministry of Health and AriSLA. He is associate editor of Frontiers in Aging Neuroscience.

OPR‐018

Circulating endocannabinoid signatures of disease activity in amyotrophic lateral sclerosis, g. senerchia 1 ; f. piscitelli 2 ; r. dubbioso 1, 1 department of neurosciences, reproductive sciences and odontostomatology, federico ii university, naples, italy; 2 endocannabinoid research group, institute of biomolecular chemistry ( icb ), national research council ( cnr ), pozzuoli, italy.

Background and aims: Evidence from the preclinical model of amyotrophic lateral sclerosis (ALS) has consistently demonstrated altered levels of circulating endocannabinoids (eCBs) that may contribute to disease activity and course. Results from human studies are sparse and inconclusive. Main aim of this study was to determine the association between eCB levels and disease activity in patients with ALS.

Methods: Serum concentrations of the eCBs 2‐arachidonoylglycerol (2‐AG) and N‐arachidonoylethanolamine (AEA), and related lipids palmitoylethanolamine (PEA), oleoylethanolamine (OEA), eicosapentaenoyl‐ethanolamide (EPA‐EA), 2‐docosahexaenoyl‐glycerol (2‐DHG) and docosahexaenoyl‐ethanolamide (DHA‐EA) were measured in samples from 65 ALS patients, 32 healthy controls (HC) and 16 neurological disease controls (NALS). Moreover, 46 ALS patients underwent a longitudinal study. Disease activity and progression were correlated with eCBs levels.

Results: Circulating eCBs were higher in ALS than in HC ( p  < 0.001), but not compared to NALS. Across clinical stages, ALS patients showed increased levels of PEA, OEA, and EPA‐EA ( p  < 0.02), which were confirmed by the longitudinal study ( p  < 0.03). Serum PEA and OEA levels were independent predictors of survival and OEA was higher in patients complaining of appetite loss. Cluster analysis revealed two distinct profiles of circulating eCBs associated with two patterns of disease activity (severe vs. mild). Patients belonging to the “severe” cluster showed significantly higher levels of OEA and lower levels of 2‐DHG compared to NALS and HC.

Comparison of circulating eCBs levels among the three groups: ALS, NALS and HC.

Circulating eCBs levels across ALS clinical stages and their association with survival.

Cluster analysis of circulating eCBs and clinical correlates of cluster membership.

Conclusion: Specific circulating eCBs profiles are indicative of different disease activities. This study paves the way for an individually‐designed rather than a “one‐fit‐all” targeting the eCB system for therapeutic purposes.

OPR‐019

Skin innervation across als clinical stages: new biomarkers of disease progression and survival, r. dubbioso 1 ; v. provitera 2 ; v. iuzzolino 1 ; g. senerchia 1 ; f. manganelli 1 ; m. nolano 2, 1 department of neurosciences, reproductive sciences and odontostomatology, university of naples federico ii , naples, italy; 2 istituti clinici scientifici maugeri irccs , skin biopsy lab, neurological rehabilitation unit of telese terme institute, telese terme, italy.

Background and aims: Aims of this study were to assess sensory involvement by applying a morpho‐functional approach on a large population of ALS patients stratified according to King's stages and to correlate these findings with the severity and prognosis of the disease.

Methods: We recruited 149 ALS patients and 41 healthy controls (HC). Patients underwent clinical questionnaires, nerve conductions studies (NCS) and 3 mm‐punch skin biopsy from leg, thigh and fingertip. We assessed intraepidermal nerve fibers (IENF) and Meissner corpuscles (MC) density by applying indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeated skin biopsies. Serum Neurofilament light chain (NfL) levels were measured in 40 patients.

Results: Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Skin biopsy showed a significant loss of IENF and MC in ALS compared with HC (all p  < 0.001). Across the clinical stages, we found a progressive reduction in MC ( p  = 0.004) and an increase in IENF (all p  < 0.027). Interestingly, the MC density inversely correlated with NfL level ( r  = −0.424, p  = 0.012), and survival analysis revealed that low MC density, higher NfL levels, and increasing IENF over time were associated with a poorer prognosis (all p  < 0.024).

Morpho‐functional assessment of peripheral nerve fibers across ALS clinical stages Bar dot plots showing (A) a significant reduction from King's stage 1 to stage 4 in the sensory nerve action potential (SNAP) recorded from the fifth finger ( p  = 0.034)

Cutaneous innervation across King's ALS clinical staging and in the longitudinal study. Confocal images of punch biopsies from hairy and glabrous skin in ALS patients (A, B, D, E, G, H, J, K, L) versus controls (C and F). Green, nerve fibres; blue, epide.

Kaplan–Meier survival curves based on morphological and NfL data, and skin biopsy longitudinal study Kaplan–Meier curves of survival probability among ALS patients stratified by median value of (A) Meissner corpuscles (MC) density ( n /mm2), (B) serum neuro.

Conclusion: In patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker.

Peripheral nerve disorders

Opr‐020, heterogeneous real‐life strategies in therapeutic approach of chronic inflammatory demyelinating polyradiculoneuropathy, a. de lorenzo 1 ; p. doneddu 2 ; f. manganelli 3 ; d. cocito 4 ; r. fazio 5 ; a. mazzeo 6 ; a. schenone 7 ; c. briani 8 ; v. di stefano 9 ; m. filosto 10 ; g. marfia 11 ; g. cosentino 12 ; a. clerici 13 ; g. antonini 14 ; l. benedetti 15 ; g. piscosquito 16 ; m. carpo 17 ; g. lauria pinter 18 ; g. siciliano 19 ; g. cavaletti 20 ; m. lucchetta 21 ; t. rosso 22 ; m. luigetti 23 ; m. inghilleri 24 ; e. nobile‐orazio 25, 1 neuromuscular and neuroimmunology unit, irccs humanitas research hospital, rozzano, milan, italy; università degli studi di milano, milano, italy; 2 irccs humanitas research hospital, rozzano (milano), milano, italy ; 3 department of neuroscience, reproductive sciences and odontostomatology, university of naples ‘federico ii ’, napoli, italy; 4 department of neuroscience, university of turin, torino, italy; 5 division of neuroscience, department of neurology, institute of experimental neurology ( inspe ), san raffaele scientific institute, milano, italy; 6 department of clinical and experimental medicine, unit of neurology, university of messina, messina, italy; 7 neurology clinic, irccs ospedale policlinico san martino genova, genova, italy; department of neuroscience, rehabilitation, ophthalmology, genetics, maternal and child health, university of genoa and irccs aou san martino‐ist , genova, italy; 8 neurology unit, department of neuroscience, university of padua, padova, italy; 9 department of biomedicine, neuroscience, and advanced diagnostic ( bind ), university of palermo, palermo, italy; 10 center for neuromuscular diseases and neuropathies, unit of neurology, asst ‘spedali civili’, university of brescia, brescia, italy; 11 dysimmune neuropathies unit, department of systems medicine, tor vergata university of rome, roma, italy; 12 department of brain and behavioral sciences, university of pavia, pavia, italy; irccs mondino foundation, pavia, italy; 13 neurology unit, circolo & macchi foundation hospital, university of insubria, varese, italy; 14 unit of neuromuscular diseases, department of neurology mental health and sensory organs ( nesmos ), faculty of medicine and psychology, ‘sapienza’ university of rome, sant'andrea hospital, roma, italy; 15 neurology clinic, irccs ospedale policlinico san martino genova, genova, italy; 16 department of medicine and surgery, neurology unit, university hospital “san giovanni di dio e ruggi d'aragona”, university of salerno, salerno, italy; 17 department of neurology, asst bergamo ovest‐ospedale treviglio, treviglio, italy; 18 unit of neuroalgology, irccs foundation ‘carlo besta’ neurological institute, milano, italy; department of medical biotechnology and translational medicine, milan university, milano, italy; 19 neurology unit, department of clinical and experimental medicine, university of pisa, pisa, italy; 20 università di milano‐bicocca , monza, italy; 21 uoc neurologia, ospedale santa maria della misericordia, rovigo, italy; 22 uoc di neurologia, ospedale san bassano, vicenza, italy; 23 neurology department, fondazione policlinico universitario agostino gemelli irccs , università cattolica del sacro cuore, roma, italy; 24 neurodegenerative diseases unit, department of human neuroscience, sapienza university, policlinico universitario umberto i, roma, italy; 25 neuromuscular and neuroimmunology unit, irccs humanitas research hospital, milan, italy; department of medical biotechnology and translational medicine, milan university, milan, italy.

Background and aims: Despite the existence of therapeutic recommendations in the 2010 EFNS/PNS and 2021 EAN/PNS guidelines for managing Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), the sequence of therapy to be used remains unsettled.

Methods: A comparative analysis was conducted, examining therapeutic strategies and responses in 524 CIDP patients from tertiary referral centers included in a large national database.

Results: Intravenous immunoglobulins (IVIg) emerged as the most commonly used first‐line therapy (53%), followed by steroids (33%) and plasmapheresis (3%). A consistent proportion of patients (8%) received combined first‐line therapy with IVIg and steroids or (3%) monotherapy with immune suppressants. In acute‐onset CIDP, IVIg and plasmapheresis were often used. There were also differences in relation to the early or late age at onset and to CIDP variants. Immune suppressants were often used as maintenance monotherapy (10%). There was a substantial variability among different centers in the choice of first‐ and second‐line therapy, number of therapies performed, use of immunosuppressants and subcutaneous immunoglobulin (SCIg). A consistent proportion of patients responded to IVIg (86%) or steroid (85%) when used as second line therapy and only 7% of the patients failed to respond to two first‐line therapies. There was no distinctive features between responder and not responder patients beside a more frequent ataxia at onset and greater disability at enrollment.

Conclusion: The absence of specific indications from guidelines may explain the notable heterogeneity in the therapeutic choice in CIDP patients. Therapeutic response significantly decreases after two failed attempts, but the identification of non‐responders remains challenging.

OPR‐021

Serum neurofilament light chain as a biomarker in guillain‐barré syndrome: origin and prognostic value, b. hafsteinsdóttir 1 ; h. zetterberg 2 ; m. axelsson 1 ; j. lycke 1, 1 department of clinical neuroscience, institute of neuroscience and physiology, the sahlgrenska academy, university of gothenburg, gothenburg, sweden; 2 department of psychiatry and neurochemistry, institute of neuroscience and physiology, the sahlgrenska academy, the university of gothenburg, mölndal, sweden.

Background and aims: Our objective was to determine the origin serum neurofilament light chain (sNfL) and the utility of the sNfL Z‐score, NfL ratio and NfL index as prognostic biomarkers in Guillain‐Barré syndrome (GBS).

Methods: We included 96 patients with GBS between 1989 and 2014 in Western Sweden. Outcome measures were GBS disability scale (GBSDS) at 3 and 12 months and the need of respiratory support. Receiver operator characteristics curves were calculated for sNfL Z‐score for the risk of respiratory support and GBSDS >2 at 3 months. NfL ratio and NfL index were compared with healthy controls (HC), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).

Results: The sNfL Z‐score was higher for respiratory support (median 3.7, IQR 3.2–4.0 vs. median 2.7, IQR 1.6–3.5), GBSDS >2 at 3 months (median 3.5, IQR 3.2–4.0, vs. median 2.6, IQR 1.7–3.4) and 12 months (median 3.6, IQR 3.5–3.8, vs. median 2.6, IQR 1.8–3.5). No association was seen between NfL ratio or index and outcome. The area under the curve for the sNfL Z‐score was 0.75 (95% CI 0.61–0.89) for respiratory support and 0.76 (95% CI 0.58–0.93) for GBSDS >2 at 3 months. The NfL ratio and index were lower in GBS than HC, MS, and ALS.

ROC curves for sNfL Z‐score. AUC for GBSDS >2 at 3 months was 0.76 (95% CI 0.59–0.93, p  = 0.009). AUC for respiratory support 0.75 (95% CI 0.61–0.89, p  = 0.004). ROC = receiver operator characteristics; AUC = area under curve.

(A) NfL ratio in healthy controls (HC), Guillain‐Barré syndrome (GBS), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). (B) NfL index in GBS, MS and ALS presented as median, interquartile range and individual values. The columns represent.

Conclusion: The sNfL Z‐score at onset is a promising predictive biomarker for prognosis in GBS. Our results suggest that peripheral nerves are a significant contributor to sNfL in GBS.

Disclosure: The study was supported by grants from the Swedish State Support for Clinical Research (ALFGBG‐722081), NEURO Sweden, NEURO Gothenburg, the Edit Jacobson Foundation, the Rune and Ulla Amlövs Foundation for Neurological Research, the MS Research Foundation of the Swedish MS Society, the Gothenburg Society of Medicine, and grants from Berit Linnea and Ragnar Bakken Foundation. Henrik Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work) Jan Lycke has received travel support and/or lecture honoraria and has served on scientific advisory boards for Amgen, Almirall, Biogen, Bristol Myers Squibb, Celgene, Genesis Pharma, Janssen, Merck, Novartis, Roche, Sanofi and Sandoz; and has received unconditional research grants from Biogen and Novartis, and financial research support from Sanofi.

OPR‐022

Activin‐iib ‐receptor inhibition prevents muscle atrophy and hastens motor recovery in experimental autoimmune neuritis, f. kohle 1 ; i. gerlach 1 ; m. koch 2 ; i. klein 1 ; g. r fink 1 ; g. gatto 1 ; m. schroeter 1 ; h. c lehmann 3, 1 department of neurology, faculty of medicine, university of cologne and university hospital cologne, cologne, germany; 2 center for biochemistry, institute for dental research and oral musculoskeletal research, faculty of medicine and university hospital cologne, university of cologne, cologne, germany; 3 department of neurology, hospital leverkusen, leverkusen, germany.

Background and aims: Muscle atrophy due to neuronal denervation is a significant determinant of the functional outcome in immune‐mediated neuropathies after cessation of autoinflammation. Activin‐IIB receptors (ActIIBR) are critically involved, and the blockade of these receptors has recently been explored in primarily degenerative muscular diseases. We examined the potential of ActIIBR blockade on motor recovery in the experimental autoimmune neuritis (EAN) animal model.

Methods: EAN was induced using myelin P253‐78 protein in female Lewis rats. With the beginning of the recovery phase at day 18 post immunization, rats were treated with either sham, 1.25 mg/kg body weight, or 5 mg/kg body weight of a synthesized ActIIBR antibody subcutaneously every fourth day. Functional motor outcome was assessed using a neuritis score, grip strength, and balance beam paired with cinematic tracing until day 30. Nerve conduction studies, histological analyses of the sciatic nerve and the tibialis anterior muscle, real‐time PCR, and muscle proteomics were performed.

Results: Treatment with 5 mg/kg ActIIBR‐antibody ameliorated EAN severity at day 30 ( p ‐value: <0.0001). The grip strength nearly returned to baseline. No group differences were seen for nerve conduction studies and cellular inflammation in the sciatic nerve. Histologically, an increased cross‐sectional area and ferret's diameter were observed. Muscle proteomics indicated alteration of the pAKT pathway, leading to a reduced expression of Atrogin1‐ and MuRF1 ( p ‐values: 0.014 and 0.038).

Treatment with 5 mg/kg of the ActIIBR antibody enhances functional recovery after EAN.

ActIIBR inhibition prevents muscle atrophy and induces muscle hypertrophy without affecting cellular inflammation of the sciatic nerve.

Proteomics and real‐time PCR analysis of the tibialis anterior muscles revealing reduced muscle degradation by downregulation of Atrogin‐1 and MuRF‐1 via ActIIBR‐inhibition.

Conclusion: Blockade of the ActIIBR prevents muscle atrophy via Atrogin‐1 and MuRF‐1 downregulation, thereby hastening motor recovery in EAN. Further studies are warranted to investigate the role of ActIIBR blockade in autoimmune neuropathy.

Disclosure: FK was supported by the Cologne Clinician Scientist Program (CCSP), Project No. 413543196. I. Gerlach, I. Klein, M. Koch, G. R. Fink, G. Gatto, H.C. Lehmann and M. Schroeter reported no disclosures related to this study.

OPR‐023

Intracutaneous amyloid deposition predicts ulterior nerve conduction studies deterioration in attrv carriers, n. schulz 1 ; d. beauvais 2 ; c. cauquil 1 ; c. labeyrie 1 ; c. adam 3 ; v. algalarrondo 4 ; d. adams 1 ; g. beaudonnet 1, 1 department of neurology, chu bicêtre, le kremlin‐bicêtre , france; 2 department of neurology, chu bordeaux, bordeaux, france; 3 department of pathology, chu bicêtre, le kremlin‐bicêtre , france; 4 department of cardiology, chu bichat, paris, france.

Background and aims: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant systemic disease, leading to harmful tissue protein deposition, mainly in the heart and nerves, with an overall poor prognosis. While new disease‐modifying treatments are being developed, it appears crucial to find markers of disease onset and progression for optimal timing in treatment initiation. Nerve conduction studies offer an objective, reproducible and non‐invasive although late mean of following large nerve disease.

Methods: We studied 107 ATTRv carriers with normal nerve conduction studies (NCS) and sought to find elements predictive of ulterior NCS decline, defined as a 20% decrease of the average of the bilateral sural and fibular sensory nerve action potential (SNAPs).

Results: During a median follow‐up of 5 years, 15/107 (14%) carriers presented a NCS deterioration. On univariate analysis, intracutaneous amyloid deposition (ICAD) (HR = 10.8, 95% CI(3.1 to 34.5), p  < 0.0001) and difference of age with age of disease onset in proband (HR = 1.1, 95% CI(1.0 to 1.1), p  = 0.002) were significantly associated with ulterior NCS decline. After multivariate analysis, skin amyloid deposition remained significantly and strongly associated with further worsening (HR = 10.3, 95% CI (2.4 to 45.5), p  = 0.0014). EOVal30Met genotype, presence at baseline of cardiac denervation, skin denervation, an interventricular septum thickness superior to 12 mm, abnormal short‐term heart rate variability, abnormal SUDOSCAN or neurological physical examination were not significantly associated with electric deterioration on univariate testing.

Conclusion: ATTRv carriers with intracutaneous amyloid deposition at initial evaluation were more likely to present NCS deterioration during follow‐up compared to those without. Search of ICAD should be recommended during follow‐up of asymptomatic carriers.

OPR‐024

Neuropathy in anti‐mag +/− igm gammopathy: population analysis and evaluation of old and innovative severity measures, d. tornabene 1 ; g. cosentino 1 ; m. todisco 2 ; g. tammam 1 ; e. antoniazzi 2 ; m. gastaldi 2 ; s. scaranzin 2 ; c. morandi 2 ; r. de icco 1 ; m. corrado 1 ; v. grillo 2 ; m. varettoni 3 ; e. vegezzi 2 ; e. marchioni 2 ; l. diamanti 2, 1 department of brain and behavioral sciences, university of pavia, pavia, italy; 2 irccs c. mondino foundation, pavia, italy; 3 irccs policlinico san matteo foundation, pavia, italy.

Background and aims: IgM Monoclonal Gammopathy (IgM‐MG) often coexists with peripheral polyneuropathy. Distal demyelinating polyneuropathy (DADS) with anti‐MAG antibodies is the best‐known variant. Lack of appropriate endpoints poses challenges in assessing treatment efficacy. We provide a thorough clinical and paraclinical characterization of 38 anti‐MAG+/− subjects with IgM‐MG and evaluate various traditional and innovative measures of disease severity.

Methods: Participants underwent detailed collection of haematological, neurological, and therapeutic history, anti‐MAG reactivity testing, and extensive electrodiagnostic assessment including Terminal Latency Index (TLI) determination. A broad clinical evaluation comprised multiple scales (mRS, ONLS, Berg Balance Scale, INCAT‐SS, IRODS), functional tests (9‐holes peg test, grip strength determination, 10‐metres and 2‐minutes walking test), and the EuroQoL questionnaire. A balance assessment was performed through posturography (i.e. the tracking of a standing subject's centre‐of‐gravity movement).

Results: 24 subjects exhibited anti‐MAG reactivity, with 21 displaying electrodiagnostic signs of demyelination. Of the 14 seronegative individuals, one showed electrodiagnostic signs consistent with DADS. TLI reduction was found in at least some nerve in many demyelinating cases, but it was frequently unassessable due to nerve inexcitability or entrapment. Attached charts illustrate the performance of each assessment as a measure of disease severity.

Comparison of disease measures in subject stratified by mRS class (left) and by a Berg balance score value (right). A Berg score of 45 or lower is predictive of a high risk of falls (Shumway‐Cook et al., Physical Therapy, 1997).

Pearson correlation coefficient for each disease measure and IRODS (left) and Berg (right) scores.

Performance of the posturography measures “length” (above) and “area” (below) as disability indexes. Data for the “open eyes” test are shown.

Conclusion: The correlation between anti‐MAG antibodies and “DADS” neuropathy is robust but not universal. TLI can help the diagnosis, but not every nerve will have an index <0.25 and its utility is limited by inexcitability or false positives due to median nerve entrapment at the wrist. Posturography emerges as a potential objective, quantitative outcome for future trials.

Cerebrovascular diseases 2

Opr‐025, prediction of the global functional outcome of intensive inpatient rehabilitation after stroke using machine learning, a. sodero ; s. campagnini; m. baccini; a. grippo; b. hakiki; c. castagnoli; p. liuzzi; c. macchi; a. mannini; f. cecchi, irccs fondazione don carlo gnocchi onlus, firenze, italy.

Background and aims: Prognostic data‐driven solutions could support the outcome prediction and, eventually, the optimisation of the rehabilitation pathway. We aimed at the development, cross‐validation, and external validation of machine learning‐based prognostic models for the prediction of the global functional outcome of patients undergoing intensive inpatient rehabilitation after stroke.

Methods: Patients addressing an evidence‐based intensive inpatient rehabilitation pathway within 30 days from stroke from two multicentric prospective studies were enrolled. Data related to standardized comprehensive multidimensional assessment were collected and fed within the model for feature selection (figure 1). The outcome of interest was the modified Barthel Index(mBI) at discharge. Different algorithms were optimised, nested cross‐validated, externally tested, and interpretability techniques were applied for the analysis of the contributions of predictors.

FIGURE 1 Analysis pipeline.

Results: Total numbers of 220 and 180 patients were considered for training and test sets, respectively (figure 2). Respectively a 50.9% and 56.7% of women, 79.5% and 78.9% of ischaemic, and a median [IQR] age of 80.0 [15.0] and 78.0 [17.0] were registered on the two datasets. The Support Vector Machine obtained the best validation performances and a median absolute error of 11.5 [15.0] and 9.2 [13.0] on the internal and external testing, respectively. The baseline variables providing with the main contributions to the predictions resulted in mBI, motor upper‐limb score, age, and cognitive score (figure 3).

FIGURE 2 Flow chart of the study.

FIGURE 3 Contributions of the predictors to the outcome prediction aggregated among each fold. In panels A‐C, bar plots of the global contributions are presented, whilst in panels B‐D, beeswarm plots with patient‐wise contributions are presented. The res.

Conclusion: Our results indicate the suitability of this solution for supporting clinicians in formulating a functional prognosis at the admission to intensive inpatient post‐stroke rehabilitation and in promptly identifying features potentially predicting an unfavourable outcome.

OPR‐026

In‐hospital death matters: a machine learning approach to anterior circulation mechanical thrombectomy, i. petrović 1 ; s. broggi 2 ; o. tomašević 3 ; a. balenović 1 ; i. milosavljević 1 ; m. ivanišević 4 ; m. killer‐oberpfalzer 5 ; j. mutzenbach 5 ; c. hecker 5 ; s. rajić 1 ; s. pikija 5, 1 faculty of medicine, university of novi sad, novi sad, serbia; 2 asst dei sette laghi, neurology and stroke unit, varese, italy; 3 faculty of technical sciences, department of systems, signals and control engineering, university of novi sad, novi sad, serbia; 4 faculty of medicine, university of belgrade, belgrade, serbia; 5 department of neurology, christian doppler university hospital, paracelsus medical university of salzburg, salzburg, austria.

Background and aims: Although the popularity of mechanical thrombectomy (MT) has grown significantly in the past decade, there is still a literature gap concerning post‐procedural in‐hospital mortality, the main contributing factors, and the possibility of predicting it. The aim was to employ interpretable machine learning (ML), which could potentially aid in understanding existing ambiguities.

Methods: This retrospective study included 602 anterior circulation ischemic stroke patients who underwent MT. Patients were divided into two groups: (I) died ( n  = 133), in which the fatal outcome occurred during the in‐hospital stay, and (II) survived ( n  = 469). Python 3.10.9 was used for the machine learning model build‐up, and based on the input features, two models were constructed: (I) the preMT model, which consisted of baseline features, and (II) the postMT model, which included baseline and MT‐related features. The ML models' training, internal evaluation, and performance testing followed feature selection. Interpretation frameworks explained the decision‐making process.

Summarized steps of the analysis. After a two‐step process of feature selection, with univariate feature selection (UFS) as the first step, and Recursive Feature Elimination (RFE) as the second, models were trained, evaluated, and tested.

Results: For the preMT model (AUC = 0.792), selected features were age, baseline NIHSS value, neutrophil‐to‐lymphocyte ratio (NLR), INR, vessel type, peripheral arterial disease (PAD), baseline glycemia, and premorbid modified Rankin scale (pre mRS), while in the postMT model (AUC = 0.837), added features included puncture to procedure end time (PET), and onset to puncture time (OPT).

(A) Evaluation metrics of the preMT model and the receiver operating characteristic curves (ROCs) of 4 classifiers; (B) The SHAP (Shapley Additive Explanations) analysis graph; (C) Local Interpretable Model‐Agnostic Explanations (LIME) plot.

(A) Evaluation metrics of the postMT model and the receiver operating characteristic curves (ROCs) of 4 classifiers; (B) The SHAP (Shapley Additive Explanations) analysis graph; C) Local Interpretable Model‐Agnostic Explanations (LIME) plot.

Conclusion: To the best of our knowledge, this study represents a pioneer research that utilized interpretable models for predicting in‐hospital death following anterior circulation MT. The constructed models need further extensive evaluation before they can be practically applied.

OPR‐027

Ethnic differences in access to care and treatment in patients with suspected acute stroke: a retrospective cohort study, i. scala 1 ; j. di giovanni 1 ; p. rizzo 1 ; s. bellavia 1 ; m. monforte 2 ; a. broccolini 2 ; p. calabresi 2 ; m. covino 3 ; g. frisullo 2, 1 catholic university of sacred heart, roma, italia; 2 department of neuroscience, sensory organs and chest, fondazione policlinico universitario agostino gemelli, irccs , rome, italy; 3 emergency department, irccs fondazione policlinico universitario agostino gemelli, rome, italy.

Background and aims: Data concerning unequal healthcare access of acute stroke patients based on ethnicity or race are inconclusive in Europeans. The primary objective was to evaluate the effect of geographic origin/race on access to acute stroke care and treatments. Secondly, we evaluated the effect of geographic origin/race on stroke risk factors, outcomes, and admission for stroke mimics.

A graphic representation of the geographical origin of the included population. The percentages refer to the number of patients from various continents compared to the total number of non‐Western Europeans.

Methods: In this retrospective, cohort study, we enrolled adult patients admitted to the emergency department of a comprehensive stroke center for suspected stroke. Based on geographic origin, patients were divided into two groups: Western Europeans (WE) and non‐Western Europeans (nWE). For each nWE subjects, we included four sex‐ and age‐propensity score matched patients in the WE group. We then divided patients in three further subgroups (White/Black/Asian) based on race. Univariate comparisons were performed using Mann–Whitney, Kruskal‐Wallis, and χ 2 ‐tests, as appropriate. Logistic regression was used to perform the adjusted analyses.

Results: 618 patients were enrolled in the nWE group and 2444 in the WE group. Belonging to the nWE group is an independent predictor of lower likelihood of receiving intravenous thrombolysis ( p  = 0.005). Considering Black/Asian/White subgroups, ED accesses for stroke mimics were less frequent among racial minority groups ( p  = 0.038). Furthermore, Black and Asian individuals had a higher incidence of brain hemorrhages than Whites ( p  = 0.003). No differences in stroke outcomes were found.

TABLE 1 Results of the multivariate logistic regression for the prediction of thrombolytic treatment.

Conclusion: Racial and ethnic disparities in healthcare are a challenging issue even in universal healthcare systems, likely due to differences in socioeconomic status, and they and should be addressed promptly through education campaigns of healthcare personnel.

OPR‐028

Polysomnographic parameters as predictors of outcome in patients with ischemic stroke: a preliminary report, m. de scisciolo ; e. rollo; g. della marca; v. brunetti, dipartimento di neuroscienze, organi di senso e torace, fondazione policlinico universitario agostino gemelli irccs , rome, italy.

Background and aims: Limited literature exists on sleep architecture in ischemic stroke (IS). This study aims to assess whether macrostructure and microstructure sleep parameters can predict outcomes in patients with IS.

Methods: Seventy‐seven with IS admitted to the Stroke Unit were prospectively collected. Patients underwent 24 hour polysomnography within seven days from the stroke. Macro and micro (Cycling Alternating Pattern ‐ CAP) sleep architecture and respiratory parameters were analyzed. Three‐month modified Ranking Scale(mRS) was used as the outcome measure. Sleep parameters were analyzed between groups with excellent (mRS = 0–1) and poor outcome (mRS = 2–6) using univariate and multivariate approaches, correcting for potential confounders (sex, age, NIHSS, pre‐stroke mRS).

Results: The study group showed a median age of 73 years (IQR = 20), and an admission NIHSS = 12 (IQR = 11). Forty‐three patients had excellent outcome (55.8%). Median total sleep time (TST) was 374 minutes (IQR = 104). Patients with excellent outcome showed higher REM sleep [13.0% (IQR = 8.6) vs. 6.9% (IQR = 7.5); p  = 0.002)], higher N1 stage of NREM sleep [13.3% (IQR = 10.5) vs. 8.2% (IQR = 5.7; p  = 0.001)], higher number or sleep cycles [3 (IQR = 2) vs. 1 (IQR = 3); p  = 0.030)], shorter daytime sleep [10 (IQR = 75) vs. 75 minutes (IQR = 126); p  = 0.005)], and higher CAP rate [43.7% (IQR = 25.0) vs. 24.9% (IQR = 30.8); p  = 0.001)]. None of the analyzed respiratory parameters were associated with outcome. Multivariate analysis confirmed that higher CAPrate( p  = 0.030) and less daytime sleep( p  = 0.017) were associated to excellent outcome.

Conclusion: Macro and, mostly, microstructure parameters of sleep in ischemic stroke seem to be correlated with outcome, in particular higher CAP rate is associated with better outcome. Further investigations are needed to reinforce these findings.

Neuroimaging in neuroinflammation

Opr‐029, amyloid pet as biomarker of white matter damage in recently diagnosed multiple sclerosis and its clinical relationship, j. barrios‐lópez 1 ; a. piñeiro‐donis 2 ; e. triviño‐ibáñez 3 ; p. casa nova‐leitao moreira 1 ; f. segovia‐román 4 ; b. marín‐romero 5 ; m. pérez‐garcía 6, 1 neurology department, hospital universitario virgen de las nieves, granada, spain; 2 nuclear medicine department, hospital universitario virgen de las nieves, granada, spain; 3 nuclear medicine department, hospital universitario virgen de las nieves, instituto de investigación biosanitaria ibs. granada , granada, spain; 4 department of signal theory, networking and communications, university of granada, granada, spain; 5 neurology department, hospital universitario virgen de las nieves, granada, spain; 6 radiology department, hospital universitario virgen de las nieves, granada, spain.

Background and aims: White matter (WM) demyelination in multiple sclerosis (MS) can be measured in vivo using amyloid positron emission tomography (PET). Our aim was to evaluate amyloid uptake in damaged (DWM) and normal‐appearing WM (NAWM) of MS patients and the relation to their clinical status.

Methods: This prospective longitudinal study enrolled patients with recent MS onset between March to May 2023. Participants underwent a neurological examination, disability (EDSS), neuropsychological (SDMT) and quality of life (EQ‐5D) assessment, brain MRI and 18F‐florbetaben PET in early (0–10′) and late phase (90′) post‐i.v., MRI and PET images were co‐registered and results are presented as standardized uptake values (SUV), using cerebellum (SUVRc) and NAWM (SUVRwm) as the reference region.

Results: Ten patients were included (35.10 ± 11.32 years; 70% female). We found, both in early‐ and late‐phase, a lower mean SUVR in DWM compared to NAWM ( p  < 0.01) in all patients. SUVRwm correlated with EQ‐5D index ( r :0.652, p  = 0.041). A trend toward lower SUVRwm was observed in the highly active onset group compared to non‐ highly active group (0.62 ± 0.43 vs.. 3.62 ± 3.20, p  > 0.05). Considering only highly active onset patients, SUVRwm correlated with EDSS score (rho = −0.896, p  = 0.0031). The lesions analysis showed a correlation between SUVmean in DWM with EDSS and SDMT scores (rho: −0.534, p  = 0.004 and rho: 0.670, p  = 0.006, respectively); and SUVRc with SDMT (rho: 0.585, p  = 0.022).

Standardized uptake values (SUV) analysis by co‐registered MRI and amyloid PET images.

Active lesion analysis by MRI and amyloid PET images.

Conclusion: Preliminary results of this work in progress suggest that amyloid PET could be a promising tool to monitor myelin changes in MS and may have a predictive role in disease activity and progression.

Disclosure: This work has received funding from the call for “NEURO‐RECA grants for scientific research in neurology in 2021” with file number NEURORECA‐0007‐2022.

OPR‐030

Validation of an automated deep learning algorithm for the identification of confluent multiple sclerosis lesions, m. pasca 1 ; l. marchi 2 ; a. mariottini 2 ; b. lambert 3 ; p. rubini 3 ; s. doyle 3 ; h. dehaene 3 ; a. tucholka 3 ; p. roca 3 ; s. filippini 4 ; l. massacesi 2, 1 department of neurology, “f. ferrari” hospital, casarano, lecce, italy; 2 department of neurosciences, drug and child health, university of florence, florence, italy; 3 pixyl , grenoble, france; 4 department neurology, florence, italy.

Background and aims: Lesion count is a crucial biomarker in Multiple Sclerosis diagnosis and follow‐up. Deep Learning (DL) models are a powerful aid for this task, providing an automated segmentation of lesions. These models tend to underestimate the true number of lesions, and segment confluent lesions as a single connected component. To improve the accuracy of the lesion counting, a novel post‐processing algorithm named LesDiv that can recognize individual lesions component in confluent lesions has been validated, automatically identifying single lesion center using the input FLAIR and lesion probability map produced by the DL segmentation model.

Methods: 60 MS patients with 440 clusters of lesions were included. Two neurologists, with expertise in Multiple Sclerosis MRi analysis, independently performed ground truth sub‐lesion counts and delineations. To compare the algorithm with alternative methods, an alternative pipeline that uses the Hessian filter instead of the LoG (described by Dworkin et al.), named Hessian Division, was implemented.

Flowchart of our proposed LesDiv algorithm.

Results: The analysis showed excellent reliability between the two human experts in terms of sublesion counting and delineation: Mean Absolute Error (MAE) = 0.45, Pearson Coefficient ( R 2 ) = 0.88, Dice = 0.526. LesDiv showed good reliability with the analysis performed by the two human experts: MAE = 0.75, R 2 = 0.75, Dice = 0.52, compared with Expert 1 analysis. Hessian Method showed a lower reliability with the two experts: MAE = 0.99, R 2  = 0.67, Dice = 0.48 compared with Expert 1 analysis.

Illustration of expert counts and automated counts.

Comparison of experts and automated counts. MAE = Mean Average Error. R2 = Pearson correlation coefficient.

Conclusion: Lesion segmentation in MS is a complex and time‐consuming analysis. LesDiv is an automated deep learning algorithm, that showed significant correlation with human analysis in the identification of single lesions from confluent MS lesions.

OPR‐031

Cellular soma and neurite density abnormalities in multiple sclerosis paramagnetic rim and core‐sign lesions, p. preziosa 1 ; e. pagani 2 ; a. meani 2 ; m. margoni 3 ; m. rubin 1 ; m. palombo 4 ; m. rocca 1 ; m. filippi 5, 1 neuroimaging research unit, division of neuroscience, and neurology unit, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy; 2 neuroimaging research unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 3 neuroimaging research unit, division of neuroscience, neurology unit, and neurorehabilitation unit, irccs san raffaele scientific institute, milan, italy; 4 cardiff university brain research imaging centre, school of psychology, and school of computer science and informatics, cardiff university, cardiff, uk ; 5 neuroimaging research unit, division of neuroscience, neurology unit, neurorehabilitation unit, and neurophysiology service, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy.

Background and aims: In multiple sclerosis (MS), susceptibility‐weighted imaging (SWI) may reveal white matter lesions (WML) with a paramagnetic rim (“paramagnetic rim lesions” [PRLs]) or diffuse hypointensity (“core‐sign lesions”), reflecting different stages of WML evolution. Using soma and neurite density imaging (SANDI) model on diffusion‐weighted magnetic resonance imaging (MRI), we characterized the microstructural abnormalities of MS PRLs and core‐sign lesions and their clinical relevance.

Methods: Forty MS patients and 20 healthy controls (HC) underwent a 3 T brain MRI. Using SANDI, the fractions of neurite (fneurite) and soma (fsoma) and size of soma (rsoma) were quantified in PRLs (including their core and rim separately), and core‐sign lesions identified on SWI.

Results: Among 1811 WMLs, 122 (6.7%) core‐sign lesions and 97 (5.4%) PRLs were identified. Compared to HC and MS normal‐appearing white matter, all MS WML showed significantly lower fneurite and fsoma and higher rsoma (FDR‐ p  < 0.001). Compared to isointense WML, core‐sign lesions showed a significantly higher fneurite, and lower fsoma and rsoma (FDR‐ p  < =0.001). Compared to isointense WML and core‐sign lesions, PRLs showed a significantly lower fneurite, higher fsoma, and higher rsoma (FDR‐ p  ≤ 0.005). The PRL‐core showed significantly lower fneurite, and higher rsoma than PRL‐rim (FDR‐ p  < 0.001). Lower PRL fneurite (β < = − 0.006, FDR‐ p  ≤ 0.015) and higher rsoma (β > =0.032, FDR‐ p  < =0.024) were significantly associated with a longer disease duration and more severe disability.

Conclusion: In PRLs, the significant and clinically‐relevant neurite loss and increased soma fraction and size possibly reflect increased astrogliosis and activated microglia. Core‐sign lesions exhibit milder axonal loss, microglia density and astrogliosis, supporting their less destructive nature.

Disclosure: P Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck, Bristol Myers Squibb, Genzyme, Horizon and Sanofi. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla (FISM). E Pagani, A Meani, M Rubin, M Palombo have nothing to disclose. M Margoni reports grants and personal fees from Sanofi Genzyme, Merck Serono, Novartis and Almiral. MA Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva; research support from MS Society of Canada, Italian Ministry of Health, Italian Ministry of University and Research, and FISM. M. Filippi received compensation for consulting or speaking activities from Alexion, Almirall, Biogen, Bayer, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol‐Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi‐Aventis, Sanofi‐Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol‐Myers Squibb, Lilly, Novartis, Sanofi‐Genzyme; he receives research support from Biogen Idec, Merck‐Serono, Novartis, Roche, Italian Ministry of Health, Italian Ministry of University and Research, and FISM.

OPR‐032

Discriminating ms from mogad using deep learning attention maps, r. cortese 1 ; m. battaglini 1 ; a. jacob 2 ; j. palace 3 ; f. paul 4 ; r. marignier 5 ; c. de medeiros rimkus 6 ; m. filippi 7 ; m. rocca 7 ; a. rovira 8 ; j. sastre‐garriga 9 ; y. liu 10 ; c. gasperini 11 ; c. tortorella 11 ; m. amato 12 ; s. groppa 13 ; s. llufriu 14 ; c. lukas 15 ; p. sowa 16 ; a. pröbstel 17 ; c. granziera 17 ; b. stankoff 18 ; f. barkhof 19 ; o. ciccarelli 20 ; n. de stefano 1, 1 department of medicine, surgery and neuroscience, university of siena, siena, italy; 2 department of neurology, cleveland clinic, abu dhabi , united arab emirates ; 3 department of clinical neurology, john radcliffe hospital, oxford, uk ; 4 experimental and clinical research center, max delbrueck center for molecular medicine and charité ‐ universitaetsmedizin berlin, berlin, germany; 5 service de neurologie, sclérose en plaques, pathologies de la myéline et neuro‐inflammation, hôpital neurologique pierre wertheimer, hospices civils de lyon, lyon, france; 6 universidade de são paulo, faculdade de medicina, departamento de radiologia e oncologia, são paulo sp , brazil; 7 neuroimaging research unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 8 section of neuroradiology, department of radiology, hospital universitari vall d'hebron, universitat autònoma de barcelona, barcelona, spain.; 9 servei de neurologia. centre d'esclerosi múltiple de catalunya, (cemcat). vall d'hebron institut de recerca, vall d'hebron hospital universitari, universitat autònoma de barcelona, barcelona, spain; 10 department of radiology, beijing tiantan hospital, capital medical university, beijing, china; 11 department of neurosciences, s. camillo‐forlanini hospital, rome, italy; 12 department neurofarba , university of florence, italy; 13 department of neurology, university medical center of the johannes gutenberg university mainz, germany; 14 neuroimmunology and multiple sclerosis unit and laboratory of advanced imaging in neuroimmunological diseases ( imaginem ), hospital clinic barcelona, fundació de recerca clínic barcelona‐idibaps and universitat de barcelona, barcelona, spain; 15 institute of neuroradiology, st. josef hospital, ruhr university bochum, bochum, germany; 16 division of radiology and nuclear medicine, oslo university hospital, oslo, norway; 17 departments of neurology, biomedicine and clinical research, and research center for clinical neuroimmunology and neuroscience basel, university hospital and university of basel, kantonsspital, basel, switzerland; 18 sorbonne university, paris brain institute, icm , pitié salpêtrière hospital, paris, france; 19 radiology & nuclear medicine, vu university medical centre, amsterdam, the netherlands; 20 mr research unit, department of neuroinflammation, queen square ms centre, ucl queen square institute of neurology, faculty of brain sciences, university college london, london, uk.

Background and aims: Relapsing remitting multiple sclerosis (RRMS) and myelin‐oligodendrocyte antibody‐associated disease (MOGAD) are distinct diseases, but their differentiation can be challenging in clinical practice due to overlapping clinical and MRI features. The application of deep learning (DL)‐models to MRI is a promising approach to provide a structurally based classification of diseases, while the study of DL‐derived attention maps may indicate the most relevant anatomical regions for DL‐stratification. We aimed to build a MRI‐based DL‐model to differentiate RRMS from MOGAD and to assess group differences using probability attention maps (PAM).

Methods: In this cross‐sectional study, we analysed 345 FLAIR brain MRIs from RRMS ( n .201, 117F, mean [SD] age: 39 years [±11], median EDSS: 2 [0–8], mean [SD] disease duration: 93 months [±94]) and MOGAD ( n .144, 81F, mean [SD] age: 41y [±13], median EDSS: 2 [0–8.5], mean [SD] disease duration: 71 months [±96]), retrospectively collected from 17 centres. Patients were divided into three independent groups (training, validation, external test sets). The study design is illustrated in Figure 1.

FIGURE 1 Schematic representation of the study design.

Results: A DL discriminatory model between the two diseases was built (accuracy/specificity/ sensitivity: 84%/85%/84%) and successfully validated in the external test set without retraining (accuracy/specificity/sensitivity: 72%/68%/76%). PAM revealed the relevant role of insula (nV: 271, z ‐score: 3.10), hippocampus (nV: 839, z ‐score: 3.44), periventricular areas (nV: 669, z ‐score: 3.47) for RRMS, while the selective role of the cingulate cortex (nV: 2360, z ‐score: 2.71) for the identification of MOGAD (Figure 2).

FIGURE 2 Topographical distributions of the areas significantly contributing to the differentiation between patients with RRMS and with MOGAD.

Conclusion: We developed a DL‐model to accurately differentiate RRMS from MOGAD on FLAIR MRI. PAM provided additional clues on how damage is distributed in the two diseases.

Disclosure: The present research was conducted thanks to the 2019 ECTRIMS‐MAGNIMS fellowship (awarded to R.C.). The Authors have nothing to disclose in relation to this work.

Sunday, June 30 2024

Child neurology/developmental neurology, opr‐033, rehabilitation of attention with a tablet‐based app in pediatric multiple sclerosis: a randomized, multicenter study, c. masciulli 1 ; e. portaccio 1 ; b. goretti 2 ; c. niccolai 2 ; m. simone 3 ; r. viterbo 4 ; m. zaffaroni 5 ; l. pippolo 5 ; e. cocco 6 ; g. fenu 6 ; m. flautano 7 ; c. celico 7 ; m. pardini 8 ; g. mancardi 8 ; r. guerrini 9 ; f. melani 9 ; f. giovannelli 9 ; m. rocca 7 ; m. filippi 7 ; m. trojano 3 ; m. amato 1, 1 department of neurofarba , university of florence, florence, italy; 2 department of neurology, don carlo gnocchi foundation, florence, italy; 3 department of precision and regenerative medicine and jonic area, university ‘aldo moro’ of bari, bari, italy; 4 department of translational biomedicine and neurosciences – dibrain , university “aldo moro” of bari, italy, bari, italy; 5 neuroimmunology unit ‐ multiple sclerosis center, hospital of gallarate, asst della valle olona, gallarate, italy; 6 multiple sclerosis centre, department of medical sciences and public health, university of cagliari, cagliari, italy; 7 neurology unit and ms center, irccs san raffaele scientific institute; neuroimaging research unit, division of neuroscience; neurorehabilitation unit and neurophysiology service; vita‐salute san raffaele university, milan, italy; 8 department of neurology, rehabilitation, ophthalmology, genetics, maternal and child health ( dinogmi ), university of genoa, genoa, italy/ irccs aou san martino‐ist , genoa, italy; 9 paediatric neurology unit and laboratories, neuroscience department, meyer children's hospital irccs , florence, italy.

Background and aims: Cognitive impairment affects approximately 30% of pediatric onset Multiple Sclerosis (POMS) patients with a negative impact on everyday life1. The aim of this study was to evaluate the feasibility and effectiveness of a home‐based, computer‐assisted training of attention in patients with POMS.

Some studies have highlighted a particular involvement of language in patients with POMS, which is commonly spared in adults. Additionally, a lower intelligence quotient (IQ) has been observed in patients with an earlier onset of the disease.

Methods: Inclusion criteria were diagnosis of MS, age 9–18 years, impairment on at least one attention test. Subjects were randomized to specific training (ST) or non‐specific training (n‐ST), delivered through a customized module based on attention exercises in COGNI‐TRAcK2. The main feature of the ST is the implementation of working load algorithms and procedures for intensiveness regulation. The effectiveness of the ST on attention was primarily assessed on the Symbol Digit Modalities Test (SDMT)3 using an analysis of variance for repeated measures. Secondary objectives included effectiveness on other cognitive tests and everyday‐life activities. The evaluations were performed at baseline, end of training, 3‐month follow‐up.

Results: 22 relapsing–remitting patients were included: data of 8 subjects in n‐ST and 4 subjects in ST were available. As for the primary outcome, SDMT score improved in the ST group (from 31.2 at baseline to 42.4 after 3 months, p  = 0.043). This effect was evident also in Trial Making Test B ( p  = 0.047). There was no benefit in other neuropsychological measures.

As for the primary outcome, mean score on the SDMT improved in the ST group (from 31.2 + 9.8 at baseline to 42.4 + 18 at the end of training, p  = 0.524) and remained stable in the n‐ST group (from 32 + 7.3 at baseline to 35.5 + 9.7 at the end of training, p  = 0.284).

The positive effect of ST was also evident in Trail Making Test B, which improved in each group of patients: in ST group from 113.5 + 16.3 at baseline to 54 + 8.5 at the end of treatment ( p  = 0.047) and in n‐ST group from 97 + 39 at baseline to 76.7 + 41.4 at the.

Conclusion: These preliminary findings point to a potential benefit of a home‐based, computer‐assisted training of attention in patients with POMS. Early rehabilitation in POMS can mitigate the negative impact of cognitive impairment in patient's lifestyle and school activities.

Disclosure: C. Masciulli nothing to disclose; E. Portaccio received fees from Biogen, Merck Serono, Sanofi, Teva and Novartis; R. G. Viterbo received speaker honoraria from Biogen Idec and Teva; M. Zaffaroni received honoraria from Almirall, Biogen Idec, Genzyme, Merck Serono, Novartis and Teva; M. Pardini received research support from Novartis and Nutricia and honoraria from Merk and Novartis, G. Mancardi received honoraria from Bayer Schering, Biogen Idec, Sanofi‐Aventis, and Merck Serono Pharmaceuticals, R. Guerrini received honoraria from Biocodex, UCB, Eisai Inc, ValueBox, and Viropharma, M. Rocca received honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva, M. Filippi received fees from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck‐Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries; M. Trojano received honoraria from Biogen, Sanofi, Merck, Roche, and Novartis; M.P. Amato received honoraria from Biogen Idec, Merck Serono, Bayer Schering Pharma, and Sanofi Aventis.

OPR‐034

Ambulatory 24‐h continuous polysomnography as diagnostic tool for narcolepsy type 1 in adult and pediatric patients, f. biscarini 1 ; c. zenesini 2 ; l. vignatelli 2 ; f. citeroni 2 ; s. vandi 1 ; l. barateau 3 ; y. dauvilliers 3 ; g. plazzi 4 ; f. pizza 1, 1 department of biomedical, metabolic and neural sciences, university of modena and reggio‐emilia , italy; 2 irccs istituto delle scienze neurologiche di bologna, italy; 3 sleep‐wake disorders unit, department of neurology, gui‐de‐chauliac hospital, chu montpellier, montpellier, france; 4 department of biomedical, metabolic and neural sciences, university of modena and reggio‐emilia , italy.

Background and aims: Narcolepsy type 1 (NT1) is diagnosed on average 10 years after the onset. We evaluated the contribution of 24‐hour continuous polysomnography (PSG) as an alternative tool for the diagnosis of NT1 in adults and children.

Methods: Consecutive patients evaluated at the Bologna Narcolepsy Center from 2013 to 2022 for suspected hypersomnia were included. The 807 participants underwent 48‐hour ambulatory PSG monitoring preceding the multiple sleep latency test (MSLT). The accuracy of night1 and day2 PSG was tested for the diagnosis of NT1 ( n  = 322), employing the 2023 international criteria as the standard reference for the ROC curve analysis.

Results: The detection of daytime‐sleep‐onset REM period (SOREMP) ≥1, with an area under the curve (AUC) of 0.84 (95% CI, 0.82–0.87), 84.4% sensitivity and 84.5% specificity, resulted superior to nighttime‐PSG measures, including nighttime‐SOREMP ( p  < 0.001) and comparable to 24‐hour‐SOREMP count. In the entire cohort, the combination of daytime‐SOREMP ≥1 with cataplexy provided 78.9% sensitivity and 98.4% specificity, with AUC 0.89 (95% CI 0.86–0.91) superior to the combination of nighttime‐SOREMP with cataplexy (AUC 0.78, 95% CI 0.76–0.81, p  < 0.001) and not inferior to MSLT criteria for narcolepsy (AUC 0.90, 95% CI 0.88–0.92). These results were confirmed separately in adult and pediatric patients, except that, in pediatric patients (130/243 with NT1), nighttime‐SOREMP (AUC 0.86, 95% CI 0.82–0.90) was not inferior to daytime‐SOREMP ≥1.

FIGURE 1 Receiver operating characteristic (ROC) curve analysis for diagnosis of narcolepsy type 1 of the polysomnographic variables from daytime (A), nighttime (B), daytime and nighttime combined (C), and all the variables together (D).

TABLE 1 Receiver operating characteristic (ROC) curve analysis for the diagnosis of narcolepsy type 1, in different age groups.

Conclusion: Continuous daytime‐PSG is accurate for identifying NT1 in all age groups and appears superior to nighttime‐PSG and not inferior to 24‐hour monitoring. Daytime‐PSG, applicable outside sleep laboratory settings, can anticipate the diagnosis of NT1 in both adults and children.

OPR‐035

Survival differences between genders in pdha1 ‐related pyruvate dehydrogenase deficiency, k. merkevicius ; j. mayr; s. wortmann, university children's hospital, salzburger landeskliniken ( salk ), paracelsus medical university ( pmu ), salzburg, austria.

Background and aims: Pyruvate dehydrogenase complex deficiency (PDHD) is the prototypic inborn error of mitochondrial metabolism, leading to neurodevelopmental disorder with lactic acidosis, CNS structural abnormalities. Disease causing variants in the X‐linked PDHA1 are the most common genetic cause of PDHD, consequently, mainly males should be affected. In the literature, both genders are reported. We here assess the gender differences in survival in PDHA1‐ related PDHD.

Methods: Affected individuals with PDHA1‐ related PDHD were recruited via literature review ( n  = 512) and international collaboration ( n  = 418). All variants were (re)classified according to {"type":"entrez-nucleotide","attrs":{"text":"NM_000284.3","term_id":"291084749","term_text":"NM_000284.3"}} NM_000284.3 reference transcript, interpreted via American College of Medical Genetics (ACMG) criteria. (Likely) benign variants were excluded. Survival probability was assessed using Kaplan–Meier estimator.

Results: In total, 930 cases with known gender and genotype were included (females 51.6%, n  = 480), harbouring a total of 324 different PDHA1 disease causing variants. The overall median survival was 12.5 years (95% Confidence interval (95% CI) 8–20 years; n  = 317). Males had significantly ( p  < 0.001) lower survival probability than females, median survival in males and females were 3.6 years (95% CI 2.5–9.42; n  = 146) and 22 years (95% CI 16.0–30.0; n  = 159), respectively. Males with neonatal or infantile presentation had significantly lower survival probability than females with neonatal ( p  < 0.001; n  = 136) or infantile ( p  < 0.001; n  = 83) presentation.

Conclusion: Interestingly, we found equal number of cases between both genders, males had significantly lower survival probability. In females, X‐inactivation could lead to milder phenotypes with better survival even with the same genotype as in males. Some males with severe phenotype could result in spontaneous pregnancy termination explaining similar frequency.

Disclosure: This abstract is part of a larger study analysing the genotypical and phenotypical landscape of PDHA1‐related PDHD. This study was made possible through large collaboration with more than 150 different specialists worldwide.

OPR‐036

Abstract withdrawn, opr‐037, clinical and instrumental gait phenotyping in subjects with glut ‐1 deficiency syndrome, m. corrado 1 ; r. de icco 1 ; v. grillo 1 ; v. de giorgis 1 ; v. vacchini 2 ; c. varesio 2 ; m. celario 2 ; d. trabassi 3 ; s. castiglia 3 ; m. serrao 3 ; c. tassorelli 3, 1 department of brain and behavioral sciences, university of pavia, pavia, italy; 2 department of child neurology and psychiatry, irccs mondino foundation, pavia, italy; 3 department of medical and surgical sciences and biotechnologies, “sapienza” university of rome, polo pontino, latina, italy.

Background and aims: Gait disturbances and movement disorders are frequent in patients with GLUT‐1 deficiency syndrome (GLUT1‐DS), a rare disease also characterized by seizures and cognitive dysfunction. This study aimed to assess the ability of a set of instrumental gait indexes to identify gait disorders in GLUT1‐DS, and to detect potential correlations with the clinical phenotype and biochemical parameters.

Methods: We recorded a 30‐meter gait of 16 subjects with GLUT1‐DS and of 16 matched healthy subjects (HS). We performed gait analysis with an inertial sensor. Based on trunk acceleration we calculated: spatio‐temporal gait parameters, pelvic kinematics, harmonic ratios (HR), recurrence quantification analysis (RQA), stride length coefficient of variation (CV), the longest short‐term Lyapunov's exponent (sLLE), and the log dimensionless jerk score (LDLJ). Along with the instrumental gait recording, we performed a comprehensive clinical and biochemical phenotyping.

Results: GLUT 1‐DS (mean age 19.1 ± 13.7 years) showed lower values of HR and single support (SS) phase (Figure 1; p  < 0.05), indicating impaired gait smoothness. Moreover, they showed higher values of CV and sLLE (Figure 2; p  < 0.01), suggestive of higher dynamic instability and variability of gait. The CV negatively correlated with ketonemia ( r  = −0.61, p  < 0.05). Nine subjects (52%) had clinically evident gait disorders, mainly characterized by choreo‐ataxic gait.

FIGURE 1 Differences in time of single support (SS) and harmonic ratio (HR) between HS (orange) and GLUT1‐DS (green).

FIGURE 2 Differences in coefficient of variation (CV, i.e. variability of stride length) and the longest short‐term Lyapunov's exponent (sLLE) between HS (orange) and GLUT1‐DS (green).

Conclusion: GLUT1‐DS exhibited multiple alterations in the trunk acceleration‐derived gait indexes, which were suggestive of impaired gait stability and smoothness. Interestingly, increased gait variability correlated with low ketonemia, possibly suggesting this feature as a marker of poor therapeutic adherence.

MS and related disorders 1

Opr‐038, long‐term outcomes of phase‐1 study of neural stem cell transplantation in progressive multiple sclerosis, m. azzimonti 1 ; i. gattuso 2 ; e. pagani 3 ; a. genchi 4 ; l. storelli 3 ; l. moiola 2 ; v. martinelli 2 ; p. vezzulli 5 ; e. brambilla 6 ; a. falini 7 ; g. martino 8 ; m. rocca 1 ; m. filippi 9, 1 neuroimaging research unit, division of neuroscience, and neurology unit, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy; 2 neurology unit, irccs san raffaele scientific institute, milan, italy; 3 neuroimaging research unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 4 neurology unit, and neuroimmunology unit, institute of experimental neurology, irccs san raffaele scientific institute, milan, italy; 5 neuroradiology unit and high field mri center, irccs san raffaele scientific institute, milan, italy; 6 neuroimmunology unit, institute of experimental neurology, irccs san raffaele scientific institute, milan, italy; 7 neuroradiology unit and high field mri center, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy; 8 neuroimmunology unit, institute of experimental neurology, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy; 9 neuroimaging research unit, division of neuroscience, neurology unit, neurorehabilitation unit, and neurophysiology service, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy.

Background and aims: Human fetal neural progenitor/stem cells (hfNPCs) transplant feasibility and safety in progressive multiple sclerosis (PMS) has been demonstrated in STEMS, a phase I clinical trial ( {"type":"clinical-trial","attrs":{"text":"NCT03269071","term_id":"NCT03269071"}} NCT03269071 ). Higher dose of hfNPCs was associated with significantly lower rates of brain and gray matter (GM) atrophy after 2 years. We present long‐term (LT) follow‐up (FU) of STEMS trial.

Methods: Patients underwent clinical (comprehensive of Expanded Disability Status Scale [EDSS] and Symbol Digit Modalities Test [SDMT]) and brain MRI evaluation at minimum 4.5 year FU. New T2‐hyperintense and Gd‐enhancing lesions were counted. T2‐lesion volume (T2LV), percentage brain (PBVC), GM (PGMVC) and white matter (PWMVC) volume changes were estimated.

Results: FU was available for 11/12 patients (median duration 5.6 years). At LT, EDSS and SDMT were significantly worsened compared to 2 year FU ( p  < =0.08). Five (45%) patients showed new T2‐hyperintense lesions, whereas T2LV was unchanged ( p  = 0.07); no patient showed Gd‐enhancing lesions. Brain, GM and WM volumes were decreased at LT compared to 2‐year FU. Interestingly, atrophy rates at LT were lower compared to the first 2‐year changes (significant for PGMVC: 2‐years vs. baseline = −0.76%; LT vs. 2‐years = −0.47%, p  = 0.04). No significant correlation was found between number of injected hfNPCs and variation of EDSS, SDMT or MRI measures.

Conclusion: Although no clear dose–response effect has been found in hampering disability, cognition or brain atrophy progression, lower rates of GM atrophy were found at LT FU, which could imply that hfNPCs maintain their neuroprotective effect over time.

Disclosure: M Azzimonti, I Gattuso, E Pagani, A Genchi, L Storelli, P Vezzulli, E Brambilla, A Falini, and G Martino have nothing to disclose. L Moiola compensation for speaking activities and/or consulting services from Merck, Biogen, Novartis, Roche, Sanofi, and TEVA. V Martinelli compensation for speaking and/or consultancies and support for participation in congresses from Biogen, Merck‐Serono, Novartis, Genzyme and TEVA Pharmaceutical Industries. MA Rocca consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva; research support from MS Society of Canada, Italian Ministry of Health (IMH), Italian Ministry of University and Research, and FISM. M. Filippi compensation for consulting or speaking activities from Alexion, Almirall, Biogen, Bayer, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol‐Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi‐Aventis, Sanofi‐Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol‐Myers Squibb, Lilly, Novartis, Sanofi‐Genzyme; he receives research support from Biogen Idec, Merck‐Serono, Novartis, Roche, IMH, Italian Ministry of University and Research, and FISM.

OPR‐039

Parental smoking exposure and risk for multiple sclerosis among adults: the envims study, c. ferri 1 ; n. merli 2 ; k. myhr 3 ; t. riise 4 ; c. wolfson 5 ; m. pugliatti 6, 1 department of neuroscience, s. anna university hospital, ferrara, italy; 2 department of neuroscience and rehabilitation, university of ferrara, italy. s. anna university hospital, ferrara, italy; 3 department of clinical medicine, university of bergen, norway; the norwegian multiple sclerosis registry and biobank, department of neurology, haukeland university hospital, bergen, norway; 4 department of global public health and primary care, university of bergen, bergen, norway/the norwegian multiple sclerosis competence centre, department of neurology, haukeland university hospital, bergen, norway; 5 department of epidemiology, biostatistics, and occupational health, school of population and global health, mcgill university, montreal, quebec, canada; 6 department of neuroscience and rehabilitation, university of ferrara, italy; s. anna university hospital, ferrara, italy.

Background and aims: Active smoking is a known risk factor for Multiple sclerosis (MS) development and poor prognosis. However, the impact of past exposure to parental smoking (ParS), including maternal smoking during pregnancy (MSDP) is not well defined. We aimed to investigate how these types of early age exposures affect MS risk among adults.

Methods: Using the data collected by the EnvIMS study, a large multinational case–control population‐based study, we investigated the association between MS and smoking habit, MSDP and maternal/paternal smoking (MaS, PaS) in Canadian, Italian, and Norwegian populations. Data were collected with EnvIMS‐Q, designed to investigate environmental exposures during early life stages. Adjusted odds ratios (aOR) for index age and participants' smoking status are presented with 95% confidence intervals (95% CI).

Results: We included 1565 Canadian, 2040 Italian, and 2674 Norwegian subjects. An association between MS and MSDP and MaS was observed among Norwegians: aOR 1.38 (1.12, 1.71) and 1.39 (1.17, 1.65), respectively. A tendency for PaS to be associated with MS was found among Canadians: aOR 1.21 (0.97, 1.51). No significant association to ParS (any) was detected in the Italian population.

Conclusion: Selective exposure to ParS at early age may differentially increase MS risk in the general population and independently from the subject's past/current smoking habit. The developmental origin of health and disease (‘DOHaD’) theory may help interpret these findings. The absence of an association between MS and past exposure to ParS in other populations may reflect its smaller effect on MS risk compared to other factors.

Disclosure: The authors declare no conflict of interest. The EnvIMS study was supported by Fondazione Italiana Sclerosi Multipla, FISM, grants n. 2007/R/14, and n. 2008/R/19; Financially supported by the European Union – Next Generation EU – NRRP M6C2 – Investment 2.1 Enhancement and strengthening of biomedical research in the NHS ‐ PNRR‐MAD‐2022‐12,376,868.

OPR‐040

Retinal layer thinning differentiates disease‐modifying treatment effects in relapsing ms when using a rebaseline, g. bsteh 1 ; h. hegen 3 ; n. krajnc 2 ; p. altmann 1 ; m. auer 3 ; k. berek 3 ; b. kornek 1 ; f. leutmezer 1 ; s. macher 1 ; t. monschein 1 ; m. ponleitner 1 ; p. rommer 1 ; c. schmied 1 ; k. zebenholzer 1 ; g. zulehner 1 ; t. zrzavy 1 ; f. deisenahmmer 3 ; f. di pauli 3 ; b. pemp 4 ; t. berger 1, 1 department of neurology, medical university of vienna, vienna, austria; 2 comprehensive center for clinical neurosciences and mental health, medical university of vienna, vienna, austria; 3 department of neurology, medical university of innsbruck, innsbruck, austria; 4 department of ophthalmology, medical university of vienna, vienna, austria.

Background and aims: We aimed to investigate whether retinal layer thinning measured by optical coherence tomography (OCT) can differentiate effects of disease‐modifying treatment (DMT) in relapsing MS (RMS) using a rebaseling concept.

Methods: From an ongoing prospective observational study, we included RMS patients, who 1) had an OCT scan 6–12 months after DMT start (rebaseline), 2) ≥1 follow‐up OCT ≥12 months after rebaseline, and 3) adhered to the DMT during follow‐up. Differences between DMT substances in thinning of peripapillary retinal nerve fiber layer (pRNFL) and macular‐ganglion‐cell‐plus‐inner‐plexiform layer (GCIPL) were analyzed using mixed‐effects linear regression adjusting for age, sex, disease duration and relapses during follow‐up.

FIGURE 1 Study design.

Results: Of 291 RMS patients (mean age 30.8 years [SD 7.9], 72.9% female, median disease duration 9 months [6–94], median rebaseline‐to‐last‐follow‐up‐interval 37 months [12–87]). Mean annualized percent loss rates (%/year) of retinal layer thinning in reference to dimethyl‐fumarate ( n  = 84, GCIPL 0.28, pRNFL 0.53) were similar under teriflunomide ( n  = 18, GCIPL 0.34, pRNFL 0.59, not significant [ns]), glatiramer acetate ( n  = 24, GCIPL 0.32, pRNFL 0.56, ns) and interferon beta ( n  = 13, GCIPL 0.33, pRNFL 0.60, ns), appeared slightly lower under sphingosine‐phosphate‐1‐receptor modulators ( n  = 27, GCIPL 0.19 [ p  = 0.093], pRNFL 0.42 [ p  = 0.097]) and cladribine ( n  = 23, GCIPL 0.20 [ p  = 0.095], pRNFL 0.42 [ p  = 0.099]), and were significantly lower under natalizumab ( n  = 47, GCIPL 0.09, pRNFL 0.24; p  < 0.001 respectively) and anti‐CD20 monoclonal antibodies ( n  = 55, GCIPL 0.10, pRNFL 0.23; p  < 0.001 respectively).

FIGURE 2 Annualized pRNFL loss differentiates disease‐modifying treatment effects in RMS.

Figure 23 Annualized GCIPL loss differentiates disease‐modifying treatment effects in RMS.

Conclusion: Applying a rebaseling concept, retinal layer thinning differentiates DMT effects in RMS and, thus, may be a useful biomarker to mediate DMT efficacy on neuroaxonal degeneration – at least on a group level.

Disclosure: Gabriel Bsteh: has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Lilly, Merck, Novartis, Roche, Sanofi‐Genzyme and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Novartis, Roche, Sanofi‐Genzyme and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis.

OPR‐041

Longitudinal changes in the periplaque area of paramagnetic rim lesions may be associated with remyelination failure, n. krajnc 1 ; v. schmidbauer 2 ; j. leinkauf 2 ; n. gantner 2 ; l. haider 2 ; g. bsteh 1 ; g. kasprian 2 ; f. leutmezer 1 ; b. kornek 1 ; p. rommer 1 ; t. berger 1 ; h. lassmann 3 ; s. hametner 4 ; a. dal‐bianco 1, 1 department of neurology, medical university of vienna, vienna, austria; 2 medical university of vienna, department of biomedical imaging and image‐guided therapy, vienna, austria; 3 center for brain research, medical university of vienna, vienna, austria; 4 division of neuropathology and neurochemistry, department of neurology, medical university of vienna, vienna, austria.

Background and aims: Paramagnetic rim lesions (PRLs) are an emerging imaging biomarker in multiple sclerosis (MS) associated with a more severe disease course.

Methods: In this prospective longitudinal study, quantitative MRI metrics of PRLs, lesions with diffuse susceptibility‐weighted imaging (SWI)‐hypointense signal (DSHLs) and SWI‐isointense lesions (SILs), their surrounding periplaque area (PPA) and normal‐appearing white matter (NAWM) were measured in people with MS (pwMS) using the multi‐dynamic multi‐echo (MDME) sequence post‐processing software “SyMRI” at baseline, after 1 and 2 years.

Results: In 15 pwMS, 18 PRLs, 31 DSHLs and 63 SILs were identified; four (26.7%) patients had no PRLs. After 2 years, intralesional T1 relaxation times increased significantly only in SILs (1200.7 (172.6) vs. 1278.6 (245.7), p  = 0.002) but not in PRLs and DSHLs (1648.6 (402.1) vs. 1810.2 (564.6), p  = 0.154; 1532.5 (402.1) vs. 1741.4 (328.1), p  = 0.086, respectively). In the PPA, significantly shorter T1 relaxation times were observed for both DSHLs (790.8 (83.2) vs. 767.9 (45.9), p  = 0.012) and SILs (747.5 (45.7) vs. 730.6 (51.2), p  = 0.007) but not for PRLs (786.7 (52.9) vs. 795.2 (30.3), p  = 0.591). Patients with PRLs also showed no shortened T1 relaxation times in the NAWM (685.0 (46.0) vs. 690.7 (18.5), p  = 0.830) in contrast to patients without PRLs (676.1 (42.9) vs. 643.3 (19.4), p  < 0.001).

Longitudinal changes in PRLs, DSHLs and SILs, their surrounding PPA and NAWM.

Conclusion: Significantly shorter T1 relaxation times in DSHL PPA and SIL PPA, but not in PRL PPA after 2 years may again point to remyelination failure in and around PRLs. T1‐quantification based on MDME in and around lesions may become a useful and applicable routine marker for silent progression in pwMS.

Disclosure: The project is supported by the Multiple Sklerose Forschungsgesellschaft.

OPR‐042

Cvs , cl and prl for the diagnostic and prognostic workup of ms, s. borrelli 1 ; m. martire 2 ; a. stölting 1 ; c. vanden bulcke 1 ; e. pedrini 2 ; f. guisset 1 ; c. bugli 3 ; h. yildiz 4 ; l. pothen 4 ; s. elands 5 ; v. martinelli 2 ; b. smith 6 ; s. jacobson 6 ; r. du pasquier 7 ; v. van pesch 8 ; m. filippi 2 ; d. reich 6 ; m. absinta 2 ; p. maggi 1, 1 neuroinflammation imaging lab ( nil ), institute of neuroscience , université catholique de louvain, brussels, belgium; 2 vita‐salute san raffaele university, milan, italy; 3 plateforme technologique de support en méthodologie et calcul statistique, université catholique de louvain, brussels, belgium; 4 department of internal medicine and infectious diseases, cliniques universitaires saint‐luc , université catholique de louvain, brussels, belgium; 5 department of neurology, hôpital erasme, hôpital universitaire de bruxelles, université libre de bruxelles, brussels, belgium; 6 national institute of neurological disorders and stroke ( ninds ), national institutes of health ( nih ), bethesda, md , usa ; 7 neurology service, department of clinical neurosciences, centre hospitalier universitaire vaudois, university of lausanne, lausanne, switzerland; 8 department of neurology, cliniques universitaires saint‐luc , université catholique de louvain, brussels, belgium.

Background and aims: The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), cortical lesions (CL), and paramagnetic rim lesions (PRL), as well as their association with clinical outcomes.

Methods: This multicenter study included: (1) a cross‐sectional analysis of CVS (proportion of CVS‐positive lesions, or simplified determination of CVS in three/six lesions ‐ Select3*/Select6*), CL, and PRL in 185 MS/100 non‐MS cases on 3T‐MRI‐brain images, including 3D T2‐FLAIR, T2*‐EPI magnitude and phase, DIR, and MPRAGE; (2) a longitudinal analysis in 61 MS cases of progression independent of relapse and MRI activity (PIRA).

Results: The presence of ≥41% CVS‐positive lesions/≥1 CL/≥1 PRL (optimal cut‐offs) had 96%/94%/93% specificity, 97%/80%/60% sensitivity, and 0.99/0.88/0.77 area under the curve (AUC), respectively, to distinguish MS from non‐MS cases. Select3*/Select6* showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/93% specificity, 98%/97% sensitivity, 0.99/0.98 AUC; p  = 0.002/ p  < 0.001). Both CL and PRL were associated with higher MS disability and severity. After 2 years follow‐up, cases with >4 PRL at baseline were more likely to experience PIRA (OR 17.8, 95% CI: 2.2–144.7; p  = 0.007), whereas no association was observed between other MRI measures and PIRA, including the number of CL.

Conclusion: The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlate with clinical measures of poor prognosis, with PRL being a predictor of PIRA.

Disclosure: S. Borrelli is supported by the Funds Claire Fauconnier, Ginette Kryksztein & José and Marie Philippart‐Hoffelt, managed by the King Baudouin Foundation. A. Stölting has the financial support of the Fédération Wallonie Bruxelles ‐ Fonds Spéciaux de Recherche (F.S.R.). C. Vanden Bulcke has the financial support of the Fédération Wallonie Bruxelles ‐ Fonds Spéciaux de Recherche (F.S.R.). D.S. Reich is supported by the intramural Research Program of NIH/NINDS. M. Absinta is supported by research grants from the Conrad N. Hilton Foundation (Marylin Hilton Bridging Award for Physician‐Scientists, grant #17313), the International Progressive MS alliance (21NS037), the Roche Foundation for Independent Research, the Cariplo Foundation (grant #1677), the FRRB Early Career Award (grant #1750327), and the National MS Society (NMSS RFA‐2203‐39,325). P. Maggi research activity is supported by the Fondation Charcot Stichting Research Fund 2023, the Fund for Scientific Research (F.R.S, FNRS; grant #40008331), Cliniques universitaires Saint‐Luc “Fonds de Recherche Clinique” and Biogen.

OPR‐043

Neuron‐specific enolase in status epilepticus versus generalized periodic discharges after cardiac arrest ( next‐cat ), morotti colleoni 1 ; m. pozzi 2 ; s. tagliabue 1 ; e. bianchi 3 ; m. normanno 1 ; f. pasini 1 ; g. cereda 1 ; a. giglio 1 ; a. stabile 1 ; g. pederzoli 1 ; s. diamanti 1 ; j. di francesco 1 ; l. stanzani 1 ; a. coppo 2 ; l. avalli 2 ; c. ferrarese 1 ; g. foti 2 ; s. beretta 1, 1 department of neurology, fondazione irccs san gerardo dei tintori, university of milano‐bicocca , monza, italy; 2 department of intensive care, fondazione irccs san gerardo dei tintori, monza, italy; 3 mario negri institute for pharmacological research irccs , milano, italy.

Background and aims: The aim of our study was to analyse the distribution of NSE levels according to specific EEG patterns in post‐cardiac arrest patients.

Methods: We conducted a prospective cohort study in patients after cardiac arrest admitted to the ICU, with at least one NSE value between 24 and 72 hours and at least one off‐sedation EEG within 72 hours after cardiac arrest. Subjects were categorized in four independent EEG patterns (benign, epileptiform non‐GPDs, GPDs, malignant non‐epileptiform). Kruskal‐Wallis test and Mann–Whitney tests were used to compare the NSE levels distribution among the four EEG patterns and in GPDs versus epileptiform non‐GPDs patterns.

Results: We recruited 341 patients from 2011 to 2023. A benign EEG pattern was observed in 161 (47%), an epileptiform pattern in 84 (25%), GPDs in 43 (13%) and a malignant pattern in 53 (15%). The median NSE level were 34 ng/mL for the benign EEG pattern, 45.8 ng/mL for the epileptiform pattern, 144 ng/mL for GPDs and 320.8 ng/mL for the malignant one. The distribution of NSE levels was statistically different among the four EEG patterns (H = 152.4, p  < 0.0001). NSE levels were approximately 100 ng/mL higher in patients with a GPDs pattern, compared to an epileptiform non‐GPDs pattern (absolute difference 98.2 ng/mL, 95% CI 66.2–126.7; p  < 0.0001).

The NSE levels distribution among the four EEG patterns.

Conclusion: The level of the prognostic biomarker NSE is higher in patients after cardiac arrest with GPDs compared to epileptiform activity. A more aggressive therapeutic approach could be justified for patients with epileptiform non‐GPDs activity after cardiac arrest.

OPR‐044

Electroencephalographic and epileptological natural history in metachromatic leukodystrophy: a longitudinal study, g. cutillo 1 ; g. fanelli 1 ; a. zambon 1 ; m. vabanesi 1 ; g. cecchetti 1 ; a. bellini 1 ; s. recupero 3 ; m. sarzana 3 ; f. ciotti 3 ; u. del carro 1 ; m. natali sora 1 ; c. baldoli 2 ; a. aiuti 3 ; f. fumagalli 3 ; m. filippi 1, 1 neurology unit and neurophysiology service, irccs ospedale san raffaele, milan, italy; 2 neuroradiology unit, irccs ospedale san raffaele, milan, italy; 3 pediatric immunohematology unit and bmt program, irccs san raffaele scientific institute, milan, italy.

Background and aims: Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by mutations in the ARSA gene. Few data are available on its epileptological history.

Methods: Single‐center, retrospective and prospective observational study on MLD patients enrolled in a natural history protocol (January 2000–December 2023). Data including clinical histories, EEG tracings, MRI evaluations and functional scales were collected.

Results: Fifty patients, 25 late infantile (LI), 12 early juvenile (EJ), 7 late juvenile (LJ), 6 adult‐onset (AD), were included. Median follow‐up was 4 years (IQR: 2–8; range: 1–20), with 360 EEG tracings. Epilepsy was documented in 76% (38/50) of patients: 80% (20/25) of LI, 100% (13/13) of EJ, 50% of AD (3/6) and 43% of LJ (3/7). Epilepsy occurred on average 30 months after disease onset in LI, 35 months in EJ, 108 months in LJ and 109 months in AD. Main seizure types reported were focal and focal‐to‐bilateral tonic–clonic seizures, often drug‐resistant. Status epilepticus was reported in 34% (13/38) of patients, coinciding with epilepsy onset in 4/38. Disease subtypes presented distinct EEG patterns: LI presented rapid background deterioration, frequent seizures, and low‐voltage rapid activity bursts. Among Juvenile‐onset patients, divergent patterns were observed, with EJ having more similarities with LI group and LJ displaying a slower progression. AD presented disorganized backgrounds with sporadic focal anomalies.

Baseline features and demographics of the patients included in the analysis, recapitulating the results section.

Conclusion: Epilepsy represent a significant comorbidity in MLD, especially LI and EJ groups, often presenting with drug‐resistant seizures. MLD subtypes present different EEG evolution, hence this could represent a tool to further characterize patients, disease progression and treatment response.

Illustrative EEG epochs of four patients in advanced diseases stages. A (LI), B (EJ), C (LJ), D (AD). Different subtype shows different degrees of background disorganization and focal anomalies.

Disclosure: The study was supported by Telethon Foundation, IRCCS San Raffaele Scientific Institute, GlaxoSmithKline (GSK), and Orchard Therapeutics. The authors have no relevant disclosure related to the present work.

OPR‐045

Epilepsypower a project to favor inclusion of people with epilepsy in workplaces, f. narducci 1 ; g. baker 2 ; d. walsh 3 ; n. casalino 4 ; b. borin 4 ; f. pigni 5 ; s. louissi 5 ; m. kateva 6 ; s. duttenhöfer 7 ; m. tombini 1 ; v. di lazzaro 1 ; g. assenza 1, 1 campus bio‐medico university, department of medicine and surgery, unit of neurology, neurophysiology, neurobiology and psichiatry, rome, italy; 2 university of liverpool, department of molecular and clinical pharmacology, liverpool, uk; 3 international bureau of epilepsy, dublin, ireland; 4 luiss business school, rome, italy; 5 grenoble ecole de management, grenoble, france; 6 chamber of commerce and industry vratsa, vratsa, bulgaria; 7 emcra gmbh , berlin, germany.

Background and aims: Despite good seizure control, unemployment and underemployment are more common among people with epilepsy (pwE), for several reasons. The EpilepsyPOWER is a European project, involving five Countries (Italy, Bulgaria, France, Ireland, Germany), aimed to improve PwE's workplace inclusion.

Methods: For this project, we made a systematic review on epilepsy and employment, selecting 55 articles from 1958 to 2023, analyzing employment rate and determinants of employment/unemployment. We reviewed legislation in involved countries and developed two anonymous surveys asking for PwE's employment condition, and higher education institutions (HEI) general knowledge and attitudes about epilepsy.

Results: For all considered countries, we have not found any specific job legislation. Unemployment rates ranged from similar to twice or three times the general population and above all factors, seizure control and employers' attitudes contributed mostly to unemployment. We collected 567 answers from PwE and 291 from HEI. Unemployment rates were: 7.9% in Italy, 6.7% Ireland, 8.5% France, 15% Germany, 9% Bulgaria; people fully employed: 42.9% in Italy, 53% Ireland, 31.7% France, 40% Germany, 47.9% Bulgaria. In Italy, 24.2% of pwE did not disclose their condition, whereas in Bulgaria 48.5%. HEI individuals correctly defined epilepsy as a neurological disorder, treatable in most cases. Although most respondents have seen a seizure, in some countries, they did not know how to give first aid.

Conclusion: Exploring pwE work conditions and HEI perspectives could help to spread a culture of inclusion and fight marginalization of pwE in workplaces, allowing them to attain correct employment.

OPR‐046

An internationally derived core outcome set for adult epilepsy treatment trials: the epset project, j. mitchell 1 ; a. noble 2 ; p. williamson 2 ; t. marson 2 ; epset project ineternational working group 3, 1 the walton centre nhs ft , uk ; 2 university of liverpool, uk ; 3 epset project.

Background and aims: A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all trials. In epilepsy, the choice of outcomes measured varies widely among existing studies, particularly in randomised controlled trials (RCTs). We have developed an internationally derived COS specific to adult epilepsy treatment trials.

Methods: We performed a rapid review of the qualitative literature exploring experiences of people with epilepsy and reviewed outcomes already measured in phase 3 and 4 epilepsy specific RCTs, to generate an outcome long‐list. In collaboration with the ILAE Big Data Commission and an international group of healthcare providers, researchers, and people with epilepsy we have performed a grouping and rationalisation process and taken 42 individual outcomes to a two‐stage, online Delphi survey followed by consensus meeting.

Long List of Outcomes for EPSET consensus process.

Results: 490 people with epilepsy, their representatives, healthcare professionals and researchers have completed the Delphi surveys in 7 languages, representing the global perspective. Inconclusive outcomes were discussed, and the final outcomes ratified at international online consensus meeting. The ratified COS includes a minimum set of seizure and non‐seizure outcomes, that should be measured and reported as a minimum in all future clinical trials.

Outcomes achieving consensus for inclusion in the COS after each Delphi round.

Conclusion: The EPSET Project has identified a COS for adults with epilepsy and derived inter‐ national consensus. This will ensure that meaningful outcomes are measured in future clinical trials, that the results of trials are relevant to people with epilepsy and facilitate systematic review and meta‐analysis.

Disclosure: Nothing to disclose related to the submitted work.

OPR‐047

Heart rate variability exhibits a reduced vagal output in patients with status epilepticus developing tako‐tsubo, s. de angelis ; p. quintieri; f. dono; d. liviello; s. cipollone; g. evangelista; s. consoli; m. russo; m. dasara; f. anzellotti; s. sensi, department of neurosciences, imaging and clinical sciences, “g. d'annunzio” university of chieti‐pescara , chieti, italy.

Background and aims: Tako‐tsubo cardiomyopathy (TTC) is an impairment of systolic function, mainly targeting the left ventricle with clinical manifestations closely resembling that of acute coronary syndrome. Although its aetiology has been related to a massive catecholamine release driven by physical and psychological stressors, certain neurologic conditions like status epilepticus (SE) also seem to increase susceptibility to TTC. However, clinical factors linking the SE to TTC are still missing. This study aims to provide reliable criteria to be employed as predictors of TTC in epileptic patients.

Methods: In this study, we examined Heart Rate Variability (HRV) changes in three patients presenting with TTC immediately after an SE. HRV analysis was performed on a 5‐minute EKG recording in resting state during and after SE. HRV variability was evaluated according to time and frequency domains and non‐linear analysis.

Results: During SE, a leaning towards cardiovagal output reduction was observed, as indicated by decreased RMSSD, HF, and SD1. In addition, an increased LF/HF ratio was also observed, an index that correlates with an overall increased risk of mortality. These imbalances tend to attenuate with SE resolution.

Conclusion: Data from our cohort suggest that HRV variations play a role in predicting cardiac dysfunction (and TTC) in epileptic patients. These data support the notion of a distinct undergoing interplay between sympathetic and cholinergic stimuli on myocardial motility in people with epilepsy.

OPR‐048

Status epilepticus in patients with brain tumors and metastases: a multicenter cohort study of 208 patients, a. strzelczyk 1 ; j. rickel 1 ; d. zeeb 2 ; s. knake 2 ; h. urban 1 ; j. konczalla 1 ; k. weber 1 ; p. zeiner 1 ; a. pagenstecher 2 ; e. hattingen 1 ; a. kemmling 2 ; e. fokas 1 ; s. adeberg 2 ; r. wolff 1 ; m. sebastian 1 ; t. rusch 2 ; m. ronellenfitsch 1 ; k. menzler 2 ; l. habermehl 2 ; m. czabanka 1 ; c. nimsky 2 ; l. timmermann 2 ; c. grefkes 1 ; j. steinbach 1 ; f. rosenow 1, 1 goethe‐university frankfurt; 2 philipps‐university marburg.

Background and aims: Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short‐ and long‐term outcomes of this population.

Methods: This retrospective, multi‐center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017.

Results: The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult‐type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1–57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1–46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post‐SE at discharge ( p  < 0.001). Mortality at discharge was 17.3% ( n  = 36), with the greatest occurring in patients with metastatic disease (26.4%, p  = 0.031) and those that met the radiological criteria for tumor progression (25%, p  < 0.001).

Conclusion: SE occurrence contributed to a decline in functional status in all cases, regardless of tumor type, tumor progression status, and SE refractoriness, while long‐term mortality was increased in those with malignant tumor entities, tumor progressions, and refractory SE.

Ageing and dementia 2

Opr‐049, cag repeats within non‐pathological range in the htt gene influence plasma nfl levels in prodromal alzheimer's disease, c. crucitti 1 ; s. mazzeo 1 ; a. ingannato 1 ; g. giacomucci 1 ; j. balestrini 1 ; v. moschini 2 ; c. morinelli 2 ; g. galdo 1 ; f. emiliani 1 ; d. frigerio 1 ; d. piazzesi 2 ; s. bagnoli 1 ; s. padiglioni 2 ; v. berti 3 ; s. sorbi 1 ; v. bessi 1 ; b. nacmias 1, 1 department of neuroscience, psychology, drug research and child health, university of florence, italy; 2 research and innovation centre for dementia‐cridem , azienda ospedaliero‐universitaria careggi, florence, italy; 3 department of biomedical, experimental and clinical sciences “mario serio”, university of florence, florence, italy.

Background and aims: HTT gene is involved in axon trafficking. It contains a key region of CAG repeats which is responsible, when expanded beyond 39 repeats, of Huntington's disease (HD). Expansions ranging from 27 to 35 are termed as intermediate alleles (IAs). Previous studies showed that increasing repeat length below the HD threshold in HTT confers advantageous changes, stabilizing the interaction with the brain‐derived neurotrophic factor. Moreover, CAG repeats seem to affect cognitive performances of patients with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Here, we aimed to explore the association between CAG repeats, Alzheimer's Disease (AD) CSF biomarkers and plasma neurofilament light chain (NfL) in patients with SCD and MCI.

Methods: We included 95 patients (36 SCD and 59 MCI) who underwent neuropsychological investigation, plasma NfL analysis, CSF biomarkers analysis, Apolipoprotein E (APOE) and HTT genotype analysis. Patients were classified as prodromal AD if they had at least one positive Aβ biomarker and positive p‐tau, otherwise they were defined as non‐AD.

Results: We tested the association between plasma NfL and CAG repeats: in prodromal AD, this relationship was described by a quadratic model ( R 2 0.243, p  = 0.009) as the NfL concentration decreases as the CAG repeat number increases up to 26 repeats (confirmed after age, diagnosis and CAG repeat number adjustment). There was no association in non‐AD patients.

Conclusion: The number of CAG repeats, below the IA threshold, may play a role in SCD and MCI modulating the neurodegeneration due to AD, implying the potential of HTT ‘s involvement in the disease's pathophysiology.

OPR‐050

Sleep and cognition: insights from sleep microarchitecture, i. filchenko 1 ; a. eberhard‐moscicka 2 ; s. duss 1 ; m. aktan süzgün 1 ; c. bernasconi 1 ; m. schmidt 1 ; c. bassetti 1, 1 department of neurology, university hospital, inselspital, bern, switzerland; 2 department of psychology, university of bern, bern, switzerland.

Background and aims: Sleep plays a pivotal role in cognition [Kong, 2023], however, to date little is known about the link between sleep microarchitecture and different cognitive domains [Qin, 2023]. This exploratory analysis aimed to comprehensively investigate this link.

Methods: The “Sleep and cognitive functioning” study included volunteers in good or excellent health condition (Eastern Cooperative Oncology Group grade of 0–1). Demographics, medical history, sleep architecture by polysomnography (electroencephalography [EEG] was recorded either with 6 electrodes or 256 electrodes [high‐density EEG, hd‐EEG]) and cognition were assessed at study inclusion (Figure 1A). Associations between cognition and sleep microarchitecture were explored using multiple linear regression with adjustment for age and arousal index.

Study design (A) and population (B).

Results: 60 participants were included (median age: 52.7 years old, interquartile range (IQR) [32.9, 64.6]; 55% men; hd‐EEG in 52%; Figure 1B). EEG analysis as based on 6 electrodes or their hd‐EEG equivalents showed limited associations between cognition and sleep microarchitecture (e.g., working and visual memory with high SS density; Figure 2), whereas high‐density EEG analysis identified multiple associations of interest with a distinct topography (e.g., visual memory with high EEG spectral power in beta band involving the right posterior region; Figure 3).

Associations between cognition and sleep microarchitecture (basic analysis).

Selected associations between cognition and sleep microarchitecture (topographic analysis).

Conclusion: While these results confirm previous findings, they also expand our understanding about the link between sleep microarchitecture and cognition by providing valuable insights for the involvement of specific cortical regions. This knowledge may serve as a basis for targeted interventions to improve sleep‐related cognitive function.

Disclosure: European Stroke Research foundation 2021.

OPR‐051

Neurotransmitters circuitry dysfunction in the alzheimer's disease continuum, l. argenti 1 ; m. losa 1 ; l. lombardo 1 ; e. peira 2 ; s. raffa 3 ; g. sambuceti 3 ; f. massa 1 ; s. garbarino 4 ; d. arnaldi 5 ; s. morbelli 6 ; a. chincarini 2 ; b. orso 1 ; m. pardini 1, 1 department of neuroscience, rehabilitation, ophthalmology, genetics, maternal and child health ( dinogmi ), university of genoa, genoa, italy; 2 istituto nazionale di fisica nucleare ( infn ), genoa, italy; 3 department of health science ( dissal ), university of genoa, genoa italy; 4 life science computational laboratory, irccs ospedale policlinico san martino, genova, italy; 5 neurophysiopatology unit, irccs ospedale policlinico s. martino, genoa, italy; 6 nuclear medicine unit, aou città della salute e della scienza di torino, turin, italy.

Background and aims: The modulation of neurotransmitters circuitry in Alzheimer's disease (AD) holds promise as a potential focus for pharmacological intervention. We aimed to study the progression of neurotransmitter's networks dysfunction associated to the accumulation of misfolded proteins throughout the AD continuum.

Methods: We enrolled 90 AD patients (72.8 ± 7.02 yo) and 42 Healthy Controls (HC, 70 ± 8.53 yo). All patients had a brain [18F]FDG‐PET scan and MMSE available. As amyloidosis biomarker, 50 patients performed CSF exam and 40 an amyloid‐PET. Patients were divided in two groups based on MMSE score (MMSE <24, n  = 24; MMSE ≥24, n  = 66) to study different disease stages. We performed a voxel‐based analysis between AD patients and HC: in the whole group, in MMSE <24 and MMSE ≥24 groups, separately. Using JuSpace toolbox we explored the correlation between [18F]FDG‐PET images and PET maps of glutamate (mGluR5), GABA (GABA‐a), dopamine (D1, D2, FDOPA), serotonin (SERT, 5HT1a, 5HT1b, 5HT2a, 5HT4), noradrenaline (NAT) and choline (VAChT).

Results: In the whole AD group, the distribution of brain hypometabolism was associated with areas of 5HT2a and mGluR5 density ( p  = 0.029, p  = 0.034 respectively). This remained significant in the MMSE <24 group ( p  = 0.006). In the whole group, 5HT2a density correlates with a lower MMSE score and greater cerebral amyloid burden.

Conclusion: The spatial pattern of brain hypometabolism in AD is related to the distribution of specific neurotransmitters. We can speculate that areas with elevated expression of receptors involved may be more susceptible to synaptic damage, as evidenced by brain hypometabolism.

OPR‐052

Universal prevention of dementia in italy: a document analysis of the 21 italian regional prevention plans, s. salemme 1 ; d. marconi 2 ; s. pani 3 ; v. casigliani 4 ; a. ancidoni 5 ; g. zamboni 6 ; g. lazzeri 2 ; n. vanacore 5 ; g. bellomo 5, 1 school of advanced studies, university of camerino, camerino, italy; 2 post graduate school of public health, university of siena, siena, italy, siena, italy; 3 university of cagliari, cagliari, italy; 4 university of pisa, pisa, italy; 5 national center for disease prevention and health promotion, national institute of health, rome, italy; 6 department of biomedical, metabolic and neural sciences, university of modena and reggio emilia, modena, italy.

Background and aims: An estimated 40% of dementia cases could be prevented through interventions targeting 12 modifiable risk factors (RFs) at different stages of life. We characterized the subnational population approaches to the prevention of dementia implemented in Italy.

Methods: We conducted a document analysis of the 21 Regional Prevention Plans (RPPs) for 2020–2025. We categorized the dementia‐specific preventive interventions according to (i) type of RF targeted, (ii) target age, and (iii) target population. Indirect potential beneficial effects of interventions were defined by critically reviewing published literature on plausible relationships between RFs. Furthermore, we developed and applied to all RPPs a checklist evaluating key elements of situational analysis and prevention planning.

Results: Physical inactivity was the only RF covered by all RPPs, as a direct target of 117/248 interventions for dementia prevention. Smoking was targeted in more than 50% of RPPs, while less than 50% covered alcohol consumption and obesity. Only 25% of RPPs had dementia‐specific interventions for social isolation, hypertension, and diabetes. Two RPPs targeted air pollution and only one TBI. No RPP directly covered low education, depression or hearing loss for dementia prevention. Total scores of the checklist ranged from a minimum score of 7 to a maximum of 28/63.

TABLE 1 Subnational coverage of potentially modifiable risk factors for cognitive decline.

Sankey Chart of the dementia‐specific preventive interventions.

Checklist scores by RPP.

Conclusion: While interventions on cardiovascular RFs can synergistically affect multiple noncommunicable diseases, their prevalence may suggest that policymakers are not fully aware of RFs more specific to dementia (e.g., social isolation and hearing loss). Therefore, policymakers, public health workers, and dementia experts should closely cooperate for the development of these policies.

OPR‐053

Neuromodulation of the mediodorsal nucleus during mrgfus thalamotomy demonstrates a causal role in reward learning, w. gilmour 1 ; g. mackenzie 1 ; i. barnard 1 ; j. macfarlane 2 ; s. khan 3 ; a. kanodia 4 ; m. canty 5 ; t. littlechild 5 ; v. marshall 5 ; e. newman 5 ; j. farah 6 ; m. radon 6 ; a. marcerollo 6 ; d. steele 1 ; t. gilbertson 1, 1 division of imaging science and technology, ninewells hospital & medical school, university of dundee, dundee, uk ; 2 medical physics, ninewells hospital & medical school, dundee, uk ; 3 department of neurosurgery, edinburgh royal infirmary, edinburgh, uk ; 4 department of radiology, ninewells hospital & medical school, dundee, uk ; 5 institute of neurological sciences, queen elizabeth university hospital, glasgow, uk ; 6 the walton centre nhs foundation trust for neurology and neurosurgery, liverpool, uk.

Background and aims: Evidence from basic neuroscience increasingly supports a specific role for the Medial Dorsal (MD) thalamic nucleus influencing decisions that guide reward‐based learning. As common clinical syndromes of impulsivity, apathy and executive dysfunction can be explained by abnormal reward‐learning across multiple clinical groups. Neuromodulation target MD nucleus may represent a potential future therapeutic intervention for disorders of cognitive control.

Methods: Thirty‐five patient's undergoing MRgFUS thalamotomy for Essential Tremor targeted at ventral intermediate nucleus (Vim) performed pre‐and post‐operative (<24 hours) cognitive testing using the 4‐armed restless bandit task. Outcome measures of task performance included probability of choosing the most rewarding bandit (Prew) and choice perseveration (Pstay). In 23 patients, post‐operative masks of (< 24 hours) oedema extension into the MD nucleus were used to analyse the relationship with cortical functional connectivity and it's influence on decision making.

FIGURE 1 Restless bandit reinforcement learning task. (A) example of fluctuating reward payout for each of the four bandits in the task (B) example trial with screenshots of computer graphics.

Results: Post‐thalamotomy, patients used a greater proportion of perseverative choices (Pstay) pre: 0.67 ± 0.07, post: 0.75 ± 0.0.05, rmANOVA, F = 11.05, p  < 0.001). Task performance indexed by choices to the best bandit (Prew) was unaffected by thalamotomy (rmANOVA, F = 3.02, p  = 0.07). Cortical functional connectivity with thalamotomy oedema extension into the MD nucleus predicted the extent to which the thalamotomy increased Pstay in individual patients (rho = 0.64, p  = 0.001).

FIGURE 1 Behavioural effects of thalamotomy on task performance. Analysis binned into six‐ 50 trial blocks (A) probability of choosing the highest value bandit (B) Probability of choosing the same bandit on two consecutive trials (Pstay).

FIGURE 3 (A) Probabalistic analysis of overlap between thalamotomy ( n  = 23) oedema (heatmap) with the medialdorsal thalamic nucleus (grey overlay) onto standard brain template in MNI space. (B) R map correlation and (B) cortical connectivity map.

Conclusion: MRgFUS thalamotomy can be used as an opportunity to study cognitive thalamic nuclear function. An experimental design for intra‐operative thermal neuromodulation is proposed to causally map the different contributions of the thalamic nuclei to cognitive control.

Disclosure: TG has received honoraria from GE Healthcare Europe. AM has received research funding from Boston scientific, Medtronic and Insightec.

Movement disorders

Opr‐054, substantia nigra and subthalamic nucleus deep brain stimulation for freezing of gait in parkinson's disease, c. ledda 1 ; c. artusi 1 ; s. gallo 2 ; d. rinaldi 3 ; c. campisi 1 ; v. rousseau 4 ; c. thalamas 5 ; r. barbosa 5 ; f. ory‐magne 5 ; c. brefel‐courbon 5 ; o. rascol 6 ; a. de barros 7 ; e. harroch 6 ; m. zibetti 1 ; m. rizzone 1 ; a. romagnolo 1 ; g. imbalzano 1 ; l. lopiano 1 ; j. houeto 8 ; m. fabbri 6, 1 department of neurosciences rita levi montalcini, university of turin, turin, italy; 2 neurology unit, department of translational medicine, university of piemonte orientale, novara, italy; 3 department of neuroscience, mental health and sense organs ( nesmos ), sapienza university of rome, rome, italy; 4 service de pharmacologie médicale et clinique, centre hospitalier universitaire et faculté de médecine de toulouse, toulouse, france; 5 service de neurologie, centre hospitalier universitaire, toulouse, france; 6 centre expert parkinson de toulouse, chu , toulouse, france; 7 department of neurosurgery, toulouse university hospital, toulouse, france; 8 department of neurology, ns‐park / f‐crin network, limoges university hospital; inserm, u1094 , epimact ‐ epidemiology of chronic diseases in tropical zone, limoges, france.

Background and aims: Freezing of gait (FoG) is a debilitating symptom of Parkinson's disease (PD) with limited response to dopaminergic medication and subthalamic deep brain stimulation (STN‐DBS). Substantia nigra pars reticulata (SNr) stimulation could improve FoG.

Methods: Two double‐blind, cross‐over, randomized trials, following an identical protocol were conducted involving STN‐DBS treated PD patients with severe FoG. Participants received: standard high frequency (HF) STN‐DBS (S), combined HF‐STN and SNr stimulation (C1), and combined HF‐STN and low‐frequency SNr stimulation (C2), for 1 month each in a randomized order. The primary endpoint was the change in the New Freezing of Gait Questionnaire (NFOG‐Q) score. Secondary analyses were performed on motor complications, axial symptoms, activities of daily living, psychiatric symptoms, sleep, and patient preference.

Stimulation method for S, C1, C2.

Results: Fifteen patients received at least one combined stimulation. No statistically significant difference in NFOG‐Q scores was found between S, C1, and C2; one‐third of patients showed a clinically significant improvement (≥8 points) with combined stimulations. Motor complications improved significantly with C1 and C2 compared to S (C1 vs. S: 3.6 ± 3.8 vs. 4.9 ± 3.8, p  = 0.046; C2 vs. S: 2.7 ± 3.1 vs. 4.9 ± 3.8, p  = 0.005). At the end of the study, 80% of patients chose combined STN‐SNr stimulation. All adverse events were manageable.

Scores after one moth of the following stimulation setting: C1, C2, and S.

VTA of the STN and of the SNr for all patient included in the study in the stimulation setting C1/C2.

Conclusion: Our study did not show a statistically significant improvement in NFOG‐Q, but one‐third of patients experienced a clinically meaningful FoG improvement. Moreover, SNr stimulation was both safe and effective in addressing motor complications., highlighting the importance of further exploration into the effects of combined STN‐SNr stimulation.

OPR‐055

Effectiveness and safety of levodopa‐entacapone‐carbidopa infusion in parkinson's disease. a real‐world data study, d. santos‐garcía 1 ; l. lópez‐manzanares 2 ; i. muro 2 ; p. lorenzo 2 ; r. garcía‐ramos 3 ; c. morata‐martínez 4 ; r. baviera‐muñoz 4 ; i. martínez‐torres 4 ; m. Álvarez‐sauco 5 ; j. suárez‐muñoz 6 ; j.  martínez‐castrillo 7 ; a. perona 8 ; j. salom 9 ; i. legarda 10 ; m.  valero‐garcía 10 ; e. cubo 11 ; n. lópez‐ariztegui 12 ; d. alonso‐modino 13 ; r. espinosa 14 ; m. mata 15, 1 chuac (complejo hospitalario universitario de a coruña), a coruña, spain; 2 hospital universitario la princesa, madrid, spain; 3 hospital clínico universitario san carlos, madrid, spain; 4 hospital universitario la fe, valencia, spain; 5 hospital general universitario de elche, spain; 6 hospital dr. negrín, las palmas de gran canaria, spain; 7 hospital universitario ramón y cajal, madrid, spain; 8 complejo hospitalario universitario de albacete, spain; 9 hospital clínico universitario de valencia, spain; 10 hospital universitario son espases, palma de mallorca, spain; 11 hospital universitario de burgos, spain; 12 hospital universitario de toledo, spain; 13 hospital universitario de la candelaria, santa cruz de tenerife, spain; 14 hospital universitario de jerez, spain; 15 hospital infanta sofía, madrid, spain.

Background and aims: Levodopa‐entacapone‐carbidopa intestinal gel (LECIG) infusion is a recently developed device‐aided therapy for advanced Parkinson's disease (PD) patients. Our aim was to present real world data (RWD) about the use of LECIG in PD patients from Spain.

Methods: A multicenter observational retrospective study of the first patients to start LECIG in Spain was performed. All neurologists with an experience of at least 2 patients treated until November 1, 2023 were invited to participate. RWD about effectiveness and safety from the medical records (V0, pre‐LECIG; V1, LECIG starting; V2, post‐LECIG follow‐up) with a total of 246 variables was collected.

Results: Fifty‐one PD patients (58.8% males; 69.7 ± 9.7 years old) from 15 Spanish centers with a mean disease duration of 13.8 ± 6.2 years were included (Table 1). Fourteen patients (27.5%) were switched directly from levodopa‐carbidopa intestinal gel. The mean treatment duration was 140.7 ± 83.7 days (range, 10–302). The mean daily OFF time decreased from 5.1 ± 3 at baseline (pre‐LECIG) to 1.9 ± 1.6 (post‐LECIG) ( N  = 45; p  < 0.0001). Global improvement was observed in more than 85% of the patients (Figure 1). No significant change was detected in the levodopa equivalent daily dose from V0 to V2 (Figure 2). Only 2 patients (3.9%) received 24‐hour infusion and 11 (21.6%) required more than 1 cartridge per day. Eighteen patients (35.3%) had at least one adverse event related to LECIG and/or the device system. Three patients (5.9%) discontinued LECIG (Table 2).

TABLE 1 Data about sociodemographic aspects, comorbidities, antiparkinsonian drugs and other therapies at baseline (V0) and LECIG starting at V1.

TABLE 2 Adverse events collected by the neurologist in patients receiving LECIG from V1 (starting LECIG) to V2 (follow‐up visit; 140.7 ± 83.7 days, range from 10 to 302).

Conclusion: LECIG was safe and effective in advanced PD patients.

Disclosure: The authors report no conflict of interest.

OPR‐056

Sgfap – a potential biomarker for disease activity in essential tremor, l. gattermeyer‐kell ; m. khalil; p. opriessnig; d. kern; s. franthal; m. kögl; p. katschnig‐winter ; r. schmidt; c. enzinger; p. schwingenschuh, department of neurology, medical university of graz, graz, austria.

Background and aims: Essential tremor (ET) constitutes a heterogeneous syndrome and possible neurodegeneration has been debated. We recently linked serum‐NfL to cognitive decline in ET‐patients with short disease duration (DD). Serum‐glial fibrillary acidic protein (sGFAP) hitherto remains unstudied in ET.

Methods: Data from 36 ET‐patients and 36 age, sex and body‐mass‐index‐matched healthy controls were analyzed. sGFAP was quantified by single‐molecule‐array in baseline (BL) and follow‐up (FU; 5 years) blood samples. ET‐patients underwent clinical evaluation (Fahn‐Tolosa‐Marin‐Tremor‐Clinical‐Rating‐Scale‐Total‐Score, FTM‐TS).

Results: BL and FU sGFAP did not differ between groups. In ET‐patients, low BL FTM‐TS was associated with higher sGFAP‐increase during the observational period ( r s = −0.551, p  = 0.002). Shorter DD correlated with low BL FTM‐TS and trended towards higher sGFAP‐increase ( r s = −0.344, p  = 0.068). Stratification in DD below/above median (10.7 years) showed higher sGFAP‐increase in short DD patients (39.6 vs. 12.6 pg/mL, p  = 0.020). In short DD patients, high BL sGFAP correlated with high FU FTM‐TS ( r s = 0.672, p  = 0.006) and FTM‐TS‐increase ( r s = 0.590, p  = 0.021). Stratification of ET‐patients according to sGFAP‐level below/above median (124.2 pg/mL) revealed that high sGFAP‐patients were older at BL (70.0 vs. 60.7 years, p  < 0.001) and disease onset (62.6 vs. 49.9 years, p  < 0.001) than low sGFAP‐patients. Annual sGFAP‐increase correlated with annual FTM‐TS‐increase in the high ( r s = 0.587, p  = 0.027) but not in the low sGFAP‐group. In patients with high sGFAP and short DD ( n  = 8), annual sGFAP‐increase correlated with annual FTM‐TS‐increase ( r s = 0.738, p  = 0.037).

Conclusion: This study shows elevated sGFAP in elderly, late‐onset ET‐patients. sGFAP‐increase is higher in earlier vs. later disease stages and correlates with worsening motor function, suggesting sGFAP as a possible biomarker of ET disease activity.

OPR‐057

Modelling pathology progression in parkinson's disease phenotypes, m. passaretti 1 ; h. zhao 2 ; m. mijalkov 1 ; b. zufiria gerboles 1 ; a. canal garcia 1 ; j. sun 1 ; d. vereb 1 ; n. rivera 3 ; g. volpe 2 ; m. bologna 4 ; j. pereira 1, 1 karolinska institutet, department of clinical neuroscience, stockholm, sweden; 2 university of gothenburg, department of physics, soft matter lab, gothenburg, sweden; 3 department of medicine solna, respiratory medicine division, karolinska institutet, stockholm, sweden; 4 sapienza university of rome, department of human neurosciences, rome, italy.

Background and aims: Understanding the relationship between phenotypic heterogeneity and the spread of pathology in Parkinson's disease (PD) is challenging. The α‐Synuclein Origin site and Connectome (SOC) model postulate that α‐synuclein aggregation first localization and spreading determine disease evolution. Accordingly, two PD subtypes were proposed: brain‐first‐PD, from central nervous system, and body‐first‐PD, from peripheral nervous structures. We aim to use the SOC model to differentiate PD phenotypes predicting disease progression.

Methods: 1120 de novo‐ PD patients, 910 prodromal‐cases, and 263 healthy controls were included from the Parkinson's progression markers initiative. Patients and prodromal‐cases with REM behavior disorder and/or autonomic symptoms at baseline were classified as body‐first, otherwise as brain‐first. All subjects underwent longitudinal (12‐years) clinical protocol and magnetic resonance imaging.

Results: Body‐first‐PD (667) demonstrated higher motor burden and complications, worse cognitive evolution, and more severe depression compared to brain‐first‐PD. Body‐first‐PD showed bilateral medial and lateral temporal atrophy (amygdala, para‐hippocampus, temporoparietal junction), cerebellum and brainstem. Brain‐first‐PD patients demonstrated circumscribed atrophy of the left hemisphere (angular gyrus, sensory‐motor cortex, inferior frontal gyrus). Body‐first‐prodromal‐cases (519) demonstrated similar results to body‐first‐PD, i.e. greater motor and cognitive impairment, involving the same domains, and grey matter atrophy in lateral temporal areas.

Conclusion: Consistent with the SOC model, the study results indicate that body‐first‐PD and prodromal‐cases had worse disease progression and more severe brain atrophy compared to brain‐first. The results underscore the importance of PD patient phenotyping since the prodromal phases. Hence, the application of the model would enable tailored therapeutic approaches and disease prevention interventions in high‐risk individuals.

Disclosure: Nothing to declare.

OPR‐058

Thoracic spinal cord stimulation may improve bradykinesia and rigidity in gait impaired parkinson's disease, m. højholt terkelsen 1 ; v. hvingelby 1 ; e. johnsen 2 ; m. møller 2 ; e. hvid danielsen 2 ; t. henriksen 3 ; a. nørgaard glud 4 ; y. tai 5 ; a. møller andersen 4 ; a. knudsen 4 ; k. meier 4 ; p. borghammer 1 ; e. moro 6 ; j. hedemann sørensen 4 ; n. pavese 1, 1 department of clinical medicine — department of nuclear medicine and pet center, aarhus university, aarhus, denmark; 2 department of neurology, aarhus university hospital, aarhus, denmark; 3 department of neurology, bispebjerg hospital, copenhagen, denmark; 4 department of neurosurgery, aarhus university hospital, aarhus, denmark; 5 department of neurosciences, imperial college healthcare nhs trust, london, uk ; 6 grenoble alpes university, chu of grenoble, division of neurology, grenoble institute of neuroscience, grenoble, france.

Background and aims: Gait impairment in Parkinson's disease (PD) is debilitating and often resistant to available therapies. Recently, spinal cord stimulation (SCS) has been suggested to be effective. Nevertheless, existing literature on SCS for gait problems is limited and possible mechanisms of action remain to be elucidated. This study is part of the SCS therapy for patients with PD and gait problems (STEP‐PD) trial (ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT05110053","term_id":"NCT05110053"}} NCT05110053 ), and here we aim to evaluate the effect on lower body motor symptoms and gait.

Methods: Fourteen non‐demented PD patients with gait impairment were included in the trial. The Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) was assessed before surgery and at 6‐ and 12‐month follow‐ups. Total motor score, lower body and gait (LBG) subscore, and the sum of lower body bradykinesia and rigidity items (Table 1) were compared using paired t‐test. Mean differences with 95% confidence intervals are presented.

TABLE 1 Details of the Movement Disorder Society‐Unified Parkinson Disease Rating Scale (MDS‐UPDRS) scores presented. LBG, lower body gait.

Results: Thirteen patients were treated with active SCS for 6 months and eight patients were treated for 1 year. While the total motor score improved slightly after both 6 months (−2.85 points [−7.07;1.38]) and 12 months (−5.63 points [−14.03;2.78]), the LBG subscore improved by −3.38 points (−4.83;‐1.93), p  = 0.0003, after 6 months and −5.25 points (−8.93;‐1.57), p  = 0.0118, after 12 months. Furthermore, lower body bradykinesia and rigidity improved by −2.31 points (−3.75; −0.86), p  = 0.0046, after 6 months and −3.88 points (−7.17; −0.58), p  = 0.027, after 12 months.

Conclusion: SCS may ameliorate lower body bradykinesia and rigidity in gait‐impaired PD patients. Furthermore, our results suggest that extended treatment duration could yield a greater improvement.

Disclosure: KM's institution (Aarhus University Hospital) has received travel support from Boston Scientific.

Motor neurone diseases 2

Opr‐059, role of brain 2‐[ 18f ] fdg‐pet for the differential diagnosis between als and als ‐mimics, g. zocco 1 ; a. martino 2 ; a. giuliani 3 ; c. moglia 1 ; r. vasta 1 ; m. grassano 1 ; s. cabras 1 ; f. di pede 1 ; p. salamone 1 ; g. marchese 1 ; f. casale 1 ; g. polverari 4 ; u. manera 1 ; m. pagani 5 ; a. calvo 1 ; a. chiò 1 ; a. canosa 1, 1 als centre, ‘rita levi montalcini’ department of neuroscience, university of turin, turin, italy; 2 department of business and management, luiss university, rome, italy; 3 environment and health department, istituto superiore di sanità, rome, italy; 4 positron emission tomography centre affidea‐irmet s.p.a., turin, italy; 5 institute of cognitive sciences and technologies, c.n.r., rome, italy.

Background and aims: The combination of brain and spinal cord 2‐[18F]FDG‐PET has shown a 81.5% accuracy in discriminating ALS and ALS‐mimics in a published study. We investigated the potential role of brain 2‐[18F]FDG‐PET as a single marker to discriminate ALS and ALS‐mimics.

Methods: Our dataset included 663 ALS cases and 40 patients referred for suspected ALS but for whom an alternative diagnosis was made (ALS‐mimics) who underwent brain 2‐[18F]FDG‐PET at diagnosis at the ALS Centre of Turin between 2009 and 2019. We randomly collected 40 ALS cases and calculated Laplacian scores in this group. This is an algorithm for the selection of features, which correspond to the voxels. It constructs a nearest neighbour graph. Laplacian score seeks those features that respect this graph structure. We retained the top features and performed feature extraction form the two groups (ALS and mimics). Then, we randomly split the sample composed of ALS and mimics in a training set (80%) and a test set (20%). The training set was used to train the classifier (Support Vector Machine) and the test set was used to evaluate the performance of the model. The procedure was randomly repeated 10 times for internal validation.

Results: SVM showed 85% specificity and 81% sensitivity on the test set, with an error rate of 17%. The classification was based on three cerebellar clusters, situated in left anterior lobe, right uvula and right culmen.

Conclusion: Our data support the possible role of brain 2‐[18F]FDG‐PET as a single diagnostic marker to discriminate ALS and ALS‐mimics.

OPR‐060

Morphometric analysis of spinal motor neuron degeneration in sporadic amyotrophic lateral sclerosis, h. aizawa 1 ; s. nagumo 2 ; t. hideyama 2 ; h. kato 2 ; s. kwak 2 ; h. terashi 2 ; y. suzuki 3 ; t. kimura 3, 1 department of neurology, sanno hospital, tokyo, japan; 2 department of neurology, tokyo medical university, tokyo, japan; 3 department of neurology, asahikawa medical center, asahikawa, japan.

Background and aims: To clarify the relationship between TDP‐43 pathology and spinal anterior horn motor neuron (AHMN) atrophy in sporadic amyotrophic lateral sclerosis (SALS).

Methods: The subjects were 8 SALS and 12 disease controls. Formalin‐fixed specimens of lumbar spinal cord samples were paraffin‐embedded and sectioned at the level of the fourth lumbar spinal cord with a thickness of 4 μm. Using a microscope (BZ‐X800), the long diameter of neurons with nucleoli was measured in spinal AHMNs stained with anti‐SMI‐32 antibody. AHMNs were divided into medial and lateral nuclei for statistical processing. Among spinal AHMNs double‐fluorescently stained with TDP‐43 and anti‐nucleoporin p62 (NUP62) antibodies against the nuclear membrane, we also measured the long diameter of AHMNs with TDP‐43 in both the nucleus and cytoplasm, which are considered as initial lesions of TDP‐43 pathology.

Results: The long diameter of the lumbar spinal AHMNs in SALS was smaller in the medial nucleus (42.54 ± 9.33 micrometer, n  = 24) and the lateral nucleus (49.41 ± 13.86, n  = 129) than in controls (medial nucleus 55.84 ± 13.49, n  = 85, p  < 0.001; lateral nucleus 62.39 ± 13.29, n  = 756, p  < 0.001, Mann–Whitney test). All 21 motor neurons with early TDP‐43 pathology were in the lateral nucleus, and their long diameter (67.60 ± 18.3) was not significantly different from controls.

Histogram of spinal motor neurons.

TDP‐43 pathology and motor neuron atrophy.

Long diameter of motor neurons.

Conclusion: Motor neuron atrophy in SALS does not occur at the initial stages of TDP‐43 pathology, and TDP‐43 pathology has already progressed in the atrophic motor neurons.

OPR‐061

Genome‐wide directional effects of transcription factor binding on amyotrophic lateral sclerosis, m. torrieri 1 ; m. grassano 2 ; a. chiò 2 ; m. basso 3 ; a. calvo 2, 1 academic neurology unit, san luigi gonzaga university hospital, orbassano, italy; 2 als centre, rita levi montalcini department of neuroscience, university of turin, turin, italy; 3 department of cellular, computational and integrative biology ( cibio ), university of trento, trento, italy.

Background and aims: The transcription factor (TF) c‐myc has been shown to be elevated in many neurological disorders, including neurodegenerative diseases. We observed an increased activity of c‐myc in astrocytes in TDP‐43 mice models of Amyotrophic Lateral Sclerosis (ALS), being related to a reduction in survival, probably due to the release of an altered protein cargo by astrocytes. The aim of our study was to test the role of TFs in the pathogenesis of ALS.

Methods: We used signed LD profile (SLDP) regression to test the activity of TFs in large case–control GWAS of both ALS and frontotemporal dementia (FTD) [1,2]. SLDP regression is a validated method used to identify genome‐wide directional effects of signed functional annotations on polygenic disease risk [3]. We ran SLDP regression using the 382 available TF annotations for both ALS and FTD gene data sets. Results were significant at a per‐trait FDR <5%. A positive association implies a greater binding of the TFs, leading to greater expression; likewise, a negative association implies a lower binding of the TFs, leading to lower expression.

Results: We used GWAS summary statistics obtained from 12.577 ALS patients (vs. 23.475 healthy controls) and 3.526 FTD patients (vs. 9.402 healthy controls). We detected 38 and 14 significant associations respectively in ALS and FTD (Tables 1 and 2). Particularly, genetic variants determining a greater binding of c‐myc were associated with an increased risk of ALS, but not FTD.

TABLE 1 SLDP regression for ALS gene data set. Significant associations obtained from 12.577 ALS patients (vs. 23.475 healthy controls) are shown. We detected 38 significant positive associations at per‐trait FDR <5%.

TABLE 2 SLDP regression for FTD gene data set. Significant associations obtained from 3.526 FTD patients (vs. 9.402 healthy controls) are shown. We detected 14 significant associations at per‐trait FDR <5%, Only 1 of these associations was negative.

Conclusion: An increased activity of c‐myc could be a specific pathogenetic mechanism in ALS, leading to premature motor neurons death.

OPR‐062

Early‐onset amyotrophic lateral sclerosis ( eo‐als ): a different phenotype with a higher resilience, s. pierro 1 ; a. maranzano 2 ; f. gentile 3 ; a. manini 4 ; a. brusati 5 ; s. peverelli 2 ; e. colombo 2 ; a. doretti 2 ; a. bertini 1 ; j. spagliardi 1 ; a. di maio 1 ; f. duca 1 ; c. morelli 2 ; s. messina 2 ; l. maderna 2 ; a. ratti 5 ; v. silani 2 ; f. verde 2 ; n. ticozzi 2, 1 neurology residency program, università degli studi di milano, milan, italy; 2 department of neurology and laboratory of neuroscience, irccs istituto auxologico italiano, milan, italy; 3 irccs ospedale san raffaele, division of genetics and cell biology, milan, italy; 4 department of pathophysiology and transplantation, università degli studi di milano, milan, italy; 5 department of medical biotechnology and molecular medicine, università degli studi di milano, milan, italy.

Background and aims: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a mean age of onset around 60 years. Evidence from the literature suggests the existence of a distinct clinical phenotype associated with earlier age at onset (EO‐ALS). Here we aim to define the clinical phenotype of EO‐ALS in comparison to late‐onset ALS (LO‐ALS).

Methods: We studied a cohort of 1165 ALS patients, divided in two groups: EO‐ALS (onset 20–45 years), and LO‐ALS (onset >45 years). Clinical phenotype, survival outcome measures and serum biomarkers were compared in the two groups Significant p ‐value was set at <0.05.

Results: We found that EO‐ALS patients had significant predominance of males (72.5% vs. 60.9%, p  = 0.010), familial ALS (15.3% vs. 9.5%, p  = 0.037), spinal‐onset (82.4% vs. 70.7%, p  = 0.047), progressive muscular atrophy phenotype (11.7% vs. 3.9%, p  = 0.00009). In the EO‐ALS group, 1.5% had a cerebellar‐ALS‐plus phenotype ( p  = 0.00004). Interestingly, a lower progression rate (median: 0.47 vs. 0.61, p  = 0.011) and prolonged survival (median values: 117.3 vs. 49.7 months, p  < 0.001) were observed in EO‐ALS as well as a longer diagnostic delay (17.8 vs. 12.5 months, p  < 0.001). Finally, in EO‐ALS serum GFAP was lower (median: 84.02 vs. 122.36 pg/mL, p  = 0.011), and CPK was higher (median: 262 vs. 160 U/L, p  < 0.001).

TABLE 1 Demographic and clinical characteristics of the study cohort, classified into the two main groups.

FIGURE 1 Kaplan–Meier plots of survival probabilities for EO‐ALS (green line) and LO‐ALS (blue line). Median values: 117.3 months for YO‐ALS and 49.7 months for AO‐ALS. +: censored cases.

Conclusion: Findings from our study indicate that EO‐ALS is associated with prolonged survival, suggesting that different pathogenetic mechanisms or enlarged motor neurons reserve might be at play in this group of patients. Compared to previous studies, we did not confirm the previously reported higher frequency of the upper motor neuron predominant phenotype in the EO‐ALS group.

Disclosure: Simone Pierro, Alessio Maranzano, Francesco Gentile, Arianna Manini, Alberto Brusati, Silvia Peverelli, Eleonora Colombo, Alberto Doretti, Alessandro Bertini, Jacopo Spagliardi, Alessandro Di Maio, Filippo Duca, Claudia Morelli, Stefano Messina, Luca Maderna, Federico Verde and Antonia Ratti report no disclosure. Vincenzo Silani received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, LiquidWeb, Srl and Novartis Pharma AG. He receives or he has received research support from the Italian Ministry of Health, AriSla, and E‐Rare Joint Translational Call. He is on the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemproal Degeneration, European Neurology, American Journal of Neurodegenerative Disease and Frontiers in Neurology. Nicola Ticozzi received compensation for consulting services from Italfarmaco, Biogen, Amylyx Pharmaceutical and Zambon Biotech SA. He received research funding from the Italian Ministry of Health and AriSLA. He is associate editor of Frontiers in Aging Neuroscience.

OPR‐063

Longitudinal progression of subcortical structural damage in amyotrophic lateral sclerosis, e. spinelli 1 ; a. ghirelli 1 ; s. basaia 2 ; e. canu 2 ; v. castelnovo 2 ; t. russo 3 ; p. schito 3 ; y. falzone 3 ; n. riva 4 ; m. filippi 5 ; f. agosta 1, 1 neuroimaging research unit, division of neuroscience, and neurology unit, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy; 2 neuroimaging research unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 3 neurology unit, irccs san raffaele scientific institute, milan, italy; 4 neurorehabilitation unit, and experimental neuropathology unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 5 neuroimaging research unit, division of neuroscience, neurology unit, neurorehabilitation unit, and neurophysiology service, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy.

Background and aims: Converging evidence suggests an early involvement of subcortical structures in the course of neuropathological progression of amyotrophic lateral sclerosis (ALS). Our aim was to explore the longitudinal evolution of structural damage to subcortical and hippocampal structures in a cohort of incident ALS patients.

Methods: Twenty‐four patients with ALS and 34 healthy controls underwent at least two longitudinal clinical evaluations and brain MRI scans on a 3 T scanner (median follow‐up time = 0.96 years). Segmentation of subcortical and hippocampal structures was obtained. ANOVA models were performed between groups at baseline. Linear mixed effect models were used to test longitudinal trajectories of atrophy.

Results: At baseline, ALS patients showed significant bilateral reduction of hippocampal volumes compared with controls (left: p  = 0.05; right: p  = 0.038), and a trend toward significance for atrophy in the right thalami ( p  = 0.08). Baseline volumes of the basal ganglia were comparable between patients and controls. Longitudinally, ALS patients showed a significant reduction of grey matter volumes of the left pallidum ( p  = 0.01) and right putamen ( p  = 0.02).

Conclusion: Our results suggest a different temporal involvement of hippocampal and subcortical structures in the course of ALS, with an early involvement of hippocampi and thalami followed by a subsequent progression of damage to the basal ganglia. We highlight the importance of subcortical structural alterations for a more comprehensive understanding of ALS, supporting the use of MRI for tracking disease progression. Funding. This study was supported by: European Research Council (StG‐2016_714388_NeuroTRACK); Foundation Research on Alzheimer Disease; Next Generation EU/National Recovery and Resilience Plan, Investment PE8‐Project Age‐It.

Disclosure: EG Spinelli, A Ghirelli, V Castelnovo, T Russo, P Schito, Y Falzone, N Riva have nothing to disclose. S Basaia research support from Italian Ministry of Health (IMH). E Canu research support form Italian Ministry of Health. M Filippi consulting or speaking activities or advisory boards for Alexion, Almirall, Biogen, Bayer, Bristol‐Myers Squibb, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol‐Myers Squibb, Lilly, Novartis, Sanofi‐Genzyme; research support from Biogen Idec, Merck‐Serono, Novartis, Roche, IMH, Italian Ministry of University and Research, and FISM. F Agosta received speaker honoraria from Biogen Idec, Italfarmaco, Roche, Zambon and Eli Lilly, and has received research supports from IMH, Italian Ministry of University and Research, ARiSLA, ERC, EU Joint Programme – Neurodegenerative Disease Research, and Foundation Research on Alzheimer Disease.

MS and related disorders 2

Opr‐064, relevance of paramagnetic rim and cortical lesions in ms at diagnosis: exploring the clinical practice biomarker toolkit, a. miscioscia ; m. puthenparampil; a. zolin; g. zanotelli; g. scialpi; a. berardi; f. rinaldi; p. perini; p. gallo, department of neuroscience, padova university hospital, padova, italy.

Background and aims: In multiple sclerosis (MS), imaging biomarkers aid the disease characterization at the time of diagnosis and support the appropriate treatment choice. The presence of paramagnetic rim lesions (PRLs) and cortical lesions (CLs) is not routinary evaluated in clinical practice. In this study, we investigated the association between a broad range of imaging biomarkers available and the clinical disability in MS patients at diagnosis.

Methods: 45 RRMS (mean disease duration: 9.6 months) underwent brain and spinal cord 3 T‐MRI and OCT. Susceptibility‐weighted imaging (SWI) and double inversion recovery (DIR) sequences were used to manually segment respectively PRLs and CLs. Neuroimaging metrics extracted are shown in Table 1. Regression models assessed the relationship of the lesion and atrophy metrics with physical disability (Expanded Disability Status Scale [EDSS]) and cognitive impairment (Symbol Digit Modalities Test [SDMT]).

Results: PRL and spinal cord lesion volume and count most strongly predicted EDSS. Only CL volume and count were significantly associated with SDMT score at diagnosis. In a regression model including non‐rim WML and PRL volume (or count), only the latter was significantly associated with EDSS along with spinal cord volume (or count). In the same model with the two WML phenotypes grouped together, the WML volume (or count) did not reach the significance.

TABLE 1 Demographics, clinical and radiological characteristics.

FIGURE 1 Probability maps of the spinal cord (a), non‐rim white matter (b), paramagnetic rim (d), and cortical lesions (d).

TABLE 2 Relationship between neuroimaging biomarkers and clinical disability. Multivariate linear regression models.

Conclusion: PRLs and spinal cord lesions describe the best association with physical disability in MS patients at diagnosis. CLs best correlate with cognitive performance. SWI and DIR sequences and the assessment of PRLs and CLs might add pivotal information at the first MS patient assessment.

OPR‐065

Evaluation of neuronal and glial serum biomarkers in patients with mogad : the multimogad study, j. villacieros‐Álvarez 1 ; s. mariotto 2 ; c. espejo 1 ; a. dinoto 2 ; g. arrambide 1 ; r. bernard‐valnet 3 ; p. kerschen 4 ; s. alsaint 5 ; v. dyon 5 ; x. montalbán 1 ; m. tintoré 1 ; Á. cobo‐calvo 1 ; r. marignier 5, 1 neurology department and multiple sclerosis centre of catalonia (cemcat), vall hebron university hospital, vall hebron research institute. barcelona (spain). uniiversitat autónoma de barcelona, barcelona, spain; 2 neurology unit, department of neurosciences, biomedicine, and movement sciences, university of verona, verona, italy; 3 neurology service, lausanne university hospital (centre hospitalier universitaire vaudois), university of lausanne, lausanne, switzerland; 4 centre hospitalier de luxembourg, luxembourg‐ville , luxembourg, france; 5 service de neurologie, sclérose en plaques, pathologies de la myéline et neuro‐inflammation‐hospices civils de lyon, hôpital neurologique pierre wertheimer, bron cedex, france.

Background and aims: The role of serum biomarkers to evaluate MOGAD prognosis is limited. We aim to characterize serum neuro‐glial biomarkers and analyze their usefulness to predict relapses and disability in MOGAD.

Methods: Retrospective longitudinal study included MOGAD and age‐matched multiple sclerosis (MS) patients with serum samples obtained within 3 months from disease onset. Clinical and laboratory data were collected. Serum neurofilament light‐chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels were determined using Simoa. A descriptive comparison between MOGAD and MS groups was performed. Within MOGAD group, Spearman test was built to assess correlations between baseline serum biomarkers and disability at sampling, as well as Cox and linear regression analyses to predict time to second relapse and disability, respectively.

Results: Eighty‐nine MOGAD and 32 MS patients were included. In MS, female were more predominant ( p  = 0.020), had lower EDSS at onset ( p  = 0.046), and higher presence of oligoclonal bands ( p  = 0.001). Baseline sNfL levels were higher in MOGAD compared to MS ( p  = 0.018). In MOGAD patients, sNfL (rho 0.289; p  = 0.008) and sGFAP (rho 0.32; p  = 0.003) correlated with EDSS at sampling. sGFAP levels were associated with EDSS at last follow‐up in univariate ( p  = 0.017), but lost significance in multivariate analysis. In multivariate Cox analysis, higher baseline sNfL values increased the risk of having a second relapse in MOGAD patients presenting with optic neuritis (hazard‐ratio 5.88 [95% CI 1.56; 22.20]; p  = 0.009).

TABLE 1 Demographic and clinical characteristics.

TABLE 2 Univariate and multivariate regression models assessing the association of baseline sGFAP and sNfL levels with EDSS at last follow‐up in MOGAD patients.

FIGURE 1 Correlation analyses between EDSS at sampling and baseline sNfL (A) and sGFAP (B). Kaplan–Meier survival curves comparing time to relapse between MOGAD patients with high or low sNfL levels in the whole cohort (C) and in the subgroup of ON (D).

Conclusion: In MOGAD patients, the neuro‐axonal and astrocytic damage is related with disability at sampling. Neuro‐axonal damage predicts a relapsing disease course in the subgroup of patients with optic neuritis.

Disclosure: Villacieros‐Álvarez has received grant from Instituto de Salud Carlos III, Spain; FI21/00282 Cobo‐Calvo has received grant from Instituto de Salud Carlos III, Spain; JR19/00007.

OPR‐066

Profiling and modelling cellular senescence in progressive multiple sclerosis brains, m. martire 1 ; f. fagiani 2 ; e. pedrini 2 ; d. maric 3 ; d. reich 4 ; m. filippi 5 ; m. absinta 2, 1 neurology unit, irccs san raffaele scientific institute, milan, italy; 2 translational neuropathology unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 3 flow and imaging cytometry core facility, national institute of neurological disorders and stroke, national institutes of health, bethesda, md , usa ; 4 translational neuroradiology section, national institute of neurological disorders and stroke, national institutes of health, bethesda, md , usa ; 5 neurology unit and division of neuroscience, irccs san raffaele scientific institute and vita‐salute san raffaele university, milan, italy.

Background and aims: Senescent cells accumulate in age‐related diseases. Whether these cells actively contribute to the tissue dysfunction leading to progressive MS is unknown. Here, we investigate the spatial distribution of senescent cells in MS brains, and we model post‐inflammatory senescence using 3D hiPSC‐derived organoids.

Methods: We performed single‐nucleus RNA‐sequencing (snRNAseq) on 31 samples of cortex and white matter (WM) from progressive MS cases ( n  = 10, mean age = 49) and controls ( n  = 4, mean age = 54); SenMayo gene set was applied to the snRNAseq datasets to identify senescent cells. As validation, multiplex immunofluorescence (26 primary antibodies, including the senescence marker p16INK4A+) was performed on 7 MS‐tissue blocks. To model inflammation‐induced senescence, we exposed 3D hiPSC‐derived organoids to the CSF (10% for 24 h) from MS patients and processed by scRNAseq.

Results: In the snRNAseq datasets, endothelia were the most prominent cells featuring senescence signatures in all WM lesion stages (3‐fold change [FC] increase) and MS cortex (2.3‐FC). Compared to control brain, senescent microglia were twice as abundant at the chronic active lesion (CAL) edge and MS cortex; senescent astrocytes predominated in the lesion core (2‐FC), CAL edge (2.6‐FC), and MS cortex (2‐FC). Consistently, MS brains displayed a higher number of p16INK4A+ cells compared to control, enriched within areas with chronic inflammation and at the ventricular ependyma. Using organoids, we observed that the short‐term inflamed‐CSF exposure promoted microglial senescence (4.2‐FC relative to untreated organoids).

Conclusion: Inflammation‐associated cellular senescence is pronounced in progressive MS and might potentially exacerbate tissue dysfunction, with key translational implications.

Disclosure: MSM has got nothing to disclose. FF has got nothing to disclose. ED has got nothing to disclose. DM has got nothing to disclose. MA received consultancy honoraria from Abata Therapeutics, Biogen, Sanofi‐Genzyme and GSK. DSR has received research funding from Abata Therapeutics and Sanofi‐Genzyme. MF is Editor‐in‐Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck‐Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol‐Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi‐Aventis, Sanofi‐Genzyme, Takeda.

OPR‐067

Factors influencing postpartum activity in multiple sclerosis patients: a prospective study and intervention strategy, c. oreja‐guevara ; c. martin‐romero ; i. gomez‐estevez ; l. garcía‐vasco ; e. alba‐suarez, neurology , hospital clínico san carlos, idissc, madrid, spain.

Background and aims: Postpartum relapses in multiple sclerosis (MS) patients significantly impact family planning decisions, often leading to cautious reproductive choices. Neurologists frequently advise these individuals on managing their condition during and after pregnancy. Objective: to analyze the factors influencing postpartum disease activity in MS patients. Additionally, we assessed the effectiveness of a proactive strategy designed to reduce postpartum relapses.

Methods: We conducted a prospective longitudinal study involving pregnant women with MS, starting in 2015. We collected and analyzed demographic, clinical, and radiological data before pregnancy, during pregnancy, and in the postpartum period. We implemented a specific strategy to minimize postpartum relapses, including initiating treatment after delivery for active patients and conducting cranial MRI scans 2 months postpartum.

Results: The study included 128 women, with a mean age of 35 years (range 25–47). Pre‐pregnancy, 28.3% had experienced relapses in the 2 years leading up to pregnancy, and similar proportions exhibited new T2 lesions (28.3%) and gadolinium‐enhancing lesions (21.6%). During pregnancy, 10% experienced relapses, with 7% having clinical relapses and 22% developing new T2 lesions within 6 months postpartum. Notably, 41.4% of patients received DMT treatment within 15 days postpartum, leading to reduced postpartum relapses. Significant correlations were found between postpartum relapses and relapse history, number of relapses, and gadolinium‐enhancing lesions.

Conclusion: This study highlights the importance of a targeted postpartum management strategy in reducing MS relapses. The proactive approach, involving early DMT treatment and postpartum MRI scans, effectively reduced postpartum relapses, demonstrating the potential for improved outcomes in MS patients considering pregnancy.

Disclosure: nothing to disclose related to the abstract.

OPR‐068

Disconnection of cerebellar motor areas and motor impairment in multiple sclerosis, f. romanò 1 ; b. signoracci 1 ; p. preziosa 2 ; m. margoni 3 ; e. pagani 1 ; m. rocca 2 ; m. filippi 4, 1 neuroimaging research unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 2 neuroimaging research unit, division of neuroscience, and neurology unit, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy; 3 neuroimaging research unit, division of neuroscience, neurology unit, and neurorehabilitation unit, irccs san raffaele scientific institute, milan, italy; 4 neuroimaging research unit, division of neuroscience, neurology unit, neurorehabilitation unit, and neurophysiology service, irccs san raffaele scientific institute, and vita‐salute san raffaele university, milan, italy.

Background and aims: The cerebellum is often affected in patients with multiple sclerosis (MS). It contains two motor representations: the anterior (ACMA, lobules I–V) and posterior (PCMA, lobule VIII) cerebellar motor areas. We assessed atrophy and T2‐hyperintense lesion loads in these areas and their association with motor impairment.

Methods: Eighty‐nine MS patients and 65 healthy controls (HC) underwent a functional assessment (gait function and hand dexterity) and structural MRI acquisition at 3.0 T. Cerebellar lobules were segmented using the SUIT atlas. Between‐groups comparisons and age/sex‐corrected partial correlations were assessed.

Results: Compared to HC, ACMA and PCMA were atrophic in MS ( p  < 0.001), with similar reductions between the two areas. More than 60% of MS patients had lesions in either motor lobule. ACMA volume was lower than PCMA in HC and MS ( p  < 0.001), whereas T2‐hyperintense lesion load was higher in ACMA than PCMA in MS ( p  = 0.040). Patients with lesions in both areas had worse motor performance than those without lesions in either area ( p  < 0.001 for all). Patients with lesions only in the ACMA or PCMA had similar motor abilities. In patients, lower ACMA and PCMA volumes correlated with worse left‐hand dexterity ( p  < 0.001), whereas higher T2‐hyperintense lesion load in both ACMA and PCMA correlated with worse performance in all motor tests ( r range = −0.358; −0.445, p  < =0.001 for all).

Conclusion: The non‐homogeneous distribution of lesions suggests an increased susceptibility of the ACMA to focal demyelinating lesions. Considering correlation analyses, disconnection of cerebellar motor areas, rather than localised lobular atrophy, seems to better explain motor impairment in MS.

Disclosure: F. Romanò, B. Signoracci and E. Pagani have nothing to disclose. P. Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck, Bristol Myers Squibb, Genzyme, Horizon and Sanofi, and research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla (FISM). M. Margoni reports grants and personal fees from Sanofi Genzyme, Merck Serono, Novartis and Almiral. MA Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche; speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva; research support from MS Society of Canada, Italian Ministry of Health, Italian Ministry of University and Research, and FISM. M. Filippi received compensation for consulting or speaking activities services from Alexion, Almirall, Biogen, Bayer, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol‐Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi‐Aventis, Sanofi‐Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol‐Myers Squibb, Lilly, Novartis, Sanofi‐Genzyme; he receives research support from Biogen Idec, Merck‐Serono, Novartis, Roche, Italian Ministry of Health, Italian Ministry of University and Research, and FISM.

Neuroimmunology 1

Opr‐069, neurologic, psychiatric and sleep investigations after initial treatment of anti‐lgi1 encephalitis: a prospective study, a. muñoz‐lopeteti 1 ; m. guasp 1 ; l. prades 2 ; e. martinez‐hernandez 1 ; m. rosa‐justicia 2 ; v. patricio 2 ; t. armangué 3 ; l. rami 2 ; r. borràs 4 ; j. castro‐fornieles 5 ; a. compte 2 ; c. gaig 1 ; j. santamaria 2 ; j. dalmau 2, 1 neurology department, institute of neurosciences, hospital clínic de barcelona, university of barcelona, barcelona, spain; 2 institut d'investigacions biomèdiques august pi i sunyer ( idibaps ), barcelona, spain; 3 pediatric neuroimmunology unit, department of neurology, sant joan de déu children hospital, university of barcelona, barcelona, spain; 4 medical statistics core facility, hospital clínic de barcelona, university of barcelona, barcelona, spain; 5 department of child and adolescent psychiatry and psychology, institute of neurosciences, hospital clínic de barcelona, university of barcelona, barcelona, spain.

Background and aims: Anti‐LGI1 encephalitis responds well to immunotherapy, but the symptoms that remain after treatment have not been well described. We aimed to characterize the clinical features of these patients over more than 1 year after initial immunotherapy.

Methods: This prospective cohort study included individuals with anti‐LGI1 encephalitis who received immunotherapy within the past year and sex and age matched healthy participants (HP). At study entry, at 6 months (not in HP), and at 12 months, participants underwent neuropsychiatric and video‐polysomnography (VPSG) assessments.

Results: Between 2019 and 2022, 24 (57%) patients with anti‐LGI1 encephalitis and 18 (43%) healthy participants were recruited. At study entry (median 88 days [IQR 67–155] from initial immunotherapy), all 24 patients had one or more symptoms: cognitive (83%), psychiatric (83%), insomnia (58%), REM sleep behaviour disorder (50%), faciobrachial dystonic seizures (FBDS 38%), and focal onset seizures (29%). FBDS were unnoticed in 17% and focal onset seizures in 21%. VPSG alterations included disruption of sleep structure (79% patients; 0 HP; p  = 0.013]), excessive fragmentary myoclonus (63% patients; 22% HP; p  = 0.039) and myokymic discharges (38% patients; 0 HP; p  = 0.0051). These findings led to additional immunotherapy in 63% of the patients, resulting in improvement or resolution in all cases, however at 12 months 65% remained with cognitive deficits.

Conclusion: Unsuspected but ongoing clinical and video‐polysomnography alterations are common in patients with anti‐LGI1 encephalitis during the year that follows initial immunotherapy. Recognition of these alterations is important because they are treatable, can be used as outcome measures in clinical trials, and may influence cognitive outcome.

OPR‐070

Clinical characterization and long‐term outcome of children and adults with anti‐ampar encephalitis, c. milano 1 ; e. saylam 2 ; c. papi 3 ; a. sankovic 2 ; j. honnorat 4 ; t. iizuka 5 ; r. höftberger 6 ; r. reinecke 6 ; m. titulaer 7 ; j. kerstens 7 ; m. simabukuro 8 ; m. benaiteau 4 ; b. joubert 4 ; m. gastaldi 9 ; l. almeida dutra 10 ; f. leypoldt 11 ; m. jansen 11 ; i. kawachi 12 ; f. graus 13 ; j. dalmau 13 ; s. magana 2 ; m. spatola 13, 1 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain; department of clinical and experimental medicine, university of pisa, pisa, italy; 2 department of pediatrics, division of neurology, nationwide children's hospital, columbus, oh , usa ; 3 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain; department of neuroscience, catholic university of the sacred heart, rome, italy; 4 reference centre on paraneoplastic neurological syndromes and autoimmune encephalitis, hospices civils de lyon, melis institute umr inserm 1314, cnrs 5284, université claude bernard lyon 1, lyon, france; 5 department of neurology. kitasato university school of medicine, japan; 6 division of neuropathology and neurochemistry, department of neurology, medical university of vienna, vienna, austria; 7 department of neurology, erasmus mc , university medical center, rotterdam, the netherlands; 8 division of neurology, hospital das clinicas ( hcfmusp ), faculdade de medicina, universidade de sao paulo, são paulo, brazil; 9 neuroimmunology laboratory, irccs mondino foundation, pavia, italy; 10 hospital israelita albert einstein, são paulo, brazil; 11 institute of clinical chemistry, university hospital schleswig‐holstein , germany; 12 department of neurology, brain research institute, niigata university, japan; 13 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain.

Background and aims: Anti‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid (anti‐AMPAR) encephalitis manifest with limbic encephalitis (LE) associated with cancer. The full clinical spectrum, prognostic factors and outcome are not well established, especially in children. We compared clinical features of children and adults and characterized the long‐term outcome of anti‐AMPAR encephalitis.

Methods: Clinical information of adults and children with anti‐AMPAR encephalitis were reviewed from medical records.

Results: Eighty‐four patients with AMPAR antibodies were included (13 children, 71 adults). Patients with other concomitant neuronal antibodies were excluded. Overall, 62% of patients presented with LE (7 children, 45 adults, p  = 0.539). Compared to adults, children experienced more frequently prodromal symptoms ( p  = 0.035), movement abnormalities ( p  = 0.032) and cerebellar symptoms ( p  = 0.025). Brain MRI was abnormal in 68% of patients, restricted to mesio‐temporal lobes (50%) or associated with extratemporal abnormalities (34%). Exclusive involvement of extratemporal areas (16%) was more frequent in children than adults (44% vs. 11%, p  = 0.035). Tumours were found only in adults (56%, mainly lung cancer and thymoma). A follow‐up >24 months was available for 34 patients (4 children, 30 adults): 64% showed neurological sequelae, including cognitive (83%), psychiatric (33%), sleep (11%), and movement (6%) disorders. Twenty‐two patients (65%) had a good outcome (modified Rankin scale [mRS] < 2) whereas 12 (35%) a bad outcome (mRS >2). At multivariate analysis, failure to respond to first‐line immunotherapy was the only predictor of bad outcome (OR 8.8, 95% CI 1.3–59.5, p  = 0.025).

Conclusion: Children with anti‐AMPAR encephalitis present distinct clinical and radiological features compared to adults. Despite most patients respond to immunotherapy, neurological sequelae are frequent.

Disclosure: M. Spatola receives research support from La Caixa Foundation and Spanish National Research Institute (Carlos III).

OPR‐071

Brain mri changes and their impact on cognition in the post‐acute stage of anti‐nmda receptor encephalitis, m. guasp 1 ; f. vivó 2 ; e. martinez‐heras 2 ; e. solana 2 ; e. martinez‐hernandez 1 ; a. muñoz‐lopetegi 2 ; t. armangué 2 ; m. rosa‐justicia 2 ; l. prades 2 ; e. fonseca 2 ; g. sugranyes 3 ; a. calvi 2 ; e. lópez‐soley 2 ; s. albà‐arbalat 1 ; j. castro‐fornieles 3 ; a. compte 2 ; j. dalmau 2 ; s. llufriu 1, 1 neurology department, institute of neuroscience, hospital clínic de barcelona, university of barcelona, barcelona, spain; 2 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain; 3 psychiatry department, institute of neuroscience, hospital clínic de barcelona, university of barcelona, barcelona, spain.

Background and aims: We aimed to characterize the course of alterations in brain grey matter (GM) volumetry and diffusion‐based white matter (WM) connectivity and their association with cognitive performance during the post‐acute stage of anti‐NMDAR encephalitis (NMDARe).

Methods: NMDARe patients were prospectively studied at 4, 8, 12 and 12–24 months from disease onset with paired cognitive and MRI assessments that quantified whole brain volume, regional GM changes, and structural integrity of WM connectivity. Differences between NMDARe patients and healthy controls (HC), similarly studied, in the longitudinal follow‐up were analyzed using multilevel linear mixed‐effect models.

Results: Twenty‐one post‐acute NMDARe patients and 19 HC were included. Compared with HC, patients showed similar global brain volume, but specific regional changes: atrophy of the middle frontal cortex, and enlargement of bilateral hippocampus and right amygdala, mainly during the first 8 months, which improved over time. NMDARe patients showed differences in 76/2020 (3.8%; p  < 0.05, family‐wise error rate) WM connections, following two distinct dynamic patterns: reduced connectivity in 63/76 (83%) connections, involving bilateral cingulate, parietal cortex and deep GM, which improved rapidly (first 8 months), and increased connectivity in 13/76 (17%) connections, mainly subcortical areas, which stabilized over time. Regional atrophy and decreased WM connectivity largely explained variability in working memory (87%) and learning and memory (86%) outcomes.

Conclusion: The first 8 months of post‐acute NMDARe were dominated by regional vulnerability to damage and rapid MRI improvements. In subsequent months (8–24), MRI changes slowed and mild residual volumetric and connectivity abnormalities persisted alongside protracted cognitive deficits in NMDARe patients.

Disclosure: J.D. holds patents for the use of NMDAR as autoantibody tests. GS received speaker fees from Angelini Pharma. SL received compensation for consulting services and speaker honoraria from Biogen Idec, Novartis, TEVA, Genzyme, Sanofi and Merck. S.L. received compensation for consulting services and speaker honoraria from Biogen Idec, Novartis, Janssen, Merck and Bristol‐Myers Squibb, and holds grants from the Instituto de Salud Carlos III. E.S. received travel reimbursement from Merck and Sanofi‐Aventis S.A. The rest of the authors declare no conflicts of interest related to this work.

OPR‐072

How to retreat patients with anti‐mag polyneuropathy after a course of rituximab a comparison between two regimens, m. bellucci 1 ; f. massa 1 ; e. baroncelli 1 ; c. castellano 1 ; l. marinelli 1 ; c. cabona 2 ; e. mobilia 3 ; a. lechiara 3 ; f. bozzano 3 ; g. pesce 3 ; a. schenone 1 ; l. benedetti 4, 1 department of neuroscience, rehabilitation, ophthalmology, genetics, maternal and child health ( dinogmi ), university of genoa, genoa, italy; 2 department of neurophysiopathology, irccs ospedale policlinico san martino, genoa, italy; 3 immunology lab, irccs ospedale policlinico san martino, genoa, italy; 4 department of neurology, irccs ospedale policlinico san martino, genoa, italy.

Background and aims: Rituximab represents an effective therapy in anti‐MAG polyneuropathy. However, a well‐established retreatment strategy is currently lacking. We aim to compare two different retreatment protocols, upon clinical relapse vs. upon memory B cell reappearance, to evaluate whether they could be associated with an increased long‐term disability.

Methods: We retrospectively evaluated 29 patients who were responsive to an initial cycle of rituximab (375/mg/m 2 /week for 4 weeks), and retreated according to two different protocols: full course at the time of clinical relapse ( n  = 20), or a single infusion of rituximab (375 mg/m 2 ) whenever the frequency of reemerging CD27+ memory B cells exceeded 0.05% in the first 2 years and 0.1% thereafter ( n  = 9). The scores obtained in the validated clinical scales INCAT, MRC, ISS scales were evaluated at baseline, after 9 months and at the last follow‐up visit.

Results: Comparing the scores obtained in the three clinical scales between baseline and the last follow‐up, we found that patients treated upon relapse disclosed a progressively more disabling clinical course, whereas none of the patients treated upon memory B cells reappearance had a significant clinical decline compared to baseline (statistical data not presented for shortness).

Conclusion: Our findings reveal that patients treated upon clinical relapse exhibit greater levels of long‐term disability than patients treated upon CD27+ lymphocyte reappearance, suggesting that the latter protocol may be an effective maintenance treatment strategy in patients with anti‐MAG polyneuropathy.

OPR‐073

Detailed characterization and evolution of brainstem tau pathology in anti‐iglon5 disease, r. reinecke 1 ; e. gelpi 1 ; m. blaabjerg 2 ; e. erro 3 ; j. ferrari 4 ; m. glatzel 5 ; a. heidbreder 6 ; b. högl 7 ; j. lewerenz 8 ; l. myllykangas 9 ; m. popovic 10 ; p. schnider 11 ; d. yilmazer‐hanke 12 ; l. sabater 13 ; c. gaig 14 ; r. höftberger 1, 1 division of neuropathology and neurochemistry, department of neurology, medical university of vienna, austria; 2 department of neurology, odense university hospital, odense, denmark; 3 department of neurology, hospital universitario de navarra, health research institute of navarra ( idisna ), pamplona, spain; 4 department of neurology, hospital barmherzige brüder vienna, vienna, austria; 5 institute of neuropathology, university medical center hamburg‐eppendorf , hamburg, germany; 6 department of neurology, johannes kepler university linz, linz, austria; 7 department of neurology, medical university of innsbruck, innsbruck, austria; 8 german center for neurodegenerative diseases ( dzne ), campus ulm, ulm, germany; 9 department of pathology, university of helsinki, and hus diagnostic center, helsinki university hospital, helsinki, finland; 10 institute of pathology, faculty of medicine, university of ljubljana, ljubljana, slovenia; 11 department of neurology, landesklinikum wiener neustadt, wiener neustadt, austria; 12 clinical neuroanatomy, department of neurology, institute for biomedical research, ulm university, ulm, germany; 13 neuroimmunology program, fundació de recerca clínic barcelona‐institut d'investigacions biomèdiques august pi i sunyer, universitat de barcelona, barcelona, spain; 14 department of neurology, hospital clínic, barcelona, spain.

Background and aims: Anti‐IgLON5 disease is a newly identified rare form of autoimmune disorder characterized by anti‐IgLON5 antibodies that, via an as‐yet‐unidentified mechanism, are associated with a brainstem‐dominant tau pathology. Recent research indicates that the tau pathology may develop in a time‐dependent manner, being absent or mild at early disease stages and very prominent after years of disease progression. This study aimed to precisely characterize the different tau phosphorylation steps and establish a sequence of markers at the different severity stages in an autopsy cohort.

Methods: We used immunohistochemistry to analyze the medullary region of 14 autopsy cases of anti‐IgLON5 disease with different severity grades of tau pathology and varying disease durations, from 6 to 180 months. We used 13 antibodies for different tau phosphorylation sites. The presence and severity of tau pathology were assessed semi‐quantitatively and compared to one PSP case and two neurologically healthy controls.

Results: We identified different tau phosphorylation sites in anti‐IgLON5 disease and were able to determine a sequence of phosphorylation steps based on the disease duration. The development of cytoplasmic tau pathology seems to occur only in later disease stages, whereas alterations of the nuclear envelope were evident in the early stages.

Conclusion: Different tau phosphorylation steps occur during the progression of anti‐IgLON5 disease. The establishment of a sequence of pathological disease markers adds support to the hypothesis that tauopathy might indeed be a time‐dependent phenomenon. Furthermore, it may aid in the neuropathological identification of cases with mild pathology, and provides insight into the earliest stages of tauopathy.

Disclosure: This work was supported by the Austrian Science Fund (FWF), project number I6565‐B (SYNABSII).

OPR‐074

High relapse rate influences the long‐term clinical outcome in anti‐caspr2 encephalitis, t. brand 1 ; s. franken 1 ; m. vermeiren 1 ; a. van sonderen 1 ; m. de bruijn 1 ; y. crijnen 1 ; j. brenner 1 ; r. van steenhoven 1 ; j. kerstens 1 ; p. sillevis smitt 1 ; s. veenbergen 2 ; m. titulaer 1 ; j. de vries 1, 1 department of neurology, erasmus mc university medical centre, rotterdam, the netherlands; 2 department of immunology, laboratory medical immunology, erasmus mc university medical centre, rotterdam, the netherlands.

Background and aims: Anti‐contactin‐associated protein‐like 2 (CASPR2) encephalitis is a young disease entity, and information on long‐term clinical outcome and relapse rate are limited. We aim to describe long‐term clinical outcome, relapse rate and treatment efficacy to guide treatment decisions.

Methods: In this nationwide observational cohort study, patients with a confirmed diagnosis of anti‐CASPR2 encephalitis were included. Clinical data were collected at diagnosis and during follow‐up, both retrospectively and prospectively. In all patients, written informed consent was obtained.

Results: Forty‐four patients with anti‐CASPR2 encephalitis were included (42/44 [95%] male; median age at onset 65 years, range 40–86). The median follow‐up time was 46.5 months, range 7–113. Relapses were present in 23/44 patients (52%). Compared to the initial disease episode, patients experienced similar but fewer symptoms during the relapse(s). However, peripheral symptoms occurred newly during a relapse in five patients. The median time to relapse was 11 months (range 3–58). At relapse, one patient was tapering prednisone, eight patients had maintenance immunotherapy, three had received Rituximab induction therapy, while 11 patients had no immunotherapy anymore. VGKC RIA titre fluctuations in serum correlated well (84%) with relapse and remission. Nine patients (24%) suffered multiple relapses. In 10 patients, a tumour was present, of which two were only discovered during a relapse.

Conclusion: The relapse rate in anti‐CASPR2 encephalitis is much higher than previously anticipated, which provides a clear rationale for prolonged immunotherapy. VGKC RIA titres in serum can guide monitoring for relapses and disease course. It is recommended to repeat tumour screening when patients relapse.

Disclosure: Marienke en Yvette funded by EpilepsieNL (NEF 14–19 & 19–08), Juliette by Dioraphte (2001 0403) Robin funded by ZonMW (VIMP scheme) Peter A.E. Sillevis Smitt holds a patent for the detection of anti‐DNER and received research support from Euroimmun. Maarten J. Titulaer has filed a patent, on behalf of the Erasmus MC, for methods for typing neurological disorders and cancer, and devices for use therein, and has received research funds for serving on a scientific advisory board of Horizon Therapeutics, for consultation at Guidepoint Global LLC, and for consultation at UCB. MT has received an unrestricted research grant from Euroimmun AG, and from CSL Behring. JdV is local investigator for the CIELO satralizumab in anti‐NMDAR and anti‐LGI1 encephalitis (Roche).

Neuro‐ophthalmology/Neuro‐otology

Opr‐075, idebenone treatment for leber hereditary optic neuropathy: time to clinically relevant recovery in the leros study, c. la morgia 1 ; t. klopstock 2 ; p. yu‐wai‐man 3 ; v. carelli 1 ; x. llòria 4, 1 irccs istituto delle scienze neurologiche di bologna, bologna, italy; 2 department of neurology with friedrich‐baur‐institute , university hospital of ludwig‐maximilians‐universität münchen, munich, germany; 3 john van geest centre for brain repair and mrc mitochondrial biology unit, department of clinical neurosciences, university of cambridge, cambridge, uk; 4 chiesi farmaceutici spa , parma, italy.

Background and aims: LHON is a mitochondrial disease resulting in bilateral vision loss. In LEROS, a Phase IV, open‐label interventional study ( {"type":"clinical-trial","attrs":{"text":"NCT02774005","term_id":"NCT02774005"}} NCT02774005 ), visual acuity (VA) outcomes following 24 months of idebenone treatment were compared to an external matched Natural History (NH) cohort. Eyes treated with idebenone had significantly higher rates of clinically relevant recovery (CRR) from baseline at 12 and 24 months compared to the NH control group. Here, we present the cumulative percentage of eyes with a CRR from baseline (KM‐estimate) by disease phase and primary mtDNA mutation as a function of treatment duration.

Methods: LEROS included patients with LHON aged ≥12 y and with a disease onset ≤5 y prior. Eyes were stratified by time since symptom onset: subacute/dynamic (≤1 y) and chronic (>1 y). CRR was defined as an improvement from “off‐chart” VA to at least 1.6 logMAR, or a ≥0.2 logMAR improvement if “on‐chart”.

Results: The intention‐to‐treat (ITT) population included 196 patients. The KM‐estimate of a CRR from baseline increased from 18.4% of eyes at Month 6 to 47.3% at Month 24 with idebenone treatment in the subacute/dynamic phase, and from 18.2% to 29.1% in the chronic phase. Improvement of visual acuity was also observed in sub‐analyses by mtDNA mutation in both subacute/dynamic and chronic eyes (Table 1).

TABLE 1 Kaplan–Meier estimates of cumulative CRR [95% CI] from baseline.

Conclusion: Longer duration of idebenone treatment (beyond 1 y) further improved visual outcomes regardless of LHON disease phase. This improvement was most pronounced for eyes with the m.14484T>C mutation.

Disclosure: CLM has acted as a consultant for Chiesi Farmaceutici, Gensight Biologics, Regulatory PharmaNet, and Thenewway srl and has also received speaker honoraria and/or financial support for meetings from these companies, as well as from First Class srl and Biologix. CLM has also acted as a principal or study investigator for clinical trials sponsored by GenSight Biologics, Santhera Pharmaceuticals, Stoke Therapeutics, Reneo Pharmaceuticals and Omeicos. PYWM, VC, and TK received research support and/or personal compensation from Santhera Pharmaceuticals, Chiesi, and GenSight Biologics. XL is an employee of Chiesi Farmaceutici S.p.A. LEROS was funded by Santhera Pharmaceuticals and medical writing support was provided by nspm ltd, Switzerland with financial support from Chiesi Farmaceutici SpA.

OPR‐076

Opr‐077, zebra or horse: diagnostic process, misdiagnosis, and bias in suspected idiopathic intracranial hypertension, n. skadkær hansen 1 ; j. juhl korsbæk 1 ; s. hamann 2 ; r. jensen 1, 1 danish headache center, department of neurology, rigshospitalet‐glostrup , university of copenhagen, copenhagen, denmark; 2 department of ophthalmology, rigshospitalet‐glostrup , copenhagen, denmark.

Background and aims: Misdiagnosis of Idiopathic Intracranial Hypertension (IIH) is prevalent and potentially harmful. We evaluate the diagnostic process in IIH and the impact of National Guideline (NG) on IIH management.

Methods: Retrospective observational study of patients referred to the Danish Headache Center bysuspected IIH,Jan 2020 to Sep 2022. We retrieved data on diagnostic work‐up (DW) and duration, causes for suspecting IIH, and mismanagement, and compared outcomes by final diagnosis (confirmed versus disproven IIH (non‐IIH)) and by period before and after the NG. Level of significance was Bonferroni‐corrected to p  < 0.002.

Results: 124 patients were referred. We excluded IIH relapse ( n  = 22) and secondary intracranial hypertension( n  = 6) leaving 96 patients with suspected new‐onset IIH. We confirmed IIH in 28% and disproved IIH in 72% Confirmed IIH was discovered by optic disc swelling in 93%. Neuroimaging indicating intracranial hypertension ( n  = 1) and clinical phenotype ( n  = 1) aided little in finding true cases, but often elicited IIH suspicion suggesting anchoring bias with premature closure. False‐positive misdiagnosis affected 9%, false‐negative misdiagnosis affected 2%. DWU was significantly more comprehensive and faster in confirmed IIH compared to non‐IIH. Mismanagement dropped by implementation of the NG (from 44% to 20%, p  = 0.022), whereas diagnostic accuracy remained low (38% before vs. 21% after, p  = 0.11).

Causes for initial IIH suspicion and final diagnosis.

Conclusion: Optic disc swelling is the main determinant leading to correct IIH diagnostics. Ophthalmic evaluation is urgent and decisive in suspected IIH and should guide DWU to mitigate unnecessary investigations. Neuroimaging and clinical phenotype have little diagnostic value and introduce bias. A national guideline optimizes the diagnostic process.

Disclosure: N. S. Hansen received funding from the Novo Nordic Foundation during the conduction of the work. J. J. Korsbæk received funding from the Lundbeck Foundation, Rigshospitalet‐Glostrup and Odense University Hospital. S. Hamann received funding from the VELUX Foundation. R. Jensen gave lectures for Pfizer, Eli‐Lilly, ATI, Merck, TEVA, Novartis, Lundbeck and Allergan. Investigator in clinical trials with ATI, Eli‐Lilly, Novartis and Lundbeck; received research funding from University of Copenhagen, Rigshospitalet, ATI, Lundbeck Foundation, The Medical Society in Copenhagen, Novo Nordisk Foundation and Tryg Foundation.

OPR‐078

Oct in multiple sclerosis: beyond the optic neuritis versus non‐optic neuritis universe, s. matos ; a. jorge; i. pais; a. martins; i. correia; c. nunes; m. macário; s. batista; j. lemos, neurology department, coimbra university hospital centre, coimbra, portugal.

Background and aims: When using optical tomography studies(OCT) in multiple sclerosis(MS) eyes are usually classified as having had clinical optic neuritis(ON), subclinical ON, or as otherwise normal. We believe such approach undermines the importance of further including and classifying eyes with signs indicative of retrochiasmal/chiasmal disease(RCD/CD).

Methods: Objectives. To analyze eyes with OCT, evidence of RCD/CD in a large database of MS patients. Methods. Eyes of MS patients examined with OCT were classified as normal, with clinical ON(diagnosed >6 months prior), subclinical ON(>7 micra inter‐eye retinal nerve fiber layer[RNFL] thickness difference and/or > 4 micra inter‐eye ganglion cell layer[GCL] thickness difference), subclinical or clinical CD(bilateral and congruent nasal GCL loss), subclinical or clinical RCD(bilateral and congruent homonymous GCL loss) and subclinical (non‐localizing) involvement (color and/or statistical RNFL/GCL map abnormalities not fulfilling criteria above).

Results: We included 273 eyes. 177(64.8%) of our MS patients had OCT abnormalities, 32.9% of which were subclinical. Eyes had evidence of ON only ( n  = 86, 31.5%), RCD/CD ( n  = 36, 13.1%), and non‐localizing findings ( n  = 55, 20.1%). When comparing between normal, ON, and RCD/CD eyes, disease duration in the right eye was different between groups ( p  = 0.020), being greater in RCD/CD ( p  = 0.019) and ON ( p  = 0.029), than in normal eyes. Disease duration in the left eye was near‐significantly different between groups ( p  = 0.076), being greater in RCD/CD ( p  = 0.037) than in normal eyes. Relapse rate in the 2 years prior in the right eye, was near‐significantly different between groups ( p  = 0.086), being greater in RCD/CD ( p  = 0.036) than in ON eyes.

Conclusion: Our work supports the use of OCT for identifying MS‐related damage of chiasmal and retrochiasmal pathways.

OPR‐079

Clinical features, video‐oculographic profile, and treatment in spinocerebellar ataxia type 27b ( sca27b ), s. fenu 1 ; d. di bella 2 ; e. sarto 2 ; d. pareyson 1 ; c. pisciotta 1 ; s. magri 2 ; e. salsano 1 ; f. taroni 2, 1 unit of rare neurological diseases, department of clinical neurosciences, fondazione irccs istituto neurologico carlo besta, milano, italy; 2 unit of medical genetics and neurogenetics, fondazione irccs istituto neurologico carlo besta, milano, italy.

Background and aims: Spinocerebellar ataxia type 27B (SCA27B) is a late‐onset, autosomal‐dominant disorder caused by a GAA‐repeat expansion in the FGF14 gene and characterized by oculomotor abnormalities. This study aims to detail the oculomotor profiles of SCA27B patients and assess the efficacy of 4‐aminopyridine.

Methods: Eight genetically confirmed SCA27B patients underwent clinical and video‐oculographic examinations using EyeSeeCam. Six received 4‐aminopyridine to evaluate its effect on nystagmus.

Results: The cohort consisted of six males and two females, mean age 69 ± 10.3 years, with disease duration of 6.6 ± 3 years. All displayed oculomotor abnormalities at both clinical and instrumental examination; half reported diplopia. Video‐oculography showed reduced smooth pursuit gain in all tested patients (6/6), but normal saccade metrics (8/8). Nystagmus was present in all, predominantly downbeat (7/8) and gaze‐evoked (3/8), with normal vestibulo‐ocular reflex gains (8/8). Treatment with 4‐aminopyridine led to both subjective and objective improvement in 5/6 cases, which was significant in three patients (see Figure) and mild in two. Only one patient had no benefit.

FIGURE 1 Gaze Holding assessment before and after treatment with 4‐aminopyridyne shows complete disappearance of nystagmus.

Conclusion: SCA27B patients exhibit primarily vestibulocerebellar impairments, with significant smooth pursuit and nystagmus abnormalities but no saccadic or vestibulo‐ocular reflex alterations. 4‐aminopyridine was effective in treating nystagmus in most patients, highlighting the potential of targeted therapy in SCA27B management. Further research is needed to optimize treatment strategies.

Muscle and neuromuscular junction disorder

Opr‐080, efgartigimod in non‐achr myasthenia gravis: a 24 months experience, c. antozzi 1 ; r. frangiamore 1 ; e. rinaldi 1 ; f. vanoli 1 ; f. andreetta 1 ; s. bonanno 1 ; l. maggi 1 ; r. arnaboldi 2 ; a. pinna 2 ; r. mantegazza 1, 1 neuroimmulogy and muscle pathology unit fondazione irccs istituto neurlogico c. besta, milan italy; 2 argenx italy, milan, italy.

Background and aims: The neonatal Fc receptor (FcRn) inhibitor Efgartigimod (EFG) has been approved for treatment of generalized Myasthenia Gravis (gMG) with anti‐AChR antibodies. We investigated the efficacy of EFG in non‐AChR gMG along a clinical follow‐up of 2 years.

Methods: We treated 13 patients with gMG without anti‐AChR antibodies: 5 MuSK+, 2 LRP4+ and 6 triple‐negative (confirmed by live CBA). EFG was administered according to the GENERATIVE protocol (consisting of a Fixed period of 2 treatment cycles of 4 infusions at weekly intervals, followed by a Flexible period during which EFG was given in case of clinical worsening) starting from November 2021. Outcomes were evaluated by means of the MG‐ADL, QMG, and MGC scores.

Results: The mean follow‐up was 14.5 ± 6.7 months. Meaningful improvement was observed with the clinical scores adopted (MG‐ADL: −5.5 ± 3.64; MGC: −8.5 ± 6.54; QMG: −4.84 ± 4.92). The number of cycles/year was 3.9 ± 0.99. The interval between cycles was 8.9 ± 3.8 weeks. MG‐ADL improvement greater than 5 points was recorded in 49% of patients. 46% of patients required hospitalization during the 2 years before treatment with EFG; during EFG none of the patients was hospitalized or required immunomodulation. No major side effects or infusion related reactions occurred.

Conclusion: EFG was effective in non‐AChR gMG and modified significantly the course of the disease. Our experience strengthens the role of FcRn inhibition as a new effective tool in the management of MG without anti‐AChR antibodies, as demonstrated by RCT in AChR‐associated gMG. A longer follow‐up will be available at the time of the meeting.

Disclosure: C. Antozzi received funding for travel, meeting attendance, or Advisory Board participation from Biogen, Sanofi, Alexion, Momenta, argenx, UCB and Janssen R. Frangiamore received funding for meeting attendance and speaking from argenx, UCB and Alexion. L. Maggi received funding for travel, meeting attendance or Advisory Board participation from Sanofi Genzyme, Roche, Alexion, AmicusTherapeutics and Biogen. S. Bonanno received funding for travel, meeting attendance or Advisory Board participation from Sanofi Genzyme, Biogen and Roche. F. Vanoli received funding for travel or meeting attendance from Alexion Pharmaceuticals and argenx R. Mantegazza received funding for travel, meeting attendance or Advisory Board participation from Alexion, Argenx, Biomarin, Catalyst, Sanofi, Regeneron and UCB A. Pinna and R. Arnaboldi are employees of argenx Italy F. Andreetta and E. Rinaldi have nothing to disclose.

OPR‐081

A real‐life comparison of eculizumab and efgartigimod in generalized myasthenia gravis patients, c. pane 1 ; v. di stefano 2 ; n. cuomo 1 ; a. sarnataro 1 ; c. vinciguerra 5 ; l. bevilacqua 5 ; m. camapnile 1 ; f. brighina 2 ; n. rini 2 ; g. puorro 1 ; a. marsili 1 ; m. garibaldi 3 ; l. fionda 4 ; f. saccà 6, 1 nsro department, federico ii university, naples, italy; 2 department of biomedicine, neuroscience and advanced diagnostic ( bind ), university of palermo, palermo, italy; 3 neuromuscular and rare disease centre, sant'andrea hospital, rome, italy.; 4 department of neuroscience, mental health and sensory organs ( nesmos ), faculty of medicine and psychology, sapienza university of rome, rome, italy; 5 neurology unit, department of medicine, surgery and dentistry, university of salerno, salerno, italy; 6 genesis department, federico ii university, naples, italy.

Background and aims: Eculizumab (ECU) and Efgartigimod (EFGA) are approved for the treatment of generalized Myasthenia Gravis (gMG). Objective of our study is to describe their clinical response in a real‐life setting.

Methods: We included patients receiving either ECU or EFGA as part of our clinic practice and retrospectively collected data on the MG activities of daily living (MG‐ADL), quantitative MG scale (QMG), MG deterioration/crises, adverse events, and prednisone use.

Results: We enrolled 63 patients, 32 treated with ECU and 31 with EFGA (Table 1). Median follow‐up was 234 days. Both treatments were well tolerated. Patients treated with EFGA were more likely to suspend treatment (HR 3.732; CI 1.041, 13.385; p  = 0.043; Figure 1A). Main reason was MG deterioration, patient choice, adverse event. ECU decreased the MG deterioration/crises rate more than EFGA (OR 0.545, CI 0.363, 0.818; P  = 0.003; Figure 1B). By week 24, MG‐ADL decreased by −6.5 points for ECU and − 5.0 for EFGA ( p  = 0.188; Figure 2A); the QMG decreased by −8.0 for ECU and − 2.9 for EFGA ( p  = 0.003; Figure 2B). Mean prednisone reduction at follow‐up was −21.3 mg for ECU and − 8.1 mg for EFGA ( p  = 0.026). Speed of CS reduction was −13.1 mg/month for ECU and − 3.2 mg/month for EFGA ( p  = 0.001).

TABLE 1 Patient demographics.

FIGURE 1 Treatment retention and MG deterioration/crisis during treatment.

FIGURE 2 Treatment effect of MG‐ADL, QMG, and Prednisone reduction.

Conclusion: Eculizumab and Efgartigimod proved to be both effective treatments in a real world setting as they reduced MG‐ADL and QMG in difficult to treat gMG patients. Patients treated with ECU were less likely to suspend treatment or show a deterioration/crisis. Prednisone sparing effect and reduction speed was higher with Eculizumab.

Disclosure: F.S. received public speaking honoraria from Alexion, argenx, Biogen, Genpharm, Madison Pharma, Mylan, Novartis, Roche, Sanofi, Teva, Viatris, Zai Lab; he also received compensation for Advisory boards or consultation fees from Alexion, Almirall, argenx, AstraZeneca, Avexis, Biogen, Dianthus, Forward Pharma, Lexeo Therapeutics, Novartis, Reata, Sandoz, Takeda; he is PI in clinical trials for Alexion, argenx, Immunovant, Novartis, Prilenia, Sanofi.

OPR‐082

Childbirth and neonatal outcomes in a nationwide myasthenia gravis cohort, j. lindroos 1 ; m. bjørk 1 ; j. cohen 2 ; k. danielsson 3 ; o. hikmat 4 ; j. hoff 5 ; n. gilhus 1, 1 department of clinical medicine, university of bergen, bergen, norway/ department of neurology, haukeland university hospital, bergen, norway; 2 centre for fertility and health, norwegian institute of public health, oslo, norway; 3 department of obstetrics and gynaecology, haukeland university hospital, bergen, norway; 4 department of paediatrics and adolescent medicine, haukeland university hospital, bergen, norway/ department of clinical medicine, university of bergen, bergen, norway; 5 faculty of health studies at vid specialized university, bergen, norway.

Background and aims: Myasthenia Gravis (MG) muscle weakness can complicate childbirth. Transient neonatal myasthenia gravis (TNMG) can result from maternofetally transferred autoantibodies. Our aim was to estimate the risks at childbirth in a maternal MG‐cohort.

Methods: A cohort study using nationwide data from the Medical Birth Registry of Norway. Maternal MG was identified by MG‐diagnosis or pyridostigmine‐use, in current or prior pregnancy. All MG‐exposed and unexposed singleton live births in Norway 1999–2022 were compared. Main outcomes were mode of delivery (caesarean section (CS) vs. vaginal, emergency CS vs. vaginal, elective CS, and operative vaginal vs. non‐operative vaginal), induction of labour, TNMG‐rate and neonatal ward admission. Odds ratios (OR) with robust standard errors adjusted for year of birth, maternal age, parity and co‐habitation were calculated.

FIGURE 1 Inclusion–exclusion flowchart of singleton live births with and without maternal myasthenia gravis (MG) exposure, years 1999–2022 in Norway.

Results: 133 MG‐births and 1,344,520 unexposed births were included. Maternal MG did not significantly increase the risk for CS (aOR 1.32, 95% CI: 0.87–1.99). Elective CS (1.90, 1.10–3.30) and induced labour (1.56, 1.05–2.33) were more common with MG. The emergency CS rate was 10% for both groups (0.97, 0.54–1.76). Among MG‐exposed children, five (4%) had TNMG and 38% were admitted to neonatal ward, compared to 10% of unexposed (5.47, 3.85–7.77).

TABLE 1 Obstetrical and neonatal outcomes with and without maternal MG exposure among all singleton live births in Norway 1999–2022.

Conclusion: The risks for elective CS and induced labour were increased, but not for emergency CS, suggesting that pregnancy planning helps avoid complications in MG‐women. Few MG‐exposed children had TNMG, but 38% were admitted to a neonatal ward. All children of mothers with MG should be observed in‐hospital for minimum 2–3 days as TNMG symptoms often develop with delay.

Disclosure: N.E. Gilhus has received financial support from UCB, Argenx, Janssen, Merck, Roche, Alexion, Immunovant, Huma, Denka, Grifols, and Dianthus. Bjørk, M H. has received speaker honoraria and/or served on scientific advisory boards for Teva, Eisai, AbbVie, Pfizer, Novartis, Lundbeck, Angelini Pharma, Jazz pharmaceuticals, and Lilly during the last 5 years. None of the assignments concerned treatment of Myasthenia Gravis. Lindroos, JLV; Cohen, JM; Danielsson, KC; Hikmat, O; Hoff, JM: Nothing to disclose.

OPR‐083

Automatic method for jitter estimation in electromyographic signals, a. malanda 1 ; c. valle 1 ; d. stashuk 2 ; o. garnés 3 ; j. rodríguez 1 ; j. navallas 1, 1 electrical , electronics and communication engineering, public university of navarra, pamplona. spain; 2 system design engineering department, university of waterloo, waterloo, canada; 3 neurophysiology service, jiménez díaz foundation university hospital.

Background and aims: Neurophysiological jitter measurement using concentric needle electrodes is a laborious and difficult task, because potentials from several fibers may appear in the recordings due to the large recording areas of these electrodes. This work presents an automatic method that estimates jitter from motor unit potential (MUP) trains recorded using single‐fiber or concentric needle electrodes.

Methods: MUP intervals likely being formed by only one muscle fiber potential are detected. Then jitter measurement is performed between pairs of these intervals. 132 electromyographic signals were recorded from 8 patients with disorders of the neuromuscular junction or different neuropathies, using a Keypoint system and facial‐concentric electrodes. These signals were decomposed into several MUP trains using DQEMG software. Jitter was then estimated manually, using a home‐made graphical interface (Figure 1A,B) and using the automatic method (Figure 1C,D).

FIGURE 1 Examples of MUP trains analyzed by the manual method, with marked negative peaks and the obtained MCD values (A, B). The same MUP trains analyzed with the automatic method, with highlighted valid intervals and MCD values (C, D).

Results: From 96 MUP trains valid for the analysis, 102 automatic and 84 manual jitter measurements were obtained. Comparative analysis (Figure 2) yielded a mean of jitter differences of 1.74 μs, a mean of absolute differences of 2.73 μs and values of −2.62, −0.35, 2.53 and 7.56 μs for the 5th, 25th, 75th and 95th percentiles of the jitter differences distribution, respectively.

FIGURE 2 Boxplots of MCD values obtained by manual and automatic methods and of the difference in MCD values (A). Histogram of the difference in MCD values (B).

Conclusion: Although more extensive tests are still required, these results suggest that the proposed automatic jitter estimation method may be a valuable technique for clinical practice.

Disclosure: This work has been funded by the Department of Health of the Government of Navarra (project GN2022/29) and by the Spanish Ministry of Science and Innovation (project PID2022‐136620OB‐I00).

OPR‐084

The lifetime outcomes of antiseizure medication in patients with mesial temporal lobe epilepsy and hippocampal sclerosis, a. dias ; p. henning; w. ferreira; m. alvim; c. yasuda; f. cendes, laboratory of neuroimaging, department of neurology, unicamp , campinas, brazil.

Background and aims: To evaluate the lifetime seizure frequency in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (mTLE‐HS).

Methods: We studied 118 patients with mTLE‐HS followed at UNICAMP. We reviewed the seizure frequency, age, duration of epilepsy, dosages and type of antiseizure medications (ASM) used. Patients were split into 3 groups: seizure‐free (no seizures in the last 2 years or more of follow‐up), fluctuating (seizure‐freedom periods of 1 year or longer) or pharmacoresistant (never had a seizure‐free period of more than 1 year). Pharmacoresistant patients did not undergo surgery either because they refused it or had contraindications. Patients who underwent surgery were not included in this study.

Results: The mean age was 56.13 years and mean follow‐up was 20.25 years (range 3–47, SD 9.83). 35.6% ( n  = 42) had right‐TLE, 50% ( n  = 59) left‐TLE and 14.4% ( n  = 17) bilateral‐TLE. Thirty‐six (30.5%) were seizure‐free, 39 (33.05%) had a fluctuating course and 43 (36.45%) were pharmacoresistant. There were no differences among groups in relation to the age they became seizure‐free, age of epilepsy onset, epilepsy duration, epilepsy family history, number of ASM used over the years or number and type of ASM in use at the last follow‐up ( p  > 0.074). The most common ASM was carbamazepine.

Conclusion: Three clinical evolution patterns were observed among patients with mTLE‐HS who did not underwent surgery: pharmacoresistant, fluctuating seizure control/pharmacoresistant, and seizure‐free. We found no significant differences in the main clinical features among groups. Further studies are necessary to define the factors that could predict these three outcome profiles.

Disclosure: Grants: CEPID ‐ FAPESP: “The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN)” 2013/07559–3; CNPQ 315953/2021–7; Conflicts of interest: Fernando Cendes participated in advisory board for Takeda Pharmaceuticals, Libbs, Eurofarma; Clarissa Yasuda participated in advisory board for Eurofarma. Received honoraria for writing educational material for Torrent and Libbs.

OPR‐085

Exploring the long‐term effects of covid ‐19 in patients with epilepsy: a multicenter italian observational study, c. corniello 1 ; f. dono 1 ; m. russo 1 ; f. lombardo 1 ; g. evangelista 1 ; s. consoli 1 ; f. narducci 2 ; g. assenza 2 ; c. liguori 3 ; c. calvello 3 ; s. sensi 1, 1 department of neuroscience, imaging and clinical science, “g. d'annunzio” university of chieti‐pescara , chieti, italy; 2 unit of neurology, neurophysiology, neurobiology, department of medicine, university campus bio‐medico of rome, rome, italy; 3 neurology unit, university hospital of rome tor vergata, viale oxford, 81, 00133, rome, italy.

Background and aims: A growing evidence in the literature support that patients recovered from COVID‐19 may develop novel neurological and psychiatric symptoms lasting from weeks to months. This condition, labeled as “long COVID”, can be observed more frequently in patients with chronic diseases. The aim of this study is to identify the long‐term effects of COVID‐19 in people with epilepsy (PwE).

Methods: PwE aged >18 who accessed to three epilepsy centers in the center of Italy during the first pandemic wave between March 2020 and December 2021 were enrolled. According to a documented clinical and laboratory SARS‐CoV‐2 infection, patients were divided into two groups: COVID+ and COVID‐. Epilepsy features (i.e., seizure frequency, treatment), and neurological and psychiatric symptoms were collected at baseline and at 6‐ and 12‐month follow‐up visits in both groups.

Results: 39 patients in COVID+ group (17/22 M/F, age: 40.6 ± 18.6 years, 33 focal epilepsy, 6 generalized epilepsy) and 91 patients in COVID‐ (42/49 M/F, age: 42.9 ± 19.7 years, 69 focal epilepsy, 22 generalized epilepsy) met the inclusion criteria. At 6‐month, COVID+ group showed a need for antiseizure medication dose adjustment compared to COVID‐ group ( p  < 0.0001). An increased diagnosis of psychiatric (i.e., anxiety and depression) and neurological (i.e., cognitive) symptoms was observed in the COVID+ group at both 6‐ and 12‐month ( p  < 0.0001). At 12‐month, up to 40% of patients in the COVID+ group revealed an increased seizure frequency ( p  = 0.002).

Conclusion: These findings suggest that PwE with previous SARS‐CoV‐2 infection may develop psychiatric and neurological long‐lasting effects.

OPR‐086

Evolution into electrical status epilepticus during sleep in patients with self‐limited focal epilepsies, m. İriş 1 ; m. atacan yaşgüçlükal 2 ; c. yalçınkaya 1 ; v. demirbilek 1, 1 department of neurology, istanbul university‐cerrahpasa , cerrahpasa faculty of medicine, istanbul, turkey; 2 department of neurology, haseki research and training hospital, health sciences university, istanbul, turkey.

Background and aims: Self‐limited focal epilepsies of childhood (SeLFE), while predominantly considered benign, are known to potentially manifest with electrical status epilepticus during sleep (ESES) in a minority of patients.

Methods: The medical records of individuals diagnosed with one of the SeLFE syndromes according to the ILAE 2022 diagnostic criteria, who have been followed in our center between 1989–2023, were retrospectively analyzed. At least two awake and sleep EEGs were performed during a minimum 2‐year follow‐up. ESES is considered as spike and wave discharges occupying ≥50% of NREM sleep with symmetrical or mildly asymmetrical bilateral or unilateral hemispheric distribution.

Results: Among 144 patients with SeLFE, 57(39.6%) were diagnosed with self‐limited epilepsy with centrotemporal spikes (SeLECTS); 65(45.1%) with self‐limited epilepsy with autonomic seizures (SeLEAS); and 22 (15.3%) with childhood occipital visual epilepsy (COVE). The mean age of seizure onset was 7.6 years, 5.6 years, 8.5 years, respectively. Twelve (8.3%) evolved into ESES (5 from SeLECTS, 6 from SeLEAS, 1 from COVE). Time elapsed between onset of first seizure and evolution into ESES ranged from 5.2 to 75 months (mean: 26.8±19.8), 6.2–42.8 months (mean: 20.1±14.7 for patients with SeLECTS; 5.2–75.0 months (mean: 32.7±24.5) with SeLEAS, and 25.0 months with COVE). All except one patient had also cognitive or behavioral regression and one patient was diagnosed with Landau–Kleffner syndrome.

Conclusion: The most recent definition of ILAE highlights that SeLFEs are no longer recognized as “benign” epilepsies. Even with a low incidence rate, clinicians should always be cautious about the risk of ESES development in these syndromes.

OPR‐087

Thalamic atrophy and parahippocampal cortical surface area may distinguish clinical response in temporal lobe epilepsy, p. henning ; a. dias; w. ferreira; b. campos; m. alvim; c. yasuda; f. cendes, laboratory of neuroimaging, department of neurology, unicamp ‐ campinas, brazil.

Background and aims: To correlate response to antiseizure medication (ASM) with cortical surface area (CSA) and subcortical volumes (SV) in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE‐HS).

Methods: 111 patients with mTLE‐HS who did not undergo surgery because they refused it, had contraindications, or had good seizure control with ASM (mean follow‐up of 21.8 years) were categorized in three groups: pharmacoresponsive (seizure‐free in the last 2 years or more), fluctuating‐response (seizure‐freedom periods of 1 year or longer) and pharmacoresistant (never had a seizure‐free period of more than 1 year). T1‐weighted MRIs (1 × 1 × 1 mm) were processed with Freesurfer‐6.0. We analyzed the following regions of interest for CSA: inferior, middle and superior temporal gyrus, parahippocampal gyrus and insula. Volumes of thalamus, hippocampus and amygdala, along with the CSA from each ASM response‐groups were compared with 112 controls.

Results: Groups were balanced for age, sex, and side of HS. Each ASM response‐group had 37 patients. Compared with controls, ipsilateral hippocampal volumes were reduced in all groups ( p  < 0.0001) without difference among groups. There was no difference in the contralateral hippocampal volumes among groups. Volumes of ipsilateral and contralateral thalami were reduced in the pharmacoresistant group ( p  < 0.003), and the contralateral thalamus was reduced in pharmacoresponsive and fluctuating‐response groups ( p  < 0.006). Amygdala was reduced in the pharmacoresponsive group ( p  = 0.03). Ipsilateral parahippocampal CSA was reduced in the pharmacoresistant group ( p  = 0.013). Other CSA did not differ among groups.

Conclusion: Bilateral thalamic atrophy and reduced ipsilateral parahippocampal CSA appears to distinguish pharmacoresistant mTLE‐HS from those with better response to ASM.

Disclosure: CEPID ‐ FAPESP: “The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN)”, grant 2013/07559–3; CNPQ 315953/2021–7.

OPR‐088

Real‐world data on continuous deep brain stimulation of the anterior nucleus of the thalamus for drug‐resistant epilepsy, r. morcos 1 ; j. sarto 2 ; m. carreño 2 ; m. centeno 2, 1 neurology department, hospital universitario vithas madrid, spain; 2 neurology department, hospital clinic barcelona, barcelona, spain.

Background and aims: This study aimed to evaluate the efficacy and safety of bilateral deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) in patients with drug‐resistant epilepsy (DRE), focusing on continuous stimulation settings.

Methods: A retrospective review was conducted on eight patients with focal DRE who underwent bilateral ANT‐DBS. Clinical and seizure data were collected, and stimulation parameters were adjusted to maximize clinical benefit. Patients were followed for a mean of 51 months, and changes in seizure frequency were assessed.

Results: Continuous ANT‐DBS demonstrated a significant (>50%) reduction in seizure frequency for all patients, with a mean reduction of 68%. The most severe seizure type showed the greatest response to stimulation. None of the patients achieved seizure freedom, but all experienced a transient post‐implantation seizure‐free period. Psychiatric adverse events were reported in 50% of patients, primarily depression, but they were manageable.

TABLE 1 Summary of results. FAS, focal aware seizure; FIAS, focal impaired awareness seizure, FBTCS, focal to bilateral tonic–clonic seizure.

Image 1 and 2. MRI reconstruction of DBS implantation: 3D (top) and axial planes (bottom).

Conclusion: This study highlights the effectiveness of continuous ANT‐DBS in reducing seizures for patients with DRE who are not candidates for resective surgery. The findings suggest that continuous stimulation may offer a valuable alternative to intermittent settings. The study underscores the importance of precise electrode placement and a network‐focused approach in selecting DBS targets. Overall, ANT‐DBS presents a safe and promising option for improving the quality of life in patients with drug‐resistant epilepsy.

Autonomic nervous system diseases

Opr‐089, abnormal dopamine transporter imaging in pure autonomic failure – a follow‐up study, g. chiaro 1 ; r. alnasser alsukhni 1 ; g. ingle 1 ; k. bhatia 2 ; c. mathias 3 ; j. bomanji 4 ; v. iodice 1, 1 autonomic unit, national hospital for neurology and neurosurgery, london, uk ; 2 department of clinical and movement neurosciences, ucl queen square institute of neurology, university college london, london, uk; 3 ucl queen square institute of neurology, faculty of brain sciences, university college london, london, uk ; 4 institute of nuclear medicine, uclh nhs foundation trust, london, uk.

Background and aims: Abnormal dopaminergic transporter imaging in pure autonomic failure (PAF) is a potential biomarker of central nervous system involvement as described in our pilot study of 10 PAF patients. In this follow‐up study, we evaluated the prevalence of abnormal 123I‐Ioflupane dopamine transporter SPECT (DaTSCAN) in a larger, prospective cohort of patients with PAF and assessed the rate of phenoconversion to more widespread alpha synucleinopathies.

Methods: Consecutive PAF patients underwent a multimodal assessment including cardiovascular autonomic function testing performed with the Finapres NOVA and DaTSCAN, as part of the Queen Square Autonomic Prodromal Project (QSA‐PRODROMAL).

Results: 70 patients with PAF with a median disease duration of 6 (IQR 3–10) years were identified. 22 developed a more widespread synucleinopathy (7 Parkinson's disease, 4 dementia with Lewy bodies, 2 multiple system atrophy‐cerebellar [MSA‐C], 9 multiple system atrophy‐parkinsonian). All phenoconverters had an abnormal DaTSCAN, apart from 2 patients who converted to MSA‐C. In patients who underwent DaTSCAN while still retaining a PAF phenotype, the median lag between imaging and phenoconversion was 8 IQR (4–16) months. 48 patients retained a PAF phenotype at last follow‐up and 4 of them had an abnormal DaTSCAN. These had a clinical REM sleep behaviour disorder. There were no differences in demographics, autonomic function, or plasma catecholamine spillover between PAF patients with normal or an abnormal DaTSCAN.

Conclusion: DaTSCAN is a biomarker of subclinical central nervous system involvement in PAF and can predict phenoconversion to more widespread alpha‐synucleinopathies in patients with a prodromal phase of up to 9 years.

Disclosure: The authors have nothing to disclose.

OPR‐090

The role of plasma norepinephrine level in differential diagnosis of alpha‐synucleinopathies, g. carrozzo 1 ; p. guaraldi 2 ; i. cani 1 ; l. baldelli 1 ; g. giannini 1 ; l. sambati 2 ; g. barletta 1 ; p. cortelli 1 ; g. calandra‐buonaura 1, 1 department of biomedical and neuromotor sciences ( dibinem ), alma mater studiorum, university of bologna, bologna, italy and irccs istituto delle scienze neurologiche di bologna, bologna, italy; 2 irccs istituto delle scienze neurologiche di bologna, bologna, italy.

Background and aims: The alpha‐synucleinopathies, including Parkinson's Disease (PD), Dementia with Lewy Body (DLB), Multiple System Atrophy (MSA) and Pure Autonomic Failure (PAF), differ for specific configurations of abnormal alpha‐synuclein aggregation across the nervous system. The variation in autonomic dysfunction observed in these conditions is attributed to the differing degrees of involvement of Autonomic Nervous System at central or peripheral level or both. This results in different patterns of plasma level of the neurotransmitter norepinephrine (NE), that could help to differentiate alpha‐synucleinopathies.

Methods: We collected blood samples for NE measurement during supine rest (at 20th and 25th min) and at 10th min of the orthostatic phase or at the occurrence of orthostatic intolerance during Head‐Up Tilt Test (HUTT), from 331 subjects (61 controls, 72 PD/DLB; 147 MSA, 51 PAF).

Results: Preliminary results showed a significant higher increment of plasma NE during HUTT in PD/DLB (mean ± SD; 155.9 ± 130.2 pg/mL) compared to MSA (82.9 ± 101.4 pg/mL) in absence of a significant difference in supine NE levels (PD/DLB, 250.3 ± 137.7 pg/mL; MSA, 259.5 ± 160.5 pg/mL). Comparisons with the other groups and cut‐off values evaluation are ongoing.

Conclusion: Our findings suggest that plasma NE patterns could potentially differentiate alpha‐synucleinopathies in the early stages of the diseases, representing a biomarker for differential diagnosis.

OPR‐091

Cardiovascular autonomic signature of hereditary transthyretin amyloidosis, i. cani 1 ; m. gianoli 1 ; g. barletta 2 ; r. rinaldi 2 ; s. longhi 3 ; c. gagliardi 3 ; n. galiè 3 ; p. cortelli 1 ; p. guaraldi 2, 1 department of biomedical and neuromotor sciences ( dibinem ), alma mater studiorum ‐ university of bologna, italy; 2 uoc clinica neurologica rete metropolitana neuromet , irccs istituto delle scienze neurologiche di bologna, bologna, italy; 3 uo cardiologia, irccs policlinico sant' orsola‐malpighi , bologna, italy.

Background and aims: Autonomic dysfunction is a fundamental hallmark in the neurological presentation of hereditary transthyretin amyloidosis (ATTRv). Despite its diagnostic significance, there is a notable lack of instrumental studies examining the cardiovascular autonomic involvement in ATTRv individuals.

Methods: To characterized cardiovascular autonomic functions in a single‐center cohort of subject with ATTRv through standardized cardiovascular reflex tests (CRTs) including head‐up tilt test (HUTT), Valsalva maneuver (VM), deep breathing, cold face test and handgrip test (Finapres Medical System). For comparative analysis, an equivalent number of healthy controls (HC) with similar age and sex distributions were recruited.

Results: The cohort included 65 ATTRv subjects (age 59.77 (14.56), 42% female). During HUTT, ATTRv subjects displayed decreased BP and HR responses compared to HC; with four patients experiencing orthostatic hypotension. All indexes of VM were reduced in ATTRv compared to HC (overshoot: 20 vs. 41 mmHg; phase IIb‐IIa: 6 vs. 15 mmHg; Valsalva ratio: 1.33 vs. 1.75). BP responses to cold face and hand grip tests were also attenuated in ATTRv compared to HC. Additionally, the inspiration/expiration ratio during deep breathing was reduced in ATTRv subjects. Among ATTRv cohort, 23 subjects were asymptomatic with no neurological or cardiological involvement. ATTRv carriers differed from HC, exhibiting significantly lower BP responses during HUTT and reduced overshoot at VM, indicating early autonomic involvement in ATTRv.

Conclusion: This study represents the largest investigation into autonomic cardiovascular regulation in ATTRv. CRT documented cardiovascular autonomic impairment in ATTRv subjects. Additionally, ATTRv carriers displayed early autonomic dysfunction, preceding the onset of neurological and cardiological manifestation. These findings provide crucial insights for earlier diagnosis and timely intervention.

OPR‐092

The catastrophic nature of vasovagal syncope in cardiovascular self‐organized criticality, n. navasiolava 1 ; a. robin 1 ; m. custaud 1 ; j. fortrat 2, 1 univ angers, inserm, cnrs , Équipe carme , sfr icat , angers, france; centre de recherches cliniques, chu angers, france; 2 univ angers, inserm, cnrs , Équipe carme , sfr icat , angers, france; service de médecine vasculaire, chu angers, france.

Background and aims: The recent elucidation of self‐organized criticality dynamics within the cardiovascular system (CV‐SOC) presents a potential explanatory framework for the occurrence of vasovagal syncope. Self‐organized criticality, a universal theory governing natural systems, posits the spontaneous emergence of unexpected large events, termed catastrophes. This study investigates the hypothesis that vasovagal syncope represents a catastrophic manifestation within the CV‐SOC. To test this hypothesis, we conducted assessments of CV‐SOC preceding an orthostatic challenge.

Methods: Thirty‐five healthy volunteers underwent an orthostatic test involving lower body negative pressure (LBNP, −50 mmHg) in the supine position to simulate orthostatic fluid shifts. Tolerance to the test was defined as completion without symptoms or no blood pressure dropping below 80 mmHg. Beat‐by‐beat heart rate was recorded in the supine position for 20 min 2 days before LBNP to determine the slope of the distribution of long bradycardia (aL), a descriptive CV‐SOC index. We compared subjects classified as orthostatic intolerant and tolerant.

Results: Nineteen subjects were intolerant, and 16 were tolerant (10 and 6 female, respectively). Despite similar heart rates between groups (67 ± 2 and 65 ± 2 bpm for intolerant and tolerant, respectively), the aL index significantly differed (0.14 ± 0.01 and 0.18 ± 0.01, T test, p  < 0.01) between tolerant and intolerant subjects.

Fig. Slope of the statistical distribution of bradycardia occurrence (no unit) as index of self‐organized criticality dynamics in healthy subjects non‐tolerant and tolerant to an orthostatic test (T− and T+, respectively). **: p  < 0.01, unpaired T test.

Conclusion: This study not only affirms the self‐organized criticality nature of cardiovascular dynamics but also provides compelling evidence linking vasovagal syncope to this inherent nature. Vasovagal syncope, within this framework, emerges as a catastrophic event within the self‐organized criticality dynamics of the cardiovascular system.

Disclosure: The VIVALDI study was funded by the European Space Agency (ESA), and the French National Center of Space Studies (Centre National d'Études Spatiales, CNES, funding n° 4800001118.

OPR‐093

Intracranial baroreflex: a review, e. schmidt 1 ; n. nasr 2 ; m. kermorgan 3 ; a. pavy le traon 3, 1 neurosurgery , toulouse, france; 2 neurology , poitiers, france; 3 neurology , toulouse, france.

Background and aims: In 2018, two independent teams demonstrated that intracranial pressure (ICP) influences the level of sympathetic activity. A modest physiological increase in ICP leads to an increase in directly recorded sympathetic nerve activity in mice, sheep and humans. This novel regulatory mechanism represents an intracranial baroreflex, bridging ICP and the autonomic nervous system (ANS). Over the last 6 years, data have been published to investigate the role of intracranial baroreflex in physiology and pathology.

Methods: We analysed the literature published on the intracranial baroreflex in the last 6 years to provide an up‐to‐date review and highlight the most important facts.

Results: 1. Astrocytes seem appear to function as intracranial baroreceptors and may play a role in ANS control. 2. Modest ICP increase induced by head‐down tilt increases sympathetic activity. 3. Intracranial baroreflex is attenuated in an ovine model of renovascular hypertension. 4 Acute ICP rise was associated with a significant increase in heart rate variability and baroreflex sensitivity.

Conclusion: The effect of ICP on the ANS and the concept of a physiological intracranial baroreflex are now supported by convergent and independent data. Intracranial and extracranial (i.e. arterial) baroreflexes behave in opposition, with excitatory and inhibitory effects on the sympathetic activity, respectively. We propose an integrated physiological scheme of ABP regulation, including intracranial and extracranial baroreflexes, which may be involved in the fine‐tuning of ABP. However, the exact role of the intracranial baroreflex in the pathophysiology of sympathetic overactivity and hypertension requires further investigation.

Intracranial baroreflex in ABP regulation.

Disclosure: no.

OPR‐094

Cutaneous phosphorylated‐synuclein: an early diagnostic biomarker for pure autonomic failure, s. koay 1 ; v. provitera 2 ; g. caporaso 2 ; e. vichayanrat 1 ; f. valerio 1 ; s. johnstone 1 ; m. lunn 3 ; m. nolano 4 ; v. iodice 1, 1 autonomic unit, the national hospital for neurology and neurosurgery, queen square, london, uk ; 2 neurology department, skin biopsy laboratory, istituti clinici scientifici maugeri irccs , telese terme, italy; 3 queen square centre of neuromuscular diseases, ucl queen square institute of neurology, london, uk ; 4 department of neurosciences, reproductive sciences and odontostomatology, university federico ii of naples, naples, italy.

Background and aims: Pure autonomic failure (PAF) is a predominantly peripheral alpha‐synucleinopathy, presenting with progressive autonomic failure in the absence of other neurological features. Atypical presentations may lead to diagnostic uncertainty. We studied whether cutaneous phosphorylated‐synuclein (p‐syn) could distinguish between PAF, multiple system atrophy (MSA), and non‐synucleinopathy related autonomic failure, and its correlation with quantitative markers of autonomic failure.

Methods: Patients underwent autonomic questionnaires, cardiovascular autonomic testing (Finapres) and bilateral distal leg skin biopsies. We noted whether p‐syn was present in nerves supplying autonomic adnexa, including sweat glands, blood vessels, arrector pili muscles, and subepidermal fibres, dermal fibres and nerve fascicles (maximum autonomic subscore 3 and total p‐syn score 6 for each sample, average calculated for both sides).

FIGURE 1 Summary of structures used for calculating autonomic p‐syn subscore (3 structures in top panel) and total p‐syn score (all 6 structures). Figure adapted from Nolano 2022, with permission from IOS Press.

Results: Thirty‐six individuals were studied (11 PAF, 13 MSA, 12 non‐synucleinopathy related autonomic failure). P‐syn was present in 22/22 (100%) PAF biopsies, 19/26 (73%) MSA biopsies, and 0/22 (0%) non‐synucleinopathy biopsies. Total p‐syn score was significantly higher in PAF (median 4.5) compared to MSA (median 1, p  < 0.001). Autonomic p‐syn subscore correlated with quantitative markers of autonomic failure related to impaired control of total peripheral resistance, including orthostatic intolerance ratio on tilt (rho = 0.63; p  = 0.0004) and blood pressure recovery time following Valsalva manoeuvre (rho = 0.44; p  = 0.03), as well as patient‐reported orthostatic intolerance (rho = 0.57; p  = 0.006).

FIGURE 2 Confocal images of cutaneous p‐syn deposits from a patient with PAF. P‐syn is seen to co‐localise along nerve fibres, marked with PGP (protein G peptide), running within dermal nerve bundles.

FIGURE 3 Cutaneous autonomic p‐syn score correlated with orthostatic intolerance ratio on tilt (change in systolic blood pressure in mmHg divided by time tolerated on tilt in minutes, to a maximum of 10 min).

Conclusion: Cutaneous p‐syn was abundant in PAF and represents a promising early diagnostic biomarker to help distinguish between predominantly peripheral and central alpha‐synucleinopathies, and non‐synucleinopathy related autonomic failure. P‐syn deposition on autonomic nerves may impair control of total peripheral resistance giving rise to symptomatic orthostatic hypotension.

Disclosure: This study was supported by the Italian Ministry of Health “Ricerca Finalizzata 2013” – project code PE‐2013‐02359028. SK was supported by the Guarantors of Brain Entry Fellowship. MPL and VI are supported by NIHR UCL Biomedical Research Centre.

Neuroimmunology 2

Opr‐095, diagnostic and prognostic biomarkers in immune checkpoint inhibitor‐related encephalitis, a. farina 1 ; m. villagrán‐garcía 1 ; a. fourier 2 ; a. pinto 1 ; n. timestit 1 ; t. alberto 3 ; j. aupy 4 ; m. benaiteau 1 ; c. birzu 5 ; l. campetella 1 ; s. dalle 6 ; c. fontaine delaruelle 6 ; d. maillet 6 ; a. pegat 7 ; d. psimaraas 5 ; m. rafiq 8 ; g. picard 1 ; v. desestret 1 ; i. quadrio 2 ; j. honnorat 1 ; b. joubert 1, 1 french reference center on paraneoplastic neurological syndromes and autoimmune encephalitis, hospices civils de lyon, hôpital neurologique, bron; umr melis team synatac , inserm1314 / cnrs5284 , lyon, france; 2 lyon neuroscience research center, hcl , lyon, france; 3 centre hospitalier de lille, lille, france; 4 centre hospitalier de bordeaux, bordeaux, france; 5 hospital group pitié‐salpêtrière , paris, france; 6 immucare , lyon, france; 7 service enmg et pathologies neuromusculaires, hcl , lyon, france; 8 centre hospitalier de toulouse.

Background and aims: Diagnostic and prognostic biomarkers are lacking in immune checkpoint inhibitors (ICI)‐related encephalitis. We aimed to characterize the clinical features of ICI encephalitis patients, and identify diagnostic biomarkers and outcome predictors.

Methods: This retrospective study included all patients with possible or definite ICI‐encephalitis whose samples and clinical data were studied in the Lyon Neurological Hospital (2015–2023). Response to treatment was defined as CTCAE (v5.0) grade <3. S‐100 calcium‐binding protein, neurofilament light chain (NfL) and glial fibrillary acidic protein levels were measured in 27 definite ICI‐encephalitis patients and 16 controls.

Results: Seventy‐six patients were identified, including 67 (88%) with definite ICI‐encephalitis (median age, 67 years, 66% male). A focal syndrome was observed in 43/67 patients (64%; limbic encephalitis, rapidly‐progressive cerebellar ataxia, and/or brainstem encephalitis), while 24 (36%) had meningoencephalitis, a non‐focal syndrome with frequent altered mental status (92%) and pleocytosis (100%). Meningoencephalitis patients had less frequent abnormal brain MRI findings (33% vs. 62%, p  = 0.025), PNS‐related antibodies (4% versus 84%, p  < 0.001), and neuroendocrine cancers (4% versus 49%; p  < 0.001) than focal encephalitis patients. Serum NfL > 273.5 pg/mL discriminated definite ICI‐encephalitis patients from controls with sensitivity of 88% and specificity of 81%. Focal ICI‐encephalitis patients responded less to treatment (15%) than ICI‐meningoencephalitis patients (72%, p  < 0.001), and PNS‐related antibodies were negatively associated with treatment response (adjusted OR 0.05; 95% CI [0.01; 0.21]). Thirty‐two patients (48%) died during the study period (median 7 months of follow‐up).

Conclusion: Analysis of serum NfL facilitates the diagnosis of ICI‐encephalitis, and focal encephalitis and PNS‐related antibodies are associated with worse treatment response.

OPR‐096

Outcome and risk of relapse in gabaar encephalitis, c. papi 1 ; c. milano 2 ; t. iizuka 3 ; m. simabukuro 4 ; l. marmolejo 5 ; e. aguilar 5 ; r. iorio 6 ; t. armangué 7 ; f. graus 5 ; j. dalmau 5 ; m. spatola 5, 1 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain; department of neuroscience, catholic university of the sacred heart, rome, italy; 2 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain; department of clinical and experimental medicine, university of pisa, pisa, italy; 3 department of neurology, kitasato university school of medicine, japan; 4 division of neurology, hospital das clinicas ( hcfmusp ), faculdade de medicina, universidade de sao paulo, são paulo, brazil; 5 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain; 6 department of neuroscience, catholic university of the sacred heart, rome, italy; 7 institut d'investigacions biomèdiques august pi i sunyer, barcelona, spain; pediatric neuroimmunology unit, neurology service, sant joan de déu ( sjd ) children's hospital, university of barcelona, barcelona, spain.

Background and aims: Autoimmune encephalitis with antibodies against γ‐aminobutyric acid type A receptor (GABAAR) is characterized by prominent seizures and multifocal brain lesions. Limited data are available on relapse risk and long‐term outcome. The study aim was to report clinical course and outcome of patients with GABAAR encephalitis.

Methods: Clinical information was obtained retrospectively from medical records. Patients were included if GABAAR antibodies were identified by 2 techniques (rat brain tissue and live cell‐based assays) in serum or cerebrospinal fluid.

Results: Nineteen patients with GABAAR encephalitis were included, 3 (16%) children and 16 (84%) adults. At onset, 17 (89%) patients developed seizures, evolving to status epilepticus in 12 (63%), alone or accompanied by other neurological symptoms, most commonly cognitive disturbances (74%). Tumor (mainly thymoma) was found in 11 (58%) patients. Brain MRI showed cortico‐subcortical T2/FLAIR abnormalities in 15 (79%) patients and isolated cerebellar lesions in 2 (11%). Immunotherapy resulted in clinical improvement in 14/16 (88%) patients. Nine (47%) patients had clinical relapses (median 1, range 1–3 relapses), manifesting with seizures in 7 (78%). Older age was associated with clinical relapses ( p  = 0.0206). After a median follow‐up of 19 months (range 1–59), 4 (21%) patients were dead, 6 (32%) completely recovered, and 9 (47%) partially recovered. Cognitive disturbances were the most frequent neurological sequelae (5/9, 56%). Overall, 10/11 (91%) patients were seizure‐free at last follow‐up, 9/10 (90%) on antiseizure medications.

Conclusion: In GABAAR encephalitis, relapses are not rare, often manifesting with seizure recurrence. Half of the patients are left with residual neurological deficits, mainly cognitive disturbances.

Disclosure: C. Papi receives support from European Academy of Neurology; M. Spatola receives research support from La Caixa Foundation and Spanish National Research Institute (Carlos III).

OPR‐097

Ataxia and movement disorders in autoimmune encephalitis and paraneoplastic neurological syndromes, j. kerstens 1 ; y. crijnen 1 ; j. brenner 1 ; r. van steenhoven 1 ; m. de bruijn 1 ; a. van sonderen 1 ; m. van coevorden‐hameete 1 ; d. bastiaansen 1 ; m. vermeiren 1 ; j. de vries 1 ; s. veenbergen 2 ; p. sillevis smitt 1 ; m. titulaer 1, 1 department of neurology, erasmus mc university medical centre, rotterdam, the netherlands; 2 department of immunology, erasmus mc , university medical centre rotterdam, rotterdam, the netherlands.

Background and aims: Movement disorders (MD) are well‐recognized symptoms of autoimmune encephalitis (AIE) and paraneoplastic neurological syndromes (PNS). Although a large variety of MD has been described in different antibody‐associated syndromes, the frequency of MD remains unknown for most antibodies. This knowledge is important to aid in early diagnosis and develop rational antibody testing strategies.

Methods: We reviewed a large cohort of all known Dutch patients with antibody‐associated AIE/PNS ( n  = 927) to describe associated movement disorders (MD) and (cerebellar) ataxia. The most common antibodies were LGI1 ( n  = 182, 19.6%), NMDAR ( n  = 166, 17.9%), high‐titer GAD65 ( n  = 122, 13.2%) and Hu ( n  = 114, 12.3%). Sensory ataxia and faciobrachiodystonic seizures were not considered MD.

Results: MD were present in 337/901 (37.4%) and were the first and/or predominant symptom in 193/297 (65.0%) and 214/297 (72.1%), respectively. Ataxia was by far the most common ( n  = 159, mainly Yo and GAD65), followed by stiff‐person syndrome ( n  = 50, mainly GAD65 and GlyR) and chorea ( n  = 35, mainly NMDAR, IgLON5 and CV2). AIE/PNS associated with antibodies against Yo and Tr presented (almost) exclusively with MD (more specifically ataxia, in 29/30 and 4/4, respectively), while the lowest MD frequency was observed with GABAbR (7/59, 11.9%) and LGI1 (5/182, 2.7%).

Conclusion: MD are common in AIE and PNS, occurring in over a third of the patients. Their frequency varies greatly between subtypes. MD can be the first, predominant and even the only manifestation of these disorders. AIE and PNS should be in the differential diagnosis of new‐onset MD, especially in the case of cerebellar ataxia and chorea.

Disclosure: JK was supported by a Research Mobility Fellowship from the European Joint Programme on Rare Diseases (EJP RD) and is currently funded by the Erasmus Trustfonds. YC and MdB were funded by EpilepsieNL (NEF 14–19 & 19–08), JB was funded by Dioraphte (2001 0403). DB was funded by ZonMW (Memorabel initiative). RvS was funded by ZonMW (VIMP scheme). PSS holds a patent for the detection of anti‐DNER and received research support from Euroimmun. MT has filed a patent, on behalf of the Erasmus MC, for methods for typing neurological disorders and cancer, and devices for use therein, and has received research funds for serving on a scientific advisory board of Horizon Therapeutics, for consultation at Guidepoint Global LLC, and for consultation at UCB. MT has received an unrestricted research grant from Euroimmun AG, and from CSL Behring. The other authors have nothing to disclose.

OPR‐098

Demographic and hla ‐related specificities in lgi1 ‐antibody encephalitis, l. campetella 1 ; m. villagrán‐garcía 1 ; a. farina 1 ; m. villard 1 ; m. benaiteau 1 ; n. timestit 2 ; g. picard 1 ; v. rogemond 1 ; b. joubert 1 ; j. honnorat 1 ; s. muñiz‐castrillo 3, 1 french reference center for paraneoplastic neurological syndromes and autoimmune encephalitis, hospices civils de lyon, lyon, france and melis – ucbl‐cnrs umr 5284 – inserm u1314 , université claude bernard lyon 1, lyon, france; 2 department of biostatistics, hospices civils de lyon, lyon, france; 3 stanford center for sleep sciences and medicine, stanford university, palo alto, ca , usa.

Background and aims: Patients with autoimmune encephalitis with leucine‐rich glioma‐inactivated 1 (LGI1) antibodies typically are older men and very often carry HLA‐DRB1*07:01. Herein, we aimed to investigate clinical and prognostic features according to patients age, sex, and HLA carrier status.

Methods: Retrospective chart review of 224 patients with isolated LGI1‐antibody positivity in serum and/or cerebrospinal fluid registered at the French Reference Center database. After computing percentiles of age distribution, patients were divided into three age subgroups: old, ≥79 years; typical, 52–78 years; young, ≤51 years. Poor outcome was defined as modified Rankin scale (mRS) >2.

Results: Among 224 patients, 148 (66%) were male, and 179 (80%) belonged to the typical age subgroup. In three‐way comparisons, female sex ( p  = 0.003) and temporal lobe seizures ( p  < 0.001) were more common in the younger subgroup ( n  = 20, 9%), while older patients ( n  = 25, 11%) presented more frequently facio‐brachial dystonic seizures ( p  = 0.034) and had higher mRS both at nadir ( p  < 0.001) and last follow‐up ( p  = 0.001). Non‐DRB1*07:01 carriers ( n  = 19/161, 12%) were more frequently female ( p  = 0.044, Figure 1) and had poorer outcome ( p  = 0.021). In a multivariate analysis, older age (odds ratio [OR]:1.12, 95% confidence interval [CI]: [1.05; 1.19]; p  = 0.001), female sex (OR: 3.4, 95% CI [1.07; 10.87]; p  = 0.039), and higher mRS at nadir (OR: 5.43, 95% CI [2.86; 10.3]; p  < 0.001) were independently associated with poor outcome, while carrying DRB1*07:01 was protective (OR: 0.04, 95% CI [0.007; 0.22]; p  < 0.001).

Population pyramid of the 161 patients with available HLA‐DRB1*07:01 carrier status.

Conclusion: Clinical manifestations differ among age subgroups, whereas poor outcome is associated with certain demographic (older age and female sex) and genetic (non‐DRB1*07:01 carrier status) features.

Disclosure: Macarena Villagrán‐Garcia is supported by a research grant from Fundación Alfonso Martín Escudero (Spain).

OPR‐099

Predictors of annualized attack rates in aqp4‐igg + nmosd patients treated with rituximab or classical immunosuppression, d. engels 1 ; m. herfurth 2 ; j. havla 1 ; p. schindler 3 ; c. schwake 4 ; m. ringelstein 5 ; k. fischer 5 ; m. hümmert 7 ; k. giglhuber 8 ; i. vardakas 10 ; m. grothe 11 ; t. etgen 12 ; c. warnke 13 ; j. naumann 14 ; f. hoffmann 15 ; m. senel 10 ; b. wildemann 9 ; a. berthele 8 ; c. trebst 7 ; v. häußler 6 ; o. aktas 5 ; i. ayzenberg 4 ; j. bellmann‐strobl 3 ; f. then bergh 2 ; t. kümpfel 1, 1 institute of clinical neuroimmunology, lmu hospital, ludwig‐maximilians university munich, munich, germany; 2 department of neurology, university of leipzig, leipzig, germany; 3 neuroscience clinical research center, charité ‐ universitätsmedizin berlin, berlin, germany; 4 department of neurology, st. josef hospital, ruhr university bochum, bochum, germany; 5 department of neurology, medical faculty, heinrich heine university düsseldorf, düsseldorf, germany; 6 department of neurology and institute of neuroimmunology and ms ( inims ), university medical center hamburg ‐eppendorf, hamburg, germany; 7 department of neurology, hannover medical school, hannover, germany; 8 department of neurology, school of medicine, technical university munich, klinikum rechts der isar, munich, germany; 9 molecular neuroimmunology group, department of neurology, university of heidelberg, heidelberg, germany; 10 department of neurology, university of ulm, ulm, germany; 11 department of neurology, university of greifswald, greifswald, germany; 12 department of neurology, kliniken südostbayern‐klinikum traunstein, germany; 13 department of neurology, university of cologne, faculty of medicine and university hospital cologne, cologne, germany; 14 department of neurology, knappschaftsklinikum sulzbach, sulzbach, germany; 15 department of neurology, martha‐maria hospital halle‐dölau , 06120 halle (saale), germany.

Background and aims: Aquaporin‐4‐IgG‐positive neuromyelitis optica spectrum disorder (AQP4‐IgG+ NMOSD) primarily manifests with attacks of optic neuritis or myelitis. Immunosuppression can prevent attacks but may be associated with risks, e.g. infections. We compared the efficacy and risk of rituximab and classical immunosuppressive agents in AQP4‐IgG+ NMOSD patients.

Methods: We compared annualized attack rates (AAR), infection rates (IR, infections per time) and laboratory parameters during rituximab (RIX), azathioprine (AZA), mycophenolate mofetil (MMF) and methotrexate (MTX) treatment cycles in a multicentric, retrospective cohort from the German Neuromyelitis Optica Study Group (NEMOS) registry.

Results: We analyzed 570 treatment episodes in 251 patients. Mean AAR during RIX treatment episodes was significantly lower than with AZA (0.24 vs. 0.61, p  < 0.001, Mann–Whitney U). The IR did not differ between RIX ( N  = 238) and all other treatment episodes ( N  = 332, 0.38 versus 0.44, p  = 0.81, Mann–Whitney U ). We identified the IR, leukocyte count and IgM serum concentration as predictors for (higher) AAR. Time from diagnosis to treatment and sex showed no effect. During rituximab treatment episodes, higher neutrophil and B cell counts, and higher IgM serum concentration were associated with higher AAR.

Conclusion: Rituximab is associated with lower AAR, but not with higher infection rates than classical immunosuppressives. Whether the IR constitutes a risk factor for attacks needs to be evaluated prospectively.

Disclosure: Daniel Engels received speaker honoraria from Alexion and Horizon. Joachim Havla reports a grant for OCT research from the Friedrich‐Baur‐Stiftung and Merck, personal fees and nonfinancial support from Merck, Alexion, Novartis, Roche, Celgene, Biogen, Bayer and Horizon and nonfinancial support of the Sumaira‐Foundation and Guthy‐Jackson Charitable Foundation, all outside the submitted work. Achim Berthele receives funding from the Innovationsausschuss of the German Federal Joint Committee (G‐BA; grant 01VSF23040) and from the German Federal Ministry of Education and Research (BMBF; grant 01ZZ2102B). He has received consulting and/or speaker fees from Alexion, Argenx, Biogen, Horizon, Merck, Novartis, Roche and Sandoz/Hexal, and his institution has received compensation for clinical trials from Alexion, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme; all outside the present work. Martin W. Hümmert received research support from Myelitis e. V., speaker honoraria from selpers og, Horizon and Alexion, and reimbursement of travel expenses and compensation for serving on an advisory board from Alexion. Tania Kümpfel has received speaker honoraria and/or personal fees for advisory boards from Novartis Pharma, Roche Pharma, Alexion/AstraZeneca and Biogen. All other authors have nothing to disclose in relation to this project.

Sleep–wake disorders

Opr‐100, topography of nrem oscillations is associated with circadian preference and rhythmicity, i. filchenko 1 ; a. eberhard‐moscicka 2 ; c. gutierrez herrera 3 ; s. bauer‐gambelli 1 ; s. duss 1 ; c. cajochen 4 ; c. bernasconi 1 ; m. schmidt 1 ; c. bassetti 1, 1 department of neurology, university hospital, inselspital, bern, switzerland; 2 department of psychology, university of bern, bern, switzerland; 3 department of biomedical research ( dbmr ), inselspital university hospital bern, university of bern, bern, switzerland; 4 centre for chronobiology, university psychiatric clinic basel, basel, switzerland.

Background and aims: Homeostatic and circadian processes play a pivotal role in sleep regulation. However, little is known about the association of NREM oscillations with circadian rhythm characteristics accessed within clinical routine. This exploratory analysis aimed to comprehensively address this link.

Methods: This analysis is based on the pooled data from two observational studies and includes volunteers in good or excellent health condition (Eastern Cooperative Oncology Group grade of 0–1). Clinical history, circadian parameters (i.e., Morningness‐Eveningness Questionnaire and actigraphy) and NREM sleep architecture (i.e., sleep spindle [SS] and slow wave [SW] density and morphology according to 256‐electride electroencephalography) were assessed at study inclusion (Figure 1A). Association between NREM architecture as dependent variables and circadian parameters as independent variables were explored using multiple linear regression with adjustments for age and arousal index.

Results: Data of 71 participants was analyzed (age: median 29.0 interquartile range (IRQ) [23.0, 35.5] years old; 52% women; Figure 1B). SS were prevalently associated with circadian parameters (Figure 2; e.g., high SS density in posterior and pre‐frontal regions vs. late L5 hour), whereas only limited associations between SW and circadian parameters were identified (Figure 3; e.g., high frontal SW amplitude vs. late M10 hours).

Selected associations between circadian parameters and sleep spindles.

Selected associations between circadian parameters and slow waves.

Conclusion: Circadian rhythm is associated with NREM oscillations in a domain‐ and topography‐specific manner, with evening preference being linked to favourable electroencephalographic markers. This knowledge may serve as a basis for targeted interventions for sleep–wake disorders.

Disclosure: European Stroke Research foundation 2021 and Interfaculty Research Cooperation grant of the University of Bern “Decoding sleep”.

OPR‐101

The impact of physical exercise and ketogenic diet on narcolepsy: a randomized, controlled trial, f. tepel 1 ; h. cintosun 1 ; d. borth 1 ; g. lammers 2 ; u. kallweit 3, 1 centre for narcolepsy and hypersomnia, clinical sleep and neuroimmunology, institute of immunology, university witten/herdecke, germany; 2 leiden university medical centre, department of neurology, leiden, the netherlands, and sleep wake centre sein , heemstede, the netherlands; 3 center for narcolepsy and hypersomnias, clinical sleep and neuroimmunology, institute of immunology, university witten/herdecke, germany and orfea sleep clinic, witten, germany.

Background and aims: Narcolepsy treatment involves pharmacological and non‐pharmacological therapies. This trial aimed to evaluate the efficacy of two specific non‐pharmacological treatments for narcoleptics: regular physical activity and ketogenic diet, respectively.

Methods: In a 10‐week trial on adults with type 1 narcolepsy (NT1), three groups were studied: regular physical activity, ketogenic diet, and control. Assessment included clinical data, treatments, Power Walking Test, and pre/post questionnaires. The sport group adhered to a training plan, keto group followed a high‐fat, low‐carb diet, and controls maintained routine. Questionnaires covered sleep, life quality, well‐being, fatigue, recovery, and stress.

Results: In total, 60 patients (41 female, mean age: 34 years) with NT1 were randomized; 44 completed the study. ESS improved from 13.9 to 11 points ( p  < 0.009) in the sports group, and 16.3 to 13.2 points ( p  < 0.005) in the keto group. For controls, no significant change was found. PSQI improved from 9.3 to 6.6 points ( p  < 0.005) in the sports group only. Quality of life measures (WHO‐5) improved from 12.3 to 15.8 points ( p  < 0.027) in the sports groups, and from 9.3 to 13.4 points ( p  < 0.013) in the keto group. Stress levels were reduced from 13.6 to 10.3 ( p  < 0.007) in the sports group.

Conclusion: Regular physical training or a ketogenic diet effectively reduce daytime sleepiness in narcolepsy. Quality of quality, well‐being, and physical aspects of life quality are also improved by regular physical training in particular. These treatments offer a convenient, cost‐effective, and efficient therapeutic option alongside pharmacological measures.

Disclosure: No disclosures.

OPR‐102

Widespread white matter axonal loss in narcolepsy type 1, j. gool 1 ; a. de brouwer 1 ; l. shan 2 ; j. bol 3 ; a. hoogendoorn 4 ; y. van der werf 3 ; g. lammers 1 ; l. jonkman 3 ; r. fronczek 5 ; g. schenk 3, 1 stichting epilepsie instellingen nederland ( sein ), sleep–wake centre, heemstede, the netherlands; 2 department neuropsychiatric disorders, netherlands institute for neuroscience, an institute of the royal netherlands academy of arts and sciences, amsterdam, the netherlands; 3 anatomy &neurosciences, amsterdam umc location vrije universiteit amsterdam, amsterdam, the netherlands; 4 department of psychiatry, amsterdam umc location vrije universiteit amsterdam, amsterdam, the netherlands; 5 department of neurology, leiden university medical centre, leiden, the netherlands.

Background and aims: Narcolepsy type 1 (NT1) is a debilitating neurological disorder marked by hypocretin deficiency (or orexin), causing excessive daytime sleepiness and cataplexy. Brain imaging studies have suggested global white matter irregularities in NT1, with unknown underlying histopathological correlates. Consistent with expected hypocretin projection patterns, the cerebellum was least affected. In a globally unique sample of human NT1 postmortem brain tissue, we assessed axonal and myelin integrity through immunohistochemical microscopy.

Methods: Postmortem brain sections from four NT1 donors and 10 controls were assessed for axonal density, axonal injury and myelin integrity. Regions of interest included subregions of the midbrain, corpus callosum, cortical regions (anterior cingulate and occipital cortex), and the cerebellum as a control region (Figure 1). Manual axon count and staining intensity assessed axonal density. Area percentage immunoreactivity of phosphorylated neurofilament chains evaluated axonal injury. Myelin integrity was assessed using staining intensity analyses.

FIGURE 1 The regions of interest: (A) reticular formation and pyramidal tract, (B) proximal and distal corpus callosum, anterior cingulate gyrus and cingulate sulcus, (C) primary and secondary visual cortices, (D) cerebellum. Scale bar is 2 mm.

Results: Significantly reduced axonal density was observed in NT1 compared to controls in the reticular formation, pyramidal tract, corpus callosum and anterior cingulate gyrus (Figure 2). No significantly different axonal density was seen in the cerebellum nor in the axonal staining colour intensity, axonal injury and myelin integrity measures, except for lower secondary visual cortex myelin density in NT1.

FIGURE 2 Axon counting results: (A–C) reticular formation (RF) and pyramidal tract (P), (D–F) proximal corpus callosum (P‐CC), anterior cingulate gyrus (ACC), (G, H) cerebellum (CB). Scale bar is 2 mm for A, D, G and 100 μm for B, C, E, F, H.

Conclusion: In NT1, there is widespread lower axonal density within and outside the ascending reticular activating system. These results align with prior in‐vivo brain imaging reports and typical hypocretin projection patterns, and may contribute to the pathophysiology of NT1, possibly stemming from hypocretin deficiency and/or chronic sleep–wake alterations.

OPR‐103

Sleep‐related hypermotor epilepsy vs. disorders of arousal: diagnostic interobserver reliability of homemade videos, l. vignatelli 1 ; l. licchetta 1 ; g. maineri 1 ; g. loddo 1 ; f. baccari 1 ; g. bruschi 2 ; l. taruffi 2 ; l. nobili 3 ; p. tinuper 2 ; f. provini 1 ; f. bisulli 1 ; on behalf of she‐doa study group 1, 1 irccs istituto delle scienze neurologiche di bologna, bologna, italy; 2 department of biomedical and neuromotor sciences, university of bologna, bologna, italy; 3 child neuropsychiatry, irccs , g. gaslini institute, department of neuroscience ( dinogmi ), university of genoa, genoa, italy.

Background and aims: Video‐polysomnography is the reference standard for diagnosing Sleep‐related Hypermotor Epilepsy (SHE)1. However, it entails high hospitalization costs and it is not exempt from the possibility of failing to capture rare events. Homevideo recording (HVR) can help the diagnosis of SHE2 but its diagnostic value remains uncertain. This study aims to assess the reliability of HVR in distinguishing between SHE and NREM Disorders of arousal (DOA) among neurologists with different clinical expertise.

Methods: We selected HVRs (performed by caregivers in real‐world setting) capturing 20 typical sleep‐related events from 10 patients with SHE and 10 with DOA. Thirteen experts and 20 general neurologists were invited to classified each HVR as “SHE”, “DOA” or “unknown”, based on seizure semiology. The experts was then asked to discuss each case, providing agreed key semeiological features for diagnosis. Baseline interobserver reliability (IR) among raters, and among general neurologists before and after experts' discussion, was calculated using Kappa statistics.

Results: The global raw agreement was 74.9% (“moderate” IR, Kappa 0.54). Agreement among experts was 75.3% (“moderate” IR, Kappa 0.55). Among general neurologists agreement improved from 74.5% at baseline to 83.8% after training, corresponding to IR “moderate” (Kappa 0.54) and “substantial” (Kappa 0.69), respectively.

Conclusion: Baseline reliability of HVR for diagnosing SHE versus DOA was found globally moderate. Educational training, focused on behavior patterns, enhanced agreement among non‐expert neurologists. These data highlight HVR as a reliable diagnostic tool in most cases for differentiating SHE from other paroxysmal non‐epileptic manifestations, thereby reducing health care costs and disparities.

OPR‐104

Cerebrospinal‐fluid orexin levels: a possible biomarker for early identification of neurodegenerative disorders, s. maio 1 ; s. lozano tovar 2 ; r. cremascoli 3 ; m. nuccetelli 4 ; g. sancesario 5 ; s. cattaldo 6 ; e. prina 7 ; f. verde 8 ; s. cappelli 9 ; s. bernardini 4 ; n. mercuri 5 ; c. liguori 1, 1 sleep medicine center, neurology unit, university hospital of rome “tor vergata”, rome, italy; 2 facultad de psicología, universidad nacional autónoma de méxico ( unam ), circuito ciudad universitaria avenida, c.u., mexico city, mexico; 3 irccs , istituto auxologico italiano, unit of neurology and neurorehabilitation, san giuseppe hospital, verbania, italy.; 4 department of clinical biochemistry and molecular biology, university of rome “tor vergata”, rome, italy; 5 department of systems medicine, university of rome “tor vergata”, rome, italy; 6 irccs , istituto auxologico italiano, laboratory of clinical neurobiology, san giuseppe hospital, verbania, italy; 7 irccs , istituto auxologico italiano, department of neurology and laboratory of neuroscience, milan, italy; 8 department of pathophysiology and transplantation, “dino ferrari” center, università degli studi di milano, milan, italy; 9 irccs , istituto auxologico italiano, laboratory of psychology, san giuseppe hospital, verbania, italy.

Background and aims: Orexin system mainly regulates sleep–wake cycle, but there is also growing evidence of its impairment in neurodegenerative diseases(NDs). In this study, we investigated cerebrospinal‐fluid(CSF) orexin levels in patients with different NDs compared to non‐demented controls. We included patients with mild or moderate–severe Alzheimer's disease(mAD, msAD), behavioral variant of Frontotemporal Dementia(bv‐FTLD), non‐fluent primary aphasia(NFPA) and idiopathic normal pressure hydrocephalus(iNPH).

Methods: Patients and controls underwent between 2012 and 2015 a neurological assessment and a lumbar puncture for CSF biomarker analysis. We evaluated 76 AD(mAD = 45, msAD = 31), 34 FTLD(bv‐FTLD = 12, NFPA = 22), 13 iNPH patients and 91 controls. CSF orexin levels were also correlated with β‐amyloid42(Aβ42), total‐tau(t‐tau), phosphorylated‐tau(p‐tau) and clinical data.

Results: CSF concentrations of Aβ42, t‐tau, p‐tau and orexin were significantly different comparing all groups ( p  < 0.001). The highest CSF orexin levels were found in the iNPH (263.31 ± 56.89). NFPA (210.86 ± 61.99) and msAD (173.04 ± 19.76) showed higher CSF orexin concentrations compared to controls (145.18 ± 27.01) ( p  < 0.001). CSF orexin levels were similar between Bv‐FTLD (190.12 ± 100.84), mAD (130.76 ± 21.70) patients and controls. Considering the correlation analysis, only in the controls the CSF levels of Aβ42 and t‐tau correlated with orexin ( p  = 0.014; p  < 0.001). Only in the mAD and msAD groups, Mini Mental State Examination scores correlated with CSF orexin levels ( r  = −0.54; p  < 0.001; r  = −0.92; p  < 0.001; respectively).

Conclusion: This study documented significant differences in CSF orexin levels in NDs patients, with the highest levels in iNPH. Our findings highlight the possibility to add orexin to the CSF biomarker panel for the early identification of NDs causing cognitive impairment and dementia.

OPR‐105

Burden of illness study among patients with central disorders of hypersomnolence in france, germany and italy, y. dauvilliers 1 ; g. plazzi 2 ; u. kallweit 3 ; s. crawford 4 ; l. jönsson 5 ; g. kobelt 6, 1 sleep‐wake disorders center, department of neurology, gui‐de‐chauliac hospital, university of montpelier, montpellier, france; 2 irccs istituto delle scienze neurologiche di bologna, bologna, italy; department of biomedical, metabolic and neural sciences, university of modena and reggio emilia, modena, italy; 3 center for narcolepsy and hypersomnias, professorship for narcolepsy and hypersomnolence research, department of medicine, witten/herdecke university, witten, germany; 4 takeda development center americas, inc., cambridge, ma , usa ; 5 karolinska institutet, solna, sweden; 6 ehe international gmbh , st moritz, switzerland.

Background and aims: Narcolepsy type 1 (NT1) and 2 (NT2) and idiopathic hypersomnia (IH), are rare, chronic neurological disorders with a high disease burden; however, no studies have attempted to establish the relationship between patient burden and disease severity.

Methods: This cross‐sectional, observational, anonymous online/email survey assessed patient burden for participants with NT1, NT2, and IH. Questions included demographics, work‐force participation, disease symptoms, daily activities, coping strategies, resource consumption, and quality of life (QoL: EQ‐5D‐5L). Disease severity was assessed with a visual analog scale (VAS; range 0–10) and three validated instruments (Epworth Sleepiness Scale [ESS], Narcolepsy Severity Scale [NSS‐CT], and Idiopathic Hypersomnia Severity Scale [IHSS]). Participants were recruited via clinical sites, patient associations, and registries across Europe.

Results: This interim analysis included 487 participants with complete disease severity data from the first three countries reaching enrolment targets. Mean (range) age was 37 (18–89) years. Mean (range) ESS scores were above normal for NT1/NT2 (15.0 [0–24]) and IH (13.2 [0–22]); self‐reported disease severity ranged from 6.2 to 6.9 (VAS). Mean (range) NSS‐CT scores were higher (greater severity) for NT1 (20.1 [0–47]) and NT2 (15.2 [1–34]) vs. IH (13.1 [0–40]); IHSS scores were higher (greater severity) for IH (32.4 [5–48]) vs. NT1 (27.0 [4–49]) or NT2 (28.7 [8–44]). Excessive sleepiness and daily naps were reported by 71% and 73%. 82% of participants were treated. Among 66% working participants, 70% reported disease affecting their work negatively. QoL was inversely related to disease severity.

Conclusion: These results illustrate the effect of narcolepsy/IH disease severity on patient‐reported quality of life.

Disclosure: YD: Received funds for seminars, board engagements and travel to congresses from Avadel, Bioprojet, Idorsia, Jazz, Orexia, and Takeda GP: Received honoraria for board engagements from Bioprojet, Idorsia, Jazz, Orexia, and Takeda. UK: Honoraria for board engagements and scientific lectures from Bioprojet, Jazz and Takeda. SC: Employee of Takeda Development Center Americas, Inc., and stockholder of Takeda Pharmaceutical Company Ltd LJ: Consultant to EHE GmbH GK: President of EHE GmbH and project manager of this study on behalf of Takeda.

Neuroimaging in neurodegeneration

Opr‐106, motor reserve impact on nigrostriatal vulnerability and motor severity in parkinson's disease, a. galli 1 ; a. pilotto 1 ; a. rizzardi 1 ; c. zatti 1 ; m. ogliani 1 ; a. lupini 1 ; c. hansen 2 ; r. romijnders 2 ; s. caminiti 3 ; e. premi 4 ; s. lucchini 5 ; f. bertagna 5 ; b. paghera 5 ; w. maetzler 2 ; m. nucci 6 ; s. mondini 6 ; a. padovani 1, 1 department of clinical and experimental sciences, university of brescia, italy; 2 department of neurology, university hospital schleswig‐holstein and kiel university, kiel, germany; 3 department of brain and behavioral sciences, university of pavia, pavia, italy; 4 stroke unit, asst spedali civili of brescia, italy; 5 nuclear medicine unit, university of brescia, italy; 6 department of general psychology, university of padua, padua, italy.

Background and aims: Increasing evidence supports beneficial effects of lifelong physical activities on cognition or mobility. Recently, motor reserve (MR) has been associated with a greater ability to cope with normal or pathological motor‐skill decline. This study investigated the possible impact of MR on dopamine binding and motor severity in early‐diagnosed patients with Parkinson's Disease (PD).

Methods: Drug‐naïve PD patients underwent cognitive and motor assessment‐ and 123I‐FP‐CIT‐SPECT imaging. Gait parameters were evaluated in normal, fast and dual‐task conditions using Mobile Health Technologies (MHT) in supervised setting. Motor Reserve Index questionnaire (MRIq) was administered and individuals were categorized into high‐MR or low‐MR. The relationship between MR and dopamine binding was assessed using a voxel‐wise regression model. Clinical differences between high and low‐MR patients were assessed using two‐sample t‐test, whereas differences in gait parameters were explored using a MDS‐UPDRS‐III, sex and height‐adjusted ANCOVA model.

Results: Forty drug‐naïve PD patients entered the study (age 68.35 ± 7.5). MR was negatively correlated with dopamine binding in left putamen and pallidum in the voxel‐wise model. High vs.. low‐MR PD had similar demographics, motor, and cognitive severity. Only in motor dual‐task conditions, high‐MR vs. low‐MR PD showed lower step‐time ( p  = 0.002), motor cost ( p  < 0.001), step‐time variability ( p  = 0.045), and higher step‐length ( p  = 0.045).

Voxel‐wise regression showing negative correlation between MRIq and dopamine binding.

Conclusion: MR emerged as important modulator of dopamine nigrostriatal circuitries at onset of PD, with an impact on motor impairment and performances assessed by MHT. These mechanisms might explain the heterogeneity of progression and response to treatments in early disease phases and need to be verified in ongoing longitudinal studies.

OPR‐107

Nerve ultrasound in friedreich's ataxia, g. di pietro 1 ; p. falco 1 ; e. ciofffi 2 ; e. galosi 1 ; g. de stefano 1 ; g. di stefano 1 ; c. leone 1 ; v. martines 3 ; s. perotti 4 ; c. casali 2 ; a. truini 1, 1 department of human neuroscience, sapienza university, rome, italy; 2 department of medico‐surgical sciences and biotechnologies, university of rome sapienza, latina, italy; 3 neuroradiology department, policlinico umberto i, rome, italy; 4 department of radiological, oncological and anatomo‐pathological sciences, sapienza university of rome, italy.

Background and aims: Friedreich's Ataxia (FRDA) is the most common hereditary ataxia, it is caused by GAA expansion of the FXN gene. Frataxin mutations lead to a damage of the Peripheral Nervous System producing a sensory neuropathy. The mechanism underling this manifestation is still a matter of debate. It is thought to be a ganglionopathy but alterations along the nerve have also been observed. In this study, we tested the usefulness of nerve ultrasound in the assessment of peripheral neuropathy in FRDA.

Methods: We prospectively enrolled 9 consecutive FRDA patients (39.3 ± 8.3 years, 2 Males). Anamnestic data, neurological examination (Scale for the Assessment and Rating of Ataxia (SARA), Activities of Daily Living (ADL 0–36) and Instrumental Activities of Daily Living (IADL)), Nerve Conduction Study (NCS) and peripheral nerves high‐resolution ultrasound (HRUS) were collected. For each patient, 26 nerve sites were evaluated both quantitatively (Cross Sectional Area (CSA) assessment) and qualitatively. CSA values were compared with 20 healthy volunteers.

Results: In FRDA, HRUS showed a significant nerve enlargement of the Median and Ulnar nerves at the axilla and at the arm ( p  < 0.001). The cumulative count of affected nerve sites was directly associated with clinical disability, as assessed by SARA, ADL 0–36, and INCAT score, while displaying an inverse correlation with IADL.

Cross Sectional Area of Median and Ulnar nerves as assessed with high resolution nerve ultrasound examination in patients with Friedreich's ataxia (orange) and control participants (blue).

Cross Sectional Area of Tibial, Peroneal and Sural nerves as assessed with high resolution nerve ultrasound examination in patients with Friedreich's ataxia (orange) and control participants (blue).

High resolution nerve ultrasound examination showing an enlarged Median (A) and Ulnar (B) nerves at the arm in Friedreich's ataxia. Yellow circles indicate the nerves and red circles indicate the arteries.

Conclusion: Nerve ultrasound can detect alterations along the nerves in Friedreich's Ataxia. While NCS do not correlate with disease severity, HRUS shows a strong correlation with disease severity scores. Nerve ultrasound is a valuable tool in the assessment of Friedreich's Ataxia.

OPR‐108

Choroid plexus volume as a novel candidate neuroimaging marker of the alzheimer's continuum: a prospective cohort study, j. jiang ; w. li; s. jiang; j. xu, beijing tiantan hospital, capital medical university, china.

Background and aims: The clinical role and potential mechanisms of the choroid plexus (ChP) in Alzheimer's disease (AD) remains unclear.

Methods: This prospective cohort study enrolled 607 participants (110 HCs, 269 MCI, and 228 AD dementia). Relationship between ChP volume and CSF hallmarks (Aβ42, Aβ40, Aβ42/40, tTau, and pTau), neuropsychological tests (MMSE, MoCA, NPI, and ADL scores), and multimodal neuroimaging measures were analyzed. The mediating effects of ChP volume were examined on the relationship between CSF hallmarks and neuropsychological tests. The ChP volume performance to differentiate the presence/absence of cerebral Aβ42 deposition was determined using ROC analysis.

Results: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited a larger baseline ChP volume than the other participants. ChP volume enlargement correlated with decreased Aβ42 and Aβ40 levels; lower MMSE and MoCA and higher NPI and ADL scores; lower volume, cortical thickness, and corrected cerebral blood flow in other cognition‐related regions. ChP volume alone mediated and ChP–hippocampal volume combined chain mediated the association of CSF Aβ42 and Aβ40 levels with the MMSE scores (16.91%, 37.15%, 14.25%, and 27.82%, respectively). ChP volume better identified the presence/absence of cerebral Aβ42 deposition than hippocampal volume (AUC: 0.762 vs. 0.724). Generalized linear mixed‐effects models discerned that baseline ChP volume was associated with subsequent decline and faster worsening in the MMSE, MoCA, and ADL scores with 10.03 ± 4.45 months' follow‐up.

FIGURE 1 Comparisons among three representative 3D‐T1 weighted images of the ChP volume in the three groups.

FIGURE 2 Simple and chain‐mediating effects of ChP volume on the association of CSF hallmarks and neuropsychological tests.

FIGURE 3 Receiver operating characteristic curves for choroid plexus and hippocampal volume for discriminating the absence/presence of cerebral pathological deposition, and distinguishing different disease stages.

Conclusion: ChP volume is a novel, candidate, non‐invasive neuroimaging marker associated with neurodegenerative changes in Alzheimer's continuum. It can detect early cerebral Aβ42 deposition and predict prognosis in clinical practice.

OPR‐109

A data‐driven and dynamic network connectivity approach differentiates atypical patterns in alzheimer's disease, l. pini 1 ; l. brusini 2 ; a. griffa 3 ; f. cruciani 2 ; g. allali 3 ; g. frisoni 4 ; m. corbetta 1 ; g. menegaz 2 ; i. boscolo galazzo 2, 1 department of neuroscience, university of padova, italy; 2 department of engineering for innovation medicine, university of verona, italy; 3 leenaards memory center, department of clinical neurosciences, lausanne university hospital, lausanne, switzerland; 4 memory clinic and lanvie ‐ laboratory of neuroimaging of aging, university hospitals and university of geneva, switzerland.

Background and aims: From a macro‐scale perspective, Alzheimer's disease (AD) can be conceptualized as a network‐based syndrome, characterized by polysynaptic communication abnormalities assessed through functional magnetic resonance imaging (fMRI). The molecular hallmark of AD encompasses abnormalities involving amyloid‐beta (A), tau (T) protein accumulation, and medial temporal lobe neurodegeneration (N).

Methods: In this study, we hypothesized that distinct ATN patterns would demonstrate specific spatiotemporal synchronization patterns measured using resting‐state fMRI (rs‐fMRI). We included individuals from the ADNI project. Dynamic functional connectivity (dFC) outcomes were measured using co‐activation patterns derived from the posterior cingulate cortex in 152 controls (74 ± 9 yrs) and projected to 334 patients (74 ± 10 yrs). ATN patterns were identified through a low‐dimensional approach in conjunction with a K‐means algorithm. Univariate, and multivariate approaches were applied to assess biological, behavioral, and dFC differences. Finally, we applied linear and non‐linear classifiers to investigate whether dFC could predict ATN classifications.

Results: We identified three main ATN clusters. The first group displayed mild pathological alterations. The second cluster exhibited typical behavioral impairment alongside AD pathology. The third cluster demonstrated similar behavioral impairment but a divergent T (low) and N (high) pattern, suggestive of non‐AD pathology. Univariate and multivariate analyses revealed two dFC patterns encompassing the default mode network and the occipito‐temporal cortex linked, respectively, with typical and atypical ATN patterns. DFC exhibited an accuracy of approximately 90% in predicting ATN groups.

Conclusion: These results support the key association between macro‐scale and molecular AD alterations. Notably, dFC markers can assist in identifying patients with AD‐like clinical profiles but with different underlying pathologies.

OPR‐110

Is it time to utilise nerve ultrasonography in the journey of amyotrophic lateral sclerosis ( als ) diagnosis, r. abdelnaby 1 ; a. samy shabib 2 ; m. hossam el din moawad 3 ; t. salem 4 ; m. wagih youssef awad 5 ; p. dawoud awad 6 ; i. maallem 7 ; h. atwan 8 ; s. adel rabie 9 ; k. ashraf mohamed 10 ; h. abdelmageed 11 ; m. karkour 12 ; m. elsayed 13 ; m. s. cartwright 14, 1 department of neurology, rwth aachen university, aachen, germany; 2 faculty of medicine, mansoura university, mansoura, egypt; 3 faculty of pharmacy clinical department alexandria university, alexandria, egypt; 4 faculty of medicine, masaryk university, brno, czechia; 5 faculty of medicine, alexandria university, alexandria, egypt; 6 department of public health, theodor bilharz research institute, giza, egypt; 7 faculty of pharmacy, university grenoble alpes, la tronche, france; 8 faculty of medicine, assiut university, assiut, egypt; 9 faculty of medicine, october 6 university, giza, egypt; 10 faculty of medicine, cairo university, cairo, egypt; 11 neurology department, university of greifswald, greifswald, germany; 12 microbiology department, faculty of science, tanta university, tanta, egypt; 13 department of psychiatry and psychotherapy iii , university of ulm, ulm, germany; 14 department of neurology, wake forest school of medicine, winston‐salem , north carolina, usa.

Background and aims: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, causing progressive atrophy of muscles, hypertonia, and paralysis. This study aimed to assess the difference in CSA of several peripheral nerves, vagus and cervical roots measured via US between ALS patients and healthy controls to identify the main nerves that have atrophy during ALS.

Dysfunction of the molecular pathway in ALS. (Figure created by BioRender).

Methods: A systematic search was conducted on Cochrane, Clarivate Web of Science, PubMed, Scopus, and Embase for the mesh terms nerve, ultrasonography, and amyotrophic lateral sclerosis. A quality assessment and a double‐arm meta‐analysis were performed.

Results: 17 studies with a total of 935 ALS patients and 604 controls were included in this review. The overall mean difference showed that individuals with ALS had a significantly smaller CSA in comparison to healthy controls for median, ulnar, C6 root, and phrenic nerves. However, no significant difference in the CSA was found in radial, vagal, sural and tibial nerves.

Mean difference of bilateral median, tibial and radial nerves CSAs between ALS patients and healthy controls.

Mean difference of bilateral ulnar, vagal, C6 root and phrenic nerves CSAs between ALS patients and healthy controls.

Conclusion: Our results confirmed anatomic sites to potentially differentiate individuals with ALS from healthy controls such as the median nerve at the mid‐arm and the ulnar nerve at the wrist and the lower third of the forearm.

Headache & pain 2

Opr‐111, evaluating the impact of lacosamide, pregabalin, and tapentadol on spinal biomarkers in human subjects, c. leone 1 ; g. di pietro 1 ; o. caspani 2 ; a. mouraux 4 ; l. garcia larrea 3 ; r. treede 2 ; a. truini 1, 1 department of human neuroscience, sapienza university of rome; 2 mannheim faculty of medicine, heidelberg univerrsity; 3 neuropain lab, lyon centre for neuroscience, inserm u1028 , neurological hospital of lyon & university claude bernard, lyon, france; 4 institute of neuroscience ( ions ), uc louvain.

Background and aims: The BioPain subtopic of IMI‐PainCare project aimed to test the effectiveness of selected biomarkers for evaluating drug effects and target interactions in new analgesic development. Within this framework, the BioPain‐RCT2 assessed the efficacy of lacosamide, pregabalin, and tapentadol against placebo on neurophysiological spinal biomarkers, specifically the RIII flexion reflex and the cervical N13 component of somatosensory evoked potentials, under normal and hyperalgesic conditions induced by high‐frequency electrical skin stimulation (HFS).

Methods: A multi‐center, double‐blind, placebo‐controlled 4‐period, 4‐way crossover pharmacodynamic and pharmacokinetic study in healthy subjects. Spinal biomarkers were measured before and at three time points after administering the three medications and placebo. The study evaluated drug effects on neurophysiological responses in induced hyperalgesia and normal states. It included blood samples for PK analysis. The primary statistical analysis focused on changes in RIII area and N13 amplitudes under tapentadol, with secondary analyses on other treatments' impacts.

Experimental design.

Results: Three different centres enrolled 24 subjects. The blinded analysis showed an effect of tapentadol on the R3 area and a trend towards the significance of pregabalin at the sensitized side, not reaching the set significance level (0.025). No significant effect of drugs on the N13 was observed. Exploratory analysis showed drug effects on the RIII threshold compared to placebo, with tapentadol and PGB also affecting pain ratings.

Conclusion: Tapentadol, and to a lesser extent Pregabalin, prevent the spinal excitability changes induced by secondary hyperalgesia models as assessed with the RIII reflex. This experimental design failed to identify a significant effect of tapentadol on the sensitized N13.

Disclosure: This project has received funding from the Innovative Medicines Initiative 2 Joint undertaking under grant agreement No 777500. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA. Disclaimer: The statements and opinions presented here reflect the author's view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained therein.

OPR‐112

Brain connectivity changes induced by monoclonal antibodies targeting the cgrp pathway in migraine patients, e. mazzotta 1 ; r. de icco 1 ; m. corrado 1 ; v. grillo 1 ; g. vaghi 1 ; f. cammarota 1 ; f. bighiani 1 ; m. semprini 3 ; a. putortì 1 ; d. martinelli 1 ; m. allena 2 ; g. sances 2 ; c. tassorelli 1, 1 department of brain and behavioral sciences, university of pavia, pavia, italy; 2 headache science & neurorehabilitation unit, irccs mondino foundation, pavia, italy; 3 italian institute of technology, genova, italy.

Background and aims: Previous studies demonstrated central and peripheral changes related to monoclonal antibodies directed against the CGRP pathway (mAbs) administration, without reaching a consensus on their mechanism of action. Our study aims to evaluate differences in resting state networks (RSNs) connectivity in migraine patients (MiG) undergoing mAbs treatment.

Methods: This is a prospective, real‐life, open label study based on three HD‐EEG recordings, namely T0 at baseline, T3 and T6 after 3 and 6 months of mAbs treatment. We assessed connectivity for separate frequency bands (alpha, beta, gamma, theta and delta) for six RSNs: default mode network (DMN), dorsal and ventral attention networks (DAN‐VAN), language network (LAN), somatomotor network (SMN) and visual network (VN). We also performed a single HD‐EEG assessment in healthy controls (HCs).

Results: We evaluated 62 migraine patients (age 45.4 ± 12.0 years, 54 females, 56.4% with chronic migraine) and 32 HCs (age 38.0 ± 14.0, 16 females). At T6, 62.9% of patients qualified as Responders (reduction in MMDs ≥50% when compared to baseline). At baseline, migraine patients presented an enhanced connectivity in delta and theta frequency bands compared to HCs for all analysed RSNs. At T6, connectivity in the delta and theta bands became comparable between Responders and HCs, while Non‐responders maintained higher connectivity in the delta and theta bands compared to both HCs and Responders.

Comparison of inter‐network connectivity between migraine patients and healthy controls at baseline. Average RSN connectivity is reported in the box and whiskers plot with median connectivity values for each band and related interquartile ranges.

Longitudinal inter‐network seed‐based connectivity analysis. Comparison between migraine patients in different treatment timepoints (T0: baseline, T3: 3 months of mAbs treatment, T6: 6 months of mAbs treatment). Coding is color‐based ranging from blue, re.

Conclusion: Our study demonstrated an enhanced slow frequencies whole‐brain connectivity in migraine patients. Treatment with anti‐CGRP monoclonal antibodies induced a positive modulation of functional connectivity in the delta and theta bands in Responder patients.

Summary of study findings. Mig: migraine patients, CM: chronic migraine, HFEM: high frequency episodic migraine patients.

OPR‐113

Role of specific micrornas in cluster headache: correlation with disease phenotype and neuropeptide levels, f. cammarota 1,2 ; r. de icco 1,2 ; f. bighiani 1,2 ; m. corrado 1,2 ; g. vaghi 1,2 ; a. antoniazzi 1,2 ; e. mazzotta 1,2 ; v. grillo 1,2 ; r. greco 1,2 ; c. demartini 1,2 ; a. zanaboni 1,2 ; m. francavilla 1,2 ; s. franchini 1,2 ; m. allena 1,2 ; g. sances 1,2 ; c. tassorelli 1,2, 1 department of brain and behavioral sciences, university of pavia, pavia, italy; 2 headache science and neurorehabilitation unit, irccs mondino foundation, pavia, italy.

Background and aims: The role of specific microRNAs was studied in episodic and chronic migraine, but their possible involvement in cluster headache is yet to be elucidated. Our objective is to evaluate the role of specific microRNAs in episodic cluster headache in active phase (AeCH), remission phase (ReCH), chronic cluster headache (cCH), and healthy controls (HCs).

Methods: In this cross‐sectional study, we assessed gene expression of miR‐382‐5p, miR‐34a‐5p, and miR‐155 in peripheral blood mononuclear cells (Relative Quantification). AeCH and cCH patients were assessed outside of an acute cluster headache attack.

Results: We enrolled 18 AeCH (45.7 ± 12.8 years, 14 males, 16.3 ± 9.6 attacks/week), 7 ReCH (48.6 ± 19.8 years, 5 males), 10 cCH (50.1 ± 16.2 years, 9 males, 21.4 ± 18.8 attacks/week), and 14 HCs (45.4 ± 15.2 years, 2 males). miR‐382‐5p expression was higher in AeCH (1.7 ± 0.8) when compared to ReCH (0.8 ± 0.2) and HCs (0.3 ± 0.1) ( p  < 0.005 for all comparisons). miR‐34a expression was higher in AeCH (1.7 ± 0.4) when compared with ReCH (1.0 ± 0.3), cCH (1.2 ± 0.3) and HCs (0.5 ± 0.2) ( p  < 0.001 for all comparisons). miR‐155 expression was lower in HCs (0.4 ± 0.1) compared to all CH subgroups ( p  = 0.001 for all comparisons), with no difference among AeCH (1.7 ± 0.5), ReCH (1.3 ± 0.3) and cCH (1.3 ± 0.5).

Conclusion: miR‐382‐5p, miR‐34a‐5p and miR‐155 expression is increased in cluster headache when compared to HCs. MiR‐382‐5p and miR‐34a‐5p were associated with disease activity, being higher in AeCH patients when compared to ReCH. MicroRNAs expression of cCH was in‐between active and remission phases of episodic cluster headache patients. Our data supports the role of specific microRNAs in the pathophysiology of different primary headaches.

Disclosure: Cristina Tassorelli has participated in advisory boards for AbbVie, Dompé, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva; lectured at symposia and is a principal investigator or collaborator in clinical trials sponsored by AbbVie, Eli Lilly, Lundbeck, Novartis, and Teva; received research grants from the European Commission, the Italian Ministry of Health, the Italian Multiple Sclerosis Foundation, and the Migraine Research Foundation; and serves as an associate editor for Cephalalgia and The Journal of Headache and Pain. Roberto Di Icco received speaker honoraria for scientific presentations from Eli‐Lilly, and Teva, and has participated as advisory board for Pfizer. Gloria Vaghi reports consultant fees from Lundbeck.

OPR‐114

Evaluation of perivascular and extracellular space properties in migraine: a potential index for glymphatic clearance, r. messina 1 ; f. genovese 1 ; e. pagani 2 ; i. cetta 1 ; l. zanandrea 1 ; b. colombo 3 ; m. rocca 1 ; m. filippi 1, 1 neurology unit and neuroimaging research unit, division of neuroscience, irccs san raffaele scientific institute, vita‐salute san raffaele university, milan, italy; 2 neuroimaging research unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy; 3 neurology unit, division of neuroscience, irccs san raffaele scientific institute, milan, italy.

Background and aims: The glymphatic system is a network of perivascular spaces (PVS) that facilitates fluid exchange and peptide clearance in the brain. We aim to investigate if glymphatic dysfunction contributes to migraine pathophysiology, and examine its variations between patients studied during the interictal phase and those studied while experiencing headache.

Methods: One hundred twenty migraine patients (95 interictal, 25 with headache) and 53 controls underwent diffusion tensor (DTI) and susceptibility weighted (SWI) magnetic resonance imaging. Using DTI and SWI, we computed the Diffusion Along Perivascular Space (DTI‐ALPS) index, reflecting diffusivity in the PVS near the left lateral ventricle. This index serves as a proxy for regional glymphatic function. Based on previous evidence showing an association between glymphatic function and changes within intra/extracellular compartments, we employed neurite orientation dispersion and density imaging to evaluate voxel‐wise maps of white matter extracellular (EVF) and intracellular (IVF) volume fraction. Thus, providing a comprehensive insights into the glymphatic system functioning. Age‐ and sex‐adjusted between‐group comparisons were run using R and FSL software.

Results: Compared to controls, migraine patients were older (mean age: patients 39 (12), controls 41 (14), p  = 0.02) and had a higher proportion of female subjects (female: patients 82, controls 24, p  = 0.006). We found no significant differences between patients and controls, neither concerning the DTI‐ALPS index nor regarding EVF and IVF. No differences were even observed between subgroups of patients.

Conclusion: These results suggest the absence of abnormalities in the PVS and white matter extracellular compartment, indicating normal functioning of the glymphatic system in migraine.

Disclosure: Nothing to disclose in relation to this work.

OPR‐115

Defining mechanisms and new treatments for headache in raised intracranial pressure, o. grech 1 ; e. rubio‐beltran 2 ; e. stanyer 3 ; a. labastida‐ramirez 2 ; g. lavery 4 ; l. hill 5 ; p. holland 2 ; a. sinclair 1, 1 institute of metabolism and systems research, college of medical and dental sciences, university of birmingham, birmingham, uk ; 2 headache group, wolfson sensory, pain and regeneration centre, institute of psychiatry, psychology and neuroscience, king's college london, london, uk ; 3 sleep and circadian neuroscience institute, nuffield department of clinical neurosciences, university of oxford, oxford, uk ; 4 centre for systems health and integrated metabolic research, department of biosciences, school of science and technology, nottingham trent university, clifton campus, nottingham, uk ; 5 school of biomedical sciences, institute of clinical sciences, university of birmingham, birmingham, uk.

Background and aims: Elevated intracranial pressure (ICP) is associated with migraine‐like headaches, but the mechanisms are unclear. Glucagon‐like peptide‐1 (GLP‐1) receptor agonism can reduce ICP, while migraines are associated with increased calcitonin gene‐related peptide (CGRP), and therapeutic benefits are observed with CGRP blockade. We investigated migraine mechanisms in a raised ICP rat model, investigating the effects of GLP‐1 receptor agonism and CGRP inhibition on ICP and nociception.

Methods: A validated rat model with intracisternal kaolin injection hindering CSF drainage was used. Mechanical hyperalgesia via von Frey filament testing, steady‐state potential and cortical blood flow responses to cortical spreading depression (CSD) were assessed. Responses were investigated following treatment with GLP‐1 receptor agonist exenatide or CGRP receptor antagonist olcegepant.

Results: Kaolin increased ICP [median(range) 15.96 mmHg (8.97) n  = 8] controls [6.02 mmHg (1.79) n  = 6 p  = 0.0007]. Mechanical thresholds were reduced in raised ICP (mean(SD) hind paw baseline: 5.78 g (2.81), day 7 3.34 g (2.22) p  < 0.001, periorbital baseline: 6.13 g (2.07), day 7 2.35 g (1.91) n  = 12 p  < 0.001). Raised ICP drastically altered CSD responses [depolarisation duration raised ICP: 108.81 s (222.12) n  = 11, controls 37.54 s (108.38) n  = 9 p  = 0.038, repolarisation duration raised ICP: 1824.26 s (3499.54) n  = 12, controls 86.96 s (140.05) n  = 9 p  < 0.0001]. CBF change was also reduced (85.55% (30.84) n  = 9) versus controls (217.64% (37.70) n  = 8 p  < 0.0001).

Conclusion: These data suggest that elevated ICP results in mechanical hyperalgesia, a sign of cutaneous allodynia. GLP‐1 receptor agonism reduced ICP, prevented changes in mechanical thresholds and restored responses to CSD. CGRP receptor antagonism prevented periorbital pain behaviour, indicating a potential role for CGRP in driving pain responses associated with elevated ICP.

Increased ICP resulted in mechanical hyperalgesia and altered CSD responses. Reducing ICP via GLP‐1 receptor agonism restored mechanical thresholds and CSD responses, while CGRP receptor antagonism prevented periorbital pain behaviour.

Disclosure: OG reports scientific consultancy fees from Invex Therapeutics 2020 which were outside the work in this article. AJS reports personal fees from Invex therapeutics in her role as Director with stock holdings, during the conduct of the study (since 28.06.2019); other for advisory boards from Allergan, Novartis, Cheisi and Amgen outside the submitted work. All other authors declare no competing interests.