EMD Serono Research Articles

Serum neurofilament light chain (NfL)and CSF glial fibrillary acidic protein (GFAP) together improve the prediction of long-term clinical outcomes in multiple sclerosis (S9.001)

Serum neurofilament light chain (NfL)and CSF glial fibrillary acidic protein (GFAP) together improve the prediction of long-term clinical outcomes in multiple sclerosis (S9.001)

Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results (S16.010)

Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results (S16.010)

Radiomics-based Unsupervised Clustering of Acute Multiple Sclerosis Lesions (P10-3.015)

<h3>Objective:</h3> To leverage radiomics and machine learning to identify clusters of focal acute MS lesions exhibiting similar spatial and/or textural patterns on conventional cross-sectional (pre- and post-contrast) T1-weighted, T2-weighted, PD-weighted and FLAIR brain MRIs. <h3>Background:</h3> Multiple sclerosis (MS) lesions exhibit substantial heterogeneity in terms of underlying pathology, anatomic location, and longitudinal evolution. Conventional MRI is sensitive to some aspects of lesion heterogeneity. Unsupervised clustering approaches may identify subtypes of acute MS lesions with specific pathologic features and help improve disease characterization and prognostication. <h3>Design/Methods:</h3> Brain MRIs from the ADVANCE trial (1,512 patients with relapsing-remitting MS, NCT00906399) were retrospectively analysed. For each scan, focal acute (gadolinium-enhancing and/or new or substantially enlarging) T2 lesions (N=3058) were identified in the white matter (WM). Each lesion was represented via its center of mass in standard ICBM-152 space and radiomics-based textural properties. Similar lesions were grouped together via k-means clustering, applied separately across the spatial and each sequence-specific textural domain. Cluster count was optimized based on the silhouette score, Davies-Bouldin index and Variance Ratio Criterion. <h3>Results:</h3> Optimal clustering quality resulted in 8 prototypical WM sites of lesion emergence, 3 prototypical textural patterns on each of post-contrast T1-, PD-weighted and FLAIR MRI and 5 patterns on each of pre-contrast T1- and T2-weighted MRI. Statistically significant cross-sectional associations were found between the occurrence of these lesion subtypes and patient age, sex, years since disease onset and EDSS score, via logistic regression analysis (p &lt; 0.05). <h3>Conclusions:</h3> Specific spatial and textural patterns of acute MS lesions were identified using unsupervised clustering. Further work will evaluate the clinical relevance of identified acute MS lesion patterns towards predicting clinical and MRI endpoints of disease progression. The longitudinal dynamics of each lesion pattern will be investigated via measurements of future lesion repair or transition towards chronic active/inactive lesion states. <b>Disclosure:</b> Mr. Caba has received personal compensation for serving as an employee of Therapanacea. Mr. Caba has received personal compensation for serving as an employee of Biogen. Mr. Caba has received personal compensation in the range of $50,000-$99,999 for serving as a Research Engineer with Therapanacea. Mr. Caba has received personal compensation in the range of $100,000-$499,999 for serving as a Scientist II, ML/AI with Biogen. Dr. Gafson has stock in Biogen. Dr. Ioannidou has received personal compensation for serving as an employee of Therapanacea. Xiaotong Jiang has nothing to disclose. Elizabeth Fisher has received personal compensation for serving as an employee of Biogen. Elizabeth Fisher has stock in Biogen. Elizabeth Fisher has received intellectual property interests from a discovery or technology relating to health care. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Celgene. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has stock in NeuroRx. Colm Elliott has received personal compensation for serving as an employee of NeuroRx Research. Nikos Paragios has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZeneca. Nikos Paragios has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ipsen. Nikos Paragios has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for ArteDrone. Nikos Paragios has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Nikos Paragios has received intellectual property interests from a discovery or technology relating to health care. Nikos Paragios has received personal compensation in the range of $100,000-$499,999 for serving as a CEO with TheraPanacea. Dr. Belachew has received personal compensation for serving as an employee of Biogen Inc. Dr. Belachew has received stock or an ownership interest from Biogen Inc.

Longitudinal Cognitive Screening Findings in Pediatric MS vs. Pediatric Controls and Adult MS in a Multi-center Cohort (S31.008)

Longitudinal Cognitive Screening Findings in Pediatric MS vs. Pediatric Controls and Adult MS in a Multi-center Cohort (S31.008)

Efficacy subgroup analyses from the phase 3 CHAMPION-NMOSD trial in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (S5.003)

Efficacy subgroup analyses from the phase 3 CHAMPION-NMOSD trial in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (S5.003)

A 2-Stage Model of Heterogenous Treatment Effects for Brain Atrophy in MS Utilizing the MS PATHS Research Network (S27.001)

<h3>Objective:</h3> To extend 2-stage models of heterogenous treatment effect (HTE) to brain atrophy outcomes utilizing the MS PATHS research network. <h3>Background:</h3> 2-stage HTE models derived from real-world datasets have the potential to advance personalized medicine in MS. Brain atrophy provides an objective measure benefiting from highly standardized MRI capture. <h3>Design/Methods:</h3> Analyses included patients in MS PATHS who initiated DMT, had complete baseline data, and ≥1 year follow-up without switching DMT. DMT groups were based on efficacy: high (natalizumab, anti-CD20 monoclonal antibodies, alemtuzumab), moderate (fumarates, S1PR modulators, and cladribine) and low (teriflunomide, interferons, glatiramer acetate). Patients were split into training (70%) and test (30%) sets, stratified by group. In stage one, baseline brain parenchymal fraction (BPF) change risk models were derived by linear mixed effect models with baseline covariates as inputs; performance was assessed by predicted versus actual BPF change R-squared in the test set. In stage 2, propensity score (PS) weighting was performed, using multinomial logistic regression with baseline BPF change risk score as one of the covariates. Average treatment effect (ATE) and HTE were calculated with low-efficacy DMT as the reference. <h3>Results:</h3> Analyses included 594 high-, 184 moderate-, and 108 low-efficacy DMT-treated patients. Risk model performance R-squared=0.56. After PS adjustment, covariate SMDs were &lt;10%. In the ATE model, moderate- and high-efficacy groups had less brain atrophy than the low-efficacy group (p&lt;0.001). In the HTE model, BPF change was similar across groups for patients with low risk of brain atrophy. In patients with high risk of brain atrophy, high- and moderate-efficacy groups remained similar; the low-efficacy group had 2-fold worse BPF change. <h3>Conclusions:</h3> HTE models suggest individuals with low baseline risk of brain atrophy may achieve similar outcomes regardless of DMT efficacy choice. The worst relative outcomes occur when patients with high brain atrophy risk are treated with low-efficacy DMTs. <b>Disclosure:</b> Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech_GN41791. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb . Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Hersh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. The institution of Dr. Hersh has received research support from Biogen. The institution of Dr. Hersh has received research support from Novartis. The institution of Dr. Hersh has received research support from Genentech_GN41791. The institution of Dr. Hersh has received research support from PCORI. Dr. Sun has received personal compensation for serving as an employee of Biogen. Dr. Sun has stock in Biogen. Cynthia Grossman has received personal compensation for serving as an employee of Biogen. Cynthia Grossman has stock in Biogen . Dr. Shen has received personal compensation for serving as an employee of Biogen. Fabio Pellegrini has received personal compensation for serving as an employee of Biogen. Fabio Pellegrini has received stock or an ownership interest from Biogen. Nolan Campbell has received personal compensation for serving as an employee of Biogen. Nolan Campbell has stock in Biogen.

Exploring New Imaging Biomarkers: 3D Conformational Analysis Of The Medulla And Upper Cervical Spinal Cord In People With Relapsing Multiple Sclerosis (P11-3.015)

<h3>Objective:</h3> Explore three-dimensional (3D) medulla-upper cervical spinal cord (MUCSC) conformational imaging metrics as biomarkers in multiple sclerosis (MS). <h3>Background:</h3> Measures of spinal cord atrophy are associated with MS disease progression but have yet to emerge as reliable biomarkers of treatment efficacy. 3D MUCSC conformational analysis is a new technique that may provide additional information about neurodegenerative changes in MS beyond conventional magnetic resonance imaging metrics. In the placebo-controlled Phase 3 TEMSO trial (NCT00134563), teriflunomide 14 mg/day lowered the risk of disability worsening and reduced brain volume loss in participants with relapsing MS. 3D MUCSC conformational analysis of the TEMSO dataset has not been explored. <h3>Design/Methods:</h3> TEMSO baseline and 2-year end of study follow-up 3D T1-Magnetization Prepared Rapid Gradient Echo (MP-RAGE) images acquired primarily at 1.5T were assessed for quality, then segmented and analyzed using in-house proprietary software. Change from baseline in MUCSC volume, local curvature and surface texture were summarized with descriptive statistics. <h3>Results:</h3> Quality assessments led to the exclusion of 481 of the 799 TEMSO participants, comprising 64.0%, 62.1%, and 54.5% of participants in the placebo, 7 mg/day, and 14 mg/day arms, respectively. Mean age and disease duration were lower for placebo participants versus teriflunomide arms. No between-group differences were apparent for mean (SD) change from baseline in MUCSC volume (−86±236, −85±218, and −75±218 mm³ for placebo, 7 mg/day, and 14 mg/day arms, respectively), mean curvature (0.01±0.06, 0.02±0.07, and 0.02±0.07 mm), or surface texture (−15.6±28.0, −21.3±26.6, and −19.0±24.2 triangle count). <h3>Conclusions:</h3> 3D conformational analysis of MP-RAGE images from the TEMSO trial showed no discernable between-group differences for MUCSC surface features or volume; however, imbalanced exclusion of participants during quality assessment likely introduced attrition bias. Further development of 3D conformational metrics as MS biomarkers may better illuminate mechanisms related to neurodegenerative changes and treatment efficacy. <b>Disclosure:</b> Miss Moog has nothing to disclose. Janneke Van Wingerden has received personal compensation for serving as an employee of Sanofi Genzyme. Dr. Sanofi has received personal compensation for serving as an employee of Sanofi. Dr. Sanofi has received personal compensation for serving as an employee of Sanofi. Dr. Sanofi has stock in Sanofi. Dr. Sanofi has stock in Sanofi. Dr. Geertsen has received personal compensation for serving as an employee of Sanofi. Dr. Rawlings has received personal compensation for serving as an employee of Sanofi. Dr. Rawlings has stock in Sanofi. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Okuda has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Celgene. Dr. Okuda has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Okuda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for VielaBio.

Acute Neurological Emergencies: Using Neurology-Trained Standardized Patients To Promote Active Learning in a Case-Based Simulation Curriculum for Neurology Clerkship Students (P9-2.004)

<h3>Objective:</h3> To describe the impact of using live, neurology-trained standardized patients (SPs) in a case-based simulation curriculum for clerkship students. <h3>Background:</h3> Simulation in neurology is limited by the inadequacy of manikins to portray neurologic exam findings. We designed a simulation curriculum using live, neurology-trained resident SPs residents for clerkship students to (1) practice taking a neurologic history, (2) perform a neurologic exam, and (3) recognize and triage neurological emergencies. <h3>Design/Methods:</h3> Two scenarios were developed: (1) evaluation of dizziness and management of acute stroke and (2) treatment of new-onset seizure. Monthly sessions involved 4–5 students. Residents SPs mimicked expected exam findings. Pre- and post-session surveys evaluated students’ self-rated knowledge, clinical skills, and confidence in gathering a history, performing a neurological exam, presenting a case, and recognizing, working up, and managing strokes and seizures. Students also rated the overall session quality and provided feedback about the experience. Paired t-tests were performed for quantitative items. <h3>Results:</h3> 54 students participated. Post-session, students reported significantly higher self-confidence in all neurological knowledge domains and clinical skills (p&lt;0.003 for all). Over 90% of students agreed sessions met the learning objectives, the course was valuable, and the simulation was a safe learning environment and would improve their clinical performance. 94% would recommend the session to others. Over 80% agreed the simulation was realistic, well-organized, and an effective way to practice teamwork and clinical skills. In open responses, students reported they appreciated evaluating neurologic emergencies, performing the exam with a trained SP, and making treatment decisions. Students wanted more cases and time; they suggested smaller groups. <h3>Conclusions:</h3> A simulation curriculum with neurology residents portraying the patient increased students’ knowledge, clinical skills, and self-confidence in recognizing and managing acute neurological emergencies. Resident SPs were cited as the most effective educational component. Future research should evaluate the sustainability of benefits gained and assess clinical skills objectively. <b>Disclosure:</b> Dr. Gheihman has nothing to disclose. Dr. Harrold has nothing to disclose. The institution of Dr. Howard has received research support from Genentech. The institution of Dr. Howard has received research support from Novartis. Dr. Howard has received personal compensation in the range of $50,000-$99,999 for serving as a Clinical Fellow with National Multiple Sclerosis Society. Dr. Albin has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Continuum: Life Long Learning in Neurology. Dr. Albin has received research support from American Academy of Neurology. Dr. Albin has received publishing royalties from a publication relating to health care. Dr. Albin has received personal compensation in the range of $500-$4,999 for serving as a Instructor with Resuscitation Leadership Academy. Dr. Kaplan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . Dr. Kaplan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono .

Frontal cognitive-behavioural deficits in patients with anti-leucine-rich glioma-inactivated protein 1 antibody encephalitis (S22.004)

<h3>Objective:</h3> To determine the prevalence of a frontal cognitive-behavioural phenotype in patients with anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis. <h3>Background:</h3> Cognitive impairment is a common manifestation of anti-LGI1 encephalitis and is typically defined as prominent memory deficits. We frequently encounter frontal cognitive-behavioural deficits when evaluating these patients, but this has yet to be well described in the literature. <h3>Design/Methods:</h3> We retrospectively identified patients from three tertiary centres in Toronto, Ontario who were diagnosed with anti-LGI1 encephalitis between October 2013 and September 2022. Patient electronic medical records were evaluated for cognitive features and frontal features were categorized based on the diagnostic criteria for behavioural variant frontotemporal dementia (bvFTD). <h3>Results:</h3> Fifteen patients were identified (median age 65 years [range 18–84]; 8 [53.3%] male). Fourteen (93.3%) patients had cognitive symptoms that localized to the frontal lobe. Two developed these symptoms during treatment with steroids and were therefore excluded from further analysis. The remaining 12 patients presented with behavioural disinhibition (n=11), apathy or inertia (n=5), perseverative, stereotyped or compulsive/ritualistic behaviours (n=4), hyperorality and dietary changes (n=4), a neuropsychological profile with predominant deficits in executive tasks (n=4), and loss of sympathy or empathy (n=1). Seven (46.7%) met diagnostic criteria for possible bvFTD. Of these, 3 had significant functional decline and none had neuroimaging findings consistent with bvFTD. Anterograde memory impairment was common (n=11), and patients also presented with language deficits (n=3) and difficulties with spatial navigation (n=3). Of the 12 patients with frontal symptoms, only 5 had faciobrachial dystonic seizures. <h3>Conclusions:</h3> Patients with anti-LGI1 encephalitis can exhibit frontal cognitive-behavioural symptoms in addition to memory impairment, and screening for these features on clinical assessment may help to identify the diagnosis. Clinicians should also consider anti-LGI1 encephalitis in the differential diagnosis of bvFTD. <b>Disclosure:</b> Dr. Lee has nothing to disclose. Dr. Climans has nothing to disclose. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Barrow Law. Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer’s Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities. Dr. Hebert has nothing to disclose. Dr. Lapointe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Ramos has nothing to disclose. The institution of Dr. Steriade has received research support from NIH. The institution of Dr. Steriade has received research support from Dorris Duke Fund to Retain Clinician Scientists. Dr. Wennberg has nothing to disclose. Dr. Muccilli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Muccilli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Muccilli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Tang-Wai has nothing to disclose.

Latinx with multiple sclerosis have greater disability and loss of deep and cortical gray matter (S31.003)

<h3>Objective:</h3> To characterize clinical and MRI features of Latinx with multiple sclerosis (MS). <h3>Background:</h3> MS affects an increasing number of Latinx patients. The clinical and radiological phenotype of Latinx MS is not well understood and may have biological or social underpinnings. <h3>Design/Methods:</h3> A retrospective cross-sectional study in the MS PATHS network was conducted with Latinx and White non-Latinx carrying a diagnosis of MS. Brain MRI conducted within 1 year of clinical visits were included in the MRI cohort. Clinical and quantitative MRI measures were extracted from MS PATHS including age- and education-adjusted processing speed tests. Comparisons between Latinx and White subjects were conducted using two-sample t-test and Wilcoxon rank-sum. Mixed effect models were used to examine clinical and MRI differences between Latinx and White subjects while adjusting for covariates including education, insurance, and employment. <h3>Results:</h3> A total of 660 Latinx and 9957 White subjects were identified with 388 Latinx and 5726 White subjects in the MRI cohort. Compared with White subjects, Latinx were younger (45.4 years [12.2] vs: 52.9 years [12.7], p &lt;0.001), had shorter disease duration (17.2 years [19.6] vs. 19.5 years [11.5], p &lt;0.001), and had lower processing speed z-score (−0.81 [1.3] vs. −0.40 [1.2], p &lt;0.001). Latinx had higher T2 lesion volume (8.0 ml [IQR 3.5–16] vs 6.5 ml [IQR 3.0–14.1], p = 0.009), and lower thalamic volume (12.8 ml [1.7] vs 13.3 ml [1.6], p &lt;0.001) compared to White subjects. Adjusted mixed models showed that Latinx subjects had lower processing speed, brain parenchymal fraction, thalamic volume, cortical volume, and deep gray matter volume (all p &lt;0.001) as well as slower walking speed (p=0.04), non-dominant manual dexterity (&lt;0.01), and higher PDDS (p=0.045). <h3>Conclusions:</h3> Latinx, despite being younger and having a shorter disease duration than Whites, had more physical disability, cognitive dysfunction, greater lesion burden, and loss of deep and cortical gray matter. <b>Disclosure:</b> Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech/Roche. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Ontaneda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech/Roche. The institution of Dr. Ontaneda has received research support from NIH. The institution of Dr. Ontaneda has received research support from PCORI. The institution of Dr. Ontaneda has received research support from NMSS. The institution of Dr. Ontaneda has received research support from Genetech. Dr. McGinley has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave. Dr. McGinley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. McGinley has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. The institution of Dr. McGinley has received research support from Novartis. The institution of Dr. McGinley has received research support from Biogen. The institution of Dr. McGinley has received research support from Genentech. The institution of Dr. McGinley has received research support from NIH. Mr. Harvey has nothing to disclose. The institution of Dr. Fitzgerald has received research support from NIH. The institution of Dr. Fitzgerald has received research support from National MS Society. Dr. Mowry has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for UpToDate. The institution of Dr. Mowry has received research support from Biogen. The institution of Dr. Mowry has received research support from Teva. The institution of Dr. Mowry has received research support from Genzyme. The institution of Dr. Mowry has received research support from Genentech. Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sage. The institution of Prof. Briggs has received research support from NIH. The institution of Prof. Briggs has received research support from Michael J. Fox Foundation.

Resident Perceptions of a Teleneurology Curriculum (P8-2.006)

<h3>Objective:</h3> To evaluate resident perceptions of a longitudinal teleneurology curriculum. <h3>Background:</h3> Thirty residents (post-graduate year two through four) participated in a novel year-long teleneurology curriculum, including lectures, interactive workshops, online modules, and level-specific simulated cases with standardized patients. <h3>Design/Methods:</h3> We administered an anonymous Qualtrics survey to participating residents at curriculum initiation and completion, assessing their perspectives on teleneurology education. <h3>Results:</h3> Ten residents completed the initial and 13 completed the follow-up survey (response rate 30% and 43%, respectively). Compared to prior, after the curriculum residents perceived lectures and informal attending feedback less useful (70% to 23%, and 90% to 77%, respectively). Online modules and simulated cases were perceived equally as useful (30% to 23% and 40% to 46%, respectively) before and after the curriculum, although formal clinical attending evaluations associated with simulations were perceived more useful (50% to 61%). Respondents also shifted in self-perception of teleneurology knowledge ability, from not at all/slightly knowledgeable to moderately/extremely knowledgeable, particularly regarding medico-legal issues (40% to 51%), ethics (50% to 69%), infrastructure (40% to 61%), and billing (20% to 38%), however not selection of appropriate patient conditions for teleneurology (70% to 69%). Respondents had no overall change in self-perceived confidence in teleneurology clinical competencies after the curriculum, including technology use (90% to 92%), telepresence and rapport (100% to 92%), examination, diagnosis, and triage (overall, 93% to 91%), and efficiency (80% to 77%). They were less confident in educating patients on teleneurology encounter set-up (80% to 69%), and more so in documentation (80% to 93%) and collaborating remotely with medical teams (50% to 61%). <h3>Conclusions:</h3> Although limited by sample size and survey response rate, our findings have guided educational content and delivery, and allocation of faculty efforts and workflow, in a subsequent teleneurology curriculum iteration. Similar multi-center curricular evaluation may suggest necessary updates in residency milestones inclusive of teleneurology knowledge and skills. <b>Disclosure:</b> The institution of Dr. Chandra has received research support from American Board of Psychiatry and Neurology Faculty Innovation in Education Award. Dr. Zha has nothing to disclose. Dr. Samudralwar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Samudralwar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Samudralwar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Bozorgui has nothing to disclose. Miss Deal has nothing to disclose. Mrs. Betner has nothing to disclose. Dr. Jagolino-Cole has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology - Neurology Clinical Practice Journal. . The institution of Dr. Jagolino-Cole has received research support from McGovern Medical School at the University of Texas Health Science Center at Houston.

Long-term Safety of Ozanimod in Relapsing Multiple Sclerosis and Moderately to Severely Active Ulcerative Colitis (P7-3.007)

Long-term Safety of Ozanimod in Relapsing Multiple Sclerosis and Moderately to Severely Active Ulcerative Colitis (P7-3.007)

Safety of the Concurrent Administration of Serotonergic Antidepressants and Ozanimod in Patients With Relapsing Multiple Sclerosis (P7-3.013)

Safety of the Concurrent Administration of Serotonergic Antidepressants and Ozanimod in Patients With Relapsing Multiple Sclerosis (P7-3.013)

In a Digital Version of the 9-Hole Peg Test, Intra-Task Speed, Accounting for Variance in Distance Traveled, May be a Better Measure of MS-Related Upper-Limb Disability Than Completion Time. (P3-3.006)

In a Digital Version of the 9-Hole Peg Test, Intra-Task Speed, Accounting for Variance in Distance Traveled, May be a Better Measure of MS-Related Upper-Limb Disability Than Completion Time. (P3-3.006)

MRI, Efficacy, and Safety of Tolebrutinib in Patients with Highly Active Disease (HAD): 2-Year Data from the Phase 2b Long-term Safety (LTS) Study (P6-3.017)

MRI, Efficacy, and Safety of Tolebrutinib in Patients with Highly Active Disease (HAD): 2-Year Data from the Phase 2b Long-term Safety (LTS) Study (P6-3.017)

Neurological Complications of Immune Checkpoint Inhibitors (P12-13.004)

<h3>Objective:</h3> To better understand the risks of neurologic toxicities associated with immune checkpoint inhibitors (ICIs). <h3>Background:</h3> Case reports have described various neurological immune-related adverse events (irAEs). There still exists a dearth of data regarding their incidence and prognosis. <h3>Design/Methods:</h3> A single center retrospective study analyzing patients between ages of 18–85 years old from the dates of 3/1/2011 to 9/30/2018 who received immunotherapy for conditions including urothelial cancer, lung cancer, gastric and colorectal cancer, head and neck cancer, lymphoma, melanoma, and renal cell carcinoma. <h3>Results:</h3> Of the 1914 subjects who received immunotherapy, 276 experienced neurotoxicity from multiple causes. Of those 276 subjects, 11 suffered neurological irAEs directly from ICI use. Of the 940 subjects who received pembrolizumab alone, 4 (0.004%) developed neurotoxicity 165 to 575 days from administration. Of the 534 subjects who received nivolumab alone, 3 (0.00956%) developed neurotoxicity 477 days from administration. Of the 594 subjects who received ipilimumab alone, 1 (0.0016%) developed neurotoxicity 27 days from administration. Of the 101 subjects who received nivolumab and ipilimumab, 1 (0.0099%) developed neurotoxicity 65 days from administration. Of the 140 subjects who received pembrolizumab and ipilimumab, 2 (0.014%) developed neurotoxicity 240 to 343 days from administration. Ninety-two subjects received atezolizumab, 7 received avelumab, and 18 received durvalumab; none of these patients experienced neurological irAEs. The neurological irAEs observed were neuropathy (45.45%), acute inflammatory demyelinating polyneuropathy (9.09%), ataxia (9.09%), seizure disorder (18.18%), autoimmune encephalitis (18.18%), receptive aphasia (9.09%) and myopathy (9.09%). Neurological irAEs were treated with steroids, intravenous immunoglobulin, and symptomatic medications like gabapentin, duloxetine, levetiracetam, and thiamine, with about 36% of subjects achieving symptom control. <h3>Conclusions:</h3> Neurological irAEs were extremely rare in our clinical population, but may correlate to the ICI used. We need larger studies to determine the most effective therapy for each neurological irAE and allow oncologists to recognize and treat them expeditiously. <b>Disclosure:</b> Dr. Babu has nothing to disclose. Dr. Sharda has nothing to disclose. Dr. Kolli has nothing to disclose. Dr. Mora-Rodriguez has nothing to disclose. An immediate family member of Dr. Boldig has received personal compensation for serving as an employee of Custom Wire Technologies. An immediate family member of Dr. Boldig has stock in Custom Wire Technologies. Tyra Gatewood has nothing to disclose. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Seagen. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Exelixis. Dr. Swank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Iovance Pharmaceuticals. Dr. Swank has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for HOPA. Dr. Pina has nothing to disclose. Dr. Peguero has nothing to disclose. Dr. Jaffer has nothing to disclose. Dr. Mokhtari has nothing to disclose. Neha Verma has nothing to disclose.

A Familial Analysis of Neurosarcoidosis Utilizing the Utah Population Database (P9-5.008)

<h3>Objective:</h3> To investigate for evidence of familial clustering within a large cohort of patients with Neurosarcoidosis utilizing the Utah Population Database. <h3>Background:</h3> Sarcoidosis is a multisystemic inflammatory disease that can affect the cardiac, integumentary, hepatic, renal, ocular, and neurologic systems. Neurologic manifestations include cranial neuropathies, meningitis, peripheral neuropathy, myelopathy, intraparenchymal mass lesions. Current evidence suggests familial clustering of sarcoidosis in Sweden as well as within the US Black population. Genes of interest include HLA-DP subregions, Annexin A11, Butyrophilinlike 2 gene, and Toll-like receptors. We investigated for evidence of shared genetics among our Intermountain West cohort of neurosarcoidosis patients. <h3>Design/Methods:</h3> We performed a retrospective review of all definite and probable neurosarcoidosis patients diagnosed and managed at our institution. Using the Utah Population Database (UPDB), a population-based genealogic resource containing medical and demographic information of over 11 million individuals, we identified high-risk pedigrees with excess familial aggregation of neurosarcoidosis using the Familial Standardized Incidence Ratio (FSIR). Unaffected subjects were identified and matched 10:1 to neurosarcoidosis patients by age, birth year, and pedigree structure in the UPDB. Familial risk analyses were performed to estimate the heritability of neurosarcoidosis FDRs, SDRs, and TDRs separately using multivariate logistic regression adjusting for sex, birth year, race, and ethnicity. <h3>Results:</h3> Out of the 54 patients in the cohort, the median age of patients was 63 years (SD 12 years), 36(66%) were female and 46 (85%) self-identified as Caucasian. A total of 12 (22%) had definite neurosarcoidosis and 42 (78%) had probable neurosarcoidosis. The initial symptom of sarcoidosis was neurologic in 34 (63%) of the patients. We studied the inter-relatedness of the patients with neurosarcoidosis. <h3>Conclusions:</h3> Neurosarcoidosis is a rare disease and thought to be a manifestation of a multisystem disease in which familial clustering and genetic analysis suggests that inherited factors play a role in the pathogenesis which requires further investigation. <b>Disclosure:</b> Dr. Crane has nothing to disclose. Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Abbatemarco has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . The institution of Dr. Abbatemarco has received research support from Horizon. Mr. Yu has nothing to disclose. Ms. Date has stock in Astrazeneca. Mr. Madsen has nothing to disclose. Ms. Fraser has nothing to disclose. Mr. Wong has nothing to disclose. Dr. Lord has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.

Myelin Water Fraction of Slowly Evolving Lesions is Associated With Disability in Multiple Sclerosis (P10-3.017)

Myelin Water Fraction of Slowly Evolving Lesions is Associated With Disability in Multiple Sclerosis (P10-3.017)

Long-term Efficacy of Satralizumab in Adults with Aquaporin-4-IgG-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Results from SAkuraMoon (S5.001)

Long-term Efficacy of Satralizumab in Adults with Aquaporin-4-IgG-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Results from SAkuraMoon (S5.001)

Association of Disease Characteristics with Utilization of Behavioral Medicine in Patients with NMOSD and MOGAD (P13-5.016)

<h3>Objective:</h3> To evaluate utilization of behavioral medicine in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD). <h3>Background:</h3> The relationship between disease characteristics, utilization of behavioral medicine, and other healthcare services has not been well-characterized in patients with NMOSD/MOGAD. <h3>Design/Methods:</h3> In this retrospective cohort study, patients with NMOSD/MOGAD confirmed by a neuroimmunology clinic with available clinical data between June 2015 and April 2022 were identified. Relevant variables were collected, including number of behavioral medicine appointments, diagnosis, number of other healthcare visits (admissions, emergency room visits, neurology appointments, outpatient physical and occupational therapy [PT/OT] visits), and number and type of relapses (brainstem, transverse myelitis, and optic neuritis). Nonparametric t-tests were performed to compare characteristics of patients who did and did not use behavioral medicine. Pearson correlations were used to explore relationships between disease characteristics and number of behavioral medicine appointments. <h3>Results:</h3> 196 patients (70.9% NMOSD [92.8% aquaporin-4 antibody positive], 29.1% MOGAD) were identified (median duration of symptoms 8.4 years, IQR [4.6, 16.4 years]). Of these, 21 patients (90.5% NMOSD, 9.5% MOGAD) attended at least one outpatient behavioral medicine appointment. These patients had more emergency room visits (median 3, IQR [1, 8]) than non-attendees (median 1, IQR [0, 2]) (p = .04). No significant difference was detected regarding number or type of relapse or utilization of other healthcare services (for all, p &gt; .05). Brainstem flares and number of PT/OT visits correlated with number of behavioral medicine appointments (r = .72 and r = .56, respectively, p &lt; .05). <h3>Conclusions:</h3> Patients with NMOSD/MOGAD who received behavioral medicine services had greater emergency room utilization than those who did not. In our cohort, nearly 1 in 8 patients attended behavioral medicine appointments. Screening for mental health disorders in neurology clinics remains critical to appropriately identify and treat NMOSD/MOGAD patients with behavioral comorbidities. <b>Disclosure:</b> An immediate family member of Dr. Swetlik has received personal compensation for serving as an employee of Pfizer. Dr. Conway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharmaceuticals. Dr. Conway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Banner Life Sciences. Dr. Conway has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Miss Widmar has nothing to disclose. Dr. Kunchok has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Kunchok has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon therapeutics . Dr. Kunchok has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. Dr. Tworek has nothing to disclose. Dr. Sullivan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Sullivan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb. Dr. Sullivan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Sullivan has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Dynamed. Rachel Galioto has nothing to disclose. Dr. Aboseif has a non-compensated relationship as a AAN Autoimmune Neurology Section -- Education Workgroup with AAN that is relevant to AAN interests or activities. Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Abbatemarco has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . The institution of Dr. Abbatemarco has received research support from Horizon.