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Investigating synaptic changes in Essential Tremor with PET Imaging (P7-11.005)

<h3>Objective:</h3> To utilize positron emission tomography (PET) imaging with the synaptic density tracer [¹¹ C] UCB-J to characterize the distribution in the cerebellum and other brain areas in essential tremor (ET) compared to healthy controls (HC). <h3>Background:</h3> Numerous lines of evidence point to a cerebellar origins of ET, with a number of studies pointing to Purkinje cell loss. Studying potential markers of cell loss <i>in vivo</i> would be of great value. [¹¹ C] UCB-J has been found to be an excellent tracer for quantitative imaging of synaptic vesicle glycoprotein 2A (SV2A), a marker of synaptic density, in the human brain. This tracer has not been used to study the ET brain. <h3>Design/Methods:</h3> Six individuals with ET with a mean age (SD) of 65 (10); three males), and sixteen demographically matched healthy comparison controls (HC; 63 (9); six males) participated in an [¹¹ C] UCB-J PET scan. Binding potential value (<i>BP</i>_ND: binding potential of available receptors) was the primary outcome measure and using the centrum semiovale as the reference region. Muller Gartner partial volume correction (PVC) was applied to control for possible volumetric differences. T-tests were calculated for between group differences, and p values were uncorrected for multiple comparisons given the exploratory nature. <h3>Results:</h3> We observed significantly lower synaptic availability in ET compared to HC in the cerebellum (−11%, p=0.04), right cerebellum (−11%, p=0.03), vermis (−12%, p=0.04), motor cortex (−21%, p=0.001), and supplementary motor cortex (−20%, p=0.006). <h3>Conclusions:</h3> This <i>in vivo</i> investigation with [¹¹ C] UCB-J PET in ET is the first sample to date (to our knowledge) and found preliminary evidence of lower synaptic availability in key brain areas. Additional data analysis is ongoing, such as applying Iterative-Yang PVC, correlating synaptic changes with clinical scores, and exploring network-based analyses. <b>Disclosure:</b> Ms. Yang has nothing to disclose. Mika Naganawa has nothing to disclose. Nora Hernandez has nothing to disclose. Mr. Nguyen has nothing to disclose. Nabeel Nabulsi, 21953 has nothing to disclose. An immediate family member of Yiyun Huang, 8202 has stock in Pfiy. An immediate family member of Yiyun Huang, 8202 has stock in Johnson and Johnson . Yiyun Huang, 8202 has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH. Richard Carson has nothing to disclose. Dr. Matuskey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Eleisver. The institution of Dr. Matuskey has received research support from Abbvie. Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt’s Textbook of Neurology. The institution of Dr. Louis has received research support from National Institutes of Health.

Pilot Implementation and Evaluation of an Outpatient Teleneurology Curriculum for Medical Students (S10.007)

<h3>Objective:</h3> To assess the feasibility and outcomes for a novel teleneurology educational curriculum <h3>Background:</h3> Stemming from the COVID-19 pandemic, medical students rotating on neurology electives were asked to participate in telehealth encounters with limited formal teaching and evaluation on the principles and practice of teleneurology. <h3>Design/Methods:</h3> We developed a 2-week outpatient teleneurology curriculum consisting of virtual asynchronous video modules and virtual synchronous patient interactions designed to address AAMC telehealth competencies. It was delivered as a supplement to an established outpatient neurology elective for 4^th year medical students from July 2021-September 2022 at a US medical school. Participation was optional. Assessments included pre and post student self-rated confidence in 6 telehealth competencies on a 4-point scale. Students participated in a summative virtual visit with a neurological patient under direct observation of an attending neurologist well-versed in telehealth. Both the observing neurologist and patient evaluated the student in the telehealth competencies. <h3>Results:</h3> Twenty-six 4^th year medical students participated in the pilot. Each student spent 1 hour viewing asynchronous video modules, and had 454 ± 200.5 (mean+/−SD) minutes of virtual patient contact over 15 ± 8.2 virtual visits. After completing the curriculum, students were 92–100% moderately or very confident regarding their capabilities across telehealth competencies, representing an improvement from 12–96% compared to pre-curriculum (average increase 0.56–1.84 on the 4–point scale; p&lt;0.005 for all competencies). Examination and regulatory competencies demonstrated the greatest improvement. Competencies were rated as effective or very effective for 88–100% of students by patients and 92–100% of students by faculty during the summative visit. <h3>Conclusions:</h3> This pilot teleneurology curriculum demonstrated that students not only increased in self-rated confidence in performing telehealth competencies, but also demonstrated meeting these competencies in the opinion of both physician and patient observers. Further research into effective methods for integrating telehealth competencies into the neurology and broader medical school curriculum is warranted. <b>Disclosure:</b> Dr. Ko has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Ko has received research support from HRSA. Dr. Ko has received research support from IU Health. Dr. Moss has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Twenty Twenty Therapeutics. Dr. Moss has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Verana Health. Dr. Moss has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink Inc. Dr. Moss has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Legal Firms. The institution of Dr. Moss has received research support from NIH. The institution of Dr. Moss has received research support from Department of Defense. The institution of Dr. Moss has received research support from Research to Prevent Blindness. Dr. Moss has received personal compensation in the range of $0-$499 for serving as a grant review panel with NASA. Dr. Moss has received personal compensation in the range of $0-$499 for serving as a grant review panel with National Institutes of Health. Dr. Moss has a non-compensated relationship as a Board of Directors with North American Neuro-ophthalmology Society that is relevant to AAN interests or activities. Dr. Mackay has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for various law firms. Dr. Ko has nothing to disclose. Dr. Chartier has received personal compensation in the range of $50,000-$99,999 for serving as a Instructional Design Consultant, IU School of Medicine PRIME Grant with Health Resources &amp; Services Administration. Dr. Reese has nothing to disclose. Dr. Wallach has nothing to disclose. The institution of Dr. Allen has received research support from AMA Accelerating Change in Medical Educaiton Program. The institution of Dr. Allen has received research support from HRSA Medical Education Program Grant.

Inebilizumab Reduces Attack Risk Independent of Low Affinity IgG Fc Region Receptor III-A Gene Polymorphisms in Neuromyelitis Optica Spectrum Disorder (P13-5.015)

<h3>Objective:</h3> To characterize the relationship between the rs396991 polymorphism and the treatment response in N-MOmentum trial participants. <h3>Background:</h3> Inebilizumab, a humanized, afucosylated IgG1 monoclonal antibody that targets CD19 for B-cell depletion, is approved to treat aquaporin 4 (AQP4) immunoglobulin G positive (IgG+) neuromyelitis optica spectrum disorder (NMOSD). Afucosylated antibodies are engineered to enhance affinity for Fc receptor III-A (FCGR3A) receptors and maximize antibody-dependent cellular cytotoxicity. The F allele of the F176V polymorphism (rs396991) is associated with decreased IgG binding affinity and reduced efficacy of rituximab in NMOSD. Data from participants with different <i>FCGR3A</i> genotypes were compared for disease severity and response to inebilizumab at timepoints up to ≥4 years. <h3>Design/Methods:</h3> N-MOmentum (NCT02200770) was a double-blind, phase 2/3 trial of inebilizumab in adults with NMOSD, with a 28-week randomized controlled period (RCP); (inebilizumab 300 mg or placebo on days 1 and 15) and an optional open-label period (OLP) of ≥2 years. A total of 142 participants (inebilizumab, n=104; placebo, n=38) consented for genotyping via TaqMan qPCR assay. <h3>Results:</h3> V-allele carriers (V-allele genotype [V/V or V/F], n=74) and F/F–allele homozygotes (n=68) did not demonstrate a significant difference in baseline demographics or disease duration. Depletion of CD20⁺ B-cells was similar in V allele vs F/F allele participants (0.6 (0.1–3.2) vs 1.3 (0.5–4.2) cells/μL at end of RCP) and was sustained in both groups throughout the duration of the study. We did not find any difference in risk of relapse (OR 0.94 (0.39, 2.24)) or Expanded Disability Status Scale worsening (OR: 1.55 (0.54, 4.70)) in V vs F/F allele participants. Annualized attack rates (Standard Error of the Mean [SEM]) for patients on inebilizumab treatment were V/V 0.00 (0.00), V/F 0.10 (0.04), and F/F 0.06 (0.03). <h3>Conclusions:</h3> Inebilizumab treated participants in the N-MOmentum trial did not demonstrate differences in clinical outcomes between those with F and V allele genotypes. <b>Disclosure:</b> Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. The institution of Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care. Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a speaker at internal meeting with Genentech. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a speaker at internal meeting and symposium with Horizon. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon Therapeutics. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reistone Bio. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Antigenomycs. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MedEdicus. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ImCyse. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Podoll. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Patterson. The institution of Dr. Bennett has received research support from Novartis. The institution of Dr. Bennett has received research support from Alexion. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atara. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Therini. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. Dr. Cree has received publishing royalties from a publication relating to health care. The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe PC (MTPC). The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aarhus University. Dr. Paul 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. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CELGENE. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACRELION. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizter. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck Serono. The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aprilbio, HanAll BioPharma, Viela Bio. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion, Biogen, Celltrion, Eisai, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok. Dr. Kim 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 Multiple Sclerosis Journal, Journal of Clinical Neurology. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung 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. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology. Dr. Patterson has received personal compensation for serving as an employee of Hospital of the University of Pennsylvania. Dr. Patterson has stock in Horizon Therapeutics. Michael Smith has nothing to disclose. William Rees has received personal compensation for serving as an employee of Horizon Therapeutics. William Rees has received personal compensation for serving as an employee of Viela Bio. William Rees has received stock or an ownership interest from Horizon Therapeutics. William Rees has received stock or an ownership interest from Viela Bio. William Rees has received intellectual property interests from a discovery or technology relating to health care. William Rees has received intellectual property interests from a discovery or technology relating to health care. Dewei She has received personal compensation for serving as an employee of Horizon Therapeutics. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Aktas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Aktas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Aktas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of Dr. Aktas has received research support from German Research Foundation. The institution of Dr. Aktas has received research support from German Ministry of Science. The institution of Dr. Aktas has received research support from Neuromyelitis optica Study Group (NEMOS).

Data-Driven Genome-Wide Association Study of Pain Trajectories in Persons with Parkinson’s Disease (P7-11.012)

<h3>Objective:</h3> To conduct the first genome-wide association study (GWAS) of pain in persons with Parkinson’s disease (PWP). <h3>Background:</h3> Pain is a common and complex non-motor symptom experienced by ~60% of PWP. Little is known about the genetic and non-genetic determinants of pain in PWP. <h3>Design/Methods:</h3> Using data spanning ~4.5 years from 8,612 PWP who are early in their disease course (&lt;3 years), and available through the Fox Insight Data Exploration Network, we empirically discerned 5 subgroups of PWP with similar longitudinal patterns of pain using latent class growth analysis. 4,411 PWP were also genotyped across two customized Illumina platforms that had significant overlap. Quality control criteria (minor allele frequency &lt;1%, Hardy Weinberg Equilibrium p&lt;5×10⁻⁵) were imposed prior imputation using the TOPMed reference panel. After post-imputation quality control (same as above + imputation R²&gt;70%), there were 7.7×10⁶ genetic variants. We retained 4,159 PWP who self-identified as White and who genetically clustered with other European samples. For this analysis, we focused on a GWAS of the most severe pain subgroup (N=97) to the least impaired subgroup (N=934). Gene-based and pathway enrichment analyses were also conducted. <h3>Results:</h3> For the GWAS of extreme pain phenotypes, top genic SNP association were <i>MAPK8</i>-rs72794357 (OR=4.6; p=1×10⁻⁶) and <i>VLDLR-</i>rs4741753 (OR=2.2; p=1.5×10⁻⁶) and top gene-based results included <i>CTNNB1</i> (p=3.5×10⁻⁵) and <i>KLK7</i> (p=7.7×10⁻⁵). These results are intriguing since <i>MAPK8</i> is involved in opioid receptor pathways, <i>VLDLR</i> is a ApoE receptor involved in brain development through Reelin signaling, <i>CTNNB1</i> promotes neurogenesis and de novo mutations have been associated with polyneuropathy in lower limbs, and <i>KLK7</i> is an astrocyte-derived amyloid-β degrading enzyme. Overall there was an enrichment of genes associated with oxytocin signaling (p=0.14), opioid signaling (p=0.045), and Wnt signaling pathway (p=0.021). <h3>Conclusions:</h3> The findings are consistent with known neuropathic mechanisms, thus therapeutic targets for these mechanisms may be relevant for PWP. <b>Disclosure:</b> The institution of Miss Liu has received research support from NIH/NIGMS. The institution of Miss Liu has received research support from Diana Jacobs Kalman/AFAR Scholarships for Research in the Biology of Aging The Program. The institution of Miss Liu has received research support from Michael J. Fox Foundation. Doug Gunzler has nothing to disclose. Dr. Gunzler has received research support from NIH/NINDS. The institution of Dr. Gunzler has received research support from Biogen. The institution of Dr. Gunzler has received research support from Amneal. Dr. Gunzler has received research support from Michael J Fox Foundation. Dr. Crawford 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 Frontiers in Genetics. The institution of Dr. Crawford has received research support from NIH/NIDDK. The institution of Dr. Crawford has received research support from NIH/NCATS. The institution of Dr. Crawford has received research support from VA. The institution of Dr. Crawford has received research support from NIH/NIGMS. The institution of Dr. Crawford has received research support from NHGRI. The institution of Dr. Crawford has received research support from NIH/NIA. Dr. Crawford has received personal compensation in the range of $500-$4,999 for serving as a Member with NIH Study Section. 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.

APOE ɛ4 Influences Within and Between Network Functional Connectivity in Atypical Alzheimer Disease (P11-6.006)

<h3>Objective:</h3> To assess functional connectivity in posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) and evaluate how within and between-network functional connectivity differs based on the apolipoprotein E (<i>APOE)</i> ɛ4 status. <h3>Background:</h3> <i>APOE</i> ɛ4 influences atrophy and tau deposition in patients with atypical Alzheimer’s disease (AD), with <i>APOE</i> ɛ4 carriers having greater predisposition to medial temporal involvement. This raises questions on whether the <i>APOE</i> genotype would influence memory network connectivity, a network mainly comprised of medial temporal structures. <h3>Design/Methods:</h3> One-hundred forty amyloid-positive PCA (n=58) and LPA (n=82) patients were recruited by the Neurodegenerative Research Group and underwent structural and resting state functional MRI. Spatially preprocessed data were analyzed to explore the default mode network (DMN), salience, language, visual and memory networks, using a region of interest approach in Conn toolbox. Bayesian hierarchical linear models (BHLM) adjusted for age and sex, assessed the influence of APOE ɛ4 on within and between-network connectivity. <h3>Results:</h3> We found reduced within-network connectivity in the memory and language networks in LPA, with an increase in salience network connectivity in PCA, in <i>APOE</i> ɛ4 carriers compared to non-carriers. <i>APOE</i> ɛ4 did not influence memory within-network connectivity in PCA. Between-network analysis showed evidence of reduced connectivity from the DMN in both groups, with reduced DMN-to-salience and DMN-to-language network connectivity in PCA <i>APOE</i> ɛ4 carriers, and reduced DMN-to-visual network connectivity in LPA <i>APOE</i> ɛ4 carriers. In addition, we found reduced connectivity from the visual-to-language and visual-to-salience networks in <i>APOE</i> ɛ4 carriers compared to non-carriers in both PCA and LPA. Both network-level and voxel-level findings concurred with the BHLM findings, specifically showing reductions in the within-network connectivity for the memory network in LPA <i>APOE</i> ɛ4 carriers. <h3>Conclusions:</h3> The <i>APOE</i> genotype influences brain connectivity, both within and between-networks, in atypical AD variants. However, there was evidence that the modulatory effects of <i>APOE</i> differ across phenotype. <b>Disclosure:</b> Dr. Singh has nothing to disclose. Mr. Martin has nothing to disclose. Dr. Graff-Radford has received personal compensation for serving as an employee of Mayo Clinic. Dr. Graff-Radford has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NINDS/NIH. Dr. Graff-Radford 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 American Academy of Neurology. The institution of Dr. Graff-Radford has received research support from NIH. The institution of Dr. Machulda has received research support from NIH. Minerva Carrasquillo has nothing to disclose. The institution of Dr. Taner has received research support from NIH. Dr. Josephs has nothing to disclose. Dr. Whitwell has nothing to disclose.

The Power of a Post-It: The Reach and Impact of the Twitter Teaching Initiative “#NeuroPostItPearls” (P7-2.001)

<h3>Objective:</h3> To assess the feasibility of using social media for neurologic education using the Twitter hashtag “#NeuroPostItPearls.” <h3>Background:</h3> Social media platforms like Twitter offer a powerful way to reach a global audience and the #neurotwitter community has grown exponentially since the COVID19 pandemic. To be searchable, educational posts are often hashtagged with a unique moniker. Creation of the #PostItPearls microteaching movement is credited to Michelle Lin, an emergency medicine physician, who in 2017 started highlighting teaching “pearls” by writing them on Post-its that were then shared on Twitter. Although widely shared, these were largely not applicable to the neurology community. <h3>Design/Methods:</h3> The hashtag #NeuroPostItPearls was launched on July 1^st, 2022 with the aim of sharing bite-sized teaching with incoming neurology residents. For this study, data was collected about the number of participants and the Twitter analytics of top posts. We used an AI-driven Twitter analytic platform (“Tweepsmap”) to create a descriptive analysis of the data and to visualize the global reach and summative impact of the hashtag through September 2022. <h3>Results:</h3> Six authors shared original Post-it “Pearls” (“Pearls” per author ranged from 1–31). The most widely liked and retweeted content focused on neurologic differentials (Retweets 133/Likes 447), hypertonic bicarb for ICP crisis (96/449), strategies for tPA reversal (71/387), anti-seizure drug interactions (76/351) and the Guillain-Barré 20/30/40 Rule (78/281). The impression of high impact tweets was between 30k and 60k views. In total, posts with the hashtag generated nearly 1 million views (972K). The 48 original “pearls” were retweeted a cumulative of 969 times by 663 individuals across 58 countries. 67.4% of the Twitter users that retweeted them were healthcare workers. <h3>Conclusions:</h3> Twitter is a viable platform for sharing microteaching with the global neurology community. Further study is needed about the long-term educational impact and best practices for teaching through social media. <b>Disclosure:</b> 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. Charidimou has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Imperative Care. Dr. Charidimou has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier, Journal of Neurological Sciences. Dr. Jones 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 American Academy of Neurology. Dr. Jones has received publishing royalties from a publication relating to health care. Dr. Jones has a non-compensated relationship as a member of the Board of Directors with 44690 that is relevant to AAN interests or activities.

Sleep quality associated with neuroimaging measures of CSF flow in individuals with Parkinson’s disease (N5.001)

<h3>Objective:</h3> To investigate the relationship between sleep quality and cerebrospinal fluid (CSF) flow in individuals with Parkinson’s disease (PD). <h3>Background:</h3> Previous studies have emphasized the role of CSF circulation in the clearance of brain waste products, with recent findings demonstrating increased CSF flow during sleep. CSF circulation impairment could play a major role in neurodegenerative proteinopathies such as PD, a commonly encountered feature of which is disrupted sleep. Here, we assessed the relationship between patient-reported sleep quality and imaging assays of CSF flow. <h3>Design/Methods:</h3> Imaging and clinical assessments were completed in 23 PD participants aged 56 to 79 (M_age=66.70; 16 males). The Montreal Cognitive Assessment (MoCA) and Unified Parkinson’s Disease Rating Scale (UPDRS) were administered; subjective sleep measurements were recorded using the Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) items from the Patient-Reported Outcomes Measurement Information System (PROMIS) scale. MRI phase contrast sequences quantified CSF flux (mL/min) via the cerebral aqueduct. Net CSF flow was defined as the difference between caudal and cranial flow, whereas absolute flow was calculated as the sum of total caudal and cranial flow per cardiac cycle. <h3>Results:</h3> Participants had mean MoCA scores of 24.17 (range 13–30) and UPDRS scores of 30.70 (7–59). PROMIS scores for SD and SRI were 20.14 (9–32) and 15.00 (8–24), respectively. Mean CSF measurements were 0.25 mL/min (−0.29–0.88) for net and 8.11 mL/min (3.55–16.34) for absolute flow. Higher SRI scores correlated with greater net CSF flow while awake (r=0.531, p=0.023). Additionally, SRI and age explained 73.4% of variation in absolute CSF flow in a linear regression model (F(3,15)=24.5, p&lt;0.0001). <h3>Conclusions:</h3> Self-reported sleep impairment is associated with increased CSF flow in awake individuals with PD. This study is the first to link patient-reported measures of sleep with alterations to CSF flow. These data support novel outcomes for clinical studies that improve sleep. <b>Disclosure:</b> Mr. Ponzo has nothing to disclose. Dr. Hett has nothing to disclose. Mr. Eisma has nothing to disclose. Mr. Elenberger has nothing to disclose. Mr. Song has nothing to disclose. An immediate family member of Dr. McKnight has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Deciphera. The institution of Dr. McKnight has received research support from RSNA. Dr. Considine has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MDisrupt. Dr. Considine has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Park Dietz &amp; Associates. The institution of Dr. Considine has received research support from NIH. The institution of Dr. Considine has received research support from DoD. The institution of Dr. Considine has received research support from Acadia Pharmaceuticals. Manus Donahue, 13717 has received personal compensation for serving as an employee of Alterity. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alterity. Manus Donahue, 13717 has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Global Blood Therapeutics. Manus Donahue, 13717 has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. The institution of Manus Donahue, 13717 has received research support from National Institutes of Health. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark . The institution of Dr. Claassen has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Alterity. Dr. Claassen has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Neuroscience. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for HD Insights. The institution of Dr. Claassen has received research support from NIH. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from HDSA. The institution of Dr. Claassen has received research support from Department of Defense. The institution of Dr. Claassen has received research support from Griffin Family Foundation. The institution of Dr. Claassen has received research support from Neurocrine. The institution of Dr. Claassen has received research support from Vaccinex. The institution of Dr. Claassen has received research support from AbbVie. The institution of Dr. Claassen has received research support from CHDI. The institution of Dr. Claassen has received research support from Genentech/ Roche. The institution of Dr. Claassen has received research support from Prilenia. The institution of Dr. Claassen has received research support from Neurocrine/ HSG.

Progression independent of relapses in multiple sclerosis is associated with spinal cord and brain atrophy (P10-3.011)

<h3>Objective:</h3> To quantify MRI predictors of disability progression and progression independent of relapse activity (PIRA) from patients with multiple sclerosis (MS) in an observational setting. <h3>Background:</h3> PIRA is a major contributor of disability worsening in MS and has been extensively studied in clinical trial cohorts. <h3>Design/Methods:</h3> We obtained demographics, patient-reported measures (patient-determined disease steps [PDDS], relapse, and MS course), and performance measures (walking speed test [WST], manual dexterity test [MDT], and processing speed test [PST]). Inclusion criteria were at least 3 measurements and ≥6 months of follow-up. Confirmed disability worsening (CDW) was defined as a 6-month-sustained increase of ≥1 in PDDS, 20% increase for WST or MDT, or 4-point decrease for PST. Fixed and roving reference methods were applied. CDW was classified as PIRA when it occurred in the absence of relapses between the onset and confirmation of CDW (±30days). MRIs acquired within 6 months of the first visit were analyzed for whole brain fraction (WBF), T2 lesion volume (T2LV), and upper cervical spinal cord area (SCA). The baseline characteristics were compared based on CDW and PIRA status. Logistic regression was performed to predict PIRA. <h3>Results:</h3> 4909 subjects were included. CDW occurred in 1825 (37%) using fixed baseline and in 2599 (53%) using roving baseline. PIRA represented 37% (679) of all CDW in fixed and 43% (1121) in roving. PIRA patients were older (p&lt;0.05), had better MDT score (p&lt;0.001), and better PST score (p&lt;0.02). PIRA subjects had lower baseline WBF (0.803 vs 0.811, p&lt;0.01) and SCA (74.6 vs 77.1, p&lt;0.01) with no difference in T2LV (p&gt;0.1). Logistic regression showed PIRA was associated with lower baseline MDT, WBF, and SCA (p&lt;0.01). <h3>Conclusions:</h3> PIRA represents a major contributor to disability accumulation in MS. Baseline brain volume and spinal cord area were associated with PIRA suggesting a potential neurodegenerative mechanism for this type of disability accrual. <b>Disclosure:</b> Dr. Nakamura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INmune Bio. The institution of Dr. Nakamura has received research support from Biogen. The institution of Dr. Nakamura has received research support from PCORI. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from Novartis. The institution of Dr. Nakamura has received research support from DOD. Dr. Nakamura has received intellectual property interests from a discovery or technology relating to health care. Scott Husak has nothing to disclose. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck Serono. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astra Zeneca. Dr. Bermel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LabCorp. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care. 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. 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.

Change in Concomitant Therapies for Generalized Myasthenia Gravis in Patients Receiving Eculizumab: a Retrospective Analysis of Registry Data (P1-5.002)

<h3>Objective:</h3> To assess the use of concomitant therapies at and after eculizumab initiation in patients with generalized myasthenia gravis (gMG) enrolled in a registry. <h3>Background:</h3> Treatment for gMG includes a broad spectrum of therapies, including typical immunosuppressive therapies (ISTs) and eculizumab, a complement C5 inhibitor. <h3>Design/Methods:</h3> Patients enrolled in a US gMG registry that collects data on the use of eculizumab in clinical practice were included if they were treated with eculizumab for ≥ 1 year and had data on concomitant therapy use 12 months prior to eculizumab initiation. Use of azathioprine (AZA), mycophenolate mofetil (MMF), intravenous immunoglobulin (IVIg)/plasma exchange (PLEX), and oral corticosteroids at initiation of, and during eculizumab treatment were analyzed. The data cut-off was July 5, 2022. <h3>Results:</h3> A total of 94 patients were included in the analysis. At eculizumab initiation, 25 (27%), 40 (43%), 25 (27%) and 3 (4%) of patients were receiving zero, one, two, or three of the concomitant therapies investigated, respectively. Nine (10%) patients were on AZA, 26 (28%) on MMF, 19 (20%) on IVIg/PLEX and 47 (50%) on oral corticosteroids. In 57 (61%) patients, the number of concomitant therapies did not change. In 26 (24%) patients, there was a reduction in the number of concomitant therapies. Thirteen (14%) patients needed more treatments after eculizumab initiation. Of the patients using each treatment at eculizumab initiation, 2/9 (22%) patients discontinued AZA, 8/26 (31%) MMF, 5/19 (26%) IVIg/PLEX and 11/47 (23%) oral corticosteroids. <h3>Conclusions:</h3> Approximately one quarter of patients with gMG treated with eculizumab were able to discontinue one or more concomitant therapy. These results from clinical practice in the US provide additional information about the ability to reduce concomitant therapies in patients with gMG on treatment with eculizumab. <b>Disclosure:</b> Dr. Pulley has received personal compensation for serving as an employee of Alexion. Dr. Pulley has received personal compensation for serving as an employee of UCB. Dr. Pulley has received personal compensation for serving as an employee of MT Pharma America. Dr. Pulley has received personal compensation for serving as an employee of Alexion. Dr. Pulley has received personal compensation for serving as an employee of Immunovant. Dr. Pulley has received personal compensation for serving as an employee of Argenx. Dr. Pulley has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Multiple law firms. Dr. Macwan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion,Argenx,Catalyst,Kabafusion, UCB. Dr. Macwan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie,Alexion,Argenx,Biohaven,Catalyst,Grifols,Supernus. The institution of Dr. Macwan has received research support from Alexion, Disimmune Disease Foundation . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cour Pharma. The institution of Dr. Nowak has received research support from Ra Pharma. The institution of Dr. Nowak has received research support from Alexion . The institution of Dr. Nowak has received research support from Momenta . The institution of Dr. Nowak has received research support from Immunovant . Dr. Nowak has received research support from argenx. Dr. Nowak has received research support from Viela Bio . Dr. Nowak has a non-compensated relationship as a Member of the Board of Directors with Myasthenia Gravis Foundation of America (MGFA) that is relevant to AAN interests or activities. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Modis Therapeutics. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB/ Ra Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Maze Therapeutics. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for National Institutes of Health. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Neuromuscular Disease Foundation. The institution of Dr. Mozaffar has received research support from NIH. The institution of Dr. Mozaffar has received research support from Muscular Dystrophy Association. The institution of Dr. Mozaffar has received research support from Sanofi-Genzyme. The institution of Dr. Mozaffar has received research support from Argenx. The institution of Dr. Mozaffar has received research support from Amicus Therapeutics. The institution of Dr. Mozaffar has received research support from Spark Therapeutics. The institution of Dr. Mozaffar has received research support from Audentes Therapeutics. The institution of Dr. Mozaffar has received research support from Cartesian. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Rodrigues has received personal compensation for serving as an employee of Alexion Pharmaceuticals. Dr. Rodrigues has stock in Alexion Pharmaceuticals. Dr. Korideck has nothing to disclose. Mr. Werneburg has received personal compensation for serving as an employee of Alexion. Dr. Narayanaswami has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Narayanaswami has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Narayanaswami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx USA. Dr. Narayanaswami 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. Narayanaswami 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 Muscle and Nerve, Wiley. Dr. Narayanaswami has stock in Moderna. Dr. Narayanaswami has stock in Dr. Reddys laboratories. Dr. Narayanaswami has stock in Pfizer. Dr. Narayanaswami has stock in Viatris. Dr. Narayanaswami has stock in Doximity. The institution of Dr. Narayanaswami has received research support from Alexion. Dr. Narayanaswami has a non-compensated relationship as a Member, Medical and Scientific Advisory Board with Myasthenia Gravis Foundation of America that is relevant to AAN interests or activities. Dr. Narayanaswami has a non-compensated relationship as a Member, Board of Directors with AANEM that is relevant to AAN interests or activities.

A Scoping Review of Functional Neurological Disorder in Sexual and Gender Minority People (P1-12.004)

<h3>Objective:</h3> To report the literature regarding sexual and gender minority (SGM) people with functional neurological disorder (FND). <h3>Background:</h3> Minority stress and resilience theory describes the risks and protective factors that constitute social determinants of health and may increase neurological disparities among SGM communities. Little is known about the prevalence and experiences of SGM people with FND. <h3>Design/Methods:</h3> A search string with descriptors of SGM identity and functional somatoform disorders was entered into PubMed, Embase, Web of Science, PsycInfo, and CINAHL for articles that included SGM people diagnosed with FND, conversion disorder, or hysteria published before May 24, 2022, yielding 2940 items entered into Covidence. Two neurologists screened titles and abstracts based on predefined criteria, followed by a full-text review. A third neurologist adjudicated discrepancies. Eligible publications underwent data abstraction and statistical description. <h3>Results:</h3> Our search identified 4 published cases of presumed cisgender sexual minority (SM) people and 1 gender minority (GM) person with an FND or related diagnosis. GM people were overrepresented (5/106 [5%]) in a FND clinic sample compared to the general population (&lt;1%). Among cases, predominant presenting symptoms included seizures (n=2), tic-like behaviors (n=1), swallowing dysfunction (n=1), or mixed presentation with disturbed consciousness (n=1). Initial diagnoses were made by electroencephalography (n=3) and clinical history and non-specific studies (n=2). No neurological exam data were reported. Stressors related to SGM experience preceded onset in 3 cases with improvement coinciding with discussion and/or affirmation of SGM identity in 3 cases. <h3>Conclusions:</h3> Despite a methodologically rigorous search, limited data exist on FND in SGM communities. The data support the relevance of minority stress and resilience theory within the broader context of a stress-diathesis framework. More research is needed to understand and address known barriers to SGM-affirming care, which may be further exacerbated by FND-related stigma. <b>Disclosure:</b> Dr. L’Erario has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ohio State University, University of Colorado, Sacred Heart University, The LOFT LGBT Community Center . Dr. L’Erario has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Weiss Law. Dr. L’Erario has received publishing royalties from a publication relating to health care. Dr. Fusunyan has nothing to disclose. Mr. Stave has nothing to disclose. Dr. Waugh has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Two independent law firms. The institution of Dr. Waugh has received research support from AAN. Dr. Wilkinson-Smith has nothing to disclose. Ms. Roldan has nothing to disclose. Dr. Keuroghlian has received publishing royalties from a publication relating to health care. Jack Turban has nothing to disclose. Dr. Perez 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 Wiley: Brain and Behavior. The institution of Dr. Perez has received research support from NIH. The institution of Dr. Perez has received research support from Sidney R. Baer Jr. Foundation. Dr. Perez has received publishing royalties from a publication relating to health care. Dr. Maschi has nothing to disclose. Dr. Rosendale 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. The institution of Dr. Rosendale has received research support from American Academy of Neurology. The institution of Dr. Rosendale has received research support from NIH StrokeNet Fellowship. Dr. Rosendale has received publishing royalties from a publication relating to health care.

Mortality and functional outcomes in patients with post-stroke epileptic seizures: a systematic review and meta-analysis (S45.006)

<h3>Objective:</h3> To conduct a meta-analysis of published data to comprehensively investigate clinical and functional outcomes in post-stroke epilepsy (PSE) patients. <h3>Background:</h3> It is critical to highlight the burden of PSE on patient outcomes. Whereas PSE has been reported to worsen outcomes in stroke patients, published data are inconclusive. <h3>Design/Methods:</h3> We used Covidence to conduct a literature search of studies published until 1-March-2022. We used Joanna Briggs Institute tool for cohort studies to assess the risk of bias. Our outcome measures include mortality and poor outcomes (Rankin Scale score 3–6). We report Odds ratio (OR) and 95% Confidence Intervals (CI) using a random-effect meta-analysis. Publication bias was assessed using Egger’s test. We conducted the statistical analyses in R version 4.2.0. (PROSPERO ID: CRD42022308648) <h3>Results:</h3> We screened 3721 studies and included 71 articles (N= 29,759 patients with PSE; 17,42,083 patients without PSE). Articles reported 3938 early and 13,067 late seizures; 12,754 seizures were not classified as early/late. Risk of bias was high in two studies, moderate in 36 and low in 33. PSE was associated with greater odds of mortality (OR 2.09; CI 1.78–2.45; N= 52 studies) and poor outcomes (OR 2.39; CI 1.91–3.00; N= 19 studies). In subgroup analyses, post-ischemic stroke epilepsy was associated with mortality (OR 2.31; CI 1.88–2.83) and poor outcome (OR 2.60; CI 1.91–3.52). Post-hemorrhagic stroke epilepsy showed consistently significant OR for the poor outcome (OR 2.04; CI 1.33–3.13) but failed to reach statistical significance for mortality (OR 1.29; CI 0.96–1.74). No significant publication bias was observed for mortality (p=0.93) and poor outcome (p=0.17). <h3>Conclusions:</h3> Our meta-analysis suggests that PSE is associated with a doubled risk of death and severe disability. Prevention of PSE should be a high research priority. The role of stroke severity or lesion volume also requires further study. <b>Disclosure:</b> Mr. Misra has nothing to disclose. Juan Vazquez, MD has nothing to disclose. Ms. Eldem has nothing to disclose. Lucas Silva has nothing to disclose. Dr. Mohadat has nothing to disclose. Dr. Hickman has nothing to disclose. Ms. Khan has nothing to disclose. Mrs. Funaro has nothing to disclose. Clarissa Yasuda has nothing to disclose. Dr. Liebeskind has received research support from Cerenovus. Dr. Liebeskind has received research support from Genentech . Dr. Liebeskind has received research support from Medtronic. Dr. Liebeskind has received research support from Stryker. Dr. Kasner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb. Dr. Kasner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Diamedica. Dr. Kasner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Kasner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Kasner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca. Dr. Kasner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Javelin. Dr. Kasner 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 UpToDate. The institution of Dr. Kasner has received research support from Bristol-Myers Squibb. The institution of Dr. Kasner has received research support from Medtronic. The institution of Dr. Kasner has received research support from WL Gore. Dr. Mishra has nothing to disclose.

Minimal acceptable functional outcomes according to surrogates and professionals caring for unconscious patients (P3-7.003)

<h3>Objective:</h3> To determine the minimum level of recovery (LOR) deemed acceptable by surrogate decision makers and healthcare professionals (HCPs) of unconscious patients with intracerebral hemorrhage (ICH). <h3>Background:</h3> Prognosticating recovery of acutely brain-injured patients is imprecise but may be improving with the development of novel technology. Understanding acceptable functional outcomes and factors that influence these thresholds for families and caregivers of patients with neurological injury is critical to ensure effective communication and the delivery of goal-concordant care. <h3>Design/Methods:</h3> We prospectively recruited surrogates and HCPs caring for unconscious patients with ICH. Participants completed a thirteen-item survey that captured data on demographics, education, and religiosity. Respondents selected the minimum LOR they would deem acceptable one-year post-injury. Response options were adapted from the Glasgow Outcome Scale–Extended and ranged from “survival” to “full recovery.” <h3>Results:</h3> A total of 134 participants completed the survey, including 85 HCPs (40 physicians/PAs, 45 RNs) and 49 surrogates. The majority of participants were female (65%) and completed at least some college (93%). HCPs were more likely than surrogates to choose a higher minimum acceptable LOR (median 4 [IQR 3–5] vs 3 [IQR 2.5–5]; OR 4.1, 95%-CI 2.1–8.1, p=0.00008). Among all respondents, participants who identify as Black/African-American were less likely to choose a higher LOR (median 3 [IQR 2–4] vs 4 [IQR 3–5]; OR 0.2, 95%-CI 0.1–0.5, p=0.002). Participants who indicated religion was “the most important part” of their life were less likely to choose a higher LOR (median 3 [IQR 2–3] vs 4 [IQR 3–5]; OR 0.3, 95%-CI 0.1–0.9, p=0.032). In a multivariate model, HCP vs. surrogate status was the only significant predictor; HCPs were more likely than surrogates to choose a higher LOR ([OR 2.2, 95%-CI 1.0–4.6, p=0.048). <h3>Conclusions:</h3> This study highlights the need for HCPs to recognize in goals of care discussions that surrogates find acceptable a lower LOR than do HCPs themselves. <b>Disclosure:</b> Mr. Heinonen has nothing to disclose. Miss Carmona has nothing to disclose. Kevin Doyle has nothing to disclose. Ms. Grobois has nothing to disclose. Miss Kruger has nothing to disclose. Dr. Velazquez has nothing to disclose. Ms. Vrosgou has nothing to disclose. Dr. Shen has nothing to disclose. Mrs. Cespedes has nothing to disclose. Ms. Yazdi has nothing to disclose. Dr. Ghoshal has nothing to disclose. Dr. Roh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Portola Pharmaceuticals. Dr. Agarwal has nothing to disclose. Dr. Park has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurocritical Care. The institution of Dr. Park has received research support from National Institutes of Health. The institution of Dr. Dugdale has received research support from McDonald Agape Foundation. Dr. Dugdale has received publishing royalties from a publication relating to health care. Dr. Dugdale has received publishing royalties from a publication relating to health care. Dr. Dugdale has received personal compensation in the range of $500-$4,999 for serving as a Speaking honoraria for various lectures with Multiple organizations. Dr. Claassen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus. Dr. Claassen has stock in iCE Neurosystems. The institution of Dr. Claassen has received research support from NINDS. The institution of Dr. Claassen has received research support from McDonnel Foundation. Dr. Claassen has received publishing royalties from a publication relating to health care. Dr. Claassen has received publishing royalties from a publication relating to health care.

Guillain-Barré Syndrome Following Primary Cytomegalovirus Infection in a Patient with Liver Transplantation: a Case Report (P10-5.002)

<h3>Objective:</h3> To report the case of a patient who underwent liver transplantation and developed Guillain-Barré syndrome (GBS) as a result of primary cytomegalovirus (CMV) infection. <h3>Background:</h3> GBS is the most common etiology of paralysis worldwide and it is an autoimmune-mediated neuropathy that is frequently caused by a preceding infection. Although the relationship between CMV and GBS is well known, only about 4% of cases are specifically attributable to this infection. Likewise, few cases of GBS have been reported in the context of liver transplant recipients, and in the majority of cases, it is not ascribable to the CMV infection. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> A 66-year-old male patient with a 5-month medical history of liver transplantation secondary to hepatocellular carcinoma, is seen in the emergency room with a progressive ascending limb weakness and foot dysesthesias for the past eight days. Interestingly, three days before the onset of the symptoms, he presented a self-resolved gastrointestinal infection. Neurological examination revealed decreased strength and areflexia in all extremities, especially in the lower limbs. Nerve conduction studies and electromyography showed an acute inflammatory demyelinating polyneuropathy (AIDP) consistent with the diagnosis of GBS. Lumbar puncture ruled out any potential neuro infections and revealed the typical albuminocytologic dissociation. Additionally, a FilmArray panel was negative for other gastrointestinal pathogens. However, a significant CMV serum viral load indicated an active infection. Therapy with IV immunoglobulin and valganciclovir was started, with symptoms considerably improving after five days. <h3>Conclusions:</h3> GBS can be a rare complication after solid organ transplantation. Although post-transplant immunosuppression is known to increase the likelihood of contracting CMV opportunistic infections, GBS has not been frequently linked to this condition. Also, to our knowledge, this is one of few reports where it occurs after a primary CMV infection in the context of a liver transplant recipient, while other frequent etiologies were ruled out. <b>Disclosure:</b> Dr. Toro has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Watch Neurology . Dr. Gaitan Alfonso has nothing to disclose. Thomas Medina has nothing to disclose. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BIIB. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Merck. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. Dr. Reyes has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen.

Precision Neurology for Dementia (P2-6.002)

<h3>Objective:</h3> To establish a precision medicine workflow for Alzheimer’s disease and related dementias (AD/ADRDs) and assess its impact. <h3>Background:</h3> AD/ADRDs are clinically, pathologically, and genetically heterogeneous. Precision medicine promises individualized, etiologic diagnosis and ultimately, targeted therapies. <h3>Design/Methods:</h3> 27 participants have been enrolled from the Houston community (n=13) or neurology outpatient clinics (n=14) at Baylor College of Medicine or Houston Methodist Hospital, including individuals with established AD/ADRD, mild cognitive impairment (MCI), or no known cognitive impairment (NCI). Participants received (i) comprehensive neurologic and neuropsychological assessments (NACC Uniform Data Set), (ii) brain MRI and amyloid PET, and (iii) CAP-CLIA whole genome sequencing. Genome data was filtered using a virtual gene panel specifically developed for this project, including 219 causes of AD/ADRD, cardiovascular diseases, or other medically-actionable conditions unrelated to dementia, along with 3 ADRD/cardiovascular risk genes. All subjects were consented for comprehensive disclosure of dementia risk. <h3>Results:</h3> Participants had a mean age=70, were 41% female, and reported mixed race/ancestry (white=66%, Hispanic/Latino=18%, African American=7%, Asian=7%). Following baseline assessments and prior to neuroimaging biomarkers, participants had clinical diagnoses of AD (n=7), Lewy body dementia (n=1), MCI (n=8), and NCI (n=11). All participants were negative for known monogenic causes of dementia. 15 individuals (56%) had increased dementia risk due to <i>APOE</i>; two participants carried the <i>lipoprotein(a)</i> cardiovascular risk allele; and three individuals had medically actionable, ACMG-reportable secondary findings. Neuroimaging studies are currently being reviewed, and results will be integrated for etiologic diagnosis using the 2018 NIA-AA research (A/T/N) framework. In disclosure visits, all participants will receive precision diagnostic results and a personalized genomic risk report. Surveys will assess perspectives including perceptions of the experience, psychological impact, self-efficacy, quality of life, advance planning, and health behaviors. <h3>Conclusions:</h3> Overall, our experience and emerging results establish feasibility and will inform implementation of precision neurology for dementia. <b>Disclosure:</b> The institution of Dr. Shulman has received research support from National Institutes of Health. Dr. Shulman has received personal compensation in the range of $10,000-$49,999 for serving as a Advisory Council member with Helis Medical Foundation. The institution of Dr. Vanegas-Arroyave has received research support from National Institutes of Health. Jamie Fong has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Sarah Elsea has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dicerna. Sarah Elsea has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers. The institution of Sarah Elsea has received research support from NIH. The institution of Sarah Elsea has received research support from Speragen. The institution of Sarah Elsea has received research support from PTC Therapeutics. The institution of Sarah Elsea has received research support from PRISMS, Inc. The institution of Sarah Elsea has received research support from Smith-Magenis Syndrome Research Foundation. The institution of Sarah Elsea has received research support from Jerome Lejeune Foundation. Dr. Lin has a non-compensated relationship as a Secretary with Broadway for Ataxia Foundation (a 501 (c) (3) non-profit organization) that is relevant to AAN interests or activities. Hiba Saade has nothing to disclose. Miss Chavez has nothing to disclose. Ms. Walker has stock in Thermo Fisher Scientific. The institution of Ms. Walker has received research support from NIH - All of Us Program. Bo Yuan has nothing to disclose. Dr. Venner has stock in Codified Genomics. Dr. Hu has nothing to disclose. Mr. Levchenko has nothing to disclose. Dr. Smith has nothing to disclose. Ms. Robinson has nothing to disclose. The institution of Prof. Pascual has received research support from NIH. The institution of Prof. Pascual has received research support from NIH. The institution of Donna Muzny has received research support from NIH. Richard Gibbs has nothing to disclose. Dr. McGuire has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Danaher Life Sciences. Dr. McGuire has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Greenwall Foundation. Dr. McGuire has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for King and Spalding. Dr. McGuire has stock in Facebook. The institution of Dr. McGuire has received research support from NIH. The institution of Dr. McGuire has received research support from Greenwall Foundation. Dr. Masdeu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Masdeu has received research support from NIH. The institution of Dr. Masdeu has received research support from Moody Foundation. The institution of Dr. Masdeu has received research support from Biogen. The institution of Dr. Masdeu has received research support from Eli Lilly. The institution of Dr. Masdeu has received research support from Eisai. The institution of Dr. Masdeu has received research support from Novartis. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received personal compensation in the range of $100,000-$499,999 for serving as a Director, Nantz Nal Alzheimer Center with HOUSTON METHODIST NEUROLOGICAL INSTITUTE.

Case Study: A Heart Transplant Recipient with New, Severe Headache (P3-12.011)

<h3>Objective:</h3> To describe a case and raise awareness of tick-borne disease as an important cause of secondary headache in transplant recipients. <h3>Background:</h3> Tick-borne illness is an uncommon but important cause of secondary headache, especially within the transplant population. Organ transplant recipients have a 2.3-fold relative risk of death and of severe, systemic infection. Identification of risk factors for tick-borne disease is essential to reduce morbidity and mortality in this patient population. <h3>Design/Methods:</h3> Case Study <h3>Results:</h3> A middle-aged patient with history of a prior heart transplant was admitted with headache for four days. The pain was mild initially but soon worsened and was exacerbated by bright lights, coughing, and changes in head position. He had never experienced similar pain or migraine. Medications included daily sirolimus, tacrolimus, and prednisone. The patient lived in the rural Midwest. The patient was afebrile and other vital signs were stable. Exam was notable for positive Jolt accentuation and negative Kernig/Brudzinski signs and no noticeable rashes. He was oriented but was unable to spell the word “world” backwards. Otherwise, exam was normal. Lumbar puncture revealed clear CSF with 0 RBC/cumm, 0 Nucleated cells/cumm, Protein 57 mg/dL (H), Glucose 62 mg/dL (serum glucose 100 mg/dL). Bacterial/fungal cultures demonstrated no organisms on Cytospin gram staining. VZV, CMV, WNV, and HSV PCR analyses were sent. Other labs were significant for hyponatremia (132 mmol/L), leukopenia (1.9 K/cumm), microcytic anemia (Hgb 10.9 g/dL, MCV 74 fL), and thrombocytopenia (81 K/cumm). CT Head and MRI brain were normal. This patient’s CSF viral PCR studies returned negative. A qualitative blood PCR assay for <i>Ehrlichia chaffeensis, E. ewingii</i>, and <i>E. canis</i> returned positive. The patient received doxycycline for a 10-day course with improvement. <h3>Conclusions:</h3> Identification of tick-borne disease in patients with a history of chronic immune suppression is necessary to avoid complications related to this relatively uncommon cause of infection. <b>Disclosure:</b> Dr. Anderson has nothing to disclose. Mary Petrulis has nothing to disclose. Dr. Wu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Progentec. Dr. Wu 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. Wu has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimmunology. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Department of Justice.

Feasibility and Insights from Automated Depression and Anxiety Screening for People with Epilepsy (P1-1.004)

<h3>Objective:</h3> To describe how systematic screening for depression and anxiety was accomplished in a tertiary epilepsy clinic and describe the insights that the data provided to quality improvement teams. <h3>Background:</h3> Mental health comorbidities are highly prevalent among people living with epilepsy (PWE), leading to poor quality of life. Thus, routine screening for anxiety and depression allows for early diagnosis, referral, and treatment of these comorbidities for PWE, improving health outcomes. Mental health screening feasibility concerns have emerged in multiple clinical practices, challenging epilepsy clinics to adopt new practices. <h3>Design/Methods:</h3> We conducted a retrospective data analysis from the Electronics Health Record as part of a Quality Improvement initiative in two tertiary epilepsy clinics (Massachusetts General Hospital and Barrow Neurological Institute), comprising January 2019 to October 2022. PWE were offered patient-reported e-questionnaires to create a cohort based on the completion of depression (PHQ-9) and anxiety (GAD-7) screenings. We stratified the records by demographic measures and classified patients based on the severity of depression and anxiety. Moreover, we created a sub-cohort that includes only the records that met Seizure Freedom criteria and calculated the number of observations for Seizure Freedom about the severity of both depression and anxiety. <h3>Results:</h3> A total of 813 PWE offering depression and anxiety e-questionnaires were filtered, of which n=500 and n=94 completed PHQ-9 and GAD-7 questionnaires respectively, with a completion rate of 73%. For PHQ-9 completed patients, 54% had no/minimal depression, 20.2% mild depression, 13% moderate depression, and 12.8% severe depression. Most patients achieving seizure freedom were with no/minimal depression. For GAD-7 completed patients, 22.3 % had no/minimal anxiety, 19.2 % mild anxiety, 30.8 % moderate anxiety, and 27.7 % severe anxiety. <h3>Conclusions:</h3> Virtual routine screening is feasible in busy tertiary epilepsy clinics as part of care for PWE to identify psychiatric comorbidities, serving as a crucial tool to guide further treatment decisions. <b>Disclosure:</b> Dr. Coelho has nothing to disclose. Dr. Donahue has nothing to disclose. Miss Sevak has nothing to disclose. Poojith Nuthalapati has nothing to disclose. Dr. Buchhalter has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Epilepsy Foundation. Dr. Buchhalter has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Epilepsy Study Consortium. Dr. Buchhalter has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Epilog. Dr. Buchhalter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Buchhalter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shackelford Pharmaceuticals. Dr. Buchhalter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Fureman has received personal compensation for serving as an employee of Epilepsy Foundation. The institution of Dr. Fureman has received research support from PCORI/Cincinnati Children’s Hospital Medical Center. The institution of Dr. Fureman has received research support from PCORI. The institution of Dr. Fureman has received research support from UCB Biopharma SPRL. The institution of Dr. Fureman has received research support from CDC. The institution of Dr. Herman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bioserenity. Dr. Herman has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for National Association of Epilepsy Centers. Dr. Herman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Treatment Options in Neurology. Dr. Herman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Neurophysiology. The institution of Dr. Herman has received research support from Epilepsy Foundation; Epilepsy Learning Healthcare System. The institution of Dr. Herman has received research support from CREMedical. The institution of Dr. Herman has received research support from NIH/NINDS. The institution of Dr. Herman has received research support from Marinus. Dr. Herman has received personal compensation in the range of $500-$4,999 for serving as a Medical Director, Neurodiagnostics Program with Laboure College. Dr. Herman has a non-compensated relationship as a Professional Advisory Board member with Epilepsy Foundation that is relevant to AAN interests or activities. Dr. Moura has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for eNova. Dr. Moura has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Epilepsy Foundation. The institution of Dr. Moura has received research support from NIH-NIA - 1K08AG053380-01A1. The institution of Dr. Moura has received research support from NIH-NIA 5R01AG062282-02 . The institution of Dr. Moura has received research support from NIH-NIA 2P01AG032952-11 . The institution of Dr. Moura has received research support from NIH- NIA 3R01AG062282-03S1 . The institution of Dr. Moura has received research support from Centers for Diseases Control and Prevention (CDC SIP20-007) . The institution of Dr. Moura has received research support from Epilepsy Foundation of America .

Profile of serum biomarkers in seronegative NMOSD (S50.009)

<h3>Objective:</h3> Aim of this study is to characterise the neuronal, axonal, and glial damage in seronegative NMOSD in comparison with AQP4+NMOSD <h3>Background:</h3> serum GFAP and NfL define disease activity in different neurological conditions. These biomarkers increase in patients with AQP4+NMOSD during clinical attacks, with contradictory results in seronegative-NMOSD. <h3>Design/Methods:</h3> patients with double (i.e. for AQP4 and MOG-Abs) seronegative-NMOSD and age-matched AQP4+NMOSD with available onset/relapse serum samples (i.e. obtained within 3 months) were retrospectively enrolled. Clinical and radiological data were collected. Serum NfL, GFAP, Tau and UCH-L1 levels were determined using an ultrasensitive paramagnetic bead-based enzyme-linked immunosorbent assay (SIMOA). Statistical analysis was performed using parametric and non-parametric tests and ROC analysis <h3>Results:</h3> 27 seronegative-NMOSD and 24 AQP4+NMOSD patients were included. Median age at sampling was 36.2 years [IQR 27.0–49] with no statistical differences between groups. Most common syndromes at sampling in both seronegative-NMOSD and AQP4+NMOSD were myelitis (37% vs 54.2%) and optic neuritis (33.3% vs 37.5%). Median EDSS at sampling was 3.5 [IQR 2.5–7.0], with no significant difference between the two groups. Serum GFAP, Tau and UCH-L1 levels were significantly higher in AQP4+NMOSD compared to seronegative-NMOSD patients (median 304.1 vs 160.5 pg/mL <i>p</i>=0.005; median 24.8 vs 13.3 pg/mL, <i>p</i>= 0.002; and median 60 vs 37.3 pg/mL, <i>p</i>=0.021, respectively), as confirmed by ROC analysis, while NfL levels were similar (<i>p</i>=0.270). In the seronegative-NMOSD group, NfL and UCH-L1 levels correlated with EDSS at attack nadir (rho 0.438, <i>p</i>=0.032 and rho 0.429 <i>p</i>=0.036, respectively), while in the AQP4+NMOSD group this correlation was observed for NfL, UCH-L1, and GFAP levels (rho 0.745, <i>p</i>=0.010; rho 0.448, <i>p</i>=0.32, rho 525, <i>p</i>= 0.010, respectively). <h3>Conclusions:</h3> serum GFAP, Tau, and UCH-L1 levels discriminate between AQP4+NMOSD and seronegative-NMOSD. The different biomarkers profile suggests heterogeneity of diseases and provides useful data to improve our understanding of these diseases <b>Disclosure:</b> Dr. Carta has nothing to disclose. Dr. Dinoto has nothing to disclose. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Marco Alfonso Narduc Capobianco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Valentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche S.p.a.. Dr. Lo Re has nothing to disclose. Ms. Chiodega has nothing to disclose. Pierre Branger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NOVARTIS. Pierre Branger has received personal compensation in the range of $0-$499 for serving as a Consultant for BIOGEN. Pierre Branger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MERCK. Pierre Branger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Bertrand Audoin has nothing to disclose. Jennifer Aboab, 8220 has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for SANOFI. Caroline Papeix has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIOGEN . Caroline Papeix has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE . Caroline Papeix has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MERCK. Caroline Papeix has received personal compensation in the range of $0-$499 for serving as a Consultant for NOVARTIS . Nicolas Collongues, MD has nothing to disclose. Philippe Kerschen has nothing to disclose. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BIogen Idec. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for novartis. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BMS. Helene Zephir has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Alain Creange has nothing to disclose. Bertrand Bourre has nothing to disclose. The institution of Dr. Flanagan 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. Flanagan 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. Flanagan 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. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received research support from Viela Bio. Dr. Flanagan has received research support from UCB. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Redenbaugh has nothing to disclose. Javier Villacieros-Álvarez has nothing to disclose. The institution of Dr. Arrambide 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. The institution of Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. The institution of Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Arrambide 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 Dr. Arrambide has received research support from Instituto de Salud Carlos III. Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving as a Travel support for scientific meetings with Novartis. Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving as a Travel support for scientific meetings with Roche. Dr. Arrambide has received personal compensation in the range of $500-$4,999 for serving as a Travel support for scientific meetings with ECTRIMS. Dr. Arrambide has a non-compensated relationship as a Member of the Executive Committee with iWiMS that is relevant to AAN interests or activities. Dr. Arrambide has a non-compensated relationship as a Member of the steering committee with BioMS-eu that is relevant to AAN interests or activities. Dr. Cobo Calvo has nothing to disclose. Sergio Ferrari has nothing to disclose. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Marignier has received personal compensation in the range of $0-$499 for serving as a Consultant for ALEXION. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROCHE. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HORIZON THERAPEUTICS. Dr. Marignier has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROCHE. Dr. Mariotto has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.