Acute Encephalomyelitis Research Articles

High-throughput Multidimensional Characterization of CD8 T cells in MOG Antibody-Associated Disease

Abstract Inflammatory demyelinating diseases of the central nervous system (CNS) include clinically and pathologically distinct disorders. Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is a recently characterized antibody-mediated inflammatory demyelinating disorder of the CNS with clinical presentations which include optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. The heterogenous clinical course of MOGAD along with unclear prognostic biomarkers makes treatment challenging, as some individuals have monophasic disease while others relapse. Recent work has attempted to identify biomarkers by performing scRNA-seq on the peripheral blood mononuclear cells (PBMC) of MOGAD patients and has highlighted an enrichment for a cytotoxic effector CD8 +T cell subset in MOGAD compared to healthy controls. However, this subset of cells remains under characterized, with questions regarding their antigen specificity, clonality, and overall involvement in MOGAD. To further characterize this cell subset, we utilize a single cell technology, TetTCR-SeqHD, to evaluate the antigen-specificity, clonality, gene expression, and surface protein expression of CD8 +T cells isolated from the PBMC of MOGAD patients. In this approach, a large library of fluorescently labeled, DNA barcoded peptide-MHC tetramers are generated utilizing peptides derived from MOG or associated proteins such as myelin basic protein and proteolipid protein which are then used to isolate antigen specific CD8+ T cells for single cell analysis. Preliminary results show an enrichment of a distinct CD161 ++TRAV1–2 +MAIT cell population in MOGAD, which has been previously implicated in other chronic inflammatory diseases. This work is supported by the Chan Zuckerberg Initiative Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award.

Neuromielitis óptica y enfermedad anti-MOG

The classic term neuromyelitis optica (NMO) has been replaced by NMO spectrum disorder (NMOSD) as a result of the identification of the diagnostic marker of the disease (IgG-AQP4) and the inclusion of features such as area postrema syndrome or diencephalic disturbances, among others. The article includes the diagnostic criteria for IgG-AQP4 positive and negative NMOSD and describes the treatments used in the acute phase and to prevent relapses (namely, oral steroid-sparing drugs, rituximab, tocilizumab, and drugs specifically developed for the disease). Some of the patients with seronegative IgG-AQP4 NMOSD will show positivity for the IgG-MOG (myelin oligodendrocyte glycoprotein) marker, which can also manifest as recurrent optic neuritis, acute disseminated encephalomyelitis, or conus medullaris syndrome, among others. The possibility of recurrences in some cases of persistently seropositive anti-MOG associated disease prompts the chronic use of immunomodulators in a similar way to TENMO, with the particularity of the usefulness of immunoglobulins in children. Finally, the epidemiological, clinical, paraclinical and therapeutic differences between multiple sclerosis, TENMO and anti-MOG disease are described.

CBL Syndrome: At the Intersection of Inborn Error of Immunity and Cancer Predisposition

CBL syndrome is a form of RASopathies due to heterozygous germline mutations of the Casitas B-lineage lymphoma (CBL) gene. CBL encodes the cbl family of proteins which function as E3 ubiquitin ligases that negatively regulate intracellular signaling by various receptor tyrosine kinases including RAS-MAPK pathway. Individuals with CBL syndrome have variable clinical presentation but phenotypically resembles Noonan syndrome with predisposition to JMML. Patients affected by RASopathies are at risk to develop autoimmune disorders given the role of Ras-MAPK signaling pathway in peripheral tolerance. Prior mice studies suggested the role of cbl protein as negative regulator of TCR-mediated signaling. We describe a case of CBL syndrome presenting with multiple autoimmune conditions and reviewed reported cases in literature.A 14-year old male presented with pancytopenia, autoimmune thyroiditis and organomegaly. His past medical history was remarkable for ADHD, speech delay, short stature, idiopathic hepatosplenomegaly and history of acute disseminated encephalomyelitis at age 5. His bone marrow evaluation was normal. A somatic NGS panel identified VUS in CBL (c.1193A>G, p.H398R) with VAF of 53%. Autoimmune work up showed elevated ANA, DNA antibody, RNP antibody titer and mildly positive anti-C3 antibody. Immunophenotyping revealed normal Ig profile, NK cytopenia, T cell lymphopenia, decreased naïve T cells and elevated CD8+ effector memory T cell activation. ALPS genetic panel revealed paternally inherited VUS in CTLA4 which was later determined to be benign. Since his cytopenias did not respond to IVIG, he was treated with corticosteroid with improvement in counts although he remained thrombocytopenic. A skin biopsy was performed and sequencing of patient’s fibroblast DNA demonstrated a germline origin of CBL variant. Parental DNA sequencing confirmed a de novo event. Literature review revealed 28 germline CBL mutations (Figure 1), most of which were missense mutations (78%). At least nine of these mutations (32%) have been associated with immune dysregulation including autoimmune cytopenias, aHUS, RA, autoimmune thyroiditis, vasculitis and HLH. JMML has been reported in more than half of these germline mutations. [Display omitted] In conclusion, immune dysregulation is a common feature of CBL syndrome in addition to JMML. CBL syndrome should be considered in the differential diagnosis of individuals with ALPS-like phenotypes.

A case of acute disseminated encephalomyelitis precipitated by Venetoclax

The authors declare no conflict of interest for this article.

Clinical and Radiologic Features of a Cohort of Adult and Pediatric Patients in the Pacific Northwest with Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) (P13-5.022)

<h3>Objective:</h3> To describe a cohort of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) seen at a tertiary center in the pacific northwest. <h3>Background:</h3> MOGAD is a newly described clinical entity comprised of various presentations of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), encephalitis, and seronegative NMOSD. Patients may sustain only one attack or have a relapsing course necessitating immunotherapy for relapse prevention. Prior reports note that MOGAD is more commonly monophasic in children (up to 70%), though 30–80% of children and adults with MOGAD will go on to have relapses and there is no way to predict who is at risk. <h3>Design/Methods:</h3> This was a single-center retrospective cohort study. <h3>Results:</h3> This preliminary sample consisted of 56 patients (20 pediatric, 36 adult) with a diagnosis of MOGAD evaluated at least once at our center between January 2017 and October 2022. Non-Hispanic White (55.4%) and Hispanic (30.4%) comprised the majority of the sample. The median age during index event was 9.27 years in the pediatric subset and 36.1 in the adults. Amongst the whole cohort, the most common presentation at onset was optic neuritis (58.9%) though the majority of pediatric cases presented with (ADEM) (40.0%). The pediatric group had more patients with relapsing disease (70.0%) compared to the adult group (55.6%). Half of relapsing pediatric patients had their first relapse more than a year after the index event with a median time to first relapse of 15.5 months. The median time to first relapse in the adult group was 7.0 months. None of the patients in the pediatric group were started on immunotherapy for relapse prevention prior to the first relapse though a subset of adult patients were (19.4%). <h3>Conclusions:</h3> This study is the first to describe the demographic and clinical features of a unique sample of patients with MOGAD evaluated in the pacific northwest. <b>Disclosure:</b> Dr. Martin has received research support from Tartar Trust. The institution of Dr. Martin has received research support from OHSU Foundation. Mrs. Srikanth has nothing to disclose. Dr. Angappan has nothing to disclose. Miss Srikanth has nothing to disclose. Dr. Kanwar has nothing to disclose. Miss Mazmanyan has nothing to disclose. Julie Falardeau has nothing to disclose. David Pettersson has nothing to disclose. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb Foundation. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD-Serono . The institution of Dr. Yadav has received research support from Department of Veterans Affairs. Dr. Yadav has received research support from NIH. Dr. Yadav has received research support from PCORI. Dr. Yadav has received research support from NMSS. The institution of Dr. Yadav has received research support from Department of Veterans Affairs. The institution of Dr. Yadav has received research support from Tykeson Family Foundation Endowed Professorship.

Neurological Manifestations Post-COVID-19 Vaccination: A Review of Case Studies (P12-3.010)

<h3>Objective:</h3> To discern the central (CNS) and peripheral nervous system (PNS) manifestations associated with COVID-19 vaccines from individual case studies and describe their clinical and imaging findings, management, and outcomes. <h3>Background:</h3> With ten vaccines approved by the World Health Organization (WHO) and nearly 64% of people fully vaccinated worldwide, we have observed several neurological presentations post-COVID-19-vaccination, such as acute disseminated encephalomyelitis (ADEM), which have been reported in the Vaccine Adverse Event Reporting System (VAERS) and the Medicines and Healthcare products Regulatory Agency (MHRA). <h3>Design/Methods:</h3> A thorough literature search of Google Scholar and PubMed was conducted from December 2020 to October 2021, which included case reports of neurological complications with the following COVID-19 vaccines: Pfizer-BioNTech, Moderna, J&amp;J/Janssen, AstraZeneca, Sinovac-CoronaVac, Sputnik V, and COVAXIN. <h3>Results:</h3> Among the 51 cases, AstraZeneca was the most frequently administered vaccine (28, 55%), followed by Pfizer-BioNTech (8, 16%), Moderna (2,4%), Janssen (2,4%), Sputnik (1, 2%), and COVAXIN (1, 2%). The most common CNS manifestation was cerebral venous sinus thrombosis (CVST) (n=14) in females (64%) younger than 50 years (71%) after the first AstraZeneca dose (93%). Others included CNS demyelinating disorders [transverse myelitis, ADEM, multiple sclerosis, and neuromyelitis optica] (n=9), encephalopathy/encephalitis (n=3), seizures (n=3), and aseptic meningoencephalitis (n=1). The most common PNS manifestation was Guillain–Barré syndrome (GBS) (n=14) in males (71%) older than 50 years (79%), followed by Bell’s palsy (n=5), small fiber neuropathy (n=1), and phantosmia (n=1); most of these occurred with AstraZeneca (28.55%) and Pfizer-BioNTech (9.18%). IVIG and steroids were the treatment of choice. Nine out of the 14 patients with CVST (64%) died. However, most cases overall (42 out of 51) were non-fatal (82%). <h3>Conclusions:</h3> Several post-marketing CNS and PNS adverse events have occurred following the COVID-19 vaccination, including CVST, GBS, and TM. Further studies with non-vaccinated controls might help understand the pathophysiologic mechanisms of these neurological manifestations. <b>Disclosure:</b> Miss Beard has nothing to disclose. Kanika Sharma has nothing to disclose. Dr. Sharma has nothing to disclose. Dr. Basha has nothing to disclose. Mr. JHA has nothing to disclose. Dr. Sriwastava has nothing to disclose.

Cerebral Attacks in MOG Antibody-Associated Disease: Clinical Spectrum and Fulfillment of ADEM criteria (S40.007)

Cerebral Attacks in MOG Antibody-Associated Disease: Clinical Spectrum and Fulfillment of ADEM criteria (S40.007)

Diseases associated antibodies anti-MOG and double seronegative NMOsd during the COVID-19 pandemic. Interim analysis of a cohort study. (P13-5.012)

<h3>Objective:</h3> To describe the clinical and demographic findings of patients from the National Institute of Neurology and Neurosurgery anti-MOG validation cohort tested for anti-MOG and anti-AQP4. <h3>Background:</h3> Anti-MOG associated diseases (MOGAD) include demyelinating disease phenotypes such as optic neuritis, longitudinally extensive transverse myelitis, acute disseminated encephalomyelitis, Neuromyelitis Optica syndrome (NMOsd) among others. In our country, the incidence of this pathology is unknown, mainly due to the lack of diagnostic tools. <h3>Design/Methods:</h3> As part of the cohort of the National Institute of Neurology and Neurosurgery in Mexico, for the validation of a MOG CBA-assay, anti-AQP4 and MOG antibody tests were requested from those patients who met the Jarius 2018 criteria for MOGAD. Measurements of central tendency are made for each group and we analyze the MOG+ and double seronegative groups with Fisher’s exact and Mann Whitney. <h3>Results:</h3> Eighteen patients were analyzed. Seven patients were MOG+, 62% women. The mean age for patients with MOG was 40 years. Presentation was 100% atypical optic neuritis. The anterior segment was more affected in 42% of the patients. Five (71.4%) patients had a deficit &gt;200/100, 3 of them improved to 20/40 regardless of whether or not they received plasmapheresis (X2 0.833 p=0.361). Post-vaccination possibility was documented in 57%. There were no significant differences between patients with different sero-status. Four patients are maintained with Rituximab support treatment. <h3>Conclusions:</h3> MOG+ patients were mostly women, despite a severe initial deficit, an adequate visual recovery was documented regardless of the plasmapheresis time. A larger number of patients are required to perform a pairwise comparison with those with AQP4+. <b>Disclosure:</b> Dr. Rodriguez has nothing to disclose. Dr. Aguilar-Gonzalez has nothing to disclose. Veronica Rivas has nothing to disclose. Dr. Flores-Rivera has nothing to disclose. Teresita Corona Vazquez has nothing to disclose.

Treatment at Onset Predicts a Longer Time-to-Relapse After Index Event in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) (S40.009)

<h3>Objective:</h3> To identify the predictors of time-to-second attack in patients with MOGAD. <h3>Background:</h3> MOGAD is a demyelinating disorder which can cause optic neuritis, transverse myelitis or acute disseminated encephalomyelitis. It can be monophasic or relapsing. Predictors of time-to-second attack in patients with an index demyelinating event are unknown in MOGAD. <h3>Design/Methods:</h3> Patients with a definite diagnosis of MOGAD, who tested positive for MOG-IgG and who are followed at Massachusetts General Hospital and Brigham and Women’s Hospital were included. Data on key clinical and demographic features including sex, age, race, treatment at onset, time-to-second attack and time to third attack were collected. A time-to-event survival analysis was performed using a Cox proportional hazards model. Univariate and multivariate regression analysis was performed. <h3>Results:</h3> We included 84 patients who had a definite diagnosis of MOGAD. The average age at first attack was 30 (IQR 17.0–46.5), and 62% of patients (n=52) were female. Median follow-up was 5.04 years (IQR 2.65–10.40). In total, 61% (n=51) of patients had a second attack, of which, 68% (n=35) experienced a third attack. After the first attack, 52% (n=42) patients were started on maintenance treatment. First available MOG titer was less than 1:100 in 29% of patients (n=25), and 1:00 or greater in 71% (n=51) of patients. Treatment status after the first attack significantly predicted longer time-to-second attack (HR = 0.46, 95% CI 0.23–0.92, p=0.028). Higher MOG titer did not predict time-to-second attack (HR=0.90, 95% CI 0.51–1.59, p=0.71). When adjusting for other covariates, MOG titers were not significantly associated with time-to-second attack. <h3>Conclusions:</h3> Early treatment after an index demyelinating event in MOGAD predicts a longer time-to-relapse, while MOG-IgG titer does not affect time-to-second attack. <b>Disclosure:</b> The institution of Dr. Molazadeh has received research support from Genentech, Inc.. Dr. Bilodeau has nothing to disclose. Ms. Salky has nothing to disclose. The institution of Dr. Bose has received research support from Multiple Sclerosis Society of Canada. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy 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. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.

Acute, Transient, Brain Lesions on Magnetic Resonance Imaging in X-linked Charcot-Marie-Tooth type 1 (P13-4.002)

<h3>Objective:</h3> NA <h3>Background:</h3> CMTX1 is an X-linked dominant form of hereditary sensorimotor polyneuropathy. It is caused by mutations in the gap junction protein beta 1(GJB1) gene on chromosome Xq13.1, which encodes connexin 32 protein. CNS can be affected and lead to transient or persistent CNS symptoms including dysarthria, dysphagia, hemiparesis or quadriparesis, ataxia, aphasia, and encephalopathy. <h3>Design/Methods:</h3> <h3>Case Report:</h3> A 22-year-old man presented with acute onset left facial droop, dysarthria and left upper extremity weakness. Two weeks prior he experienced a one-day episode of gastroenteritis. Neurological examination showed weakness in the left lower face, distal muscle weakness in toe extension, ankle dorsiflexion and hand intrinsic muscles, absent lower extremity reflexes, diminished vibration and temperature senses in length-dependent pattern, high-arched feet and hammertoes. Family history of early onset polyneuropathy, never genetically tested. Brain MRI showed marked and symmetric restricted diffusion lesions involving bilateral fronto-parietal white matter, corpus callosum and posterior limb of internal capsule without contrast enhancement. CSF analysis was unremarkable. The patient was given pulse steroid therapy for possible demyelinating disease, his symptoms completely resolved within 48 hours. Two prior similar symptoms, one was diagnosed as acute disseminated encephalomyelitis (ADEM) and treated with steroids. Brain MRI of these two episodes showed similar restricted diffusion abnormalities. Repeat brain MRI seven months after the second episode showed complete resolution of restricted diffusion lesions. Leukodystrophy genetic panel was negative. Genetic testing showed hemizygous pathogenic mutation c.491G&gt;A in GJB1 gene, associated with X-linked Charcot-Marie-Tooth disease - CMTX1. <h3>Results:</h3> NA <h3>Conclusions:</h3> Young patients with history of polyneuropathy presenting with acute CNS symptoms with bilateral white matter and corpus callosum lesions, CMTX1 should be included in the differential diagnosis. Upon confirmation of CMTX1 diagnosis, patient reassurance is important as well as education regarding potential provoking factors that lead to CNS involvement. <b>Disclosure:</b> Dr. Altarazi has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Sankaraneni has nothing to disclose.

MOG antibody-associated encephalitis in adult: clinical phenotypes and outcomes (P13-5.020)

<h3>Objective:</h3> We investigated the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis (MOGAE) in adult patients. <h3>Background:</h3> Although MOG antibody-associated disease (MOGAD) can be associated with autoimmune encephalitis, the clinical features and outcomes of MOGAE in adults are largely unknown. <h3>Design/Methods:</h3> From an institutional cohort, we analyzed adult patients with MOGAE followed-up for more than one year. Disease severity was assessed using the modified Rankin scale (mRS) and Clinical Assessment Scales in Autoimmune Encephalitis (CASE) scores. Immunotherapy profiles, outcomes, and disease relapses were evaluated along with serial brain MRI data. <h3>Results:</h3> A total of 40 patients were enrolled and categorized into cortical encephalitis (18 patients), limbic encephalitis (LE, 5 patients), and acute disseminated encephalomyelitis (ADEM, 17 patients). 80.0% of patients achieved good clinical outcomes (mRS 0–2) and 40.0% relapsed. The LE subtype was associated with an older onset age (<i>P</i>=0.004) and poor clinical outcomes (<i>P</i>=0.014) than the other subtypes but with a low rate of relapse (0.0%). 21/25 (84.0%) relapse attacks were associated with an absence or short (≤6 months) immunotherapy maintenance. On MRI, the development of either diffuse cerebral or medial temporal atrophy within the first six-month was correlated with poor outcomes. MOG-antibody was co-present with anti-N-methyl-D-aspartate receptor (NMDAR)-antibody in 13 patients, in whom atypical clinical presentation (cortical encephalitis or ADEM, <i>P&lt;</i>0.001) and disease relapse (46.2% vs. 0.0%, <i>P&lt;</i>0.001) were more frequent compared to conventional NMDAR encephalitis without MOG-Ab. <h3>Conclusions:</h3> Outcomes are different according to the three phenotypes in MOGAE. Short immunotherapy maintenance is associated with relapse, and brain atrophy was associated with poor outcomes. Patients with dual antibodies of NMDAR and MOG have a high relapse rate. <b>Disclosure:</b> Prof. Lee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Advanced Neural Technologies. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biofire Diagnostics. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GC pharma. The institution of Prof. Lee has received research support from GC pharma. Prof. Kim has received intellectual property interests from a discovery or technology relating to health care. Prof. Chu has nothing to disclose. Prof. Lee has nothing to disclose. Woo-jin Lee has nothing to disclose.

Pediatric Neuroinflammatory Disease in the Era of COVID-19: Single Center Survey of the Medical and Social Impact of COVID-19 and COVID-19 Vaccines (S34.006)

<h3>Objective:</h3> We explore the impact of COVID-19 in pediatric patients with neuroinflammatory disorders and describe parent/guardian vaccination concerns and self-reported side effects of the COVID-19 vaccination. <h3>Background:</h3> Neurological manifestations of COVID-19 in children range from mild to severe. There is limited data surrounding COVID-19 and the COVID-19 vaccine in pediatric populations with known neuroinflammatory disorders. <h3>Design/Methods:</h3> A survey was distributed to guardians of 68 children enrolled in a single center neuroimmunology registry. Clinical data was obtained from the registry. <h3>Results:</h3> 26 (38%) responded to the survey (62% female). Diagnoses included multiple sclerosis (5, 19%), myelin oligodendrocyte glycoprotein antibody-associated disease (8, 31%), acute disseminated encephalomyelitis (1, 4%), autoimmune encephalitis (1, 14%), and other (16, 57%). 10 (38%) had a confirmed COVID-19 diagnosis, and 3 were classified as probable COVID-19 cases based on CDC clinical and exposure criteria. Neurological symptoms in the 6-weeks after confirmed or probable COVID-19 infections were: behavioral changes (4, 31%), paresthesias (1, 8%), taste changes (3, 23%) vision changes (2, 15%) urinary retention (1, 8%), and gait abnormalities (1, 8%). 12 (46%) received at least one COVID-19 vaccine dose. For unvaccinated children, 50% of respondents were “not at all willing” to vaccinate and lack of knowledge of long-term side effects was the most common reason. Neurological side effects in the 6-weeks following the vaccination included: behavioral changes (2, 17%), parasthesias (1, 8%), and gait abnormalities (1, 8%). Of children with confirmed or probable COVID-19 or who received a COVID-19 vaccine, none experienced neurological disease flares requiring treatment alterations or hospitalization. <h3>Conclusions:</h3> Half of children with a neuroinflammatory disease had confirmed or probable COVID-19 and less than half were vaccinated against COVID-19. Children with COVID-19 or who received the COVID-19 vaccine did not have disease flares requiring change in immunotherapy or hospitalization. Guardians are concerned about long term side effects of COVID-19 vaccines. <b>Disclosure:</b> Ms. Bahri has nothing to disclose. Ms. Hurst has nothing to disclose. Ms. Alexander has nothing to disclose. Dr. Hutchinson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Katz, Korin, Cunningham Attorneys At Law.

A Case of HSV-2 Meningitis Retention Syndrome (P12-10.004)

<h3>Objective:</h3> Not applicable <h3>Background:</h3> Meningitis Retention Syndrome (MRS) is a rare disorder characterized by the development of urinary retention in the context of aseptic meningitis with CSF pleocytosis¹. In many cases, no underlying cause is determined, but pathogens such as mycobacteria, listeria, EBV and HSV-2 have been reported as causative agents in the literature². The underlying pathophysiology remains unclear, but possible causes have been suggested including spinal shock secondary to meningeal irritation, sacral myeloradiculitis due to direct viral inflammation, or a post-infectious acute disseminated encephalomyelitis process^3,4. We discuss here an unusual case of a young man presenting for urinary retention who was found to have HSV-2 meningitis. <h3>Design/Methods:</h3> <h3>Case report:</h3> A 17-year-old male with chronic constipation presented to the emergency department for urinary retention of 2 days duration. He endorsed the sensation to void with an inability to empty his bladder despite straining in the setting of a two-week history of mild headaches, diffuse back pain, myalgias and low-grade fevers. He was non-toxic appearing and neurological exam was normal. Abdominal X-ray showed a moderate stool burden. Spine MRI demonstrated subtle enhancement of the cauda equina. CSF evaluation were notable for an elevated opening pressure to 34 mmHg and a lymphocytic pleocytosis (693 white blood cells), and elevated protein of 60. Multiplex panel for central nervous system infections by polymerase chain reaction was positive for HSV-2. He was admitted to the hospital for IV acyclovir and management of urinary retention. <h3>Results:</h3> Not applicable <h3>Conclusions:</h3> This case demonstrated the importance of keeping meningitis retention syndrome on the differential for individuals presenting with acute urinary retention after a viral infection. Keeping a high index of suspicion is crucial, especially in cases like the one described where the patient only had some vague viral symptoms but no obvious meningeal signs, radicular pains or genital ulcers. <b>Disclosure:</b> Dr. Aoun has nothing to disclose. Dr. Raj Ghosh has nothing to disclose. Dr. Kuball has nothing to disclose. The institution of Dr. Abreu has received research support from Adult Polyglucosan Body Disease Research Foundation. The institution of Dr. Abreu has received research support from Sanofi Genzyme. The institution of Dr. Abreu has received research support from Takeda. The institution of Dr. Abreu has received research support from Sangamo.

Placental transmission of MOG-IgG to neonate from mother with MOGAD (P13-5.026)

Placental transmission of MOG-IgG to neonate from mother with MOGAD (P13-5.026)

A Case of CNS Lymphoma Imitating Post-Vaccination ADEM (P14-13.003)

<h3>Objective:</h3> NA <h3>Background:</h3> A previously healthy 42-year-old male presented acutely with slurred speech, confusion and urinary incontinence several weeks after receiving a COVID booster and Tdap vaccination. <h3>Design/Methods:</h3> NA <h3>Results:</h3> Initial workup revealed multifocal enhancing T2 white matter hyperintensities in the bilateral frontal/parietal lobes, corpus callosum and bilateral midbrain, sparing the cerebellum and spinal cord. Contrast enhanced CT of the chest, abdomen and pelvis showed no masses or lymphadenopathy. Cerebrospinal fluid analysis showed a mild lymphocytic pleocytosis (12) with normal RBC, protein, glucose, negative meningitis/encephalitis PCR, cytology and autoimmune encephalitis antibodies. Serum testing was negative for HIV, RPR, NMO, MOG and antinuclear antibodies. Working diagnosis of acute disseminated encephalomyelitis was made and he was started on IV methylprednisolone 1g daily for 5 days followed by an oral steroid taper with a weekslong improvement in symptoms to his neurologic baseline followed by relapse. We repeated MRI brain which demonstrated mixed response to treatment and two repeat CSF analyses showed 2 WBC with negative cytology. Given symptom recurrence, 1g daily IV methylprednisolone was re-administered for 5 days with another brief improvement, followed by IVIG 2g/kg over 5 days. Despite aggressive immunotherapy, his symptoms continued to worsen, and he was referred for brain biopsy confirming the diagnosis of primary diffuse large B-cell lymphoma of the CNS. At the direction of neuro-oncology, the patient underwent 6 cycles of systemic high-dose methotrexate and rituximab and 2 cycles of temozolomide with PET/MRI evidence of complete response (no lesion enhancement). His performance status improved significantly, and he underwent autologous hematopoietic stem cell transplant for consolidative therapy. <h3>Conclusions:</h3> CNS lymphoma should be considered in the differential for contrast-enhancing FLAIR hyperintensities and can be steroid responsive. Brain biopsy should not be delayed in cases where CNS lymphoma is a leading differential as it can guide early disease management and help improve patient outcomes. <b>Disclosure:</b> Dr. Frank has nothing to disclose. Dr. Alalami has nothing to disclose. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. An immediate family member of Dr. Livingston has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. The institution of an immediate family member of Dr. Livingston has received research support from Vertex. The institution of an immediate family member of Dr. Livingston has received research support from Roche. The institution of an immediate family member of Dr. Livingston has received research support from AstraZeneca. The institution of an immediate family member of Dr. Livingston has received research support from Enanta. Dr. Hu has nothing to disclose. Dr. Shadbehr has nothing to disclose.

Clinical features of patients with MOG-IgG associated disorders and analysis of the relationship between fibrinogen-to-albumin ratio and the severity at disease onset.

The study aimed to investigate the differences in clinical features between pediatric and adult patients with first-episode MOG-IgG associated disorders (MOGAD) and evaluate the relationship between the fibrinogen-to-albumin ratio (FAR) and the severity of neurological deficits at disease onset. We retrospectively collected and analyzed biochemical test results, imaging characteristics, clinical manifestations, expanded disability status scale (EDSS) score, and FAR. The Spearman correlation analysis and logistic regression models were used to examine the association between FAR and severity. Receiver operating characteristic (ROC) curve analysis was to analyze the predictive ability of FAR for the severity of neurological deficits. Fever (50.0%), headache (36.1%), and blurred vision (27.8%) were the most common clinical manifestations in the pediatric group (<18 years old). However, in the adult group (≥18 years old), the most common symptoms were blurred vision (45.7%), paralysis (37.0%), and paresthesia (32.6%). Fever was more common in the pediatric group, while paresthesia was more common in the adult patients, with all differences statistically significant (P < 0.05). The most frequent clinical phenotype in the pediatric group was acute disseminated encephalomyelitis (ADEM; 41.7%), whereas optic neuritis (ON; 32.6%) and transverse myelitis (TM; 26.1%) were more common in the adult group. The differences in clinical phenotype between the two groups were statistically significant (P < 0.05). In both pediatric and adult patients, cortical/subcortical and brainstem lesions were the most common lesions on cranial magnetic resonance imaging (MRI), whereas, for spinal MRI, cervical and thoracic spinal cord lesions were the most commonly observed. According to binary logistic regression analysis, FAR was an independent risk factor for the severity of neurological deficits (odds ratio = 1.717; 95% confidence interval = 1.191-2.477; P = 0.004). FAR (r = 0.359, P = 0.001) was positively correlated with the initial EDSS score. The area under the ROC curve was 0.749. The current study found age-dependent phenotypes in MOGAD patients as ADEM was more commonly observed in patients < 18 years old, while ON and TM were more frequently found in patients ≥18 years old. A high FAR level was an independent indicator for more severe neurological deficits at disease onset in patients with a first episode of MOGAD.

Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids.

The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.

Central Nervous System Neuroimmunologic Complications of COVID-19.

Autoimmune disorders of the central nervous system following COVID-19 infection include multiple sclerosis (MS), neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune encephalitis, acute disseminated encephalomyelitis, and other less common neuroimmunologic disorders. In general, these disorders are rare and likely represent postinfectious phenomena rather than direct consequences of the SARS-CoV-2 virus itself. The impact of COVID-19 infection on patients with preexisting neuroinflammatory disorders depends on both the disorder and disease-modifying therapy use. Patients with MS do not have an increased risk for severe COVID-19, though patients on anti-CD20 therapies may have worse clinical outcomes and attenuated humoral response to vaccination. Data are limited for other neuroinflammatory disorders, but known risk factors such as older age and medical comorbidities likely play a role. Prophylaxis and treatment for COVID-19 should be considered in patients with preexisting neuroinflammatory disorders at high risk for developing severe COVID-19.

Central nervous system reactivation of herpesviridae family in patients with COVID-19.

The objective of this study is to describe our COVID-19 patients with herpesviridae reactivation in the central nervous system (CNS). Four patients were described including two with acute encephalitis and two with acute encephalomyelitis. Three of four patients had abnormal findings on neuroimaging studies. One of four patients died, one survived with major neurological sequelae, and two others fully recovered. Herpesviridae reactivation in the CNS in patients with COVID-19 is a rare but serious coincidence. The optimal therapeutic management has not been investigated and until more information is available, it is prudent to treat these patients with appropriate antivirals with or without anti-inflammatory agents.

Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens.

Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (IIDD) after ZikV infection have been reported in Brazil. The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent IIDD of the central nervous system (CNS). A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens. Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation. Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals.