Cerebral Cortical Encephalitis Research Articles

Insights into Myelin Oligodendrocyte Glycoprotein Associated Disease (MOGAD): Prevalence, Clinical Manifestations, and Treatment Responses in a Four-Year Retrospective Cohort Study

Introduction: This study aims to delineate the prevalence, clinical characteristics, diagnostic findings, and treatment outcomes of Myelin Oligodendrocyte Glycoprotein Associated Disease (MOGAD) in a cohort over four years, providing a basis for improved diagnostic criteria and therapeutic strategies. Materials and Methods: In a retrospective cohort study at a tertiary care center, we analyzed medical records of 90 patients presenting with CNS demyelinating symptoms, focusing on those diagnosed with MOGAD based on the International MOGAD Panel criteria. Data on clinical presentation, serum Anti-MOG antibody testing, MRI, VEP scans, CSF analysis, and treatment outcomes were evaluated. Results: Among the cohort of 90 patients, 7 patients were identified with positive Anti-MOG antibodies, indicating a prevalence of 7.8%. Clinical manifestations varied widely, including optic neuritis, myelitis, and cerebral cortical encephalitis. Diagnostic findings highlighted the absence of oligoclonal bands in CSF analysis and diverse MRI lesions. Most patients responded well to immunosuppressive treatments, though relapses occurred in two cases. The study underscores the heterogeneity of MOGAD presentations and the importance of personalized treatment approaches. Conclusion: Our findings contribute to the growing understanding of MOGAD, emphasizing its distinct clinical and diagnostic features compared to other CNS demyelinating disorders. The study advocates for the integration of MOG antibody testing in clinical practice to enhance diagnostic accuracy and patient outcomes. Future research should aim at longitudinal and multicentric studies to validate our findings and further refine MOGAD management strategies.

Myelin oligodendrocyte glycoprotein antibody‐associated disorders: An overview

AbstractIn recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD‐specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders.

Clinical and radiographic features of a cohort of adult and pediatric subjects in the Pacific Northwest with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a newly described clinical entity comprised of isolated or recurrent attacks of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), encephalitis, or seronegative NMOSD. Prior studies report that 30–80 % of children and adults with MOGAD go on to have relapses though there are no reliable predictors. The objectives of this study were to (1) describe the demographic, clinical, and radiographic patterns of MOGAD at our center and (2) identify possible predictors of relapsing disease. MethodsSingle-center retrospective cohort study of pediatric and adult subjects with MOGAD evaluated at least once at our center between January 1, 2017 and September 30, 2022. Eligible subjects had a history of positive MOG-IgG and consistent clinical syndrome comprised of an initial attack of optic neuritis (ON), transverse myelitis (TM), ADEM, cerebral cortical encephalitis, seronegative neuromyelitis optica (simultaneous ON and TM), isolated brainstem or cerebellar syndrome, or other (not fitting into another group). Relapsing subjects or those remaining monophasic at 12 months were included in the analyses of predictors of relapsing disease. Covariates included age, sex, race/ethnicity, and index event phenotype. Unadjusted and adjusted risk ratios were calculated for pediatric and adult subjects. ResultsWe describe the demographic, clinical, and radiographic characteristics of 58 subjects with MOGAD. Covariates from 48 subjects were analyzed for predictors of relapsing disease. In adults, Hispanics and non-White non-Hispanics were at increased risk of relapsing disease compared to non-Hispanic Whites [Adjusted RR 1.52 (95 % CI: 1.01, 2.30)]. There were no significant associations in the pediatric group. ConclusionThis study is the first to describe a cohort of MOGAD in the Pacific Northwest. Our findings highlight racial and ethnic differences in risk of relapsing MOGAD in adults. Further studies on racial and ethnic differences in MOGAD are needed to confirm these findings.

Increased Intracranial Pressure in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Elevated intracranial pressure (ICP) in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) has been largely unexplored. The objectives of this study were to determine the frequency of increased ICP in MOGAD and its association with disease course and outcomes and to highlight cases requiring medical and/or surgical management of increased ICP. In this retrospective, single-center cohort study, we examined the clinical and paraclinical data from the initial presentation and follow-up data of children diagnosed with MOGAD. In those with opening pressure (OP) measurements, univariate analyses were used to evaluate factors associated with increased ICP, which was defined as OP > 28 cm H2O. We also present a case series of patients with or without OP measurement who required medical and/or surgical management of increased ICP. Of 86 children with MOGAD, 43 (50.0%) had an OP recorded and 7 (8.1%) required ICP management. In those with OP recorded, the median (interquartile range) OP for the different MOGAD phenotypes were: 30.0 (22.8-41.6) (acute disseminated encephalomyelitis, ADEM), 20.5 (16.1-23.6) (optic neuritis), 17.0 (17.0-22.5) (myelitis), and 19.5 (16.5-29.3) (other) cm H20. Overall, 20.9% had increased ICP based on an OP > 28 cm H2O, of whom 77.8% presented with ADEM. In a subgroup analysis of those presenting with ADEM, those with an elevated ICP had longer hospital stay (p = 0.007) and neurologic disability (defined as modified Rankin Scale >1) (p = 0.049). In those with or without OP recorded, 7 (6 with ADEM, one with cerebral cortical encephalitis) required ICP-directed therapies. Findings on brain MRI in these 7 children revealed extensive disease burden with bilateral cerebral involvement and evidence of restricted diffusion. While neuropsychological data in this small subset revealed significant variability, all sustained identifiable deficits after discharge, including attention-deficit hyperactivity disorders and language and learning disorders. In pediatric MOGAD, increased OP and ADEM at initial presentation were associated with longer hospital stays and greater long-term morbidity. Although invasive ICP monitoring has not been specifically advocated in the management of MOGAD, it is important to recognize signs and symptoms of increased ICP in these patients and consider ICP monitoring and management strategies based on clinical and radiologic findings, especially in those presenting with ADEM and with OP > 28 cm H2O.

Epidemiology of myelin oligodendrocyte glycoprotein antibody-associated disease: a review of prevalence and incidence worldwide.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) with the presence of conformation-sensitive antibodies against MOG. The spectrum of MOGAD includes monophasic/relapsing optic neuritis, myelitis, neuromyelitis optica spectrum disorder (NMOSD) phenotype without aquaporin 4 (AQP4) antibodies, acute/multiphasic demyelinating encephalomyelitis (ADEM/MDEM)-like presentation, and brainstem and cerebral cortical encephalitis. There is no apparent female preponderance in MOGAD, and MOGAD can onset in all age groups (age at onset is approximately 30 years on average, and approximately 30% of cases are in the pediatric age group). While prevalence and incidence data have been available for AQP4+ NMOSD globally, such data are only beginning to accumulate for MOGAD. We reviewed the currently available data from population-based MOGAD studies conducted around the world: three studies in Europe, three in Asia, and one joint study in the Americas. The prevalence of MOGAD is approximately 1.3-2.5/100,000, and the annual incidence is approximately 3.4-4.8 per million. Among White people, the prevalence of MOGAD appears to be slightly higher than that of AQP4+ NMOSD. No obvious latitude gradient was observed in the Japanese nationwide survey. The data available so far showed no obvious racial preponderance or strong HLA associations in MOGAD. However, precedent infection was reported in approximately 20-40% of MOGAD cases, and this is worthy of further investigation. Co-existing autoimmune disorders are less common in MOGAD than in AQP4+ NMOSD, but NMDAR antibodies may occasionally be positive in patients with MOGAD. More population-based studies in different populations and regions are useful to further inform the epidemiology of this disease.

Pathogenesis, Clinical Features, and Treatment of Patients with Myelin Oligodendrocyte Glycoprotein (MOG) Autoantibody-Associated Disorders Focusing on Optic Neuritis with Consideration of Autoantibody-Binding Sites: A Review.

Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG) autoantibody-associated disease (MOGAD), there is still uncertainty regarding the MOG protein function and the pathogenicity of anti-MOG autoantibodies in this disease. It is important to note that the disease characteristics, immunopathology, and treatment response of MOGAD patients differ from those of anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS). The clinical phenotypes of MOGAD are varied and can include acute disseminated encephalomyelitis, transverse myelitis, cerebral cortical encephalitis, brainstem or cerebellar symptoms, and optic neuritis. The frequency of optic neuritis suggests that the optic nerve is the most vulnerable lesion in MOGAD. During the acute stage, the optic nerve shows significant swelling with severe visual symptoms, and an MRI of the optic nerve and brain lesion tends to show an edematous appearance. These features can be alleviated with early extensive immune therapy, which may suggest that the initial attack of anti-MOG autoantibodies could target the structures on the blood-brain barrier or vessel membrane before reaching MOG protein on myelin or oligodendrocytes. To understand the pathogenesis of MOGAD, proper animal models are crucial. However, anti-MOG autoantibodies isolated from patients with MOGAD do not recognize mouse MOG efficiently. Several studies have identified two MOG epitopes that exhibit strong affinity with human anti-MOG autoantibodies, particularly those isolated from patients with the optic neuritis phenotype. Nonetheless, the relations between epitopes on MOG protein remain unclear and need to be identified in the future.

Fulminant Anti-Myelin Oligodendrocyte Glycoprotein-Associated Cerebral Cortical Encephalitis: Case Series of a Severe Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Phenotype

BackgroundWe describe a cohort of children with severe myelin oligodendrocyte glycoprotein (MOG)-IgG-associated cerebral cortical encephalitis (CCE), manifesting with bilateral cortical cytotoxic edema and critical neurological illness. MethodsWe retrospectively reviewed our pediatric MOG antibody-associated disease (MOGAD) database and identified patients with specific radiographic pattern of bilateral, multifocal cortical cytotoxic lesions. We collected demographic, clinical, and outcomes data from these patients and compared select variables with radiographically distinct cerebral MOGAD syndromes (case-control analysis). We assessed the correlation of quantitative clinical variables with severity/outcomes measures using simple linear regression. ResultsSixty-five of 88 total MOGAD cases had cerebral disease, and six of 88 met inclusion criteria for fulminant CCE (f-CCE). Age range was 2 to 7 years; five of six were male. Six of six were critically ill with severe encephalopathy and seizures, two of six required barbiturate coma, and two of six required invasive intracranial pressure monitoring. Six of six required treatment escalation beyond steroids. Four of six had favorable outcome; two of six had moderate-severe disability. Compared with other cerebral MOGAD cases (n = 59), children with f-CCE were more likely to have critical illness and poor neurological outcomes scores. Neurofilament light chain and treatment latency positively correlated with intensive care unit length of stay and outcomes scores; cerebrospinal fluid (CSF) white blood cell count and neutrophil-to-lymphocyte ratio did not. ConclusionsPediatric CCE with bilateral cytotoxicity is associated with more fulminant disease and worse outcomes than other cerebral MOGAD syndromes.

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

<h3>Objective:</h3> To characterize cerebral attacks of myelin oligodendrocyte-glycoprotein-antibody-associated disease (MOGAD) and assess for fulfillment of acute-disseminated encephalomyelitis (ADEM) criteria. <h3>Background:</h3> The clinical spectrum of MOGAD cerebral attacks has not been fully elucidated and it is unclear what proportion adhere to ADEM criteria. <h3>Design/Methods:</h3> We retrospectively searched our Mayo Clinic MOGAD database, and inclusion criteria were: 1) Symptomatic cerebral attack; and 2) Abnormal brain MRI; 3) MOG-IgG positivity. We assessed if included children and adults fulfilled current ADEM criteria of: A) First, polyfocal clinical central nervous system demyelinating event; B) encephalopathy (not explained by fever); C) no new clinical/MRI findings beyond 3 months; D) abnormal brain MRI (typically large, poorly-demarcated T2-hyperintensities involving white or deep gray matter, while T1-hypointense lesions are rare). <h3>Results:</h3> We included 90 patients. The median age was 23 (range, 2–75), and 61% were female. In 22 (24%), recurrent cerebral attacks occurred. Clinical manifestations from the first cerebral attack included: headache, 51 (57%); brainstem symptoms, 41 (46%); encephalopathy, 34 (38%); cerebellar symptoms, 36 (40%), seizures, 17 (19%). In 16 patients (18%), the attack fell within the spectrum of cerebral cortical encephalitis. Concomitant myelitis was noted in 44 and 17 had concomitant optic neuritis. Acute MRI images were available for re-review in 81/90 and abnormalities included: poorly demarcated lesions, 55/81 (68%); deep gray matter lesions, 35/81 (43%); cerebral T1-hypointense lesions 46/81 (57%). In our cohort, 7 (8%) fulfilled ADEM criteria, and 83 (92%) did not due to ≥1 of: subsequent relapse, 58 (64%); absence of encephalopathy, 38 (42%); preceding demyelinating attack, 27 (30%); encephalopathy with fever, 15 (17%), and single lesion 4 (5%). <h3>Conclusions:</h3> Cerebral MOGAD attacks have a wide spectrum and usually do not fulfill ADEM criteria when retrospective applied. Future revisions of ADEM criteria might consider a disease-associated ADEM category to better capture MOGAD cerebral attacks. <b>Disclosure:</b> Dr. Hooshmand has nothing to disclose. Dr. Li has nothing to disclose. John J. Chen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. John J. Chen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. John J. Chen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Redenbaugh has nothing to disclose. Dr. Banks has nothing to disclose. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA. Dr. Valencia Sanchez has nothing to disclose. Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Lopez 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. Sechi has nothing to disclose. Dr. Tillema has nothing to disclose. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock 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. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. 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.

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.

Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease.

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) is a spectrum of diseases, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and cerebral cortical encephalitis. In addition to distinct clinical, radiological, and immunological features, the infectious prodrome is more commonly reported in MOGAD (37-70%) than NMOSD (15-35%). Interestingly, pediatric MOGAD is not more aggressive than adult-onset MOGAD, unlike in multiple sclerosis (MS), where annualized relapse rates are three times higher in pediatric-onset MS. MOGAD pathophysiology is driven by acute attacks during which T cells and MOG antibodies cross blood brain barrier (BBB). MOGAD lesions show a perivenous confluent pattern around the small veins, lacking the radiological central vein sign. Initial activation of T cells in the periphery is followed by reactivation in the subarachnoid/perivascular spaces by MOG-laden antigen-presenting cells and inflammatory CSF milieu, which enables T cells to infiltrate CNS parenchyma. CD4+ T cells, unlike CD8+ T cells in MS, are the dominant T cell type found in lesion histology. Granulocytes, macrophages/microglia, and activated complement are also found in the lesions, which could contribute to demyelination during acute relapses. MOG antibodies potentially contribute to pathology by opsonizing MOG, complement activation, and antibody-dependent cellular cytotoxicity. Stimulation of peripheral MOG-specific B cells through TLR stimulation or T follicular helper cells might help differentiate MOG antibody-producing plasma cells in the peripheral blood. Neuroinflammatory biomarkers (such as MBP, sNFL, GFAP, Tau) in MOGAD support that most axonal damage happens in the initial attack, whereas relapses are associated with increased myelin damage.

A Case of Recurrent Anti-MOG-Associated Cerebral Cortical Encephalitis Mimicking Viral Encephalitis and Hemiplegic Migraine

A Case of Recurrent Anti-MOG-Associated Cerebral Cortical Encephalitis Mimicking Viral Encephalitis and Hemiplegic Migraine

A Case of Recurrent Cerebral Cortical Encephalitis in MOG Antibody-Associated Disease

Objective NA. Background Cerebral cortical encephalitis is a recently recognized syndrome of myelin-oligodendrocyte-glycoprotein-antibody-associated disease (MOGAD), yet most descriptions report single episodes without recurrence. Design/Methods Case report of recurrent cerebral cortical encephalitis in MOGAD. Results This is a case report of a 32-year-old patient who initially developed meningoencephalitis when he was three. He was stable until age 31, when he developed headaches followed by status epilepticus secondary to cerebral cortical encephalitis with accompanying unilateral right temporal cerebral cortical T2-hyperintensity with leptomeningeal enhancement. Cerebrospinal fluid analysis revealed 505 white cells/µl (normal, 0-5) but oligoclonal bands were negative. Over the subsequent two weeks he developed bilateral severe vision loss (20/400 bilaterally) accompanied by bilateral optic disc edema, and MRI orbits showed bilateral anterior segment optic nerve enhancement extending &gt;50% of the length of each nerve, confirming bilateral optic neuritis. MOG-IgG was tested in serum and was positive at a titer of 1:100. He was treated with intravenous methylprednisolone 1 gram daily for 5 days and a subsequent slow oral prednisone taper along with anti-epileptic treatment with levetiracetam, later transitioned to oxcarbazepine, although he later self-discontinued all anti-epileptics. He received maintenance intravenous immunoglobulins (IVIg) 0.4 g/Kg weekly, that was later weaned to 1 g/Kg every 4 weeks. He then developed recurrent cerebral cortical encephalitis 18 months after his prior episode manifesting with seizures and left occipito-temporal T2-hyperintensity and swelling with leptomeningeal enhancement. He was treated with high dose IV steroids, an oral prednisone taper and his IVIg dose was changed back to 0.4 g/Kg once weekly and anti-seizure medications reinitiated. Conclusions Cerebral cortical encephalitis in MOGAD can be recurrent. Close scrutiny of the MRI in patients with MOGAD who develop seizures after prior cerebral cortical encephalitis is important as it can discriminate a recurrent cerebral cortical encephalitis attack from a breakthrough seizure related to prior damage.

Acute symptomatic seizures secondary to myelin oligodendrocyte glycoprotein antibody-associated disease.

To report the clinical presentations and outcomes of patients with seizure and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We retrospectively reviewed the electronic medical records for clinical and paraclinical features among patients with seizures and MOG-IgG (immunoglobulin G) seropositivity. We identified 213 patients with MOG-IgG seropositivity who fulfilled criteria for MOGAD. Seizures attributed to central nervous system (CNS) autoimmunity were observed in 10% of patients (n=23: 19 children, 4 adults). The majority (n=19, 83%) had pediatric disease onset. Focal motor seizures were the most common seizure semiology (16/23; 70%). Focal to bilateral tonic-clonic seizures were present in 12 patients (53%), and 3 patients (13%) developed status epilepticus. All patients had features of encephalitis at onset of seizures. Cerebral cortical encephalitis (CCE) was the most common radiological finding (10 unilateral and 5 bilateral cases). Eight of 23 patients (35%) had only CCE, six of 23 patients (26%) had only acute disseminated encephalomyelitis (ADEM), and seven of 23 patients (30%) had features of both. Fifteen patients (65%) had leptomeningeal enhancement. Three patients (13%) had coexistence of N-methyl-d-aspartate receptor (NMDAR) IgG. Only 3 of 23 patients (13%) developed drug- resistant epilepsy. Although the majority had MOGAD relapses (14/23, 60%) had only 5 of 23 patients had recurrence of episodes of encephalitis with associated seizures. Twenty-one of 23 patients (91%) had seizure freedom at last follow-up. MOG-IgG evaluation should be considered in patients who present with encephalitis and focal motor and/or focal to bilateral tonic-clonic seizures, especially pediatric patients with magnetic resonance imaging (MRI) brain findings consistent with CCE, ADEM, or other MOGAD presentations. The majority of these seizures are self-limited and do not require maintenance/chronic antiseizure medications. Although seizure recurrence is uncommon, many patients have MOGAD relapses in the form of encephalitis and optic neuritis.

Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease.

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

Myelin Oligodendrocyte Glycoprotein Antibody Associated Cerebral Cortical Encephalitis: Case Reports and Review of Literature.

Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease of the central nervous system that is present in both adults and children. The most common clinical manifestations are optic neuritis, myelitis, acute disseminated encephalomyelitis, and brainstem syndrome. Cerebral cortical encephalitis (CCE) is a rare clinical phenotype of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), which usually begins with seizures, headaches, and fever, and may be misdiagnosed as viral encephalitis in the early stages. Herein, we report two typical MOG antibody (MOG-Ab)-positive patients presenting with CCE, both of whom presented with headache, fever, seizures, and who recovered completely after immunotherapy. In addition, we performed a systematic review of the present literature from the perspectives of population characteristics, clinical symptoms, MRI abnormalities, treatments, and prognosis. Among the patients reported in 25 articles, 33 met our inclusion criteria, with the age of onset ranging from 4 to 52 years. Most of the patients had seizures, headache, fever, and unilateral cortical lesions on brain MRI. For acute CCE, 30 patients were treated with high-dose intravenous methylprednisolone, and the symptoms of most patients were completely relieved after immunotherapy. This study reported our experience and lessons learned in the diagnosis and treatment of MOG-Ab-positive CCE and provides a systematic review of the literature to analyse this rare clinical phenotype.

Decreased subcortical T2 FLAIR signal with cortical T2 FLAIR hyperintense lesions in unilateral cerebral cortical encephalitis with myelin oligodendrocyte glycoprotein antibody

BackgroundUnilateral cerebral cortical encephalitis (UCCE) with myelin oligodendrocyte glycoprotein (MOG) antibody comprises a new spectrum of disease entities that are characterized by unilateral cerebral cortical T2-weighted fluid-attenuated inversion recovery (T2 FLAIR) hyperintense lesions on MRI. MethodsIn this retrospective study, the brain MRI of 39 consecutive Japanese patients with anti-MOG antibody-associated UCCE was examined. ResultsWe found that 37 patients (95%) also presented with T2 FLAIR hypointensity in subcortical white matter that was adjacent to the cortical lesions. ConclusionT2 FLAIR hypointensity in subcortical white matter is a characteristic finding in anti-MOG antibody-associated UCCE that might develop secondary to cortical lesions.

Seizures in myelin oligodendrocyte glycoprotein antibody-associated disorders and related immune factors

PurposeEpileptic seizures in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGAD) have been increasingly reported in the past two decades. However, the characteristics and possible mechanism largely remain unknown. This study aimed to investigate the clinical characteristics and immune mechanism of epileptic seizures in children with MOGAD. MethodsWe conducted a retrospective single-center case-control study from February 2019 to February 2021. Clinical characteristics and immune parameters of enrolled patients with seizures (n = 12) in MOGAD (n = 32), as compared with the antibody-negative (n = 13) and control (n = 23) groups were then analyzed. ResultsSeizures occurred in 24.5% (12/49, including cases that were not enrolled) of MOGAD. In this group, magnetic resonance imaging (MRI) abnormalities, especially unilateral cortical lesion and leptomeningeal enhancement, were more frequent in patients with seizures than in individuals without seizures (p < 0.05). Levels of thyroid peroxidase antibodies (TPOAb) in the seizure+/MOG+ group were significantly (p < 0.05) higher than those in the seizure-/MOG+ and control groups, whereas no significant differences as compared with the seizure+/MOG- group were observed. TPOAb level and brain MRI performance may be associated with disease course, since two cases with increased TPOAb and abnormal brain MRI were reported, after a second seizure attack occurred. ConclusionUnilateral cerebral cortical encephalitis and isolated seizures, especially in clusters and focal seizures, may be special phenotypes of seizures in MOG-AD. TPOAb may be associated with seizures in immune-related neurological diseases, but not a specific marker of MOGAD. Therefore, TPOAb may be considered but not strongly recommended to be monitored in MOGAD.

MOG antibody‐positive cerebral cortical encephalitis: Two case reports and literature review

To investigate the clinical and MRI features of myelin oligodendrocyte glycoprotein (MOG) antibody-positive cerebral cortical encephalitis. To summarize the clinical manifestations, magnetic resonance imaging (MRI) features, and diagnosis and treatment of two children diagnosed with MOG antibody-positive cortical encephalitis in our hospital, and to analyze all of the literature on MOG antibody-positive associated cerebral cortical encephalitis published in the last 10years. A total of 24 patients, 20 adults, and 4 children were included. The main symptoms of all observed patients were as follows: seizures 20/24 (83%), headache 18/24 (75%), fever 13/24 (54%), and increased cell number in cerebrospinal fluid 22/24 (92%). The main radiological sign was enhanced FLAIR signal in cortical 24/24 (100%), including enhanced fluid-attenuated inversion recovery (FLAIR) signal in unilateral cortical 20/24 (83%). The clinical manifestations of MOG antibody-positive cerebral cortical encephalitis are complex and varied, and long-term follow-up is needed to clarify the prognosis and recurrence, providing reference for the clinical treatment.

Neuromyelitis optica spectrum disorder in Asia: Epidemiology and risk factors

AbstractIn Asia, prior to the discovery of aquaporin 4 (AQP4) antibody, many cases of neuromyelitis optica spectrum disorder (NMOSD) were misdiagnosed as multiple sclerosis (MS) or the so‐called opticospinal multiple sclerosis (OSMS). The AQP4 antibody discovery was an important milestone in the field of NMOSD, leading to correct diagnosis and reclassification of NMOSD cases, and the subsequent appropriate therapy. This is especially pertinent in Asia where the prevalence of MS is generally much lower than the Caucasian populations. East Asians have a higher NMOSD prevalence rate (~4/100 000) than Caucasians (~1‐1.5/100 000) and other Asian racial groups (Austronesians: 1.2‐1.5/100 000; South Asians: ~1/100 000; Arabs: ~1‐1.5/100 000). Myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) comprises cases of AQP4‐antibody‐negative NMOSD, optic neuritis, myelitis, and certain unique phenotypes such as cases with acute disseminated encephalomyelitis (ADEM)‐like presentation, and cerebral cortical encephalitis. MOGAD appears not too uncommon among Japanese, Chinese, Sri Lankans and Indians, but data in different Asian populations and geographical locations are needed. There exist some differences in clinical features of NMOSD and MOGAD between Asians and other populations. As for risk factors, genetic studies have identified certain HLA associations with NMOSD among Asians that were different from other populations. North‐South latitudinal gradient as seen in MS was not observed in NMOSD in Japan and China. Seasonal variation and preceding infection are among some risk factors worth further investigations. Population‐based MOGAD study in Asia, and further genetic and environmental studies are useful to further inform the epidemiology and potential pathogenetic mechanism of this unique neuroinflammatory disease.

Clinical and Radiological Features of Adult Onset Bilateral Medial Frontal Cerebral Cortical Encephalitis With Anti-myelin Oligodendrocyte Glycoprotein Antibody.

Objective: To clarify the clinical and radiological features of adult onset anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated bilateral medial frontal cerebral cortical encephalitis (BFCCE).Methods: We systematically reviewed the literature for patients with anti-MOG antibody-associated BFCCE. Patients who were also positive for other encephalitis-related autoantibodies were excluded from the study. The frequency of several characteristic neurological symptoms and lesion distributions were analyzed.Results: We identified six patients with anti-MOG antibody-associated BFCCE. Among them, 6/6 had headache, 4/6 had fever, 3/6 had seizure, 2/6 had paraparesis, 2/6 had lethargy, and 2/6 had memory disturbance. CSF pleocytosis was observed in 5/6 patients, while CSF myelin basic protein was not elevated in any of the six patients. On brain MRI, 6/6 had bilateral medial frontal cortical lesions, 3/6 had corpus callosum lesions, and 3/6 had leptomeningeal enhancements. Most of the lesions were distributed in the territory of the anterior cerebral artery (ACA).Conclusion: Our results indicate that anti-MOG antibody-associated BFCCE presents with characteristic clinical symptoms and MRI findings, which might reflect lesion formation in the ACA territory.