Rituximab Therapy for Double Seronegative Neuromyelitis Optica Spectrum Disease.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system disease presenting as optic neuritis, myelitis, and brainstem syndromes. It may be aquaporin-4 seropositive, anti-myelin oligodendrocyte glycoprotein (MOG) antibody seropositive, or double seronegative. Double-seronegative NMOSD can pose a diagnostic and therapeutic challenge. Treatment typically aims to decrease the incidence of relapse, for which high-dose intravenous methylprednisolone is the first-line agent. Non-steroid treatments include azathioprine, mycophenolate mofetil, and rituximab. This case describes a 45-year-old female presenting with left arm numbness and weakness for three months. She had been previously diagnosed with optic neuritis in 2013 but was lost to follow-up. Progression of weakness warranted admission to the neurology department. Diagnostic work and imaging were suggestive of neuromyelitis optica. Tests for aquaporin-4, anti-MOG, immunoglobulin G, and immunoglobulin M in the cerebrospinal fluid were all negative. Initial treatment comprised methylprednisolone; however, due to the progression of symptoms, she was given two cycles of rituximab. Rituximab targets the CD20 antigen in B cells and is thought to reduce the risk of relapse and the severity of NMOSD. The patient's Barthel index score, expanded disability status scale score, and motor examination improved after two cycles of rituximab.

Extremely Longitudinally Extensive Transverse Myelitis in a Patient With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Longitudinally extensive myelitis with 15 or more vertebrae in length is extremely rare, with limited evidence regarding clinical features and therapeutic response. We report a case of a 29-year-old male patient with extremely longitudinally extensive myelitis ultimately diagnosed as myelin oligodendrocyte glycoprotein-associated disease (MOGAD). The patient presented with an acute onset of meningismus, limb weakness, sensory disturbance below the C5 level, ataxia, and urinary retention. T2-weighted imaging on MRI showed an extremely longitudinally extensive spinal cord lesion ranging from C2 to the medullary conus, together with a left pontine lesion. Positive anti-myelin oligodendrocyte glycoprotein antibodies were serologically detected, which led to the diagnosis of MOGAD. Intravenous methylprednisolone followed by 1 mg/kg oral prednisolone with taper resulted in complete symptomatic and radiological resolution. The striking complete resolution despite the symptomatic and radiological severity observed in this case has been described in a few previously reported MOGAD cases. Extremely longitudinally extensive myelitis with excellent therapeutic response may be a characteristic presentation of MOGAD.

Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

A Case of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Peripheral Neuropathy With Positive Anti-Myelin Oligodendrocyte (MOG) Antibodies.

Peripheral neuropathy is a common manifestation of Eosinophilic Granulomatosis with Polyangiitis (EGPA), a rare autoimmune disorder caused by eosinophilic infiltration of multiple organs including the nervous system. Recent research has shown an association between myelin oligodendrocyte glycoprotein (MOG) antibodies and various neurologic conditions. We present a unique case of EGPA with positive MOG antibodies in the cerebrospinal fluid (CSF) in a patient presenting with peripheral neuropathy. We also highlight a few diagnostic dilemmas with EGPA and the importance of early diagnosis and appropriate treatment. Clinical, laboratory, radiological, and electrophysiologic findings are discussed.

Brazilian autoimmune encephalitis network (BrAIN): antibody profile and clinical characteristics from a multicenter study.

Background: The frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients. Methods: We evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed. Results: Of the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001). Conclusion: Most common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

Dual positivity for anti-MOG and oligoclonal bands: Unveiling unique clinical profiles and implications.

BACKGROUND: Distinguishing between MOG-associated disease (MOGAD) and multiple sclerosis (MS) presents a considerable challenge, as there are instances of overlapping clinical presentations. This complexity is further magnified in cases where patients concurrently exhibit both anti-myelin oligodendrocyte glycoprotein (anti-MOG) positivity and detectable oligoclonal bands (OCBs) This retrospective study investigates the clinical and imaging attributes of dual-positive patients, those with both anti-MOG positivity and OCBs, The study aims to show potential areas of overlap between multiple sclerosis (MS) and MOGAD. METHODS: Utilizing data gathered from three medical centers, we evaluated a cohort of 45 patients, stratifying them into two groups: those exclusively positive for anti-MOG antibodies and those displaying dual positivity. Our analysis encompassed a wide range of clinical and imaging parameters. The statistical techniques employed comprised Fisher's Exact Test along with Benjamini-Hochberg correction to ensure robustness of the findings. RESULTS: The study involved 45 patients with anti-MOG antibodies; 30 exhibited isolated anti-MOG positivity without OCBs, while 15 were dual-positive. The first group's average age was 10±7 years, compared to 28±17 years in the double-positive group (p = 0.001). CSF analysis showed no significant differences in pleocytosis, protein levels, or opening pressure between the groups. In the exclusive anti-MOG positivity cohort, 9 out of 15 patients received IVIG treatment; a larger subgroup with dual positivity chose anti-CD20 treatment. Notably, papilledema incidence was higher in the single-positive group (p = 0.014). Optic nerve enhancement (p = 0.0038) and nerve thickening (p = 0.0017) were markedly elevated in the single-positive population, with a trend towards pre-chiasmatic lesions (p = 0.06). Double-positive cases exhibited more polyfocal presentation (p = 0.013) and higher attacks per case (p = 0.002, HR=10.2, 95 % CI: 2.19 to 49.23). The double-positive group had more brain lesions (p = 0.0063) but no significant distinctions in other aspects. CONCLUSION: The results emphasize the challenges inherent in differentiating between MS and a more MOGAD. While the data suggest two plausible scenarios-either falling within the spectrum of MS or representing an intensified MOGAD-we recognize the need for stronger evidence to definitively classify these instances. This study underscores the imperative for thorough investigations to ascertain whether these cases align with the MS spectrum or denote an inflammatory variant of MOGAD.

Asynchronous combined central and peripheral demyelination (CCPD) in a girl with anti-MOG positivity: A case report and review of the literature.

The occurrence of combined central and peripheral demyelination (CCPD) is rare, data are limited to small case and cohort studies, mainly concerning adults. In few patients positivity to anti MOG antibody is reported, thus widening the spectrum of anti-MOG associated disorders (MOGAD). We describe a 7-year-old girl with optic neuritis followed 8 years later by peripheral demyelination, with fluctuating anti-MOG antibody positivity at cell-based assay. From the review of the literature, MOGAD-CCPD appear very rare in childhood, especially with asynchronous course. Clinicians should keep this possibility in mind to better define diagnosis in atypical demyelination syndromes, with therapeutical implications.

Mechanisms and Emerging Therapies for Treatment of Seizures in Pediatric Autoimmune Encephalitis and Autoinflammatory/Autoimmune-Associated Epilepsy.

There has been increasing understanding of the role of inflammation in seizures and epilepsy, as well as targeted immunomodulatory treatments. In children, immune-mediated seizures often present acutely in the setting of autoimmune encephalitis and are very responsive to immunotherapy with low rates of subsequent epilepsy. Conversely, seizures in autoimmune-associated epilepsies, such as Rasmussen syndrome, can remain refractory to multimodal therapy, including immunomodulation. In this review, the authors discuss the presentations of immune-mediated seizures in children, underlying mechanisms, and emerging therapies.

Association of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease with Coronavirus Disease 2019 Vaccination and Infection: A Case Report of Cortical Encephalitis and Transverse Myelitis Relapse.

We herein report a case of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) that occurred following coronavirus disease 2019 (COVID-19) vaccination and its subsequent relapse after COVID-19 infection. A 34-year-old woman developed cortical encephalitis in the right temporoparietal lobe one week after receiving the mRNA-1273 vaccine. The cerebrospinal fluid was positive for anti-MOG antibody. Her symptoms gradually improved after three courses of intravenous methylprednisolone therapy. Six months later, she experienced a relapse of transverse myelitis following COVID-19 infection. Despite treatment with plasma exchange, the patient remained paralyzed in both lower limbs. We herein review the relationship between MOGAD and COVID-19 vaccination/infection.

Myelin Oligodendrocyte Glycoprotein Optic Neuritis Presenting With Orbital Apex Syndrome.

A 36-year-old man presented with an acute onset of a right eye monocular altitudinal defect associated with pain on eye movement upon waking up from sleep. His right eye subsequently developed outward deviation and a total loss of vision. Clinical examination of the right eye revealed a visual acuity of no light perception (NLP) with the presence of relative afferent pupillary defect (RAPD) and involvement of cranial nerves II, III, IV, and VI. A marked optic disc swelling and peripapillary hemorrhages were seen in the right fundus. Contrast-enhanced computed tomography of the brain and orbit showed a unilateral enlargement and enhancement of the right intraorbital and intracanalicular segments of the optic nerve with surrounding fat stranding and orbital apex crowding. Magnetic resonance imaging showed T2/fluid-attenuated inversion recovery hyperintensity and enhancement of the optic nerve and the myelin sheath. Serum anti-myelin oligodendrocyte glycoprotein antibodies were detected. He was treated with corticosteroids, plasma exchange, and intravenous immunoglobulin. His vision improved slowly after treatment. This case report shows the diverse manifestations of myelin oligodendrocyte glycoprotein antibody disease, which includes the orbital apex syndrome.

Evolution in anti-myelin oligodendrocyte glycoprotein antibody detection and its clinical significance: a narrative review.

Myelin oligodendrocyte glycoprotein (MOG) is a protein exclusively expressing on the surface of myelin sheaths and oligodendrocyte plasma membrane in the central nervous system of mammals, and it has a highly conserved nucleotide and amino acid structure between species. Evidence from animal research support that anti-MOG antibodies (MOG-Abs) are pathogenic antibodies rather than a bystander secondary to myelin destruction. Similarly, immunoglobulin-G against myelin oligodendrocyte glycoprotein (MOG-IgG) is considered a demyelinating disease-associated autoantibody in human beings. In clinical studies, several detection methods, including ELISA, immunoblot, radio immunoprecipitation assays and Cell-based assays (CBAs), have been applied in identifying MOG-Abs in idiopathic inflammatory demyelinating diseases (IIDDs) of human beings. CBAs method is recommended by many proposed diagnostic criterions for MOG-Abs-associated disorders (MOGAD). This method involves transfection of mammalian cells with MOG antigen, binding of MOG-Abs to MOG antigen, binding of secondary antibodies to MOG-Abs and quantification method. However, the reliability for CBAs systems of MOG-Abs detection can be influenced by numerous factors, such as length of MOG antigen, expression vectors, cell lines, secondary antibodies, and read-out systems. In addition, there are controversial results on the studies of IIDDs with MOG-IgG positive. Nowadays, more and more evidence suggests that patients positive for MOG-IgG share common features, but further clinical and laboratory researches are needed to clarify if MOGAD is an independent disease entity. In this review, we intend to summarize the detection methods of MOG-Abs and their sensitivity and specificity to MOGAD in human.

A case of unusual presentation with anti-glycine receptor (GlyR) and myelin oligodentrocyte glycoprotein (MOG) antibody.

Movement disorders can be a prominent feature in autoimmune encephalitis. Here we present a rare case of a 73-year-old woman, who presented with a complex phenotype with encephalopathy, parkinsonism, cervical dystonia, left-sided hemidystonia and hemifacial spasm of subacute onset and was found to have breast cancer and positive anti-Glycine Receptor (GlyR) and Myelin Oligodentrocyte Glycoprotein (MOG) antibodies.

Anti-MOG Antibody-Associated Unilateral Cortical Encephalitis with Bilateral Meningeal Involvement: A Case Report.

A 27-year-old Han Chinese woman presented with fever, headache, lethargy, and difficulty in expression. Magnetic resonance imaging (MRI) detected extensive hyperintensity of the left-sided frontoparietal, temporal, occipital, and insular cortices via fluid-attenuated inversion recovery (FLAIR) imaging. Post-contrast MRI revealed linear enhancement in the frontoparietal, temporal, and occipital sulci bilaterally. The detection of anti-myelin oligodendrocyte glycoprotein (MOG) was positive in the cerebrospinal fluid (CSF) and serum. The patient was diagnosed with anti-MOG antibody-associated unilateral cortical encephalitis with bilateral meningeal involvement. The patient received low doses of intravenous dexamethasone followed by oral prednisone, which was tapered until withdrawal. The treatment significantly improved the patient's symptoms. A one-month follow-up showed that the patient gradually resumed her normal lifestyle. No further relapse was recorded after a one-year follow-up. MRI performed almost a year after the initial symptom onset showed that the FLAIR signal had decreased in the left insular lobe, and the abnormal cortical signal of the FLAIR in the original left frontotemporal occipital lobe had disappeared. Thus, we report a rare case of anti-MOG antibody encephalitis (unilateral cortical encephalitis with bilateral meningeal involvement) in an adult patient. This study provides a reference for the clinical diagnosis and treatment of MOG antibody-associated unilateral cortical encephalitis.

[Absence of cortical lesions after the first seizure in a patient with anti-myelin oligodendrocyte glycoprotein-associated cortical encephalitis].

A 31-year-old man developed headache and generalized convulsions. At the time of the first seizure, there was no distinct MRI abnormality. He was admitted to the hospital with repeated seizures, left-sided hemiparesis, and left-sided neglect. He had a slight fever, elevated cerebrospinal fluid (CSF) pressure, and increased CSF cell count with predominance of mononuclear cells. A repeat MRI scan on day 8 after the recurrent seizure showed cortical edema in the right cerebral hemisphere on fluid-attenuated inversion recovery (FLAIR), abnormal high signal on DWI, and decreased apparent diffusion coefficient. The patient was diagnosed with aseptic meningoencephalitis and treated with antiviral drugs and methylprednisolone pulse therapy. Serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was subsequently detected, and prednisolone was added to treat the FLAIR-hyperintense lesions in anti-MOG antibody associated encephalitis with seizures (FLAMES). It is important to identify the clinical picture and typical images of FLAMES to allow early treatment.

Seizure Evolution and Outcome in Pediatric Autoimmune Encephalitis.

BACKGROUND: Our study aimed to characterize seizure incidence and seizure outcome of pediatric autoimmune encephalitis (AE) focusing on subgroup analysis based on antibody (Ab). METHODS: Among 110 pediatric patients with AE, we compared seizure characteristics and outcomes in 68 patients with seizure, who satisfied the proposed criteria of pediatric AE. Accordingly, patients were classified into three groups, anti-myelin oligodendrocyte glycoprotein (anti-MOG) AE, anti-N-methyl-D-aspartic acid receptor (anti-NMDAR) AE, and Ab-negative AE. Univariate and multivariate analyses were performed to evaluate the risk factors for postencephalitic seizures, defined as persisting seizures six months after onset. RESULTS: Seizure incidence in the anti-NMDAR (88.9%) and Ab-negative (71.1%) groups differed from anti-MOG group (37.8%). Median seizure frequency within six months was higher in the Ab-negative group (6.0, interquartile range [IQR] 3.0 to 13.0) than in the anti-NMDAR group (3.0, IQR 2.0 to 4.5) and anti-MOG group (2.0, IQR 1.0 to 5.0). Patients in the Ab-negative group tended to develop postencephalitic seizures more frequently and have a lower seizure freedom rate than those in the anti-NMDAR and anti-MOG groups. Ab-negative status, high seizure frequency within six months, and the presence of status epilepticus were associated with the development of postencephalitic seizures on univariate analysis. On multivariate analysis, Ab-negative status remained the only significant variable linked with postencephalitic seizure (odds ratio, 4.17; 95% confidence interval, 1.02 to 18.05). CONCLUSIONS: We delineated the seizure incidence, evolution, and outcome of pediatric patients with Ab-positive and Ab-negative AE. Ab-negative status is predictive of higher seizure burden, more frequent development of postencephalitic seizures, and less favorable seizure outcome than anti-NMDAR and anti-MOG Ab-positive status.

Relapsing Anti-MOG Antibody-associated Disease following COVID-19 Vaccination: A Rare Case Report and Review of the Literature.

Anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that mainly occurs post-infection or post-vaccination. MOGAD after inoculation with coronavirus disease 2019 (COVID-19) vaccines is rare, and we herein report a rare case of a patient with MOGAD after vaccination using the Pfizer-BioNTech COVID-19 vaccine (BNT162b2, Pfizer Japan, Tokyo). Our report highlights the fact that MOGAD following inoculation with COVID-19 vaccine may show clinical relapse during reduction of the oral steroid dose, and continuous treatments with immunological agents is needed to prevent disease recurrence.

Stroke-like presentation of autoimmune chorea with positive anti-Yo and anti-MOG antibodies: a case report.

With the in-depth study of autoimmune encephalitis, more and more antibody combinations and clinical manifestations appear in our sights, enriching the spectrum of autoimmune encephalitis. Here, we report a case of a 58-year-old male patient with sudden involuntary movement of the left limb. The brain MRI was normal. CSF analysis showed slightly elevated protein (548.38 mg/L) and normal cell count(1.00 10^6/L). No tumors were detected by the whole-body PET-CT. Positive anti-Yo and anti-MOG antibodies were found in the blood. So we considered the diagnosis of autoimmune chorea with positive anti-Yo and anti-MOG antibodies, after immunoglobulin shock and methylprednisolone shock therapy were used, the patient's involuntary movement gradually disappeared. This is the first case of autoimmune encephalitis with both anti-Yo and anti-MOG antibodies, and stroke-like chorea is also rare. This case enriches the clinical presentation of double antibody-associated encephalitis.

Assessing the Correlation Between Visual Acuity and Critical Fusion Frequency in Acute Optic Neuritis Before and After Steroid Therapy.

Background Optic nerve diseases include inflammatory optic nerve diseases such as vasculitis, metabolic optic neuropathy, ischemic optic neuropathy, and optic neuritis. In this study, patients with acute optic neuritis are classified with better and poor visual acuity based on visual acuity after one month of steroid pulse therapy. To determine prognosis, initial visual acuity and critical fusion frequency (CFF) values will be compared with those recorded one month after treatment and at the last visit. Methods Visual acuity and CFF were evaluated one month after the start of treatment in patients diagnosed with acute optic neuritis, and follow-up was available for at least three months at Hiroshima University Hospital. Results All patients received steroid pulse therapy as initial treatment. After one month of treatment, visual acuity and CFF at the last visit were significantly improved in the group with improved visual acuity compared to the group with impaired visual acuity. Conclusions Visual acuity at the initial visit did not affect treatment outcome, and final visual acuity and CFF after one month of treatment for acute optic neuritis were better in patients with better visual acuity. Therefore, visual acuity values one month after treatment initiation may affect treatment outcomes.