Anti-myelin Oligodendrocyte Glycoprotein Antibody Research Articles

Emergent Management of Central Nervous System Demyelinating Disorders.

This article reviews the various conditions that can present with acute and severe central nervous system demyelination, the broad differential diagnosis of these conditions, the most appropriate diagnostic workup, and the acute treatment regimens to be administered to help achieve the best possible patient outcomes. The discovery of anti-aquaporin 4 (AQP4) antibodies and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in the past two decades has revolutionized our understanding of acute demyelinating disorders, their evaluation, and their management. Demyelinating disorders comprise a large category of neurologic disorders seen by practicing neurologists. In the majority of cases, patients with these conditions do not require care in an intensive care unit. However, certain disorders may cause severe demyelination that necessitates intensive care unit admission because of numerous simultaneous multifocal lesions, tumefactive lesions, or lesions in certain brain locations that lead to acute severe neurologic dysfunction. Intensive care may be necessary for the management and prevention of complications for patients who have severely altered mental status, rapidly progressive neurologic worsening, elevated intracranial pressure, severe cerebral edema, status epilepticus, or respiratory failure.

Prevalence of anti-myelin oligodendrocyte glycoprotein antibodies across neuroinflammatory and neurodegenerative diseases

Inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), are characterized by humoral immune abnormalities. Anti-MOG antibodies are not specific to MOGAD, with their presence described in MS. Autoantibodies may also be present and play a role in various neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease driven by motor neuron dysfunction. While immune involvement in ALS has been recognized, the presence of antibodies targeting CNS myelin antigens has not been established. We aimed to establish a live cell-based assay for quantification of serum anti-MOG IgG1 in patients with CNS diseases, including MS and ALS. In total, 771 serum samples from the John L. Trotter MS Center and the Northeast ALS Consortium were examined using a live cell-based assay for detection of anti-MOG IgG1. Samples from three cohorts were tested in blinded fashion: healthy control (HC) subjects, patients with clinically diagnosed MOGAD, and an experimental group of ALS and MS patients. All samples from established MOGAD cases were positive for anti-MOG antibodies, while all HC samples were negative. Anti-MOG IgG1 was detected in 65 of 658 samples (9.9%) from MS subjects and 4 of 108 (3.7%) samples from ALS subjects. The presence of serum anti-MOG IgG1 in MS and ALS patients raises questions about the contribution of these antibodies to disease pathophysiology as well as accuracy of diagnostic approaches for CNS inflammatory diseases.

Myelitis associated with COVID-19: clinical, radiological, and laboratory characteristics

Aim: The current study aimed to describe various types of myelitis associated with a novel coronavirus infection [coronavirus disease 2019 (COVID-19)] as well as to analyze cytokine profiles and cerebrospinal fluid (CSF) parameters in affected patients and to compare them to patients with other immune-mediated disorders—multiple sclerosis (MS), in order to identify possible common pathogenetic pathways and consequently treatment targets. Methods: Clinical, radiological, and laboratory characteristics were studied based on patients’ history. CSF from patients with myelitis associated with COVID-19 (11 patients) was compared with CSF of healthy controls (HC) (7 patients) and patients with MS (37 patients) from the non-COVID era. CSF cytological examination, protein levels and oligoclonal bands (OCBs) evaluation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus detection and cytokine profiling using Bio-Plex Pro Human Inflammation Panel 1, 37-Plex were performed. Results: In total 11 patients with different types of myelitis developed up to 3 months after COVID-19 were enrolled in the study. Radiological findings were diverse: short transverse myelitis (lesion of fewer than 3 segments) (n = 6), longitudinal extensive transverse myelitis (LETM) (n = 2), multifocal spinal cord lesions (n = 1), and myelitis involving dorsal and lateral columns (n = 2). The most pronounced response to treatment was observed in patients with partial transverse myelitis and patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG Abs). Multiple comparisons have demonstrated decreased levels of interleukin-10 (IL-10), interferon-α2 (IFN-α2), IFN-β, and thymic stromal lymphopoietin (TSLP), and increased IL-19 and B cell activating factor (BAFF) in patients with COVID-19 myelitis (CM) compared to the MS group. The highest BAFF and a proliferation-inducing ligand (APRIL) concentrations were found in patients with the most profound neurological disability. Conclusions: Myelitis associated with COVID-19 is clinically and radiologically heterogeneous. Evaluation of cytokine profiles in patients with myelitis associated with COVID-19 revealed their relative similarity with ones of MS patients, except for a few cytokines. BAFF/APRIL system as well as IL-10 is well-known for the role in the development and progression of autoimmune diseases, however, their links with COVID-19 and effects on the development of immune-mediated central nervous system (CNS) disorders after SARS-CoV-2 remain to be further studied.

Clinical Approach to Myelopathy Diagnosis.

This article describes an integrative strategy to evaluate patients with suspected myelopathy, provides advice on diagnostic approach, and outlines the framework for the etiologic diagnosis of myelopathies. Advances in diagnostic neuroimaging techniques of the spinal cord and improved understanding of the immune pathogenic mechanisms associated with spinal cord disorders have expanded the knowledge of inflammatory and noninflammatory myelopathies. The discovery of biomarkers of disease, such as anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies involved in myelitis and other immune-related mechanisms, the emergence and identification of infectious disorders that target the spinal cord, and better recognition of myelopathies associated with vascular pathologies have expanded our knowledge about the broad clinical spectrum of myelopathies. Myelopathies include a group of inflammatory and noninflammatory disorders of the spinal cord that exhibit a wide variety of motor, sensory, gait, and sensory disturbances and produce major neurologic disability. Both inflammatory and noninflammatory myelopathies comprise a broad spectrum of pathophysiologic mechanisms and etiologic factors that lead to specific clinical features and presentations. Knowledge of the clinical variety of myelopathies and understanding of strategies for the precise diagnosis, identification of etiologic factors, and implementation of therapies can help improve outcomes.

Characteristics of cerebrospinal fluid oligoclonal band in anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disease

ObjectiveTo analyze the immune parameters of cerebrospinal fluid (CSF) and oligoclonal band (OCB) type in patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). MethodsPatients who were seropositive for MOG-IgG and diagnosed with MOGAD according to the diagnosis criteria in the Department of Neurology, Huashan Hospital, Fudan University from December 2020 to June 2022 were retrospectively included in this study. Complete clinical data, blood and cerebrospinal fluid samples were collected from all the participants. Paired serum and CSF MOG-IgG and autoimmune encephalitis antibody were assayed by Cell Based Assay (CBA) based on transfected target antigens. Paired serum and CSF albumin and IgG were detected by turbidimetric scattering method, and OCB was detected by standard operation procedure as described. ResultsA total of 86 patients (44 males and 42 females) with MOGAD were included in this study, with a median age of 30 years (range: 5–82 years). Among all the patients, 73 patients showed OCB type I, 12 patients showed OCB type II, and one patient showed OCB type III. The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of CSF in the OCB-positive group (n = 13) was higher than that in the OCB-negative group [n = 73, 0.62 (0.26) vs 5.11 (13.67), P = 0.003]. Subgroup analysis revealed that the positive rates of CSF-OCB in the single MOG group (n = 61) and the group combined with other antibodies (n = 25) were 14.8 % and 16.0 %, respectively. The incidence of meningoencephalitis (13/61 vs 13/25, P = 0.011) was significantly different between the two groups. The proportion of patients with high (≥1:32) or low (≤1:10) CSF MOG-IgG also showed significant difference in the group combined with other antibodies (P = 0.032). Optic neuritis was more common in the relapse course group (n = 49) than the monophasic course group (n = 37, P < 0.001) No significant diferences of CSF immune parameters were found in the MOG-IgGserum+/CSF− group and the MOG-IgGserum+/CSF + group, and the titer of MOG-IgG in the serum or CSF did not influence CSF immune parameters in different subgroups. ConclusionThe overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of cerebrospinal fluid in the OCB-positive group was higher than that in the OCB-negative group. This study illustrated OCB characterization in MOGAD patients, and will shed light on the standardization of OCB test in the study of immune diseases.

Successful Maintenance Therapy with Intravenous Immunoglobulin to Reduce Relapse Attacks and Steroid Dose in a Patient with Refractory Myelin Oligodendrocyte Glycoprotein Antibody-positive Optic Neuritis.

A 25-year-old Japanese man developed visual disturbance with eye pain and was diagnosed with optic neuritis associated with anti-myelin oligodendrocyte glycoprotein antibodies. His symptoms improved temporarily after steroid therapy but chronically relapsed many times after tapering the steroid dose. He became highly steroid-dependent and was referred to our department for reconsideration of the treatment strategy. Maintenance intravenous immunoglobulin (IVIg) therapy successfully decreased the annual recurrence rate from 1.15 to 0.27 times/year and the maintenance dose of oral prednisolone from 35 to 5 mg/day. Maintenance IVIg therapy is a promising option for preventing disease relapse in such cases.

Clinical Features and Prognostic Factors in Anti-Myelin Oligodendrocyte Glycoprotein Antibody Positive Optic Neuritis

ABSTRACT In order to review the clinical features of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis (MOGON), we investigated the clinical characteristics, visual function, optical coherence tomography findings, and magnetic resonance imaging of 31 patients (44 eyes). MOGON was more common in middle age without sex difference and was characterised by pain on eye movement and optic disc swelling. Magnetic resonance imaging lesions tended to be long with inflammation around the optic nerve sheath; longer lesions were associated with worse visual acuities at onset. Recurrence was significantly associated with retinal nerve fibre layer thinning, and thus, it is important to reduce recurrence as much as possible.

Oligoclonal Bands in CSF May be Associated with Chronic Graft Versus Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation

Introduction Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a straightforward and effective therapy for hematology patients, and chronic graft-versus-host disease (cGVHD) is recognized as a major and important complication of haplo-HSCT. cGVHD can affect a number of organs, such as the skin, eyes, oral mucosa, liver, and lung.In addition to classical manifestations, cGVHD can imitate almost any autoimmune disease, and its central nervous system (CNS) involvement is exceedingly rare. In our studies, IgG synthesis and anti-myelin oligodendrocyte glycoprotein antibody were risk factors for CNS demyelination ( Annals of Hematology, 2018), aGVHD and hypertension were associated with posterior reversible encephalopathy syndrome ( Bone Marrow Transplantation, 2020), and aGVHD and cGVHD were identified as factors for idiopathic inflammatory demyelinating disease ( Am J Hematol, 2021). However, there are limited data available on cGVHD in the CNS. Therefore, we performed a thorough assessment of cGVHD, including examining the CSF of patients with cGVHD. Methods We performed a retrospective nested case‒control study in patients receiving haplo-HSCT between January 2013 and June 2022 in our center. In total, 86 patients suffering from cGVHD who also received CSF examinations were analyzed, of whom 42 patients showed evidence of CNS-cGVHD. Written informed consent was, and ethical approval was obtained before sample collection by the Ethics Committee of Peking University People's Hospital. The CSF samples were collected by lumbar puncture (LP). At least 1 ml of CSF was obtained from all patients by nontraumatic LP. All CSF samples were routinely screened for infection with bacterial, fungal, and virological pathogens, examined by histopathology and analyzed by fluorescence-activated cell sorting to identify tumor cells. Immune biomarkers were also evaluated. Results The median time from transplantation to cGVHD was 236 days. In the 86 cGVHD patients, aGVHD (HR 0.431, 95% CI 0.229-0.812, P=0.009), CSF protein (HR 0.634, 95% CI 0.484-0.784, P=0.)and oligoclonal bands (OCB) (HR 0.527, 95% CI 0.312-0.890, P=0.017) were identified as risk factors for the onset of cGVHD after haplo-HSCT. Moreover, we combined the variables to establish a nomogram for the cumulative incidence of cGVHD. The test showed that the fitness of the multivariate logistic regression model was suitable (P = 0.9516). The area under the ROC curve was 0.741. There were no differences in overall survival (OS), disease-free survival (DFS), or the cumulative incidence of relapse (CIR) between the cGVHD group and the control group without cGVHD. Nonetheless, there was a significant difference in nonrelapse mortality (NRM) (P=0.009). The 2-year cumulative NRM was 48.2% (95% CI 45.8%-50.6%) versus 12.6% (95% CI 12.2%-13.0%) between the cGVHD and without cGVHD groups, respectively. Then, we performed multivariate analysis for data from 42 patients who were diagnosed with CNS-cGVHD. The underlying diseases (HR 1.334, 95% CI 1.027-1.733, P=0.030) and CSF proteins (HR 0.313, 95% CI 0.126-0.776, P=0.012) were independently associated with the occurrence of CNS-cGVHD. Conclusions In conclusion, CSF immunity may be associated with the onset of cGVHD after haplo-HSCT, especially OCB, and the identification of cGVHD increases NRM after haplo-HSCT. Further multicenter prospective studies are needed to confirm the results and establish the standard diagnostic criteria and therapy for CNS-cGVHD.

Distinct features of B cell receptors in neuromyelitis optica spectrum disorder among CNS inflammatory demyelinating diseases

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing.MethodsFrom a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups.ResultsBlood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups.ConclusionsNMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual’s lifetime.

Anti-aquaporin-4 antibody (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG) in the cerebrospinal fluid.

Anti-aquaporin-4 antibody (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG) in the cerebrospinal fluid.

Clinical characteristics and prognosis of optic neuritis in Taiwan - a hospital-based cohort study.

Optic neuritis (ON) is an inflammatory disease of optic nerve. The distinct etiologies of ON significantly influence its clinical manifestation, neuroimaging findings, and visual outcomes. However, the clinical characteristics might be influenced by the racial differences. The purpose of this study is to investigate the clinical characteristics of various types of ON at a Taiwanese tertiary center. This cohort study analyzed 163 patients who received treatment and continued following-up for ON between 2015 and 2022. We selected patients who had been tested for anti-aquaporin-4 antibody (AQP4-Ab) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab). The participants were classified into four groups on the basis of their etiologies, specifically (1) multiple sclerosis (MS)-related, (2) AQP4-Ab-positive, (3) MOG-Ab-positive, or (4) idiopathic ON. The researchers recorded the patients' clinical characteristics, treatment course, magnetic resonance imaging and optical coherence tomography (OCT) findings, and visual outcomes. MOG-Ab-positive group had higher percentages of disk swelling and pain with eye movement. Long optic nerve and perineural enhancement are the hallmarks of MOG-Ab-related ON. The ON relapse rate was higher in AQP4-Ab-positive group. Although members of AQP4-Ab-positive group received immediate steroid pulse therapy, these patients experienced the worst visual outcomes. Moreover, a thinner retinal nerve fiber layer (RNFL) was noted in AQP4-Ab-positive group. MS group had a higher incidence of extra-optic nerve lesions. Multivariate regression identified pretreatment visual acuity and RNFL thickness as the important factors affecting visual outcomes. This cohort study identified the clinical features of different types of ON. Patients with AQP4-Ab-positive ON had poorer visual outcomes, which may be attributed to multiple relapses and profound nerve damage, as revealed by OCT findings. Patients with MOG-Ab-positive ON displayed long optic nerve enhancement but had more favorable prognoses. Thus, antibody-based classification facilitates treatment and prognosis in ON.

Serum proteins for monitoring and predicting visual function in patients with recent optic neuritis

It is unclear whether serum proteins can serve as biomarkers to reflect pathological changes and predict recovery in inflammation of optic nerve. We evaluated whether serum proteins could monitor and prognosticate optic neuritis (ON). We prospectively recruited consecutive patients with recent ON, classified as ON with anti-aquaporin-4 antibody (AQP4-ON), ON with anti-myelin oligodendrocyte glycoprotein antibody (MOG-ON), and double-seronegative ON (DSN-ON). Using ultrasensitive single-molecule array assays, we measured serum neurofilament light chain and glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF). We analyzed the markers according to disease group, state, severity, and prognosis. We enrolled 60 patients with recent ON (15 AQP4-ON; 14 MOG-ON; 31 DSN-ON). At baseline, AQP4-ON group had significantly higher serum GFAP levels than did other groups. In AQP4-ON group, serum GFAP levels were significantly higher in the attack state than in the remission state and correlated with poor visual acuity. As a prognostic indicator, serum BDNF levels were positively correlated with follow-up visual function in the AQP4-ON group (r = 0.726, p = 0.027). Serum GFAP reflected disease status and severity, while serum BDNF was identified as a prognostic biomarker in AQP4-ON. Serum biomarkers are potentially helpful for patients with ON, particularly those with AQP4-ON.

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 comparative analysis of demographic, clinical and imaging features of myelin oligodendrocyte glycoprotein antibody positive, aquaporin 4 antibody positive, and double seronegative demyelinating disorders - An Indian tertiary care center prospective study.

The aim of the study was to study the demographical, clinical, radiological features, and outcome of anti-myelin oligodendrocyte glycoprotein (MOG) antibody spectrum disorder and compare these features with patients negative for anti-MOG antibody. MOG antibody-associated disease (MOGAD) and aquaporin-4 (AQP4) antibody-related diseases are immunologically distinct pathologies. Our aim was to compare the clinical and radiological features of MOG antibody-related diseases with AQP4 antibody-related diseases and seronegative demyelinating diseases (Non-multiple sclerosis). This was a prospective and cohort study conducted at an apex tertiary care institute in the northern part of India from Jan 2019 to May 2021. We compared clinical, laboratory, and radiological findings of patients with MOGAD, AQP4 antibody-related diseases, and seronegative demyelinating disease. There were a total of 103 patients - 41 patients of MOGAD, 37 patients of AQP4 antibody-related diseases and 25 seronegative demyelinating disease. Bilateral optic neuritis was the most frequent phenotype in patients with MOGAD (18/41) whereas myelitis was the most common phenotype in the AQP4 (30/37) and seronegative groups (13/25). Cortical, juxtacortical lesions, anterior segment optic neuritis, optic sheath enhancement, and conus involvement in myelitis were radiological findings that separated MOGAD from AQP4 related diseases. Nadir Expanded Disability Status Scale (EDSS) and visual acuity were similar across the groups. Last follow-up EDSS was significantly better in the MOG antibody group as compared to AQP4 antibody group (1 [0-8] vs. 3.5 [0-8]; P = 0.03). Encephalitis, myelitis, and seizures were more common in the younger population (<18 vs. >18 years) in MOGAD (9 vs. 2, P = 0.001; 9 vs. 7, P = 0.03; 6 vs. 0, P = 0.001). We identified several clinical and radiological features that can help physicians to distinguish MOGAD from AQP4-immunoglobulin G+neuromyelitis optica spectrum disorder. Differentiation is vital as treatment response might vary among both groups.

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.

Mimics of Pediatric Small Vessel Primary Angiitis of the Central Nervous System.

Small vessel primary angiitis of the central nervous system is a rare and often severe disease characterized by central nervous system-restricted inflammatory vasculitis on histopathology. Diagnosis requires brain biopsy for confirmation and is suggested prior to starting immunotherapy when feasible. However, emerging evidence suggests that other neuroinflammatory conditions may have a clinical and radiographic phenotype that mimics small vessel primary angiitis, at times with overlapping pathologic features as well. Such diagnoses, including myelin oligodendrocyte glycoprotein antibody-associated disease and central nervous system-restricted hemophagocytic lymphohistiocytosis, can be non-invasively diagnosed with serum antibody or genetic testing that would prompt different monitoring and treatment paradigms. To determine the ultimate diagnosis of patients who were suspected prior to biopsy to have small vessel primary angiitis, we reviewed the clinical, radiographic, and pathological features of a cohort of patients at a single center undergoing brain biopsy for non-oncologic indications. Clinical data were retrospectively extracted from the medical record. Pathology and neuroimaging review was conducted. We identified 21 patients over a 19-year time-period, of whom 14 (66.7%) were ultimately diagnosed with entities other than small vessel primary angiitis that would have obviated the need for brain biopsy. Diagnoses included anti-myelin oligodendrocyte glycoprotein antibody associated disease (n=9), central nervous system-restricted hemophagocytic lymphohistiocytosis (n=3), anti-GABAA receptor encephalitis (n=1), and Aicardi-Goutières syndrome (n=1). This study highlights the importance of pursuing now readily available non-invasive testing for mimicking diagnoses before performing a brain biopsy for suspected small vessel primary angiitis of the central nervous system. ANN NEUROL 2023;93:109-119.

Clinical and diagnostic spectrum of optic neuritis: A single-center retrospective study of disorders associated with multiple sclerosis, anti-aquaporin-4 and anti-myelin oligodendrocyte glycoprotein antibodies

ObjectiveOptic neuritis (ON) is an immune-mediated optic neuropathy associated with multiple immune-mediated neurological conditions. Our aim was to characterize the clinical and diagnostic features of first or initial episodes of ON associated with multiple sclerosis (MS)-associated (typical) and antibody-related (atypical) ON. MethodsRetrospective, single institution, medical record review. We analyzed demographic, clinical, laboratory, and radiographic findings of 139 patients who presented with first episodes of MS-associated ON (MS-ON), aquaporin 4 antibody–associated ON (AQP4-ON), and myelin oligodendrocyte glycoprotein antibody–associated ON (MOG-ON) between January 2015 and October 2019 without preceding diagnosis. Simple hypothesis testing assessed differences between groups were performed. ResultsOf 139 patients (109 [79 %] women; 29 [21 %] men; mean age 47 [SD, 14] years), 106 had MS-ON, 25 had AQP4-ON, and 8 had MOG-ON. Patients with MOG-ON had the highest recurrence rate (88 %) relative to MS-ON (28 %) and AQP4-ON (56 %) patients (P < .001). Patients with AQP4-ON had the highest mean visual functional system scores (4.3 [SD, 1.8]) relative to MS-ON (2.0 [SD, 1.9]) and MOG-ON patients (2.8 [SD, 2.0]) (P < .001). ConclusionPatients presenting with initial episodes of ON exhibit a range radiographic and laboratory feature depending on the underlying associated disease. Understanding the variable characteristics of typical (MS-associated) and atypical (antibody-associated) ON may help physicians accurately diagnose and effectively treat ON.

Seropositive Neuromyelitis Optica in a Case of Undiagnosed Ankylosing Spondylitis: A Neuro-Rheumatological Conundrum

Seropositive Neuromyelitis Optica in a Case of Undiagnosed Ankylosing Spondylitis: A Neuro-Rheumatological Conundrum

Myelin oligodendrocyte glycoprotein antibodies in genetic leukodystrophies

Accumulation of intermediate metabolites due to enzyme deficiencies and demyelination can provoke inflammation in genetic leukodystrophies. Thirty patients with genetic leukodystrophy and 48 healthy control sera were tested for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies by fixed and/or live cell-based assays. MOG-IgG was detected in two late infantile metachromatic leukodystrophy (MLD) cases, both of which were also weakly positive for IgG1, and one with IgG3 as the dominant anti-MOG IgG subclass. MOG-IgG was borderline positive in a vanishing white matter (VWM) disease patient. These results suggest that inherited metabolic or degenerative processes can have an autoimmune component, possibly as an epiphenomenon.

Longitudinally Extensive Transverse Myelitis: One Disease, Variable Outcomes-A Case Series.

Longitudinal extensive transverse myelitis (LETM) is a rare form of widespread inflammation of the spinal cord causing T2 hyperintensity in spinal magnetic resonance imaging (MRI) extending across three or more vertebral segments. It is an acute onset of sensory, motor, and autonomic dysfunction of variable etiology with a likely poor outcome. We present a case series of three cases wherein children between the ages of 4 and 13 years had diverse symptoms from gradual painless loss of vision in both eyes with headache, vomiting and seizure, and a normal central nervous system examination except involvement of the optic nerve to another child with abdominal pain, urinary retention and constipation for 3 days with exaggerated DTR, and patchy sensory loss without any definite sensory level, and to the third child with fever and weakness of lower limbs, hypotonia and grade 1–2/5 power in lower limbs and normal upper limb power. Contrast-enhanced MRI spine of all children showed long segment T2 hyperintensity with variable involvement of the brain. The first two children were treated with pulsed dose methylprednisolone, and the last child received intravenous immunoglobulin followed by methylprednisolone. All were followed with oral prednisolone. LETM has a varied presentation with different etiologies. Antineuromyelitis optica immunoglobulin G (IgG) antibody (Aquaporin-4 IgG) and antimyelin oligodendrocyte glycoprotein antibody are strongly recommended though they may not be locally available or not affordable. Early and aggressive immunomodulatory therapy may help faster recovery, as did with two of our three children.