Inflammatory Demyelinating Disease Research Articles

Physiological aging and inflammation-induced cellular senescence may contribute to oligodendroglial dysfunction in MS

Aging affects all cell types in the CNS and plays an important role in CNS diseases. However, the underlying molecular mechanisms driving these age-associated changes and their contribution to diseases are only poorly understood. The white matter in the aging brain as well as in diseases, such as Multiple sclerosis is characterized by subtle abnormalities in myelin sheaths and paranodes, suggesting that oligodendrocytes, the myelin-maintaining cells of the CNS, lose the capacity to preserve a proper myelin structure and potentially function in age and certain diseases. Here, we made use of directly converted oligodendrocytes (dchiOL) from young, adult and old human donors to study age-associated changes. dchiOL from all three age groups differentiated in an comparable manner into O4 + immature oligodendrocytes, but the proportion of MBP + mature dchiOL decreased with increasing donor age. This was associated with an increased ROS production and upregulation of cellular senescence markers such as CDKN1A, CDKN2A in old dchiOL. Comparison of the transcriptomic profiles of dchiOL from adult and old donors revealed 1324 differentially regulated genes with limited overlap with transcriptomic profiles of the donors’ fibroblasts or published data sets from directly converted human neurons or primary rodent oligodendroglial lineage cells. Methylome analyses of dchiOL and human white matter tissue samples demonstrate that chronological and epigenetic age correlate in CNS white matter as well as in dchiOL and resulted in the identification of an age-specific epigenetic signature. Furthermore, we observed an accelerated epigenetic aging of the myelinated, normal appearing white matter of multiple sclerosis (MS) patients compared to healthy individuals. Impaired differentiation and upregulation of cellular senescence markers could be induced in young dchiOL in vitro using supernatants from pro-inflammatory microglia. In summary, our data suggest that physiological aging as well as inflammation-induced cellular senescence contribute to oligodendroglial pathology in inflammatory demyelinating diseases such as MS.

Human endogenous retrovirus W in multiple sclerosis: transcriptional activity is associated with decline in oligodendrocyte proportions in the white matter of the brain.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease. One of the basic mechanisms in this disease is the autoimmune response against the myelin sheet leading to axonal damage. There is strong evidence showing that this response is regulated by both genetic and environmental factors. In addition, the role of viruses has been extensively studied, especially in the case of human endogenous retroviruses (HERVs). However, although several associations with MS susceptibility, especially in the case of HERV-W family have been observed, the pathogenic mechanisms have remained enigmatic. To clarify these HERV-mediated mechanisms as well as the responsible HERV-W loci, we utilized RNA sequencing data obtained from the white matter of the brain of individuals with and without MS. CIBERSORTx tool was applied to estimate the proportions of neuronal, glial, and endothelial cells in the brain. In addition, the transcriptional activity of 215 HERV-W loci were analyzed. The results indicated that 65 HERV-W loci had detectable expression, of which 14 were differentially expressed between MS and control samples. Of these, 12 HERV-W loci were upregulated in MS. Expression levels of the 8 upregulated HERV-W loci had significant negative correlation with estimated oligodendrocyte proportions, suggesting that they are associated with the dynamics of oligodendrocyte generation and/or maintenance. Furthermore, Gene Set Enrichment Analysis (GSEA) results indicated that expression levels of three upregulated HERV-W loci: 2p16.2, 2q13, and Xq13.3, are associated with suppression of oligodendrocyte development and myelination. Taken together, these data suggest new HERV-W loci candidates that might take part in MS pathogenesis.

Impact of comorbidities on relapsing rates of Neuromyelitis Optica Spectrum Disorders: Insights from a longitudinal study in Taiwan

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear. Methods: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006-2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined. Results: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9%) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26-1.11) for adults and 0.39 (IQR: 0.21-0.77) for pediatric patients. Comorbidities included malignancy (6.7%) and autoimmune diseases (21.7%). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities. Conclusions: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan.

The ratio of circulating CD56dim NK cells to follicular T helper cells as a promising predictor for disease activity of relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system primarily mediated by CD4+ T helper cells. This study investigated the dynamic changes of natural killer (NK) cells and follicular T helper (Tfh) cells and their associations in relapsing-remitting MS patients. The findings revealed inverse relationships between NK cells and CD4+ T cells or Tfh cells. Specifically, CD56dim NK cells, not CD56bright NK cells, were negatively correlated with CD4+ T cells and Tfh cells. However, no significant correlations were found between NK cells and sNfL levels or EDSS scores. The ratio of CD56dim NK cells to circulating Tfh (cTfh) cells demonstrated superior discriminatory ability in distinguishing relapsing MS patients from healthy controls (HCs) and remitting patients, as determined by receiver operating characteristic (ROC) analysis. Following treatment with immunosuppressants or disease-modifying therapies (DMTs), a significant increase in the CD56dim NK/cTfh ratio was observed. These findings suggest that the CD56dim NK/cTfh ratio holds promise as a prognostic indicator for clinical relapse and treatment response in MS.

Gas6/TAM system as potential biomarker for multiple sclerosis prognosis.

The protein growth arrest-specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, and Mer (TAM) are ubiquitous proteins involved in regulating inflammation and apoptotic body clearance. Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system leading to progressive and irreversible disability if not diagnosed and treated promptly. Gas6 and TAM receptors have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available regarding clinical correlation in MS patients. We aimed to evaluate soluble levels of these molecules in the cerebrospinal fluid (CSF) and serum at MS diagnosis and correlate them with short-term disease severity. In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay. At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS<3 at diagnosis (p = 0.04; p = 0.037). Serum Gas6 correlates to a lower MSSS (r2 = -0.32, p = 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS (p = 0.005; p = 0.002) and MSSS (r2= 0.27, p = 0.03; r2 = 0.39, p = 0.001). Results were corroborated using multivariate analysis. Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

Optic chiasm involvement in multiple sclerosis, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein–associated disease

Background: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated. Aims: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON−) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers. Methods: Twenty-eight relapsing-remitting multiple sclerosis (RRMS), 24 AQP4 + NMOSD, 28 MOGAD patients and 32 healthy controls (HCs) underwent clinical evaluation, MRI and optical coherence tomography (OCT) scan. Multivariable linear regression models were applied. Results: ON + IDD patients showed lower OC MTR than HCs (28.87 ± 4.58 vs 31.65 ± 4.93; p = 0.004). When compared with HCs, lower OC MTR was found in ON + AQP4 + NMOSD (28.55 ± 4.18 vs 31.65 ± 4.93; p = 0.020) and MOGAD (28.73 ± 4.99 vs 31.65 ± 4.93; p = 0.007) and in ON− AQP4 + NMOSD (28.37 ± 7.27 vs 31.65 ± 4.93; p = 0.035). ON+ RRMS had lower MTR than ON− RRMS (28.87 ± 4.58 vs 30.99 ± 4.76; p = 0.038). Lower OC MTR was associated with higher number of ON (regression coefficient (RC) = −1.15, 95% confidence interval (CI) = −1.819 to −0.490, p = 0.001), worse visual acuity (RC = −0.026, 95% CI = −0.041 to −0.011, p = 0.001) and lower peripapillary retinal nerve fibre layer (pRNFL) thickness (RC = 1.129, 95% CI = 0.199 to 2.059, p = 0.018) when considering the whole IDD group. Conclusion: OC microstructural damage indicates prior ON in IDD and is linked to reduced vision and thinner pRNFL.

Thách thức trong chẩn đoán và điều trị xơ cứng rải rác khởi phát rất muộn: ca lâm sàng

Multiple sclerosis is a prevalent chronic inflammatory demyelinating disease of the central nervous system that affects mainly young adults. Patients with onset after the age of 50 years are defined as late-onset MS (LOMS), and the others with onset after 60 years are termed very late-onset MS (VLOMS). Due to the rarity, and variations in clinical presentation, coupled with the lack of clinical trials for disease-modifying therapies (DMTs), diagnosis and treatment are challenging in these groups. In our clinical case, we describe a patient diagnosed with VLOMS at the Neurology Department of Military Hospital 175.

Use of Complementary and Alternative Medicine in Patients With Idiopathic Inflammatory Demyelinating Diseases of the Central Nervous System: A Cross-Sectional Study in Thailand

BackgroundComplementary and alternative medications (CAM) are common among patients with multiple sclerosis (MS) for physical and psychological support. However, there is insufficient data regarding the application of CAM in the different cultures and beliefs of each community as well as patient's status. ObjectiveTo evaluate the prevalence and modalities of the use of CAM among patients with central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) in a tertiary care hospital MethodsA cross-sectional study was conducted at Siriraj Hospital from June to December 2021 involving patients with MS, neuromyelitis optic spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic transverse myelitis (iTM), and optic neuritis (ON) to examine the prevalence and mode of CAM use and its correlation with patient characteristics. ResultsThere were 107 patients. The diagnoses were MS (38), NMOSD (55), MOGAD (5), iTM (7), and ON (2). Most of the patients were female (89.7%), and 61.7% were diagnosed over 5 years. The mean Expanded Disability Status Scale was 2.63 (S.D., 2.38), and the median ambulation index was 0 (range 0–8.5). There were 68 patients (63.6%) with a history of CAM use for at least 3 months, while those with current use decreased to 62 (58.5%). Vitamins and minerals were the most commonly used, particularly vitamin D (97.1%) and calcium (47.7%). Both treatments were primarily prescribed (95.3%) rather than self-administered (24.3%). The main reasons for the use of CAM were to strengthen their health (48.6%) and relieve existing symptoms (28.0%). ConclusionsThe use of CAM is common among patients with Thai CNS-IIDD. Further exploration of patient perspectives and preferences regarding CAM usage may contribute to a more comprehensive management approach for patients with CNS-IIDD.

Epidemiological Characteristics of Inflammatory Demyelinating Diseases of the Central Nervous System Including Multiple Sclerosis

Relevance. Demyelinating diseases of the central nervous system and multiple sclerosis, in particular, make their debut at a young age and can lead to profound disability and death within a few years. In the last decade, there has been an increase in the number of cases of demyelinating diseases in Russia and in the world, which necessitates an in-depth study of these pathologies. Goal. To study the dynamics and features of the formation of morbidity, prevalence and mortality from demyelinating diseases of the central nervous system, including multiple sclerosis in various population groups in the Russian Federation. Materials and methods. The study design is a descriptive retrospective epidemiological study (continuous). The data was sampled from the forms of the federal state statistical observation on the distribution of the deceased by gender, age groups and causes of death of Rosstat (FSN S-51), as well as from the statistical collections of the Federal State Budgetary Institution "Central Research Institute of the Ministry of Health of the Russian Federation "Morbidity of the population" from 2009 to 2021. Results. The analysis of the data showed that in 2009-2021 in Russia there was an increase in idiopathic inflammatory demyelinating diseases (IDD) and multiple sclerosis (MS) among the adult population and adolescents aged 15 to 17 years. There is no tendency to increase or decrease the incidence among children under 14 years of age. The highest average long–term incidence rates of IDD and MS among adults are observed in the Ufa region (7.13 ± 0.27 and 5.31 ± 0.23 per 100 thousand adults, respectively), among children under 14 - IDD in the Central Federal District (1.88 ± 0.18 per 100 thousand contingent) and MS in the Central Federal District and Volga Federal District (0.22 ± 0.07 per 100 thousand contingent). Among children from 15 to 17 years of age, the highest incidence of IDD is noted in the Northwestern Federal District (4.41 ± 1.10 per 100 thousand contingent) and the Ural Federal District (4.40 ± 1.09 per 100 thousand contingent), RS – in the Central Federal District (2.67 ± 0.51 per 100 thousand contingent). IDD and MS are the least common among all age groups in the Far Eastern Federal District. Over the period from 2000 to 2020, there has been a decrease in MS mortality in the Russian Federation by 34%, from 0.72 to 0.48 per 100,000 population. The average annual mortality rate from MS among men was 0.4 ± 0.021 cases per 100 thousand of the contingent, among women 0.5 ± 0.023 cases per 100 thousand of the contingent. Conclusion. The increase in the incidence of demyelinating diseases and MS, in particular, is an important medical and social problem. These pathologies significantly reduce the quality of life and shorten the duration of work, due to the development of persistent disability in the young population. The study showed the uneven distribution of the disease across the territories of the Russian Federation, which in the future will improve the logistics of drug delivery and the provision of medical personnel, which confirms the relevance of constant and in-depth study of the epidemiology of idiopathic inflammatory demyelinating diseases in Russia.

Multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain. In this review, the spectrum of MS lesion s and their relation to the inflammatory process is described. Pathology suggests that inflammation drives tissue injury at all stages of the disease. Focal inflammatory infiltrates in the meninges and the perivascular spaces appear to produce soluble factors, which induce demyelination or neuro- degeneration either directly or indirectly through microglia activation. The nature of these soluble factors, which are responsible for demyelinating activity in sera and cerebrospinal fluid of the patients, is currently undefined. Demyelination and neurodegeneration are finally accomplished by oxidative injury and mitochondrial damage leading to a state of “virtual hypoxia.”

Multiple sclerosis: A descriptive series

IntroductionMultiple sclerosis (MS) is a chronic multifocal inflammatory demyelinating disease that progresses with neurodegeneration and is associated with a high risk of disability. ObjectivesWe describe a series of patients diagnosed with MS in the past 10 years at a secondary hospital in Colombia. MethodsWe conducted a descriptive, retrospective study of a series of patients attended at the outpatient clinic of the neurology department of Hospital Regional de la Orinoquía, in Colombia, between 2013 and 2022, and who were diagnosed with MS according to the McDonald criteria. ResultsWe included 15 patients with a confirmed diagnosis of MS; 66.7% were women, with a mean age of 42 years (range, 16–71). Mean time from symptom onset to inclusion in the study was 87.4 months; 20% of patients presented disability. The distribution by type of MS was as follows: 20% patients had primary progressive MS, 20% had secondary progressive MS, 40% had clinically isolated syndrome, and 20% had relapsing–remitting MS. The mortality rate was 20%, with a median survival time of 89.83 months. ConclusionsAlthough treatment achieves significant improvements in symptoms and quality of life at every stage of the disease, early diagnosis is essential to prevent progression to disability.

Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) accompanied by blood-brain barrier (BBB) disruption. Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD. However, there is limited evidence on the functional relevance of circulating lipids in CNS demyelination, cellular metabolism, and microglial function. Here, we found that serum low-density lipoprotein (LDL) was positively correlated with markers of neurological damage in NMOSD patients. In addition, we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB, directly activating microglia. This activation leads to excessive phagocytosis of myelin debris, inhibition of lipid metabolism, and increased glycolysis, ultimately exacerbating myelin damage. We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD. These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage, highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

Mechanisms Governing Oligodendrocyte Viability in Multiple Sclerosis and Its Animal Models.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disease of the central nervous system (CNS), which is triggered by an autoimmune assault targeting oligodendrocytes and myelin. Recent research indicates that the demise of oligodendrocytes due to an autoimmune attack contributes significantly to the pathogenesis of MS and its animal model experimental autoimmune encephalomyelitis (EAE). A key challenge in MS research lies in comprehending the mechanisms governing oligodendrocyte viability and devising therapeutic approaches to enhance oligodendrocyte survival. Here, we provide an overview of recent findings that highlight the contributions of oligodendrocyte death to the development of MS and EAE and summarize the current literature on the mechanisms governing oligodendrocyte viability in these diseases.

The role of autoimmune processes in demyelinating diseases of the nervous system: focus on multiple sclerosis

Background. Demyelinating diseases of the central nervous system (CNS) are a heterogeneous group of disorders characterized by a damage to the myelin sheath of nerve cell axons. Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the CNS affecting more than 2.9 million people worldwide. The purpose was to summarize current information about the features of the immunopathogenesis of multiple sclerosis according to the data from open sources of information. Materials and methods. The selection of publications covering the features of the immunopathogenesis of multiple sclerosis was carried out in the PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection and Google Scholar databases using the following keywords: multiple sclerosis, demyelinating diseases, neurodegeneration, oligodendrocytes. Results. The course of MS has three successive phases/forms known as relapsing-remitting, primary progressive and secondary progressive. Abnormalities of immune mechanisms are proposed as protagonists of the pathogenesis of MS. Autoreactive myelin-specific lymphocytes are activated outside the CNS, they cross the blood-brain barrier and form new inflammatory demyelinating lesions. The myelinating oligodendrocyte is a target during the adaptive immune response in MS. The inflammatory reaction in the brain of patients with progressive MS is observed mainly in the large connective tissues of the meninges and the periventricular space. Treatment of MS can be divided into three categories: treatment of acute relapse, disease-modifying treatment, and symptomatic treatment. Conclusions. On the T cell side, both hel-per (CD4+) and cytotoxic (CD8+) T cells are involved in the CNS damage in MS. Peripherally activated subsets of T cells (CD4+ Th1 and Th17, CD8+) migrate through the blood-brain barrier and activate B-cells and macrophages, which causes a neuroinflammatory reaction and leads to demyelination and neurodegeneration in the CNS. Oligodendrocyte progenitor cells, which are widely distributed throughout the CNS, mediate myelination and remyelination. One of the desired features of new methods for treating MS is the restoration of antigen-specific tolerance.

Bibliometric analysis of myelin imaging studies of patients with multiple sclerosis (2000-2022).

Multiple sclerosis (MS) is a condition that can impact the central nervous system (CNS) and cause damage to the myelin, which is responsible for facilitating the normal transmission of electrical impulses along the nerves. We performed a bibliometric analysis of the scientific publications on myelin imaging in MS to reveal the development trends in this field and to evaluate research trends in myelin imaging in MS. The Web of Science Core Collection was searched for articles related to myelin imaging in MS published between January 2000 and December 2022. CiteSpace, VOSviewer, and R language were used to evaluate and visualize contributions by and co-occurrence relationships among countries and institutions, authors, journals, citations, keywords, and so on. A total of 1,639 articles addressed the topic of myelin imaging in MS. The United States had the largest number of annual publications. The University of London was the institution with the highest number of publications (n=118) and citations (n=9,885). The top 3 productive authors were all from the University of British Columbia in Canada. An article published by Mackay et al. in 1994 had the most citations (n=272). Neuroimage [impact factor (IF) =7.40, Journal Citation Reports quartile 1 (Q1)] was the most productive journal in terms of the number of articles relating to myelin imaging in MS (n=149). In recent years, myelin water imaging, synthetic magnetic resonance imaging (SyMRI), inhomogeneous magnetization, positron emission tomography (PET) imaging, and aquaporin-4 (AQP4) have been researched hotspots of myelin imaging in MS. With advancements in the pathophysiological research on myelin changes in MS, myelin imaging is playing an important role in the diagnosis and treatment of MS. In addition, the use of new sequences of myelin imaging to distinguish MS from other inflammatory demyelinating diseases is a future development trend in this field.

Clinical Features of Patients with Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and Isolated Seizure Symptoms.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated encephalitis is a new clinical phenotype of inflammatory demyelinating diseases. Some MOG antibody-positive patients with central nervous system demyelinating events present with isolated seizures. However, there are gaps in the epidemiological knowledge regarding seizures with MOG antibody-associated encephalitis in adults. This study characterized the clinical features and treatment of MOG antibody-positive patients with isolated seizures. We reviewed all the patients admitted to Tianjin Huanhu Hospital between Jan. 1st 2017 and Jan. 1st 2022, to screen the MOG antibody-positive patients with isolated seizures, and collected the concerned patients' information regarding epidemiology, clinical presentations, laboratory and radiological characteristics, electroencephalogram (EEG), treatments, and prognoses. We collected six MOG antibody-positive adult patients who had isolated symptomatic seizures. The mean age of the patients was 33 years (range, 29-40 years), and five (83.3%) were men. All patients presented with motor seizures, five (83.3%) had cognitive dysfunction, and only one (16.7%) had status epilepticus. Five (83.3%) patients had a good response to immunotherapy and antiseizure medications; only one had a sequela. The cerebrospinal fluid or serum anti-MOG antibody test turned negative over time. The most common seizure type in patients with MOG antibody-associated encephalitis with isolated seizures was focal to bilateral tonic-clonic seizures, and most patients had a good prognosis. Adding antiseizure medications were beneficial for MOG antibody-positive patients with seizures. Relapses and sequelae were associated with low-dose, short-time, or delayed therapy, and wide-range demyelinating brain damage.

Cell-Based Assay to Detect the Autoantibody Serostatus in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).

Cell-based assay (CBA) is an immunofluorescence assay that is extensively used for the confirmatory diagnosis of inflammatory demyelinating diseases of the central nervous system, like neuromyelitis optica spectrum disorder (NMOSD). Detecting the type of autoantibody present in the sera of the patients is the primary goal. CBA is the most sensitive and recommended detection method among all similar tools. Briefly, serum autoantibody is screened by transfecting specific cells seeded on cover glasses with full-length specific antigen fused with green fluorescent protein (GFP), followed by treating them with the patient serum used here as the source of primary antibody. The autoantibody-treated cells are further labeled with a rhodamine-conjugated secondary antibody. The co-localization of GFP and rhodamine is visualized by confocal microscopy, and the intensity of fluorescence is evaluated to determine the presence of autoantibody. A detailed protocol to screen antibodies against AQP4 and MOG in human sera using this method is described.

Rapidly progressive neuromyelitis optica, report of a case

Aims/Purpose: To describe a clinical case of rapidly sequential bilateral optic neuritis associated with positive serological antibodies against myelin oligodendrocyte glycoprotein (MOG) in a 54‐year‐old Moroccan woman, who present loss of visual acuity in her left eye (OS) of 1 week of evolution.Methods: In the ophthalmological examination, she presented a visual acuity (VA) of 4/10 in the right eye (RE) and counting fingers at 1 meter in OS, with an afferent pupillary defect in OS. The ocular fundus shows papilledema in OS, with bilateral retinal nerve fibre layer (RNFL) thickening by optical coherence tomography (OCT). Rest of exploration normal. A complete analytical study and magnetic resonance imaging (MRI) are requested. While waiting for results, she returned to the emergency room due to greater visual loss, showing VA of hand movement in OD and perception of light in OS. OCT showed increased RNFL thickening and fluorescein angiography showed papillary hyperfluorescence. The visual field revealed severe generalized depression in both eyes.Results: Brain and orbital MRI showed bilateral enhancement of the anterior optic nerves, with extension of enhancement to their intracranial portion, chiasm, and right optic tract. The analytical study showed a positive result for MOG antibodies with a titre of 1:80. We proceeded to intravenous treatment with methylprednisolone 1 gd/day for 5 days followed by oral corticosteroids and plasmapheresis. The patient presented a remarkable clinical improvement with VA improvement to 6/10 in both eyes, disappearance of optic nerve edema, and normalization of RNFL.Conclusions: The discovery of MOG‐Immunoglobulin G as a biomarker for inflammatory demyelinating diseases of the Central Nervous System other than Multiple Sclerosis represents a paradigm shift in the field of neuroimmunology. Myelin oligodendrocyte glycoprotein‐associated disorder has the potential to cause devastating long‐term visual impairment.

A Case of Multiple Sclerosis Presenting with Tumefactive Lesions

Inflammatory demyelinating diseases including multiple sclerosis (MS) are usually diagnosed based on characteristic clinical and radiological findings. However, some demyelinating diseases have presented with growing large mass-like lesions, and it is difficult to differentiate those demyelinating lesions from brain tumors. We report a case of biopsy-proven MS mimicking brain tumor. This case suggests that inflammatory demyelinating diseases including MS have a wide spectrum and can present with the same radiological features as brain tumors such as lymphoma or high-grade glioma.

A Case of Multiple Sclerosis Presenting with Tumefactive Lesions

Inflammatory demyelinating diseases including multiple sclerosis (MS) are usually diagnosed based on characteristic clinical and radiological findings. However, some demyelinating diseases have presented with growing large mass-like lesions, and it is difficult to differentiate those demyelinating lesions from brain tumors. We report a case of biopsy-proven MS mimicking brain tumor. This case suggests that inflammatory demyelinating diseases including MS have a wide spectrum and can present with the same radiological features as brain tumors such as lymphoma or high-grade glioma.