Search

Background: Optic neuritis, myelitis, and neuromyelitis optica spectrum disorder (NMOSD) have been associated with antibodies against myelin oligodendrocyte glycoprotein-immunoglobulin G (anti-MOG-IgG). Furthermore, patients with radiological and demographic features atypical for multiple sclerosis (MS) with optic neuritis and myelitis also demonstrate antibodies against aquaporin-4 and anti-MOG-IgG. However, data on the diagnosis, treatment, follow-up, and prognosis in patients with anti-MOG-IgG are limited. Aims: To evaluate the clinical, radiological, and demographic characteristics of patients with anti-MOG-IgG. Study Design: Multicenter, retrospective, observational study. Methods: Patients with blood samples demonstrating anti-MOG-IgG that had been evaluated at the Neuroimmunology laboratory at Ondokuz Mayıs University's Faculty of Medicine were included in the study. Results: Of the 104 patients with anti-MOG-IgG, 56.7% were women and 43.3% were men. Approximately 2.4°% of the patients were diagnosed with MS, 15.8% with acute disseminated encephalomyelitis (ADEM), 39.4% with NMOSD, 31.3% with isolated optic neuritis, and 11.1% with isolated myelitis. Approximately 53.1% of patients with spinal involvement at clinical onset demonstrated a clinical course of NMOSD. Thereafter, 8.8% of these patients demonstrated a clinical course similar to MS and ADEM, and 28.1% demonstrated a clinical course of isolated myelitis. The response to acute attack treatment was lower and the disability was higher in patients aged > 40 years than patients aged < 40 years at clinical onset. Oligoclonal band was detected in 15.5% of the patients. Conclusion: For patients with NMOSD and without anti-NMO antibodies, the diagnosis is supported by the presence of anti-MOG-IgG. Furthermore, advanced age at clinical onset, Expanded Disability Status Scale (EDSS) score at clinical onset, spinal cord involvement, and number of attacks may be negative prognostic factors in patients with anti-MOG-IgG. [ABSTRACT FROM AUTHOR]

Objective: Study the effects of COVID-19 on health status and alterations in managing patients with CNS-IDDs. Materials and Methods: A questionnaire-based approach was commenced at the MS and Related Disorders Clinic at Siriraj Hospital in Thailand from March 2021 to December 2021. The data obtained from the questionnaire was subjected to statistical analysis. Results: The study comprised 92 patients with CNS-IDDs, with 72.8% female and a mean age of 44.6±14.0 years. Overall, 67.4% of patients were vaccinated following Thai National guidelines. Only two patients were confirmed to have contracted COVID-19 infection. The most common treatment administered in the 92 CNS-IDD patients was Azathioprine (39.1%), prednisolone (32.6%), then 14.1% each in MMF and Rituximab. Sixty-one patients (66.3%) reported no relapse in the past year and no statistically significant difference among the diseases. The mean self-rated quality of life (QoL) score was 8.0±1.9 before the COVID-19 pandemic then drastically decreasing to 5.4±2.4 during the pandemic period. Overall, 56.5% indicated at least some impact on physical well-being, and 69.6% reported challenges to psychological health. 16.3% postponed or canceled their appointments during the COVID-19 pandemic, and 8.3% transitioned from face-to-face meetings with doctors in the clinic to telemedicine or telephone follow-up. Conclusion: Our study revealed that patients with CNS-IDDs experienced no significant change in relapse and a low incidence of COVID-19 infection. During the pandemic, overall, patients' QoL decreased both physically and psychologically. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is the most common cause of non-traumatic disability in young individuals. There are limited reports of developing demyelinating events following the coronavirus disease 2019 (COVID-19) vaccination. Methods: We reported all individuals (n = 8) with new MS diagnoses with recent exposure (≤ 6 weeks) to the Sinopharm (BBIBP-CorV) vaccine between September 2021 and June 2022. We also reviewed the related literature published as of September 2023. Results: Of 338 newly diagnosed patients with MS who attended our tertiary referral MS center during the study period, 8 (2.36%) had their first demyelinating attack with a median interval of 2 [2.0, 4.0] weeks following the Sinopharm vaccine (sex ratio 1:1, median age: 20.5 [18.0, 27.0] years). No personal or family history of autoimmune/neurological disorders was documented, except for one patient's history of a previous potential demyelinating event and another's family history of immune thrombocytopenic purpura (ITP). [ABSTRACT FROM AUTHOR]

Background: Neuroimmunological diseases in children encompass a range of disorders that lead to neurological complications in patients due to immune responses and systemic circulating antibodies. Limited research has been conducted on therapeutic plasma exchange's efficacy and potential side effects in children with neuroimmunological diseases. Objectives: This study aimed to investigate this procedure's effectiveness and potential side effects in children afflicted by these diseases. Methods: This cross-sectional study examined a cohort of 18 children with neuroimmunological diseases who were admitted to the neurology department of Mofid Hospital over one year from March 2021 and underwent therapeutic plasma exchange. Results: The study included 18 patients, with an equal distribution of 9 females and 9 males. A total of 121 procedures were performed across 6 different disease groups: Multiple Sclerosis (22%, n = 4), Autoimmune Encephalitis (22%, n = 4), Neuromyelitis Optica Spectrum Disorder (22%, n = 4), Guillain-Barré syndrome (22%, n = 4), Acute Disseminated Encephalomyelitis (6%, n = 1), and Optic Neuritis (6%, n = 1). Following the plasma exchange, 17 patients (95%) showed immediate clinical improvement, while one patient diagnosed with optic neuritis did not respond to the treatment. During the follow-up period, 14 patients (78%) demonstrated significant improvement, one patient (6%) showed moderate improvement, and two patients (11%) exhibited mild improvement compared to their pre-plasmapheresis condition. Laboratory examinations revealed that only one patient experienced thrombocytopenia, which resolved without requiring treatment. No complications were observed during the follow-up visits for any of the patients. Conclusions: Plasma exchange is a safe procedure for children with neuroimmunological diseases and yields favorable clinical responses. [ABSTRACT FROM AUTHOR]

Secondary demyelinating diseases comprise a wide spectrum group of pathological conditions and may either be attributed to a disorder primarily affecting the neurons or axons, followed by demyelination, or to an underlying condition leading to secondary damage of the myelin sheath. In the elderly, primary demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis, are relatively uncommon. However, secondary causes of CNS demyelination may often occur and in this case, extensive diagnostic workup is usually needed. Infectious, postinfectious, or postvaccinal demyelination may be observed, attributed to age-related alterations of the immune system in this population. Osmotic disturbances and nutritional deficiencies, more commonly observed in the elderly, may lead to conditions such as pontine/extrapontine myelinolysis, Wernicke encephalopathy, and demyelination of the posterior columns of the spinal cord. The prevalence of malignancies is higher in the elderly, sometimes leading to radiation-induced, immunotherapy-related, or paraneoplastic CNS demyelination. This review intends to aid clinical neurologists in broadening their diagnostic approach to secondary CNS demyelinating diseases in the elderly. Common clinical conditions leading to secondary demyelination and their clinical manifestations are summarized here, while the current knowledge of the underlying pathophysiological mechanisms is additionally presented. [ABSTRACT FROM AUTHOR]

Objective: To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action. Methods: This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively. Results: GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05). Conclusion: GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS. [ABSTRACT FROM AUTHOR]

Introduction: Recently, psychological therapies increasingly used as complementary treatment along with medication to help patients with multiple sclerosis (MS). This present study compared the effectiveness of gestalt therapy (GT) behavioral activation (BA) and placebo on the anxiety in women with MS. Methods: This study was a clinical trial (pre/posttest with control group and 3-month follow-up). Using the inclusion criteria and implementation of Beck's anxiety inventory (BAI),60 women with MS who had an active case in MS clinic of Rasool Hospital in Tehran, were randomly blocked and assigned into four equal groups including 3 interventional groups and a control group. The psychotherapy groups were received GT and BA intervention for 8 weekly sessions. During this period, in the placebo group, capsules containing rice flour were used once a day. The control group was placed on the waiting list. Again, at the end of interventions, all of participants were retested with BAI and 3-month after the post-test, follow-up test was performed. Data was analyzed using SPSS25 and the repeated measures ANOVA and Bonferroni's post hoc test. P-value less than 0.05 was considered statistically significant. Results: The results showed GT and BA in comparison with placebo and control groups decreased anxiety mean scores in post-test and follow-up stages (p=0.001). GT and BA had no significant difference. Conclusion: GT and BA are equally effective on anxiety reduction in women with MS. Placebo had no effect on reducing the anxiety of these women. [ABSTRACT FROM AUTHOR]

Abstract Background CADASIL is the most common single-gene disorder causing ischemic stroke. CADASIL has been linked to mutations in NOTCH3 gene, due to heterozygous missense mutations. The disease is of insidious onset, presenting with initial clinical features in third and fourth decade of life. However, it is now being increasingly acknowledged that individual clinical presentation, age, time of onset as well as disease severity are quite varied among patients with CADASIL most likely leading to under- or mis-diagnosis. The authors thereby report a genetically confirmed case of CADASIL with atypical clinical course and findings. Case presentation A 48-year-old woman presented with complaints of episodic headache, relapsing–remitting neurological illness, progressive cognitive impairment, and acute-onset loss of speech and ambulation. She was earlier being treated as a case of CNS demyelination for 10 years. On examination, vital parameters were within normal limits. Neurological examination revealed that the patient was drowsy, not verbalizing, not obeying commands, with movement of all four limbs on painful stimuli, hypertonia of all limbs, grade 3 + deep tendon reflexes, bilateral striatal toe and extensor plantar response. Magnetic resonance imaging of brain showed involvement of anterior temporal lobe and external capsule along with multiple acute infarcts. Cerebrospinal fluid analysis was found to be normal. Exome sequencing revealed heterozygous missense mutation in exon 2 of NOTCH3 gene. A definite diagnosis of CADASIL was made and patient was started on fluoxetine and aspirin, following which there was significant improvement over 4–6 weeks. Patient is able to carry out daily activities independently although continues to have mild persistent cognitive impairment with excessive talking and over familiarity. Conclusions As CADASIL has a relapsing and partially remitting course with frequently observed varied clinical presentation, patients may receive treatment for demyelination which may not be necessary. Hence, detailed family history along with knowledge of characteristic magnetic resonance imaging findings seen in CADASIL can help discern the diagnosis.

Objective: To describe the clinical and radiological features, as well as outcomes following glucocorticoid therapy and recurrence in adults suffering from cortical encephalitis associated with myelin oligodendrocyte glycoprotein (MOG) antibody. Methods: The clinical information of nine adult patients suffering from cortical encephalitis associated with MOG antibody admitted to the Affiliated Brain Hospital of Nanjing Medical University from 2020 to 2022 was systematically reviewed. The clinical symptoms, laboratory data, imaging results, outcomes following glucocorticoid therapy and recurrence were evaluated. Result: A total of 9 patients positive for MOG antibody and suffering from cortical encephalitis were included in our study (55.6% men, median age 29years, 15-57years). The most common clinical symptoms included headache (77.8%), fever (66.7%), and generalized seizures (55.6%). Some patients also experienced limb shaking (22.2%), leg numbness (22.2%), transient motor aphasia (11.1%), and vision loss (11.1%). The main features of cerebrospinal fluid () examination were increased intracranial pressure, pleocytosis, and elevated cerebrospinal fluid (CSF) protein. In addition, N-methyl-D-aspartate receptor (NMDAR) and MOG antibodies were found in the CSF of 3 patients, and NMDAR, MOG, and glial fibrillary acidic protein antibodies were found in the CSF of 1 patient. All patients were subjected to magnetic resonance imaging (MRI) and the images of eight of them showed T2 and/flair image hyperintense lesions, three showed meningeal or lesion enhancement and four showed white matter lesions, which were mostly located in the midline structures (75%). All patients received glucocorticoid therapy in the acute phase and in remission, and eight of them received an intravenous high dose of methylprednisolone, including one patient who received a simultaneous immunoglobulin therapy. One patient was treated with low-dose prednisolone tablets. Seven (77.8%) patients were wholly recovered at discharge, and 2 (22.2%) patients were left with slight symptoms. During the median 9-month follow-up (range: 2-36months), 2 (22.2%) patients developed recurrence. Conclusion: The clinical manifestations of adult MOG antibody-associated cortical encephalitis were significantly different from those of the typical MOG antibody-associated disease (MOGAD). Patients in the acute phase of the disease were prone to show signs similar to central nervous system infection, requiring clinicians to have the ability to recognize the disease to avoid misdiagnosis. In addition, seizures were common in MOG antibody-related encephalitis, and the type of seizures was age-related. Brain MRI results showed that the distribution of cerebral cortex lesions was closely related to the classification of cortical encephalitis. Based on the patient's response to the treatment, glucocorticoid therapy was effective against MOG antibody-associated cortical encephalitis, which is consistent with the treatment response and clinical prognosis of MOGAD. Therefore, our opinion was that MOG antibody might be the "responsible antibody" in MOG antibody-associated cortical encephalitis, although further studies are needed to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

We report a case of conus medullaris syndrome presenting with lower limb and bladder symptoms. MR imaging showed an abnormality in the lowest part of the spinal cord as a first presentation of myelin oligodendrocyte glycoprotein (MOG)-associated disease. While such cord swelling can mimic a tumour, these patients respond well to corticosteroids, with good outcomes. MOG-associated disease is an immune-mediated syndrome distinct from aquaporin 4 antibody positive neuromyelitis optica syndrome and is now considered an independent entity. Although there can be overlapping phenotypes, there are also differences, and MOG-associated disease generally has a much better prognosis compared with aquaporin 4 antibody-positive neuromyelitis optica syndrome. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese medicine (TCM), a main form of complementary and alternative medicine provides a potential possibility for demyelinating disease of the central nervous system (DDC) management and has been applied in considerable amounts of patients with this disorder. Nevertheless, powerful real-world evidences regarding the epidemiological and clinical characteristics, safety, and outcomes of TCM in DDC are lacking. The primary objective of the Demyelinating Diseases of the Central Nervous System Registry for Patients with Traditional Chinese Medicine (DATE-TCM) is to create an organized multicenter data collection structure to define integrative characteristics of DDC patients treated with TCM in an endeavor to fill these knowledge gaps to better inform clinical care and health policy. Method: This study provides a prospective and voluntary registry by using a web-based system. Baseline data will be recorded and subsequently regular follow-up visits will be implemented every 3–6 months for a total of 5 years. The primary outcome is Annualized Aggregate Relapse Rate at 5-year follow-up. Results: DATE-TCM is currently designed to capture the multidimensional (epidemiologic, demographic, clinical, etc.) features of DDC patients receiving TCM treatment, the type and long-term safety and efficacy of TCM intervenes in the DDC populations, as well as the interaction of TCM treatments and disease modifying therapies in the management of DDC, aiming to include 2000 eligible adult DDC patients with TCM intervenes from 35 participating centers, covering 77.4% of provincial administrative regions of mainland China. Conclusion: DATE-TCM is the first, largest, most geographically extensive, and standard registry-based observational study that systematically document the real-world data regarding the TCM application in the DDC populations, which will be extraordinarily important for clarifying the comprehensive characteristics and outcomes of TCM in DDC, further shed light on standardizing and optimizing the TCM measures for DDC management and establishing evidence-based clinical practice guidelines for TCM application in DDC. [ABSTRACT FROM AUTHOR]

Several case studies which include a 43‑year‑old non‑diabetic non‑hypertensive gentleman with recurrent attacks of optic neuritis, hemiparesis and incoordination; and a 28‑year‑old right‑handed gentleman was diagnosed with a case of beta thalassemia major, is presented. Topics include Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) with associated non‑neurological manifestations; and Direct Immunofluorescence showed glomerular deposition and negative for any complement deposition.

Neuroretinitis spectrum disorder (NMOSD) is generally regarded as an acute or subacute inflammatory demyelinating disease of the central nervous system, mainly involving the optic nerve and spinal cord, mediated by humoral immunity. To address these questions, this work established an immunomic library of the heavy chain complementarity determinant 3 (gHI-CDR3) of peripheral blood lymphocyte B cell receptors. The library was established in patients with a spectrum of neurosyphilis-retinitis disorders. Six NMOSD patients and six healthy volunteers were recruited, and the NMOSD group was divided into an early-onset group and a stable group according to treatment conditions. The IgH-CDR3 gene fragment cultured in vitro was amplified by multiplex PCR technology, and the gene was sequenced by the second-generation high-throughput sequencing technology, and the statistical analysis was carried out by the method without reference. The quantity, type, and diversity of IgH-CDR3 in peripheral blood B lymphocytes of NMOSD patients were significantly lower than those of normal group (P > 0.05); the variation of IgH-CDR3 sequence in the initial stage of treatment was higher than that in the stable stage (P > 0.05); the replication frequency of the characteristic gene "CASSICLGSGCGGYYYGMDVW" was significantly increased in patients at the initial stage of NMOSD treatment (P < 0.05). The conclusion was that the gene expression and gene expression analysis of NMOSD patients could accurately judge the condition of NMOSD patients, evaluate their efficacy, and provide new molecular targets and new theoretical basis for clinical application. [ABSTRACT FROM AUTHOR]

Background: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder due to the deficiency of arylsulfatase A enzyme. Materials and Methods: This is a retrospective analysis of all clinically suspected MLD cases and confirmed by genetics, enzyme assay, and/or nerve biopsy between June 2015 and May 2020 at a tertiary care center. The clinical profile, enzyme levels, nerve conduction studies, MRI of the brain, and variants of ARSA gene causing MLD were analyzed. Results: Out of the 19 cases of MLD, four were juvenile, and the rest were late infantile variants. Eleven were male. The mean age of presentation in the late infantile variant was 28.4 months, and that of the juvenile variant was 44.5 months. The clinical features of the late infantile variant were developmental delay (30.75%), neuroregression (100%), spasticity (66.6%), dystonia (66.6%), small head (60%), whereas the juvenile variant presented with gait difficulties and neuroregression in all (100%), and seizures in 3 (75%). MRI of the brain showed bilateral symmetrical confluent white matter T2 hyperintensities with sparing of subcortical-U-fibers in all cases. The tigroid pattern was seen in two cases. Normal enzyme level was seen in one, but this child had a pathogenic variant PSAP gene resulting in saposin B deficiency. The targeted next-generation sequencing was done in 11/19 cases and showed ARSA gene variant in 10 and PSAP gene in one child. Nerve conduction studies were done in 12 children, and all showed features suggestive of demyelinating motor polyneuropathy. Nerve biopsy showed metachromatic granules in four children. Conclusion: MLD can present with a developmental delay with or without regression, with or without seizures, with normal or small head. MRI and nerve conduction studies are helpful in diagnosis. Normal enzymes do not rule out MLD. Nerve biopsy may be useful in non-affordable families. [ABSTRACT FROM AUTHOR]

Background: The primary central nervous system (CNS) demyelinating disorders are witnessing significant advancement in terms of treatment options and the diagnostics. However, a resource poor country like ours has to rely more on our clinical findings. Aims and Objectives: To study the spectrum of different clinical manifestations in patients of various primary CNS demyelinating disorders in the hospital setting; categorizing them to the most possible extent into its various types viz. multiple sclerosis(MS), neuromyelitis optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis(ADEM), idiopathic optic neuritis(ON). Metarials and Methods: An observational study was conducted for 2 years including old and newly diagnosed cases in whom detailed clinical assessment was done for every attack including the previous and subsequent ones. Statistical analysis was done using SPSS version 21. Results: Of the 47 patients included, 26 (55.3%) were cases of NMOSD, 12 (25.5%) of MS, 4 (8.5%) of ADEM and 5 (10.6%) were isolated cases of ON. 30 were female and 17 were male (ratio 1:0.6). The total mean age for primary CNS demyelinating disorders at presentation was 27.09 ± 13.44 years. Maximum patients fell in the age range of 11-20 years. Among the clinical manifestations, motor abnormalities (97.6%), sensory abnormalities (69%), bladder dysfunction (59.5%), visual manifestations (54.8%) (Unilateral in all MS patients, both bilateral and unilateral in NMOSD) were the most common presentations. In MS, the most common manifestations were motor dysfunction followed by sensory symptoms, optic neuropathy (mostly unilateral), and bladder dysfunction. In NMOSD, the most common clinical manifestations were motor dysfunction, followed by bladder dysfunction, optic neuropathy and then sensory abnormalities. In ADEM, most common manifestations were motor abnormalities, acute encephalopathy, headache, optic neuropathy. Among idiopathic ON, most patients presented with painful diminution of vision (80%). Mean number of attacks was 2.53. Conclusion: A wide spectrum of clinical presentations in various disorders of primary CNS demyelination was found with maximum patients presenting with motor dysfunction in various forms. [ABSTRACT FROM AUTHOR]

Background: CADASIL is the most common single-gene disorder causing ischemic stroke. CADASIL has been linked to mutations in NOTCH3 gene, due to heterozygous missense mutations. The disease is of insidious onset, presenting with initial clinical features in third and fourth decade of life. However, it is now being increasingly acknowledged that individual clinical presentation, age, time of onset as well as disease severity are quite varied among patients with CADASIL most likely leading to under- or mis-diagnosis. The authors thereby report a genetically confirmed case of CADASIL with atypical clinical course and findings. Case presentation: A 48-year-old woman presented with complaints of episodic headache, relapsing–remitting neurological illness, progressive cognitive impairment, and acute-onset loss of speech and ambulation. She was earlier being treated as a case of CNS demyelination for 10 years. On examination, vital parameters were within normal limits. Neurological examination revealed that the patient was drowsy, not verbalizing, not obeying commands, with movement of all four limbs on painful stimuli, hypertonia of all limbs, grade 3 + deep tendon reflexes, bilateral striatal toe and extensor plantar response. Magnetic resonance imaging of brain showed involvement of anterior temporal lobe and external capsule along with multiple acute infarcts. Cerebrospinal fluid analysis was found to be normal. Exome sequencing revealed heterozygous missense mutation in exon 2 of NOTCH3 gene. A definite diagnosis of CADASIL was made and patient was started on fluoxetine and aspirin, following which there was significant improvement over 4–6 weeks. Patient is able to carry out daily activities independently although continues to have mild persistent cognitive impairment with excessive talking and over familiarity. Conclusions: As CADASIL has a relapsing and partially remitting course with frequently observed varied clinical presentation, patients may receive treatment for demyelination which may not be necessary. Hence, detailed family history along with knowledge of characteristic magnetic resonance imaging findings seen in CADASIL can help discern the diagnosis. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical characteristics of anti - myelin oligodendrocyte glycoprotein - IgG associated disorders (MOGAD) complicated with antibody overlap syndrome. Methods and Results Ten patients with MOGAD complicated with antibody overlap syndrome treated in the First Affiliated Hospital of Zhengzhou University and the Fifth Affiliated Hospital of Zhengzhou University from April 2016 to April 2021 were included, including 7 patients with N-methyl-D-aspartate receptor (NMDAR)- IgG positive, 2 patients with contactin-associated protein 2 (CASPR2)-IgG positive and one patient with glial fibrillary acidic protein (GFAP)-IgG. The ratio of male to female was 1:2.33, and the average age of onset was 20.70 years old. Five cases had a history of precursor infection. Headache and fever were the most common initial symptoms. The average Expanded Disability Status Scale (EDSS) score at admission was 2.40. Intracranial pressure (ICP) increased in 5 cases, white blood cell count in cerebrospinal fluid (CSF) increased in 8 cases, and there was no tumor. Head MRI abnormalities in 9 cases, involving both supratentorial and infratentorial, were common in subcortical white matter, brainstem, thalamus and cerebellum. Enhancement scan showed patchy and nodular enhancement, with some linear enhancement of meninges. Spine MRI abnormalities were found in 6 cases, especially in cervical and thoracic spinal cord, which showed long segment spinal cord injury. Optic nerve was involved in 2 cases. Partial or complete remission was achieved after immunomodulatory treatment. The EDSS score decreased by 1-3.50 at discharge. The average follow - up was 12.80 months. Three cases recurred and responded well after immunomodulatory treatment again. Conclusions MOGAD complicated with antibody overlap syndrome can detect MOG-IgG and other types of autoimmune antibodies at the same time or successively, but it can only show the symptoms of one of the diseases. It has a good response to immunomodulatory treatment, and immunomodulatory treatment is still effective after recurrence. [ABSTRACT FROM AUTHOR]

Myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) is a nervous system (NS) demyelination disease and a newly recognized distinct disease complicated with various diseases or symptoms; however, MOGAD was once considered a subset of neuromyelitis optica spectrum disorder (NMOSD). The detection of MOG-IgG has been greatly improved by the cell-based assay test method. In one study, 31% of NMOSD patients with negative aquaporin-4 (AQP-4) antibody were MOG-IgG positive. MOGAD occurs in approximately the fourth decade of a person's life without a markedly female predominance. Usually, optic neuritis (ON), myelitis or acute disseminated encephalomyelitis (ADEM) encephalitis are the typical symptoms of MOGAD. MOG-IgG have been found in patients with peripheral neuropathy, teratoma, COVID-19 pneumonia, etc. Some studies have revealed the presence of brainstem lesions, encephalopathy or cortical encephalitis. Attention should be given to screening patients with atypical symptoms. Compared to NMOSD, MOGAD generally responds well to immunotherapy and has a good functional prognosis. Approximately 44-83% of patients undergo relapsing episodes within 8 months, which mostly involve the optic nerve, and persistently observed MOG-IgG and severe clinical performance may indicate a polyphasic course of illness. Currently, there is a lack of clinical randomized controlled trials on the treatment and prognosis of MOGAD. The purpose of this review is to discuss the clinical manifestations, imaging features, outcomes and prognosis of MOGAD. [ABSTRACT FROM AUTHOR]

The differential diagnosis of pediatric multiple sclerosis (MS) presents a wide spectrum of diseases. Sjögren syndrome (SS) is also a rare cause of this disease. Neurological involvement in SS ranges from peripheral neuropathies to the central nervous system (CNS). We report the case of a 5-year-old boy with a possible diagnosis with SS based on positive minor salivary gland biopsy findings and positive anti-smooth muscle antibodies, also fulfilling the 2017 McDonald criteria. If a patient is younger and meets the MS criteria clinically and radiologically, it is suggested to carefully examine the CNS demyelination in a patient for autoimmune diseases, particularly SS. [ABSTRACT FROM AUTHOR]

The article reports that Myelin oligodendrocyte glycoprotein‑associated disorder (MOGAD) is an autoimmune oligodendrocytopathy, whereas neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy. Topics include Cell‑based assay shows strong immunofluorescence to aquaporin and myelin oligodendrocyte protein in the serum tested on transfected cell lines; and enhancement in the medial temporal lobe following contrast administration Coronal FLuid Attenuated Inversion Recovery.

The article presents the discussion on Multiple sclerosis (MS) being a CNS (central nervous system) demyelinating autoimmune neurodegenerative disorder. Topics include MS emphasizing on the clinical and radiological features for the diagnosis of MS with an emphasis for excluding other alternative diagnosis or MS mimic; and studying the prevalence of the autoimmune disorders, autoantibodies, and the significance.

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD. [ABSTRACT FROM AUTHOR]

Background: Co-occurrence of other autoimmune disorders (AID) and autoantibodies in patients with autoimmune demyelinating CNS disorders have not been studied previously in patients of Indian origin. Objective: To determine the frequency of concomitant autoimmune disorders, anti-nuclear antibody (ANA) and antithyroid antibody (ATAb) and to evaluate the impact on clinical course of disease. Materials and Methods: A total of 111 patients with MS and 152 patients with non-MS demyelinating disorders were included. Demographics, clinical course and disability were recorded. History of other autoimmune disorders (AIDs) in patients and first degree relatives was noted. Serum ANA and ATAb were tested. Results: Concomitant AIDs were seen in 21% of MS and 19% of non-MS patients. Autoimmune thyroid disease was most frequent and seen in 10.8% of MS and 6.6% of non-MS disorders. Frequency of ATAb was significantly higher among MS group (MS 25.5% vs non-MS 13.2% P = 0.04) but that of ANA was similar between the 2 groups (MS 19.8% vs non-MS 26.9% P = 0.17). A positive family history of autoimmune disorders was noted in 20% of MS and 15.1% of non-MS disorders. Clinical course was unaffected by presence of concomitant AID and autoantibodies. Conclusion: Cooccurrence of autoantibodies and AID are seen in a significant number of patients with MS and non-MS disorders and influences clinical management. [ABSTRACT FROM AUTHOR]

Background: Rituximab, an anti-CD20 monoclonal antibody, has been used worldwide as an off-label therapy in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Objective: The aim of the present study was to evaluate the efficacy and safety of rituximab in central nervous system demyelinating disorders in the Indian context. Methods: We conducted a retrospective analysis of patients with MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who were treated with rituximab at a single tertiary care centre in Mumbai. Results: The study enrolled 102 patients (61 MS, 37 NMOSD and 4 MOGAD) from June 2008 to January 2020. Following rituximab therapy, 96.7% of MS, 67% of NMOSD, and 50% of MOGAD patients were free of relapses. The mean annualized relapse rate reduced from 2.17 to 0 for patients with relapsing remitting MS (RRMS), from 0.8 to 0 for secondary progressive MS (SPMS), from 2.5 to 0.14 for NMOSD, and from 3.43 to 1.04 for MOGAD. The median expanded disability status scale improved significantly in RRMS patients, worsened non-significantly in the SPMS group, and remained unchanged in NMOSD and MOGAD patients. On follow-up magnetic resonance imaging, there was a significant reduction in the number of MS patients developing new contrast enhancing lesions or new T2 lesions. Adverse events (infusion reactions or severe infections) occurred in 12 patients. Conclusion: Rituximab is effective and safe in Indian patients with MS and NMOSD. [ABSTRACT FROM AUTHOR]

Objective CNS demyelinating syndromes occurring in the context of SLE may represent a manifestation of neuropsychiatric lupus, or an overlap of SLE and multiple sclerosis (MS). We evaluated prospectively patients presenting with demyelinating syndrome for clinical and serological evidence of SLE and characterized the evolution of their clinical syndrome to a defined disease. Methods Patients with CNS demyelinating syndromes not fulfilling the criteria for MS were evaluated in a rheumatology unit for features of SLE and followed longitudinally (enrolment period 2016–20). Clinical, laboratory and neuroimaging data were recorded at every visit, following multidisciplinary evaluation. At end of follow-up, patients were assessed for their final neurological and rheumatological diagnosis, and classified accordingly. Results A total of 79 patients were included in the study [91.1% female, mean (s. d.) age at first demyelinating episode 38.4 (10.3) years, median (interquartile range) observation period 39 (57) months]. At last follow-up, 38 patients (48.1%) had evolved into MS. Of the remaining patients, 7 (17.1%) had SLE, while 34 (82.9%) had features of systemic autoimmunity without fulfilling classification criteria for SLE. The most common rheumatological features of these patients were inflammatory arthritis (73.5%), acute cutaneous lupus (47.1%) and positive ANA (72.1%). Importantly, these patients were less likely to have elevated IgG index (odds ratio 0.11, 95% CI 0.04, 0.32) and positive oligoclonal bands (odds ratio 0.21, 95% CI 0.08, 0.55). Conclusion A significant number of patients with demyelination do not fulfill criteria for either MS or SLE at follow-up. These patients exhibit lupus-like autoimmune features and may represent a distinct entity, 'demyelination with autoimmune features'. [ABSTRACT FROM AUTHOR]

Objective: To review the pharmacological characteristics, clinical evidence, and place in therapy of satralizumab for the treatment of neuromyelitis optica spectrum disorders (NMOSDs). Data Sources: A comprehensive literature search was conducted in PubMed (January 2000 to October 15, 2020). Key search terms included satralizumab and neuromyelitis optica spectrum disorders. Other sources were derived from product labeling and ClinicalTrials.gov. Study Selection and Data Extraction: All English-language articles identified from the data sources were reviewed and evaluated. Phase I, II, and III clinical trials were included. Data Synthesis: NMOSD is an autoimmune disease characterized by inflammatory lesions in the optic nerves and spinal cord. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. Phase III trials showed that protocol-defined relapse was 30% for satralizumab and 50% for placebo (P = 0.018) when patients with NMOSD were treated with satralizumab monotherapy; protocol-defined relapse was 20% for satralizumab and 43% for placebo (P = 0.02) when satralizumab was added to immunosuppressant treatment. Satralizumab is generally well tolerated, with common adverse effects including injection-related reaction. Relevance to Patient Care and Clinical Practice: Satralizumab has the potential to become a valuable treatment option for patients with NMOSD. Conclusion: Satralizumab appears to be safe and effective as monotherapy or in combination with an immunosuppressant for patients with NMOSD and has the potential to become a valuable treatment option for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination and brain pericyte dysfunction might be involved in MS pathogenesis Our aim was to evaluate whether the factors in serum affect pericyte survival. Method: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce experimental autoimmune encephalomyelitis (EAE). To confirm the animal model, the sera level of anti-MOG antibody in mice and platelet-derived growth factor-BB (PDGF-BB) in patients was measured by ELISA. Human brain vascular pericytes (HBVP) cell lines were incubated with sera of EAE mice and primer progressive MS (PPMS), seconder progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients. The viability of HBVP is measured with Annexin V-FITC/propidium iodide staining with flow cytometry. Results: Annexin V-FITC/propidium iodide staining with flow cytometry showed increased ratios of early apoptosis and decreased survival following incubation with sera of EAE and progressive MS. Levels of platelet-derived growth factor-BB were identical in serum and cerebrospinal fluids of patients with different forms of MS. Conclusion: Our results suggest that serum factors might contribute to progressive MS pathogenesis via pericyte dysfunction. [ABSTRACT FROM AUTHOR]

Although Epstein-Barr virus (EBV) is hypothesized to be a prerequisite for multiple sclerosis (MS), up to 15% of children with a diagnosis of MS were reported to be EBV-seronegative. When re-evaluating 25 EBV-seronegative children out of 189 pediatric patients with a diagnosis of clinically isolated syndrome/MS, we found anti-myelin oligodendrocyte glycoprotein (MOG) antibody in 11 of 25 (44%) EBV-seronegative but only 9 of 164 (5.5%, p < 0.001) EBV-seropositive patients. After critical review, MS remained a plausible diagnosis in only 4 of 14 EBV-seronegative/MOG antibody-negative patients. In children with an MS-like presentation, EBV seronegativity should alert clinicians to consider diagnoses other than MS, especially MOG-antibody disease. ANN NEUROL 2021;89:1234-1239. [ABSTRACT FROM AUTHOR]

Objective: The diagnosis of patients with atypical demiyelinating lesions has always been challenging, sometimes leading to a biopsy. Recent literature has radiologically classified atypical inflammatory demyelinating lesions as ring-like, Balo-like, infiltrative, megacystic, and unclassified lesions. In this study, we aimed to assess the demographics and clinical and radiologic findings in patients with atypical lesions. Materials and Methods: The records of 320 patients with demyelinating disorders were retrospectively assessed using iMed database. Patients with atypical lesions and whose magnetic resonance imaging evaluations were included. Clinical and radiologic findings were evaluated and lesions were classified according to the recommended criteria. Results: Twenty-seven patients (16 females) were included and the mean age was 34.26±6.12 (range: 26-49) years. Fourteeen patients had ring-like, three had Balo-like, three had megacystic, five had infiltrative, and two patients had unclassified lesions. Diffusion restriction was observed in contrast-enhancing sites in ring-like lesions, heterogeneously in infiltrative lesions and also peripherally in Balo-like lesions. Two patients with infiltrative lesions had additional lesions on follow-up and had to undergo biopsy. Two patients died despite aggressive treatment. Two patients with Balo-like lesions were evaluated as having acute disseminated encephalomyelitis and did not have further relapses. Seventeen patients from the study group converted to multiple sclerosis (MS) on follow-up. Conclusion: Differential diagnosis of atypical inflammatory demyelinating lesions is not always easy, the prognosis is not different from MS lesions. Mostly, ringlike lesions seem to convert to MS with recurrent relapses; however, infiltrative lesions seem to have poorer outcomes, especially if patients have additional relapses. [ABSTRACT FROM AUTHOR]

Although recent studies indicate the involvement of monocytes in accelerating the lesion formation of neuromyelitis optica spectrum disorder (NMOSD), the precise mechanism of the innate immune system activation remains elusive. Thus, in this study, we aimed to clarify the mechanisms of NMOSD pathogenesis from the viewpoint of innate immunity activation. We established anti-AQP4 recombinant autoantibodies (Ab) from plasmablasts in NMOSD patient's CSF. Human astrocytes treated with anti-AQP4 Ab produced a significant amount of CCL2 and contributed to the efficient recruitment of monocytes. Moreover, mitochondrial DNA (mtDNA), which activated monocytes via Toll-like receptor 9 (TLR9), was released from astrocytes treated with anti-AQP4 Ab. MtDNA further enhanced CCL2 production by monocytes, and it was demonstrated that mtDNA concentration correlated with the efficiency of monocyte recruitment in the CSF of NMOSD patients. In conclusion, these observations highlight that mtDNA which was released from astrocytes damaged by anti-AQP4 Ab has a central role in establishing the inflammatory loop of monocyte recruitment and activation via an innate immunity pathway. [ABSTRACT FROM AUTHOR]

Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9-64), and the median interval from attack to biopsy was 1 month (range 0.5-96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population. WHAT THIS PAPER ADDS: Rituximab appears to control disease in most anti-myelin oligodendrocyte glycoprotein-positive patients with relapsing neuroinflammatory disease. Rituximab was associated with transitory, mild-to-moderate infusion-related effects. Half of patients treated with rituximab developed leukopenia or hypogammaglobulinemia. No opportunistic infections were observed. [ABSTRACT FROM AUTHOR]

Objective: Glutaminase 1 (Gls1) is the first enzyme in glutaminolysis. The selective Gls1 inhibitor bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl)ethyl sulfide (BPTES) suppresses Th17 development and ameliorates experimental autoimmune encephalomyelitis (EAE). The present study was undertaken to investigate whether inhibition of glutaminolysis is beneficial for the treatment of systemic lupus erythematosus (SLE), and the involved mechanisms. Methods: MRL/lpr mice were treated with BPTES or vehicle control, and disease activity was examined. Then naive CD4+ T cells from patients with SLE were cultured under Th17‐polarizing conditions with BPTES or vehicle. Furthermore, using newly generated Gls1 conditional‐knockout mice, in vitro Th17 differentiation was examined, and EAE was induced in the mice. Glutaminolysis and glycolysis were measured with an extracellular flux analyzer. The expression of hypoxia‐inducible factor 1α (HIF‐1α) was examined by Western blotting. Results: Treatment of MRL/lpr mice with BPTES improved autoimmune pathology in a Th17‐dependent manner. T cells from patients with SLE treated with BPTES displayed decreased Th17 differentiation (P < 0.05). Using the conditional‐knockout mice, we demonstrated that both in vitro Th17 differentiation (P < 0.05) and the development of EAE were dependent on Gls1. Gls1 inhibition reduced glycolysis and the expression of HIF‐1α protein, which induces glycolysis. Conclusion: We demonstrated that inhibition of glutaminolysis represents a potential new treatment strategy for patients with SLE and Th17‐related autoimmune diseases. Mechanistically, we have shown that inhibition of glutaminolysis affects the glycolysis pathway by reducing HIF‐1α protein in Th17 cells. [ABSTRACT FROM AUTHOR]

Acquired demyelinating syndromes of the central nervous system are rare disorders in childhood. Immune-mediated damage affects the myelin sheath of the optic nerves, brain and spinal cord. The majority are monophasic. Relapsing demyelinating syndromes include multiple sclerosis, aquaporin-4 antibody-associated disease and myelin oligodendrocyte glycoprotein antibody-associated disease. The relapsing syndromes are associated with gradual accrual of neurological deficits and cognitive impairment. In this review, we discuss the presentation, diagnosis and management of monophasic and relapsing acquired demyelinating syndromes. We highlight the fact that CNS autoantibody mediated disorders are distinct clinical entities separate to multiple sclerosis and discuss the treatment options and prognosis for each. Finally, we detail current available therapeutic drugs for paediatric demyelinating conditions and their adverse effects. [ABSTRACT FROM AUTHOR]

Objective: To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions.Methods: This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI.Results: MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype.Conclusion: High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels. [ABSTRACT FROM AUTHOR]

Objective: Central nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis course a "surface-in" process of injury suggesting progressive biology may begin.Methods: We focused on the thalamus, which notably has both a cerebrospinal fluid (CSF) interface and a white matter interface. Thalamic volume trajectories were assessed in a prospectively followed cohort of children from initial presentation with either multiple sclerosis or monophasic acquired demyelination, and healthy controls. Voxelwise volume changes were calculated using deformation-based morphometry, and analyzed in relation to distance from the CSF interface by mixed effects modeling and semiparametric smoothing methods.Results: Twenty-seven children with multiple sclerosis and 73 children with monophasic demyelination were prospectively followed with yearly brain scans (mean follow-up = 4.6 years, standard deviation = 1.9). A total of 282 healthy children with serial scans were included as controls. Relative to healthy controls, children with multiple sclerosis and children with monophasic demyelination demonstrated volume loss in thalamic regions adjacent to the white matter. However, only children with multiple sclerosis exhibited an additional surface-in gradient of thalamic injury on the ventricular side, which was already notable in the first year of clinical disease (asymptote estimate = 3.01, 95% confidence interval [CI] = 1.44-4.58, p = 0.0002) and worsened over time (asymptote:time estimate = 0.33, 95% CI = 0.12-0.54, p = 0.0021).Interpretation: Our results suggest that a multiple sclerosis disease-specific surface-in process of damage can manifest at the earliest stages of the disease. ANN NEUROL 2019;85:340-351. [ABSTRACT FROM AUTHOR]

A 68-year-old woman presented with a three-week history of confusion and anomic aphasia. Imaging of her head demonstrated a single large left frontal mass. Pathology revealed metastatic adenocarcinoma of Müllerian origin. Subsequent surgery revealed a small primary site in a fallopian tube, high left para-aortic lymphadenopathy, and no disseminated intraperitoneal disease. This case was remarkable in that CNS metastasis was her presenting symptom and was restricted to a solitary brain lesion, and other disease sites were limited to retroperitoneal lymphadenopathy and a small fallopian tube primary. [ABSTRACT FROM AUTHOR]

Rhizomes of Panax japonicus (RPJ), a traditional herbal medicine, was used for treating arthritis and physical weakness in China from the Ming dynasty. Triterpene saponins are the main bioactive components of RPJ. In this work, for the first time, we evaluate the therapeutic effect of the total saponin from RPJ (TSPJ) on experimental autoimmune encephalomyelitis (EAE) mice induced by myelin oligodendrocyte glycoprotein (MOG) 35-55 , a commonly used animal model of Multiple sclerosis (MS). To evaluate the therapeutic effect of TSPJ on EAE and explored its possible underlying mechanisms. EAE was induced by MOG 35-55. Mice were administrated with TSPJ (36.5 mg/kg, 73 mg/kg) and prednisone acetate (positive control) orally once daily up to 28 days postimmunization, and their neurological deficit was scored. Hematoxylin and Eosin (HE), Luxol Fast Blue (LFB), and transmission electron microscopy (TEM) were carried out to evaluate the EAE-induced pathological changes in the brain and spinal cord. IL-17a and Foxp3 levels in central nervous system (CNS)were evaluated by immunohistochemical staining. The changes in IL-1β, IL-6, and TNF-α levels in serum and CNS were measured with ELISA. Quantitative reverse transcription PCR (qRT-PCR) was used to access mRNA expression in CNS of the above indices. The percentages of Th1, Th2, Th17and Treg cells in spleen were determined by Flow Cytometry (FCM). Furthermore, 16S rDNA sequencing was used to detect the intestinal flora of mice in each group. In vitro studies, lipopolysaccharides (LPS)-induced BV2 microglia cells were used and the expression of TLR4, MyD88, p65, and p-p65 in cells was detected by Western blot. TSPJ treatment significantly alleviated neurological impairment caused by EAE. Histological examination confirmed the protective effects of TSPJ on myelin sheath and the reduction of inflammatory cell infiltration in the brain and spinal cord of EAE mice. TSPJ notably downregulated the ratio of IL-17a/Foxp3 at protein and mRNA levels in CNS, as well as Th17/Treg and Th1/Th2 cell ratios in the spleen of EAE mice. The levels of TNF-α, IL-6, and IL-1β in CNS and peripheral serum also decreased post-TSPJ treatment. In vitro, TSPJ suppressed LPS-induced production of inflammatory factors in BV2 cells via TLR4-MyD88-NF-κB signaling pathway. More importantly, TSPJ interventions altered the composition of gut microbiota and restored the ratio of Firmicutes to Bacteroidetes in EAE mice. Furthermore, Spearman's correlation analysis revealed that a relationship existed between statistically significantly altered genera and CNS inflammatory indices. Our results demonstrated TSPJ had therapeutic effects on EAE. Its anti-neuroinflammation property in EAE was related to modulating gut microbiota and inhibiting TLR4-MyD88-NF-κB signaling pathway. Our study indicated that TSPJ may be a potential candidate for the treatment of MS. [Display omitted] • The therapeutic potential of TSPJ on EAE was firstly investigated. • TSPJ treatment alleviated inflammatory cell infiltration and demyelination in EAE. • TSPJ-treated reduced Th17/Treg cell ratio and pro-inflammatory cytokines levels. • TSPJ's anti-neuroinflammatory effects were related to the regulation of gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a common and debilitating feature of multiple sclerosis (MS) that remains without reliably effective treatment. Transcranial direct current stimulation (tDCS) is a promising option for fatigue reduction. We developed a telerehabilitation protocol that delivers tDCS to participants at home using specially designed equipment and real-time supervision (remotely supervised transcranial direct current stimulation (RS-tDCS)). Objective: To evaluate whether tDCS can reduce fatigue in individuals with MS. Methods: Dorsolateral prefrontal cortex left anodal tDCS was administered using a RS-tDCS protocol, paired with 20 minutes of cognitive training. Here, two studies are considered. Study 1 delivered 10 open-label tDCS treatments (1.5 mA; n = 15) compared to a cognitive training only condition (n = 20). Study 2 was a randomized trial of active (2.0 mA, n = 15) or sham (n = 12) delivered for 20 sessions. Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)—Fatigue Short Form. Results and conclusion: In Study 1, there was modest fatigue reduction in the active group (−2.5 ± 7.4 vs −0.2 ± 5.3, p = 0.30, Cohen’s d = −0.35). However, in Study 2 there was statistically significant reduction for the active group (−5.6 ± 8.9 vs 0.9 ± 1.9, p = 0.02, Cohen’s d = −0.71). tDCS is a potential treatment for MS-related fatigue. [ABSTRACT FROM AUTHOR]

Purpose: To promote understanding of cognitive impairment in multiple sclerosis (MS), recommend optimal screening, monitoring, and treatment strategies, and address barriers to optimal management. Methods: The National MS Society (“Society”) convened experts in cognitive dysfunction (clinicians, researchers, and lay people with MS) to review the published literature, reach consensus on optimal strategies for screening, monitoring, and treating cognitive changes, and propose strategies to address barriers to optimal care. Recommendations: Based on current evidence, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society: [ABSTRACT FROM AUTHOR]

e-Health (or digital healthcare) is becoming increasingly relevant in multiple sclerosis (MS) clinical management. We aim to review and discuss current status and future perspective of e-health in people with multiple sclerosis (pwMS). The first part of this review describes how information on MS can be conveyed through the Web and digital media. The second part illustrates recent advances in digital technology that can improve clinical management and in motor and cognitive rehabilitation of pwMS. Finally, this review advocates future development of the “digital case manager” as a new figure to coordinate clinical management and care of pwMS. The digital revolution is changing the medical approach to MS in terms of information conveying and sharing, rehabilitation, and healthcare management. [ABSTRACT FROM AUTHOR]

Despite proven efficacy of alemtuzumab in multiple sclerosis (MS), approximately 50% of individuals will develop a new autoimmune disease following treatment. To date, these have largely been antibody mediated and organ specific (primarily affecting the thyroid gland). In a retrospective case series of 187 patients from two UK specialist centres (Cardiff and Cambridge) followed up for a median of 10 years, we report three (1.6%) cases of sarcoidosis following alemtuzumab treatment of MS. This report increases the spectrum of auto-inflammatory disease following alemtuzumab and should be considered by clinicians when using this therapeutic agent for MS. [ABSTRACT FROM AUTHOR]

Background: Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown. Objectives: To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS. Methods: Children <18 years with a first demyelinating event were prospectively included and followed. Soluble CD27 was determined in CSF using an enzyme-linked immunosorbent assay (ELISA). Cox regression analyses were used to calculate hazard ratios (HRs) for CDMS. Results: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS–) n = 61). Of the 61 ADS– children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis (n = 29) than in monophasic ADS+ (n = 30), monophasic ADS– (n = 28) and relapsing non-MS patients (n = 7; p < 0.001). In ADS– patients, sCD27 was associated with CDMS (HR = 1.8 per 100 U/mL increase in sCD27 levels, p = 0.031), after adjustments for age, oligoclonal bands and the presence of dissemination in space on baseline magnetic resonance imaging (MRI). Conclusion: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics. [ABSTRACT FROM AUTHOR]

Background: Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. Objective: We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. Methods: We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. Results: In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p < 0.0001) and 0.12 (seronegative; p = 0.0001). In those started on mycophenolate mofetil, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.79 and 1.45, respectively. On-treatment annualized relapse rates declined to 0.29 (seropositive; p < 0.0001) and 0.30 (seronegative; p < 0.005). Conclusion: In this international collaboration involving a large number of neuromyelitis optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments. [ABSTRACT FROM AUTHOR]

Background: In a minority of patients with neuromyelitis optica spectrum disorder (NMOSD) and aquaporin-4 antibodies (AQP4-IgG), the disease has a paraneoplastic origin. It is unknown whether these patients have distinctive clinical features. Objective: To report the clinical features of a series of patients with paraneoplastic NMOSD and AQP4-IgG and to review previously reported cases. Methods: Retrospective analysis of clinical records of 156 patients with NMOSD and AQP4-IgG and review of previously reported patients with paraneoplastic NMOSD and AQP4-IgG. Paraneoplastic patients were defined as those with cancer identified within 2 years of the diagnosis of NMOSD. Results: Five (3.2%) of 156 patients had paraneoplastic NMOSD, and 12 previously reported patients were identified. The most common tumors were adenocarcinoma of the lung (five patients) and breast (five). Compared with the 151 non-paraneoplastic NMOSD patients, the 17 (5 current cases and 12 previously reported) were older at symptom onset (median age = 55 (range: 17–87) vs 40 (range: 10–77) years; p = 0.006), more frequently male (29.4% vs 6.6%; p = 0.009), and presented with severe nausea and vomiting (41.2% vs 6.6%; p < 0.001). The frequency of longitudinal extensive transverse myelitis (LETM) as heralding symptom was similar in both groups, but patients with paraneoplastic NMOSD were older than those with non-paraneoplastic NMOSD (median age: 63 (range: 48–73) vs 43 (range: 14–74) years; p = 0.001). Conclusion: Patients, predominantly male, with NMOSD and AQP4-IgG should be investigated for an underlying cancer if they present with nausea and vomiting, or LETM after 45 years of age. [ABSTRACT FROM AUTHOR]

Background: Transverse myelitis (TM) is an inflammatory disorder that can be idiopathic or associated with central nervous system autoimmune/dysimmune inflammatory diseases, connective tissue autoimmune diseases, or post-infectious neurological syndromes. Prognosis of initial TM presentations is uncertain. Objective: To identify outcome predictors in TM. Methods: Retrospective study on isolated TM at onset. Scores ⩾3 on the modified Rankin scale (mRS) marked high disability. Results: A total of 159 patients were identified. TM was classified as follows: idiopathic (I-TM, n = 53), post-infectious (PI-TM, n = 48), associated with multiple sclerosis (MS-TM, n = 51), or neuromyelitis optica spectrum disorders/connective tissue autoimmune diseases/neurosarcoidosis (n = 7). At follow-up (median, 55 months; interquartile range, 32–80), 42 patients were severely disabled, and patients with I-TM or PI-TM showed the worst outcomes. Predictors of disability were infectious antecedents, sphincter and pyramidal symptoms, high mRS scores, blood–cerebrospinal fluid barrier damage, lumbar magnetic resonance imaging (MRI) lesions on univariate analysis, and older age (odds ratio (OR), 1.1; 95% confidence interval (CI), 1.0–1.1), overt/subclinical involvement of the peripheral nervous system (PNS) (OR, 9.4; 95% CI, 2.2–41.0), complete TM (OR, 10.8; 95% CI, 3.4–34.5) on multivariate analysis. Conclusion: Our findings help define prognosis and therapies in TM at onset. Infectious antecedents and PNS involvement associate with severe prognosis. Nerve conduction studies and lumbar MRI could improve the prognostic assessment of this condition. [ABSTRACT FROM AUTHOR]

Introduction. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for studying immunopathology of multiple sclerosis (MS) because it repeats the hallmarks of the human disease, such as focal inflammation and demyelination of the central nervous system, subsequently leading to axonal and neuronal loss. The interrelationships, timing and sequence of different pathological processes that lead to histologically observed lesions in SM are still incompletely understood. Material and methods. EAE was induced in female C57Bl/6 mice by active immunization with MOG35-55 antigen. Development of the neurological symptoms in the animals was monitored and on that basis spinal cords were collected in three successive phases of the disease (onset, peak, chronic). Total leukocytes, T cells, macrophages/ /microglia, oligodendrocytes, damaged axons and surviving neuronal cell bodies were visualized using appropriate immunohistochemical markers and their density was quantitatively assessed using image analysis software. Results. The density of all studied cells except neurons was significantly higher in EAE mice than in the control mice. The density of total leukocytes, T cells, and damaged axons increased from the onset to the peak phase and decreased in the chronic phase to reach values lower than those in the peak phase. The density of macrophages/ /microglia increased in the peak phase and remained at the elevated level in the chronic phase. Oligodendrocytes showed the highest density in the onset phase and gradually decreased afterwards. The density of neuronal cell bodies decreased only in the chronic phase of the disease. Conclusions. In mouse model of EAE, inflammatory cells predominate in the early phases of the disease. This study shows for the first time that inflammation precedes oligodendrocyte death and neuronal loss and that macrophages/ microglia are the only cells persisting in large numbers in the chronic phase of the disease, probably because of the switch from proinflammatory to anti-inflammatory phenotype. [ABSTRACT FROM AUTHOR]

Objective: Neuromyelitis optica (NMO) is a very severe autoimmune disorder of the central nervous system. It affects young subjects and has a poor prognosis both on a functional and vital level. Therefore, it is imperative to reduce the frequency of relapses. The purpose of this study was to evaluate the clinical and neuroradiological effectiveness of rituximab (RTX) on active forms of NMO.Methods: We conducted a 2-year open prospective multicenter study that included 32 patients treated with RTX at a dose of 375 mg/m2/week for 1 month. When the number of circulating CD19+ B cells reached 1%, a maintenance therapy was started, consisting of two infusions of 1 g of RTX, administered at a 15-day interval. The primary objective was to reduce the annual relapse rate (ARR), in comparison to that observed in the 2 years before treatment onset.Results: Rituximab administration reduced the ARR from 1.34 to 0.56 (p = 0.0005). The average Expanded Disability Status Scale (EDSS) score significantly improved by 1.1 point, from 5.9 (2-9) to 4.8 (0-9) after 2 years (p = 0.03). Anti-aquaporin-4 antibodies’ level predicted treatment failure (p = 0.03). Frequency of Gad+ lesions in spinal cord decreased from 23.3 to 14.2%. RTX treatment did not prevent the death of three patients (treatment failure in two patients and acute myeloid leukemia in a patient previously treated with mitoxantrone).Conclusion: Rituximab is clinically effective in active forms of NMO, although few patients are resistant to the treatment. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4+ and CD8+ T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically. [ABSTRACT FROM AUTHOR]