Progressive multifocal leukoencephalopathy in a patient with systemic sclerosis treated with methotrexate: A case report and literature review

Reactivation of viruses occurs in autoimmune disorders in the setting of certain immunosuppressive drugs. We describe a 54-year-old female with systemic sclerosis and extensive cutaneous calcinosis who had been treated with methotrexate for 18 months and presented with headache and neurological deficits. She was diagnosed with progressive multifocal leukoencephalopathy, a rare disease caused by JC virus. Methotrexate was discontinued and mirtazapine plus mefloquine were added. The patient showed a slow recovery and five years later she had complete resolution of progressive multifocal leukoencephalopathy clinical manifestations. Calcinosis had a limited response to various agents and severely affected daily activities of the patient. This case report, highlights the importance of clinical suspicion for progressive multifocal leukoencephalopathy in every patient with immune-mediated disease, even on weak immunosuppressant, who presents with central nervous system manifestations and also the unmet therapeutic need for systemic sclerosis-associated calcinosis. © The Author(s) 2020

Quality of life in people with multiple sclerosis receiving glatiramer acetate or interferon in Greek clinical practice

Aim: To evaluate glatiramer acetate (GA) or IFN-β effects on quality of life (QoL) in people with relapsing/remitting multiple sclerosis (PwRRMS) in Greece. Methods: A prospective, practice-based study. QoL/function/symptoms were assessed by seven questionnaires/scales. Results: Significant increases in Short Form-36 (SF-36) health survey scores occurred with GA in four of the eight domains and three of the eight domains at 6 and 12 months, respectively, versus baseline. Similar and significant SF-36 score improvements occurred with GA in treatment-naive PwRRMS. SF-36 scores were unaffected in GA-treated, IFN-β treatment-experienced PwRRMS, or with IFN-β versus baseline. Slight improvements in fatigue and sexual satisfaction were evident (6 months). No deteriorations were seen in the other four instruments. Conclusion: The findings show that 12-month treatment with GA, but not IFN-β, improved certain QoL parameters in treatment-naive PwRRMS. Plain language summary People with relapsing/remitting multiple sclerosis (PwRRMS) are treated with drugs, for example, glatiramer acetate (GA) or IFN-β. We checked if these drugs improved quality of life (QoL) in PwRRMS in Greece. QoL was measured by seven questionnaires, asking many questions on aspects of life. One survey showed significant improvements with GA treatment in almost half of the question groups. Similar improvements in this survey were seen with GA in patients who had no other previous treatments. No changes were seen in GA-treated PwRRMS who previously received IFN-β, or treated with IFN-β alone. Slight improvements in fatigue and sexual satisfaction were seen. No QoL deteriorations were seen in the other four questionnaires. Twelve months of GA treatment, but not IFN-β, improved certain QoL parameters in treatment-naive PwRRMS. © 2022 Future Medicine Ltd

Regulatory B and T lymphocytes in multiple sclerosis: friends or foes?

Current clinical experience with immunomodulatory agents and monoclonal antibodies in principle has established the benefit of depleting lymphocytic populations in relapsing–remitting multiple sclerosis (RRMS). B and T cells may exert multiple pro-inflammatory actions, but also possess regulatory functions making their role in RRMS pathogenesis much more complex. There is no clear correlation of Tregs and Bregs with clinical features of the disease. Herein, we discuss the emerging data on regulatory T and B cell subset distributions in MS and their roles in the pathophysiology of MS and its murine model, experimental autoimmune encephalomyelitis (EAE). In addition, we summarize the immunomodulatory properties of certain MS therapeutic agents through their effect on such regulatory cell subsets and their relevance to clinical outcomes. © 2018, The Author(s)

Autoimmune hepatitis in patients with multiple sclerosis: The role of immunomodulatory treatment

Background: Development of autoimmune hepatitis (AIH) has been sporadically reported in patients with multiple sclerosis (MS) either concurrently or after treatment with immunomodulatory drugs, including interferon-beta (IFN-β) and steroids. Aim: To report a large cohort of 14 patients with MS diagnosed with AIH during an assessment of deranged liver function tests (LFTs). Patients and methods: From 2005 to 2017, we prospectively identified 14 (13 women) patients with MS who suffered also from AIH after investigation in our department for the presence of deranged LFTs. Age at diagnosis of MS was 36.7 ± 9.3 years while at diagnosis of AIH 43.1 ± 12 years. Results: AIH diagnosis was based on elevation of aminotransferases in all patients [alanine aminotransferase: 520 IU/L (range: 115–1219)], elevation of IgG in 6, compatible autoantibody profile in all, including 5 patients with liver-specific autoantibodies and typical or compatible histological features in 11 patients. 5 patients were under treatment with IFN-β plus methylprednisolone pulses, 3 with IFN-β plus oral steroids, 1 with IFN-β, 4 with methylprednisolone pulses whereas 1 patient was free of treatment. The median time from IFN-β initiation to the development of hepatitis was 12 months (range:1–120). Treatment for AIH was initiated in 13 patients with prednisolone (0.5–1 mg/kg/day) plus mycophenolate myfetil (2 g/day) in 10 and prednisolone plus azathioprine in 3 with complete and partial response in 11 and 2 patients, respectively. Conclusions: The differential diagnosis of hepatitis in MS patients should include AIH and in particular when immunomodulatory treatment has been preceded. Autoantibody testing and liver histology play fundamental role in establishing a prompt diagnosis of AIH in these patients. Treatment of AIH in patients with MS seems safe and efficient as complete or partial response was recorded in all of our patients. © 2018 Elsevier Masson SA

Recurrent episodes of syncope requiring pacemaker implantation as an initial presentation of neuromyelitis optica spectrum disorder

Neuromyelitis Optica Spectrum Disorders (NMOSD) can manifest with a variety of heterogeneous symptoms, mainly encompassing optic neuritis, acute myelitis and area postrema syndrome (hiccups, nausea, and vomiting). Syncopal episodes have rarely been described as an initial manifestation of NMOSD. Here, we report a case of a 42-year-old male who was diagnosed with NMOSD after initially presenting with intractable hiccups and recurrent episodes of syncope. This report is of particular interest, as it suggests that NMOSD should be included in the differential diagnosis of patients with intractable hiccups and heart rhythm disorders. © 202

Anti-MOG Positive Bilateral Optic Neuritis and Brainstem Encephalitis Secondary to COVID-19 Infection: A Case Report

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation of anti-MOG positive optic neuritis as well as anti-MOG positive encephalitis after COVID-19 infection. (2) Case Report: A 59-year-old female patient, with a recent history of COVID-19 infection, presented a progressive reduction of visual acuity and bilateral retrobulbar pain for the last 20 days. An ophthalmological examination revealed a decreased visual acuity (counting fingers) and a bilateral papilledema. An MRI scan of the brain revealed a mild thickening of the bilateral optic nerves and high-intensity lesions in the medial and right lateral pons. A high titer of IgG and IgM antibodies against SARS-CoV-2 in serum and antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) in serum and CSF were revealed. The diagnosis of anti-MOG brainstem encephalitis and optic neuritis was set. (3) Conclusions: The history of COVID-19 infection should raise awareness about these autoimmune and infection-triggered diseases, such as anti-MOG antibody disease. © 2022 by the authors

A comprehensive analysis of antigen-specific autoimmune liver disease related autoantibodies in patients with multiple sclerosis

Introduction: Abnormal liver function tests are frequently seen in patients with multiple sclerosis (MS) and their origin at times is attributed to the possible co-occurrence or the de novo induction of autoimmune liver diseases (AILD), namely autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but comprehensive analysis of AILD-related autoantibody has not been carried out. Aim: To assess the presence of AILD-related autoantibodies in a well-defined cohort of MS patients, and to assess their clinical significance. Materials and methods: 133 MS (93 female) patients (102 RRMS, 27 SPMS, and 5 PPMS), mean age 42.7 ± 11.9 SD years, mean duration of disease 11.2 ± 7.2 years were studied. 150 age and sex-matched healthy individuals were tested as normal controls (NCs).Autoantibody testing was performed by indirect immunofluorescence (IF) using triple tissue and HEp-2, a multiparametric line immunoassay detecting anti-LKM1(anti-CYP2D6), anti-LC1(anti-FTCD), soluble liver antigen/liver-pancreas(anti-SLA/LP), AMA-M2, and AMA-MIT3 (BPO), PBC-specific ANA (anti-gp210, anti-sp100 and anti-PML), and ELISA for anti-F-actin SMA and anti-dsDNA antibodies. Results: Reactivity to at least one autoantibody was more frequent in MS patients compared to NCs (30/133, 22.6% vs 12/150, 8%) NCs (p = 0.00058). SMAs by IIF were more frequent in MS patients (18/133, 13.53%) compared to NCs (6/150, 4%, p = 0.002%). The AIH-1 related anti-F-actin SMA by ELISA were present in 21 (15.8%), at relatively low titres (all but three of the SMA-VG pattern by IF); anti-dsDNA in 3 (2.3%), and anti-SLA/LP in none; AIH-2 anti-LKM1 autoantibodies in 1 (0.8%, negative by IF), and anti-LC1 in none; PBC-specific AMA-M2 in 2 (1.5%, both negative for AMA-MIT3 and AMA by IF) and PBC-specific ANA anti-PML in 6 (4.5%), anti-sp100 in 1 (0.8%) and anti-gp210 in 1 (0.8%). Amongst the 30 MS patients with at least one autoantibody positivity, only 4 (3%) had overt AILD (2 AIH-1 and 2 PBC). Autoantibody positivity did not differ between naïve MS patients and patients under treatment. Conclusions: Despite the relatively frequent presence of liver autoantibodies, tested either by IF or molecular assays, overt AILD is rather infrequent discouraging autoantibody screening strategies of MS patients in the absence of clinical suspicion. © 2020 The Author(s)

Brain volume dynamics in multiple sclerosis. A case-control study

Objectives: In this study, we aimed to explore the extent and clinical relevance of brain volume dynamics in relapsing remitting multiple sclerosis (RRMS). Methods: Sixty-three patients with RRMS with a disease duration of about 5 years (36 women, mean age 39.9 ± 9.4 years; mean EDSS1.4 ± 1.2, mean relapse rate 0.98 ± 1.17) and 50 healthy control individuals (24 women, mean age 39.1 ± 10.2 years) were recruited and imaged on a MRI scanner by using post-gadolinium high-resolution3D T1W sequences. Cross-sectional and longitudinal volumetric data were obtained by using SIENA(X) and FIRST software. Results: Patients showed significantly lower subcortical volumes compared to healthy controls. Interestingly, the educational level predicted the rate of right thalamus atrophy. The mean annualized percentage of brain volume change (aPBVC) was −0.92% (±1.64%) and was presented in higher rates during the first five years after MS diagnosis. Conclusion: Brain atrophy mainly involved subcortical grey matter structures and was more conspicuous during the first years of MS diagnosis. The buffering role of education in atrophy was also corroborated by this study. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group