Neurological syndromes and potential triggers associated with antibodies to neuronal surface antigens.

BACKGROUND: Autoantibodies against surface neuronal antigens have been associated with specific neurological presentations including autoimmune encephalitis (AE), with variable association with neoplasia and infections. METHODS: We described the phenotype and environmental associations of patients with neurological syndromes associated with antibodies against neuronal surface antigens who were referred to a tertiary center in the South of Brazil. All patients were tested for neuronal autoantibodies using cell-based assays. Clinical, radiological, and laboratory findings were retrospectively reviewed. RESULTS: We identified 16 patients, 15 had subacute, and one had a progressive disease course. Among patients with subacute onset, 11 (73 %) were N-Methyl-d-Aspartate receptor (NMDAr-IgG)+, 3 (20 %) were Leucine-rich Glioma-Inactivated-1 (LGI1-IgG)+, and 1 (6 %) was positive for Glycine receptor-IgG. The patient with a progressive disease course had antibodies against IgLON5. Most patients had disease onset in spring and summer suggesting environmental factors for the development of AE. Also, we observed a different pattern of brain lesions when NMDAr-IgG encephalitis followed herpes encephalitis and a previously unreported association with Rosai-Dorfman-Destombe disease. All patients with encephalopathy met criteria for possible AE and all proven NMDAr-IgG+ met criteria for NMDAr-IgG encephalitis. However, only one LGI1-IgG+ patient fulfilled clinical criteria for limbic encephalitis. All but one received high-dose intravenous methylprednisolone, 11 also had intravenous human immunoglobulin, and 4 plasma exchange. Furthermore, all patients received second-line immunotherapy. Importantly, most patients improved with immunotherapy, even when initiated later in the disease course. CONCLUSION: We identified seasonal variability associated with neuronal surface antibodies suggesting environmental triggers. Also, we described the coexistence of NMDAr-IgG encephalitis with histiocytosis. In our series, most patients received second-line immunotherapy. We observed neurologic improvement after treatment even in cases of delayed diagnosis. Increasing the recognition and availability of tests and treatments for these conditions is of paramount importance in low- and middle-income countries.

Mechanisms of myelin repair, MRI techniques and therapeutic opportunities in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The remyelination process requires the activation, migration and differentiation of oligodendrocyte progenitor cells (OPC) in demyelinated areas. The metabolic dysfunction in chronic demyelinating lesions impairs the activation of OPCs, the myelin debris clearance by microglia decreases with age, along with diminished secretion of factors promoting OPC differentiation. Conventional magnetic resonance imaging (MRI) sequences have limited ability to differentiate unmyelinated and remyelinated lesions. Advanced MRI sequences based on magnetization transfer ratio (MTR), myelin water fraction (MWF) and diffusion tensor imaging (DTI) have been used to evaluate remyelination in clinical trials. More recently, the q-space myelin map (qMM) has been used on experimental and exploratory clinical studies. The improvement of myelin-specific MRI sequences with high reliability and standardization among centers will allow a more accurate evaluation of new therapies to improve remyelination. These new remyelination promoting treatments alone or in combination with current options may reduce the risk of long-term disability in MS.

Treatment of MOG-IgG associated disease in paediatric patients: A systematic review.

Aim to perform a systematic review of the literature on treatment of paediatric patients with MOG-IgG associated disease (MOGAD). Method We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The search was conducted in Pubmed (MEDLINE) seeking articles of treatment of MOGAD in patients ≤ 18 years published between January 2012 and April 25th, 2020. Results We found 72 non-controlled studies (observational studies, case reports and expert recommendations). There were no randomized controlled trials (RCTs). The most commonly reported acute phase treatment was intravenous methylprednisolone in 88% followed by oral steroids in 67%, intravenous human immunoglobulin (IVIG) in 66% and plasma exchange in 33% of the studies. Long-term maintenance treatment was described by 53 studies mainly in relapsing disease course. The most frequently reported treatments were prolonged oral corticosteroids in 53% of the studies followed by azathioprine (51%), mycophenolate mofetil (45%), rituximab (41%) and periodic intravenous immunoglobulin (26%). Interpretation long-term treatment was reported mainly in relapsing MOGAD paediatric patients. However, the most frequently used medications are not those that have shown higher reduction in the annualised relapse rate in observational studies. RCTs with standardized outcomes are needed to confirm the safety and efficacy of current and new treatments.

Unraveling B lymphocytes in CNS inflammatory diseases: Distinct mechanisms and treatment targets.

Specific therapies targeting B lymphocytes in multiple sclerosis (MS) have demonstrated reductions in disease activity and disability progression. Several observational studies have also shown the effects of targeting B lymphocytes in other rare CNS inflammatory diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis (AE). However, some drugs targeting cytokine receptors involved in B-lymphocyte maturation and proliferation resulted in negative outcomes in MS. These apparently conflicting findings have stimulated research on the pathophysiologic mechanisms of B lymphocytes in CNS inflammatory diseases. It has been demonstrated that B lymphocytes participate in the pathogenesis of these conditions as antigen-presenting cells, producing proinflammatory cytokines that induce Th1 and Th17 responses and producing antibodies. However, they are also able to produce anti-inflammatory cytokines, such as interleukin-10, functioning as regulators of autoimmunity. Understanding these diverse effects is essential for the development of focused treatments. In this review, we discuss the possible mechanisms that underlie B-lymphocyte involvement in MS, NMOSD, and AE and the outcomes obtained by treatments targeting B lymphocytes.