Seasonal variation in myasthenia gravis incidence.

Introduction: Environmental factors may contribute to myasthenia gravis (MG) development, sometimes with seasonal patterns of exposure. However, whether seasonality has an impact on MG incidence remains unclear. We aimed to investigate the association between seasonality and MG onset.

275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management, 9-11 February 2024, Hoofddorp, the Netherlands.

The 275th ENMC workshop on the diagnosis and management of seronegative myasthenia gravis (SNMG) was held on February 9-11, 2024. The participants included experts in the field of adult and pediatric MG together with patient representatives. This workshop aimed to redefine SNMG in view of recent diagnostic and therapeutic updates and to identify patient unmet needs.

Serological Markers of Clinical Improvement in MuSK Myasthenia Gravis.

Background And Objectives: In this retrospective longitudinal study, we aimed at exploring the role of (a) MuSK-immunoglobulin G (IgG) levels, (b) predominant MuSK-IgG subclasses, and (c) antibody affinity as candidate biomarkers of severity and outcomes in MuSK-MG, using and comparing different antibody testing techniques.

Methods: Total MuSK-IgGs were quantified with radioimmunoassay (RIA), ELISA, flow cytometry, and cell-based assay (CBA) serial dilutions using HEK293 cells transfected with MuSK-eGFP. MuSK-IgG subclasses were measured by flow cytometry.

Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells.

Anti-NMDA receptor (NMDAR) autoantibodies cause NMDAR encephalitis, the most common autoimmune encephalitis, leading to psychosis, seizures, and autonomic dysfunction. Current treatments comprise broad immunosuppression or non-selective antibody removal. We developed NMDAR-specific chimeric autoantibody receptor (NMDAR-CAAR) T cells to selectively eliminate anti-NMDAR B cells and disease-causing autoantibodies.

A score that predicts aquaporin-4 IgG positivity in patients with longitudinally extensive transverse myelitis.

Background And Purpose: Longitudinally extensive transverse myelitis (LETM) associated with aquaporin-4 autoantibodies (AQP4-IgG) can cause severe disability. Early diagnosis and prompt treatment are critical to prevent relapses. A novel score is described based on clinical and neuroimaging characteristics that predicts AQP4-IgG positivity in patients with LETM.

Thymectomy in severe (Myasthenia Gravis Foundation of America classes IV-V) generalized myasthenia gravis: is the game really worth the candle?

Objectives: Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis (MG). Patients with severe generalized MG present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. The aim of our study is to investigate neurological and surgical results in patients with Myasthenia Gravis Foundation of America (MGFA) class IV and V MG following thymectomy.

Immunological response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis treated with Rituximab.

In this study we employed a comprehensive immune profiling approach to determine innate and adaptive immune response to SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis receiving rituximab. By multicolour cytometry, dendritic and natural killer cells, B- and T-cell subsets, including T-cells producing IFN-γ stimulated with SARS-CoV-2 peptides, were analysed after infection and mRNA vaccination. In the same conditions, anti-spike antibodies and cytokines' levels were measured in sera.

Efficacy and safety of rituximab in myelin oligodendrocyte glycoprotein antibody-associated disorders compared with neuromyelitis optica spectrum disorder: a systematic review and meta-analysis.

Background: Rituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears to be lower than in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSDs). The aim of this systematic review and meta-analysis is to assess the efficacy and safety profile of RTX in patients with MOGAD and to compare RTX efficacy between MOGAD and AQP4-IgG+NMOSD.

Methods: We searched original English-language articles published between 2012 and 2021 in MEDLINE, Cochrane, Central Register of Controlled Trials and clinicaltrials.

Safety and tolerability of SARS-Cov-2 vaccination in patients with myasthenia gravis: A multicenter experience.

Background And Purpose: During the COVID-19 pandemic, myasthenia gravis (MG) patients have been identified as subjects at high risk of developing severe COVID-19, and thus were offered vaccination with priority. The lack of direct data on the safety and tolerability of SARS-CoV-2 vaccines in MG have contributed to vaccine hesitancy. To address this issue, the safety and tolerability of SARS-CoV-2 vaccines were assessed in a large cohort of MG patients from two referral centers.

Clinical features and outcome of patients with autoimmune cerebellar ataxia evaluated with the Scale for the Assessment and Rating of Ataxia.

Background And Purpose: This study was undertaken to assess the long-term outcome of patients with paraneoplastic and non paraneoplastic autoimmune cerebellar ataxia (ACA) using the Scale for the Assessment and Rating of Ataxia (SARA).

Methods: Patients with subacute cerebellar ataxia admitted to our institution between September 2012 and April 2020 were prospectively recruited. Serum and/or cerebrospinal fluid was tested for neural autoantibodies by indirect immunofluorescence on mouse brain, cell-based assays, and radioimmunoassay.

Cholinergic hyperactivity in patients with myasthenia gravis with MuSK antibodies: A neurophysiological study.

Objective: Patients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment.

Methods: Patients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020.

Heterogeneity in myasthenia gravis: considerations for disease management.

: Myasthenia gravis is a rare disease of the neuromuscular junction and a prototype of B cell-driven immunopathology. Pathogenic antibodies target post-synaptic transmembrane proteins, most commonly the nicotinic acetylcholine receptor and the muscle-specific tyrosine kinase, inducing end-plate alterations and neuromuscular transmission impairment. Several clinical subtypes are distinct on the basis of associated antibodies, age at symptom onset, thymus pathology, genetic factors, and weakness distribution.

Assessing the role of a tissue-based assay in the diagnostic algorithm of autoimmune encephalitis.

Tissue-based assay (TBA) is a widely-used method to detect neural autoantibodies, but the diagnostic accuracy for autoimmune encephalitis (AE) has not yet been adequately measured. We retrospectively evaluated the sensitivity and specificity of an indirect immunofluorescence TBA (IIF-TBA) in 159 patients with suspected AE. Serum and cerebrospinal fluid (CSF) specimens were collected and tested from December 2012 to September 2020.

Human Leukocyte Antigen Class II associations in late-onset Myasthenia Gravis.

Objective: Genetic factors predisposing to late-onset myasthenia gravis (LOMG) have not been clearly defined yet. However, genome-wide association studies identified Human Leukocyte Antigen (HLA) Class II alleles as a hotspot in this disease subtype. The aim of this study was to analyze the correlations of HLA Class II alleles with clinical data and titin antibodies in this patient subgroup.

In sickness and in health: when myasthenia gravis is a conjugal matter.

Objective: Genes and environment contribute to the multifactorial etiology of autoimmune diseases. Familial clusters of autoimmune diseases are often observed among first-degree relatives sharing the same genetic background and environmental exposure. Rarer is the occurrence of the same autoimmune diseases in non-consanguineous spouses.

Acetylcholine receptor antibody positivity rate in ocular myasthenia gravis: a matter of age?

Background: Anti-acetylcholine receptor antibodies (AChR Abs) are detected in 85% of myasthenia gravis (MG) patients, at higher rates in patients with late-onset disease. AChR Ab frequency is generally thought to be much lower in ocular MG (OMG), although recent studies reported positivity rates higher than 70%. We hypothesized that the improved AChR Ab diagnostic yield in OMG could be related to an increased frequency of late-onset disease, as observed in generalized MG.

Unprotected stroke management in an undiagnosed case of Severe Acute Respiratory Syndrome Coronavirus 2 infection.

Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this scenario, managing acute medical conditions, such as stroke, requires a timely treatment together with proper strategies that minimize the risk of infection spreading to health care workers and other patients. We report the case of a 79-year-old woman, who was admitted for a wake-up stroke due to occlusion of the left middle cerebral artery.

An Italian Neurology Outpatient Clinic Facing SARS-CoV-2 Pandemic: Data From 2,167 Patients.

Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients. Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments.

Long-Lasting Rituximab-Induced Reduction of Specific-But Not Total-IgG4 in MuSK-Positive Myasthenia Gravis.

The use of rituximab (RTX), an anti-CD20 monoclonal antibody (Ab), in refractory myasthenia gravis (MG) is associated with a better response in patients with Abs to the muscle-specific tyrosine kinase (MuSK) than in other MG subgroups. Anti-MuSK Abs are mostly IgG4 with proven pathogenicity and positive correlation with clinical severity. The rapid and sustained response to RTX may be related to MuSK Ab production by short-lived Ab-secreting cells derived from specific CD20 B cells.