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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. SARA and modified Rankin Scale (mRS) score were employed to assess patients’ outcome. Results: Fifty-five patients were recruited, of whom 23 (42%) met the criteria for cerebellar ataxia of autoimmune etiology. Neural autoantibodies were detected in 22 of 23 patients (Yo–immunoglobulin G [IgG], n = 6; glutamic acid decarboxylase 65–IgG, n = 3; metabotropic glutamate receptor 1–IgG, n = 2; voltage-gated calcium channel P/Q type–IgG, n = 2; Hu-IgG, n = 1; glial fibrillary acidic protein–IgG, n = 1; IgG-binding unclassified antigens, n = 7). Thirteen patients were diagnosed with paraneoplastic cerebellar syndrome (PCS) and 10 with idiopathic ACA. All patients received immunotherapy. Median SARA score was higher in the PCS group at all time points (p = 0.0002), while it decreased significantly within the ACA group (p = 0.049) after immunotherapy. Patients with good outcome (mRS ≤ 2) had less neurological disability (SARA < 15) at disease nadir (p = 0.039) and presented less frequently with paraneoplastic neurological syndrome (p = 0.0028). The univariate linear regression model revealed a good correlation between mRS and SARA score both at disease onset (p < 0.0001) and at last follow-up (p < 0.0001). SARA score < 11 identified patients with good outcome. Conclusions: Patients with idiopathic ACA significantly improved after immunotherapy. SARA score

In the last years, significant advances have improved the knowledge of myasthenia gravis (MG) immunopathogenesis and have enabled to realize new molecules with a selective action targeting compounds of the immunological system. This review discusses emerging treatments for MG, including complement inhibitors, neonatal Fc receptor targeting agents, and B cell interfering drugs, focusing on benefit and danger. In the second section of the review, several related adverse events of immunotherapy, including MGonset, are debated.

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. Methods: This study consecutively enrolled anti-acetylcholine receptor antibody-positive, non-thymoma patients with generalized LOMG. All patients were of Italian ancestry. HLA-DRB1 and -DQB1 genotyping and serum titin antibody testing were performed in this population. Results: A total of 107 patients (females: 28/107, 26.2%; median age of onset: 68 years, range: 50-92) were included. We found a positive association with HLA-DRB1*07 (P = 1.1 × 10-5), HLA-DRB1*14 (P = 0.0251) and HLA-DQB1*02 (P = 0.0095). HLA-DRB1*03, HLA-DRB1*11, and HLA-DQB1*03 were protective alleles (P = 7.9 × 10-5, P = 0.0104, and P = 0.0067, respectively). By conditional haplotype analysis, HLA-DRB1*07-DQB1*02 was found to be the major risk haplotype (OR = 4.10; 95% C.I.: 2.80-5.99; P = 6.01 × 10-11). The mean age at onset was 73.4 years in DRB1*07 homozygotes, 69.7 years in heterozygotes, and 66.6 in non-carriers (P = 0.0488). DRB1*07 carriers and non-carriers did not differ in disease severity and response to therapy. Titin antibodies were detected in 61.4% of the cases, having no association with HLA alleles or specific clinical characteristics. Interpretation: In our study, we identified the HLA DRB1*07-DQB1*02 haplotype as a predisposing factor for the development of generalized LOMG in the Italian population.

BACKGROUND: Autoimmune encephalitis (AE) represents a complex syndrome with diverse clinical manifestations and therapeutic outcomes. Aim of this study is to report the clinical characteristics and the long-term outcome of patients with paraneoplastic and idiopathic AE. METHODS: All patients with subacute encephalopathy admitted to the Neurology Department of our Institution from January 2012 to May 2019 were consecutively enrolled. Patients' serum and cerebrospinal fluid (CSF) were tested for neural-specific autoantibodies (Ab) by indirect immunofluorescence assays on mouse brain, rat neurons, cell-based assays and immunoblots. Outcome was assessed by the modified Rankin Scale score (mRSs). RESULTS: From 107 adult patients with subacute encephalopathy, 50 patients were finally diagnosed with AE. Neural Ab were detected in 45/50 patients (90%). Lgi1-IgG was the most frequent (6/50, 12%) Ab specific to neural surface antigens (NsAb) detected in adults with AE. Paraneoplastic encephalitis was diagnosed in 16/50 patients (32%). The presence of bilateral temporal lobe lesions at MRI and CSF-restricted oligoclonal bands (OCB) was associated with higher probability to detect cancer at the time of AE diagnosis. All patients with NsAb had a good outcome at last follow-up. Severe disability at AE onset and the lack of long-term immunosuppression predicted a poor outcome. CONCLUSIONS: Lgi1-IgG was the most frequent Ab detected. Patients with bilateral temporal lobe lesions and OCB have higher probability to harbor an occult tumor. In these patients a strict surveillance and monitoring for cancer detection is recommended.

Myasthenia graviswith antibodies to themuscle-specific tyrosine kinase(MuSK+ MG)is a rare diseasewith distinctive pathogenic mechanisms and clinical features. An acute onset and predominant bulbar muscle weakness are very commonand highly suggestive of the disease.On the other hand, amore indolent course, atypical ocular presentation, and signs of cholinergic hyperactivity may complicate the diagnosis. ThoughMuSK+ MGis still a severe disease, over the years we have observed a steady reduction in the rate of respiratory crisis and a significant improvement in the clinical outcome, both likely related to earlier diagnosis and timely treatment. Despite the improved management, MuSK+ MG patients tend to remain dependent on long-term immunosuppressive treatment and may develop permanent disabling weakness. In uncontrolled studies, B cell depletion with rituximab proved effective in most patientswith refractory disease, inducing prolonged clinical responses associatedwith a sustained reduction of serum antibody levels. Promising results fromexperimental studies and case reports suggest that both 3,4-diaminopyridine and albuterol may be effective as symptomatic agents.