Helly Hammer

Background: Reporting of sex-specific analyses in multiple sclerosis (MS) is sparse. Disability accrual results from relapses (relapse-associated worsening) and independent thereof (progression independent of relapses). Objectives: A population of MS patients during relapse treated per standard of care was analyzed for sex differences and short-term relapse outcome (3–6 months) as measured by Expanded Disability Status Scale (EDSS) change. Design: Single-center retrospective study. Methods: We analyzed 134 MS relapses between March 2016 and August 2020. All events required relapse treatment (steroids and/or plasma exchange). Demographic, disease, and paraclinical characteristics [cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI)] were displayed separated by sex. Multivariable linear regression was run to identify factors associated with short-term EDSS change. Results: Mean age at relapse was 38.4 years (95% confidence interval: 36.3–40.4) with a proportion of 71.6% women in our cohort. Smoking was more than twice as prevalent in men (65.8%) than women (32.3%). In- and after-relapse EDSSs were higher in men [men: 3.3 (2.8–3.9), women: 2.7 (2.4–3.0); men: 3.0 (1.3–3.6); women: 1.8 (1.5–2.1)] despite similar relapse intervention. Paraclinical parameters revealed no sex differences. Our primary model identified female sex, younger age, and higher EDSS at relapse to be associated with EDSS improvement. A higher immunoglobulin G (IgG) quotient (CSF/serum) was associated with poorer short-term outcome [mean days between first relapse treatment and last EDSS assessment 130.2 (79.3–181.0)]. Conclusion: Sex and gender differences are important in outcome analyses of MS relapses. Effective treatment regimens need to respect putative markers for a worse outcome to modify long-term prognosis such as clinical and demographic variables, complemented by intrathecal IgG synthesis. Prospective trials should be designed to address these differences and confirm our results.

Background and purpose Neuronal autoantibodies can support the diagnosis of primary autoimmune cerebellar ataxia (PACA). Knowledge of PACA is still sparce. This article aims to highlight the relevance of anti‐neurochondrin antibodies and possible therapeutical consequences in people with PACA. Methods This is a case presentation and literature review of PACA associated with anti‐neurochondrin antibodies. Results A 33‐year‐old man noticed reduced control of the right leg in May 2020. During his first clinic appointment at our institution in September 2021, he complained about gait imbalance, fine motor disorders, tremor, intermittent diplopia and slurred speech. He presented a pancerebellar syndrome with stance, gait and limb ataxia, scanning speech and oculomotor dysfunction. Within 3 months the symptoms progressed. An initial cerebral magnetic resonance imaging, June 2020, was normal, but follow‐up imaging in October 2021 and July 2022 revealed marked cerebellar atrophy (29% volume loss). Cerebrospinal fluid analysis showed lymphocytic pleocytosis of 11 x 10 3 /L (normal range 0–4) and oligoclonal bands type II. Anti‐neurochondrin antibodies (immunoglobulin G) were detected in serum (1:10,000) and cerebrospinal fluid (1:320, by cell‐based indirect immunofluorescence assay and immunoblot, analysed by the EUROIMMUN laboratory). After ruling out alternative causes and neoplasia, diagnosis of PACA was given and immunotherapy (steroids and cyclophosphamide) was started in January 2022. In March 2022 a stabilization of disease was observed. Conclusion Cerebellar ataxia associated with anti‐neurochondrin antibodies has only been described in 19 cases; however, the number of unrecognized PACAs may be higher. As anti‐neurochondrin antibodies target an intracellular antigen and exhibit a mainly cytotoxic T‐cell‐mediated pathogenesis, important therapeutic implications may result. Because of the severe and rapid clinical progression, aggressive immunotherapy was warranted. This case highlights the need for rapid diagnosis and therapy in PACA, as stabilization and even improvement of symptoms are attainable.