Clinical Characteristics of Japanese Cases of Anti-Metabotropic Glutamate Receptor Type 1 Antibody-Associated Cerebellar Ataxia

Abstract Anti-metabotropic glutamate receptor type 1 (mGluR1) antibody-associated cerebellar ataxia is a rare autoimmune cerebellar ataxia. Although its clinical spectrum has been recognized mainly from Western cohorts, its features in other populations remain uncharacterized. We investigated the clinical characteristics of this disease in a Japanese cohort with reference to overseas cases. We retrospectively reviewed patients testing positive for anti-mGluR1 antibodies in our laboratory between 2018 and 2025, comparing their clinical, laboratory, and radiological profiles with reference to 40 previously reported overseas cases. Of 699 screened patients, 12 were antibody-positive. Asymmetrical limb ataxia was documented in 75.0% of Japanese patients, whereas asymmetry was explicitly described in only four of twenty-eight overseas patients (14.3%) (p < 0.001); however, this comparison is exploratory and may reflect documentation differences. Japanese patients showed lower cerebrospinal fluid (CSF) inflammatory markers, with lower cell counts (median 4.5/µL vs. 27/µL, p = 0.014) and protein levels (median 36.5 mg/dL vs. 60.0 mg/dL, p = 0.048), although neither remained significant after Bonferroni correction. Two Japanese cases developed neurological symptoms within 1 month of COVID-19 infection. Although all Japanese patients received immunotherapy (corticosteroids in 100%), long-term functional recovery remained suboptimal; among 9 patients followed for ≥ 6 months, only 33.3% achieved functional independence (modified Rankin Scale ≤ 2) at final follow-up. In this first Japanese multicenter case series, asymmetrical limb ataxia was frequently documented and CSF inflammation was often limited. These exploratory findings may generate hypotheses to facilitate earlier diagnosis and treatment, but require cautious interpretation.