Autoimmune cerebellar ataxia (ACA) refers to immune-mediated cerebellar ataxia. The autoantibodies involved in ACA can be detected in patients and are important biomarkers. In this study, we aimed to identify a novel autoantibody in patients with ACA. We screened for autoantibodies in serum samples from patients with cerebellar ataxia using immunohistochemical and immunocytochemical assays. Immunoprecipitation and mass spectrometry were used to identify the target antigens of the detected autoantibodies. We found that IgG reacted with transmembrane protein family 132 A (TMEM132A), which is enriched in the central nervous system (CNS), in serum samples of patients with cerebellar ataxia. A cell-based binding assay (CBA) was used to identify TMEM132A-IgG in serum samples obtained from 436 patients with cerebellar ataxia requiring differential diagnosis for ACA, 62 patients with autoimmune encephalitis, 27 patients with multiple system atrophy with predominant cerebellar ataxia, 24 patients with multiple sclerosis, 17 patients with neuromyelitis optica spectrum disorders, 17 patients with Parkinson's disease, 7 patients with anti-myelin oligodendrocyte glycoprotein antibody-associated disease, and 14 healthy subjects. We detected TMEM132A-IgG in serum samples from two patients with cerebellar ataxia, including the patient whose study first led to the identification of this autoantibody. None of the other participants had these autoantibodies. The two autoantibody-positive patients showed progressive predominant cerebellar ataxia with pyramidal tract signs and albuminocytologic dissociation. Brain MRI findings indicated cerebellar atrophy in one patient and bilateral inferior olivary nuclei hyperintensity changes and pseudohypertrophy in the other patient. TMEM132 A-IgG may be a novel autoantibody associated with autoimmune CNS diseases, including ACA.

Functional movement disorders (FMDs) are commonly classified along canonical non-ataxic movement disorder patterns, creating a potential blind spot for frequently observed ataxia-like presentations. At the same time, normal diagnostic findings and episodic symptom variability in some cerebellar ataxias predispose to an incorrect FMD diagnosis. We present three cases that illustrate pitfalls in the differential diagnosis of ataxia. First, a patient treated for presumed immune-mediated cerebellar ataxia was diagnosed with FMD based on clinical signs. Next, a patient with intermittent and inconsistent symptoms was diagnosed with FMD after extensive exclusionary workup, but was then found to have a novel type of spinocerebellar ataxia. The third patient had a genetically confirmed spinocerebellar ataxia but developed additional functional motor symptoms. Differentiating cerebellar ataxias from FMDs and recognising mixed presentations is essential. Enhanced clinical awareness and systematic diagnostic evaluation are crucial to avoid misdiagnosis and ensure optimal treatment.

Anti-mGluR1 encephalitis is a form of autoimmune encephalitis, with limited reports globally and only two cases reported from Japan. There are uncertainties regarding the optimal immunosuppressive agents and individual drug responses. Herein, we report a case of anti-mGluR1 encephalitis from Japan, notable for a favorable outcome after an early rituximab initiation and an observed increase in cerebellar blood flow during the early disease stages. The patient was a 65-year-old woman who experienced dizziness for 3 months, followed by worsening gait instability. She was referred to our department due to progressive difficulty standing and walking. Neurological examination revealed dysarthria, severe cerebellar ataxia, and impaired performance on the finger-to-nose and knee-to-heel tests. Blood tests were negative for rheumatologic autoantibodies, and cerebrospinal fluid (CSF) analysis showed a cell count of 4/µL and a protein level of 40.0 mg/dL. However, the IgG index was elevated at 1.35, and oligoclonal bands were positive. Brain magnetic resonance imaging showed no abnormalities, but ¹²³I-iodoamphetamine single-photon emission computed tomography revealed mild hyperperfusion in the bilateral cerebellar hemispheres. Based on the clinical presentation, immune-mediated cerebellar ataxia was suspected. The patient was treated with intravenous methylprednisolone, oral prednisolone, and intravenous immunoglobulin. Further diagnostic testing using tissue- and cell-based assays detected mGluR1 antibodies in pretreatment serum and CSF, confirming the diagnosis of anti-mGluR1 encephalitis. As the initial treatment was insufficient, rituximab was administered, leading to significant improvement, including the ability to walk unaided. At the most recent follow-up, >6 months postonset, she showed no symptom progression or cerebellar atrophy. We experienced a case of anti-mGluR1 encephalitis with increased cerebellar blood flow, where early RTX administration led to a favorable outcome. Its early use, as an acute treatment and for maintenance, may help prevent recurrence and contribute to a positive prognosis.

Pediatric seronegative immune-mediated cerebellar ataxia (IMCA) remains a poorly defined and often under-recognized diagnosis, particularly in young children, where symptoms are frequently misattributed to self-limited post-infectious processes. We report the case of a 2.5-year-old girl who presented with acute-onset ataxia (mSARA score: 14). Cerebrospinal fluid analysis revealed pleocytosis and positive oligoclonal bands, while serial brain imaging and extensive autoantibody panels were unremarkable. However, indirect immunohistochemistry (TIIF/IHC) demonstrated a positive intracellular signal in cerebellar Purkinje cells, supporting the diagnosis of isolated seronegative IMCA. The patient showed sustained clinical improvement with prolonged corticosteroid therapy (mSARA score: 1). To date, only a few similar cases have been reported in the literature. It remains unclear whether these presentations fall within the spectrum of autoimmune encephalitis (AIE) or represent a distinct pediatric phenotype, potentially expanding the age range of primary autoimmune cerebellar ataxia previously described in adults. We recommend incorporating TIIF/IHC into the diagnostic workup of both isolated and combined pediatric cerebellar ataxia syndromes to support diagnosis and guide individualized treatment. Additionally, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are emerging as promising biomarkers in this context and warrant further investigation.

Subacute progressive cerebellar ataxia poses a diagnostic challenge due to its wide-ranging etiologies and symptom overlap with acute and chronic cerebellar disorders. Prompt identification and treatment are essential to improve clinical outcomes. A 62-year-old woman presented with worsening vertigo, gait instability, and evolving neurological signs over five months, consistent with a syndrome of subacute progressive cerebellar ataxia. Despite normal findings on serial MRI and PET imaging, as well as negative serological and genetic testing, her recent history of influenza vaccination and clinical progression suggested immune-mediated cerebellitis. High-dose corticosteroid therapy resulted in marked improvement, allowing her to achieve near-complete recovery, with a final diagnosis of autoimmune cerebellar ataxia reached by exclusion. Even when imaging findings are unremarkable, it is crucial to recognize immune-mediated cerebellar ataxia in patients with progressive symptoms, particularly following potential triggers such as vaccination. Empirical corticosteroid therapy demonstrated both diagnostic and therapeutic value, facilitating recovery. Subacute cerebellar ataxia with normal imaging requires careful consideration of immune-mediated etiologies. This case demonstrates the potential benefits of corticosteroid therapy in achieving favorable outcomes, even in diagnostically challenging scenarios.