A Case Report of Reversible Mitochondrial Bioenergetic Dysfunction in PBMCs in Anti-GAD65–Associated Cerebellar Ataxia

Abstract Immune-mediated cerebellar ataxias lack dynamic biomarkers that reflect systemic metabolic changes during treatment. In this longitudinal case of anti-GAD65 cerebellar ataxia, high-resolution respirometry of peripheral blood mononuclear cells (PBMCs) revealed treatment-associated shifts in mitochondrial bioenergetic organization that occurred in temporal association with clinical improvement. A 61-year-old woman presented with a 6-month history of progressive gait instability, downbeat nystagmus, dysarthria. Diagnostic workup revealed a highly elevated anti-GAD65 antibody index (> 400.0), while brain MRI and routine cerebrospinal fluid analysis were unremarkable, confirming a diagnosis of anti-GAD-associated cerebellar ataxia. Serial high-resolution respirometry was used to assess PBMC mitochondrial function at baseline and following successive therapies. At baseline, the patient exhibited a Complex I–dominant profile with suppressed Complex II activity, reduced glycerophosphate dehydrogenase (GpDH) flux, and impaired mitochondrial coupling. While corticosteroids yielded negligible metabolic or clinical changes, subsequent plasmapheresis was followed by increased Complex II and GpDH flux, normalized coupling parameters, and expanded respiratory reserve. These bioenergetic shifts paralleled significant clinical recovery, as evidenced by a reduction in the Scale for the Assessment and Rating of Ataxia (SARA) score from 17 to 12, and were further accompanied by a decrease in the anti-GAD65 antibody index. This case suggests that PBMC mitochondrial bioenergetics may reflect systemic metabolic changes during treatment in anti-GAD ataxia. These observations provide a preliminary metabolic perspective on immunotherapy response and warrant validation in larger patient cohorts.