Describe the importance of CSF GAD65 antibody evaluation in patients with subacute cerebellar ataxia in the setting of type 1 diabetes mellitus (T1DM).

Serum GAD 65 can be present in up to 80% of patients with T1DM. GAD 65 autoantibodies are also associated with several neurologic syndromes like stiff person syndrome, cerebellar ataxia, epilepsy, and limbic encephalitis. Therefore, patients with progressive ataxia should be evaluated for autoimmune causes, including GAD 65 autoantibodies. To confirm diagnosis, demonstration of intrathecal GAD antibody synthesis is recommended, as serum positivity alone may reflect underlying T1DM.

61-year-old female with T1DM presented with subacute progressive gait instability dysarthria, and headache that worsened in the last weeks. She required assistance to ambulate, and exhibited bilateral dysmetria, worse on the left, diminished vibration sense in lower extremities with preserved strength and a 7-year history of left gaze diplopia that acutely worsened to all gazes. Initial workup including CT brain and spine, serum autoimmune panel, and brain MRI with cerebellar protocol were unremarkable. Given high suspicion for autoimmune cerebellar ataxia, IV methylprednisolone was started. A second LP on day three of pulse steroids showed positive CSF GAD65 antibody, elevated gamma globulin, and monoclonal IgG with lambda light chain on immunofixation, confirming intrathecal antibody synthesis. Malignancy screening was negative. On day 4 of steroid therapy, marked improvement was noted with resolution of dysmetria, improved speech, gait, and diplopia limited to lateral gaze only. She was discharged on an oral prednisone taper with outpatient follow-up.

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This case highlights the importance of GAD 65 autoantibodies evaluation in CSF in progressive cerebellar ataxia as normal brain MRI does not exclude it. In patients with T1DM CSF testing is recommended since serum GAD65 positivity may show diabetes alone. Prompt immunotherapy treatment is recommended to preserve cerebellar function as 35-51% improve with treatment.