Clinical Reasoning: A 60-Year-Old Woman With Progressive Dysarthric Speech and Gait Instability

A 60-year-old woman presented with a 2-month history of progressive dysarthric speech and gait instability, accompanied by chronic constipation and significant weight loss. Neurologic examination revealed cerebellar ataxia and diffuse hyperreflexia with bilateral Hoffman signs, concurrent with significant orthostatic hypotension. Initial investigations demonstrated cerebellar, left temporal, and hippocampal atrophy on brain MRI, alongside an inflammatory CSF profile. Although routine commercial antibody panels for paraneoplastic and autoimmune cerebellar ataxias yielded negative results, tissue-based assays (TBAs) identified an intense anti-neural antibody tissue-staining pattern, providing objective evidence of an underlying autoimmune etiology. As the disease evolved, the emergence of bilateral blepharospasm and slow saccades provided further diagnostic clues. Specialized testing in a neuroimmunology laboratory ultimately revealed the diagnosis. Readers will navigate a stepwise clinical reasoning approach to subacute cerebellar ataxia, which illustrates the importance of recognizing systemic red flags and monitoring phenotypic evolution as well as how specialized testing based on positive TBA results can resolve diagnostic dilemmas when commercial assays remain unrevealing.