To describe a case of subacute ataxia induced by CRMP-5 (collapsin response mediator protein-5) presenting as gait imbalance.

A 74-year-old male with a history of smoking and hypothyroidism presented with progressive internal vertigo, upper extremity clumsiness, and falls over 3 months. His gait deteriorated significantly three weeks prior to presentation, requiring transition from walker-assistance to wheelchair. Examination revealed mild, symmetric upper extremity ataxia and dysmetria. Notably, he needed assistance from two people to stand and walk, exhibiting a wide-based, ataxic gait and tendency to lean backward. MRI of the brain showed a known chronic, non-occlusive right sigmoid sinus thrombus. Total spine MRI indicated mild cervical canal stenosis and multilevel mild-moderate neuroforaminal narrowing throughout the cervical and lumbar regions. CSF analysis showed 4 white blood cells, normal protein levels, and normal glucose. Autoimmune paraneoplastic panel revealed a reactive CRMP-5 IgG titer of 1:30720 in the serum and >1:1024 in the CSF. CT scan of the chest, abdomen, and pelvis did not reveal malignancy. The patient was transferred closer to home for initial treatment with plasmapheresis and immunotherapy consideration.

We report a case of seropositive CRMP-5 presenting primarily as gait disturbance. The CRMP-5 antibody is a neuronal intracellular autoantibody that targets CRMP-5, a protein crucial for neuronal migration and axonal growth. Small cell lung cancer and thymomas are the most associated malignancies. CRMP-5 can manifest as painful peripheral neuropathy, cerebellar ataxia, chorea, limbic encephalitis, and ocular symptoms. While cerebellar ataxia occurs in about 25% of cases, it is less frequently seen in isolation. Due to low incidence, heterogeneity, and limited clinical reports, there remains gap in establishing standard treatments and long-term outcomes for CRMP-5 associated syndromes. We hope this report raises awareness, particularly amongst neurologists who frequently evaluate gait and movement disorders.