2026 American Academy of Neurology Autoimmune Abstract Website

Objective:

To illustrate the challenge of progressive cerebellar degeneration in autoimmune cerebellar ataxias despite immunotherapy.

Background:

The relationship between inflammatory activity and neurodegeneration in immune-mediated cerebellar ataxias remains poorly understood. No evidence-based guidelines define the optimal duration of immunotherapy after clinical stabilization or absence of active inflammation.

Design/Methods:

Results:

A 53-year-old woman presented with progressive dysarthria, dysphagia, dysmetria, and ataxia. MRI showed cerebellar atrophy. Workup revealed CRMP5 antibody positivity. She received steroids, IVIG, and plasma exchange without improvement; cyclophosphamide stabilized her clinical course. Seven years after onset, PET revealed non-Hodgkin lymphoma, and rituximab was initiated. She remained radiologically stable without new lesions. However, has worsened clinically, and developed progressive brainstem and cerebellar atrophy.

A 47-year-old woman presented with three years of progressive imbalance, dysarthria, diplopia, and dysphagia. A prior episode of SIADH and psychosis suggested earlier autoimmune disease. MRI showed persistent enhancing supra- and infratentorial lesions over five years. Extensive evaluation was initially negative, including negative autoantibodies in serum and CSF and genetic testing. IVIG provided partial benefit, and she was maintained on rituximab. Despite resolution of enhancing lesions, ataxia and cerebellar atrophy progressed.

A 49-year-old man presented with progressive imbalance and dysarthria. MRI showed brainstem T2 hyperintensities with punctate enhancement. Steroids led to mild clinical but no radiologic improvement. Rituximab did not provide improvement. He later developed additional CNS lesions; systemic workup was negative. Infliximab resolved neuroinflammation, and prevented new lesions, but cerebellar degeneration progressed clinically and radiographically. Genetic testing for cerebellar ataxia was negative.

Conclusions:

Cerebellar degeneration may progress despite control of neuroinflammation with immunotherapy. This dissociation underscores the need for biomarkers to distinguish neuroinflammatory disease from irreversible neurodegeneration and to guide optimal immunotherapy duration and intensity.