2025 American Academy of Neurology Abstract Website

Objective:

To assess the diagnostic yield of genetic testing and highlight our experience at our recently established multidisciplinary ataxia clinic.

Background:

Hereditary ataxias are a heterogenous group of progressive neurodegenerative disorders primarily affecting the cerebellum. Many patients do not have a responsible gene identified. Our ataxia clinic serves to streamline the genetic testing process and deliver integrated care.

Design/Methods:

From 2021-2024, we enrolled 80 adults with clinical signs strongly suggestive of hereditary ataxia but without a genetic diagnosis into our IRB-approved study. Samples were collected for DNA analysis, with repeat expansion panel performed first followed by targeted and/or whole exome sequencing if prior workup was unrevealing. Patients were offered neurologic physical therapy targeted towards patients with ataxia.

Results:

Our cohort included 42 men and 38 women (average age 63, range 23-89). After genetic testing through our protocol, 40 patients (50%) had confirmed genetic diagnoses: 14 with cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS), 8 with spinocerebellar ataxia 27B (SCA27B), 4 with SCA6, 3 with SCA8 and 11 with other subtypes of ataxia. 37 patients (46.2%) remained without a genetic diagnosis. Three patients (3.8%) were subsequently determined to have non-genetic causes (1 with MSA-C, 2 with ataxia secondary to vascular insult). Patients were offered medical therapy based on symptoms and/or genetic diagnoses. Notably, of the 8 patients diagnosed with SCA27B, 7 (87.5%) reported symptomatic improvement with dalfampridine. Forty-nine patients (61.3%) attended at least one session of neurologic physical therapy at our institution.

Conclusions:

Significant progress has been made particularly with the recent discoveries of CANVAS and SCA27B. Further work involves quantifying response to pharmacotherapy and physical therapy across different genetic subtypes. Establishing a genetic diagnosis can enhance the multidisciplinary clinic experience by customizing treatment plans to align with specific patient needs, ultimately translating to better care.