BACKGROUND: Ataxia with downbeat nystagmus (A-DBN) has recently been associated with an intronic GAA repeat expansion in the FGF14 gene. The objectives of our study were to describe the clinical, radiological, and genetic findings, as well as the long-term response to aminopyridine (AP) treatment, in a cohort of patients with ataxia with DBN.
METHODS: Demographic, clinical, and radiological data were obtained through medical records. Genetic analysis of the FGF14 GAA expansion was performed. All patients were under compassionate treatment with AP. Scale for Assessment and Rating of Ataxia (SARA) score pre-treatment was compared with the current SARA score. Patient Clinical Global Impression (CGI-p) and the presence of adverse events were also assessed.
RESULTS: Eight patients were included. Median (quartiles 1 and 3) age at disease onset was 63.5 (54-67) years. Before treatment, patients complained of gait instability with daily fluctuations and visual disturbances. They showed DBN with predominant involvement of gait and posture on the SARA. Brain MRI disclosed mainly vermian atrophy. An FGF14 GAA expansion (>250 repeats) was demonstrated in all patients. After a median AP treatment duration of 43 (14.25-137.25) months, the CGI-p showed a median improvement of 65% (60-80%) in their disability, and the total SARA score remained without significant changes (P=.348). Only one patient complained of transient gastric upset and nausea with AP treatment.
CONCLUSIONS: Patients with A-DBN due to the FGF14 GAA expansion predominately show an axial involvement with fluctuating disability. Long-term treatment with AP is well tolerated and effective, and seems to slow disease progression in our patients.
