Neurological, Cardiological, and Oculomotor Progression in 104 Patients with Friedreich ataxia during long-term follow-up

Abstract

Background: Friedreich ataxia (FA) is the most frequent autosomal recessive cerebellar ataxia. Although the phenotype is well known, disease progression has not been evaluated in a prospective manner. Objective: To perform a long-term prospective follow-up of neurological, cardiological, and oculomotor function in patients with FA (FA patients). Design: In this open-labeled prospective survey, we examined 104 FA patients every 6 months during a median period of 5 years (range, 6 months to 7 years), with a systematic standardized protocol. Data are reported as mean ± SD. Setting: Neurological examinations were performed at the Federation of Neurology and the Department of Genetics of the Salpêtrière Hospital, Paris, France. Cardiological follow-up was performed at the Department of Cardiology; oculomotor examinations were performed at the Institut National de la Santé et de la Récherche Médicale Unit 679, at the same hospital. Patients: We studied 104 FA patients with a confirmed molecular diagnosis. None were receiving antioxidant therapy at baseline; 88 accepted treatment with the coenzyme Q10 analogue idebenone (5 mg/kg per day). Sixteen preferred not to be treated. Interventions: Neurological status was evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and a quantitative writing test. Cardiological evaluations included echocardiography, electrocardiography, and Holter monitoring. Oculomotor function was evaluated by electrooculography to determine the frequency of square wave jerks. Results: The total ICARS score worsened during followup, whether or not the patientsweretreated with idebenone (1.93±0.25 and 4.43±1.56 points per year, respectively). The total ICARS score increased faster in patients with onset before age 15 years compared with the others (2.6±0.4 [n=51] vs 1.1±0.3 [n=37]; P=.05). The posture subscore increased faster in patients able to stand at baseline, who also had shorter disease durations than patients unable to stand (1.25±0.12 vs 0.47±0.22 point per year; P