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Pascale Ribaï, MD; Françoise Pousset, MD; Marie-Laure Tanguy, MD; Sophie Rivaud-Pechoux, PhD; Isabelle Le Ber, MD; Franchesca Gasparini, MD; Perrine Charles, MD, PhD; Anne-Sophie Béraud, MD; Michele Schmitt, PhD; Michel Koenig, PhD; Alain Mallet, MD; Alexis Brice, MD; Alexandra Dürr, MD, PhD

Arch Neurol. 2007;64(4):558-564.

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 electro-oculography to determine the frequency of square wave jerks.

Results  The total ICARS score worsened during follow-up, whether or not the patients were treated 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<.001). Neurological progression was underestimated, however, by the ICARS scores, which reached a plateau in patients with long disease durations. Oculomotor function slightly deteriorated (0.09 ± 0.02 Hz per year; P<.001). Left ventricular mass index decreased (–4.1 ± 1.5 g/m² per year; P = .008), as did ejection fraction (–1.32% ± 0.29% per year; P<.001).

Conclusions  The neurological condition of FA patients deteriorated slowly over time, even with idebenone treatment. Although cardiac hypertrophy decreased under treatment, cardiac function did not improve. The ICARS scale is not appropriate to evaluate the progression of FA in patients with long disease durations. Additional quantitative measures may improve the reliability of this scale.

Author Affiliations: Departments of Genetics (Drs Ribaï, Rivaud-Pechoux, Charles, Brice, and Dürr), Cardiology (Drs Pousset and Béraud), and Biostatistics (Drs Tanguy and Mallet) and Fédération de Neurologie (Drs Le Ber, Gasparini, and Brice), Assistance Publique–Hôpitaux de Paris, and Institut National de la Santé et de la Récherche Médicale (INSERM) 679 (formerly 289), Federative Institute for Neuroscience Research (Dr Ribaï, Le Ber, Brice, and Dürr), Salpêtrière Hospital, and Salpêtrière Medical School, Pierre and Marie Curie University (Dr Brice), Paris, France; Department of Clinical Genetics, Hôpitaux Universitaires de Strasbourg, Strasbourg, France (Drs Schmitt and Koenig); and Institute of Genetics, Molecular and Cellular Biology, Centre National de la Recherche Scientifique/INSERM/University Louis Pasteur, Illkirch, France (Dr Koenig).

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