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BACKGROUND Juvenile Huntington disease (JHD) is a rare clinical entity characterized by an age at onset younger than 20 years. Patients usually have an expansion of more than 60 CAG repeats in the Huntington disease (HD) gene, and the disease is usually inherited from the father. In general, precise age at onset is difficult to assess in HD because of insidious onset and anosognosia. Onset of motor difficulty signs is usually used to define age at onset. OBJECTIVES To evaluate diagnosis delay in patients with JHD and to analyze the clinical and genetic features of JHD. DESIGN Retrospective clinical and genetic review. SETTING Referral center for HD at Salpêtrière Hospital, Paris, France. PATIENTS Twenty-nine patients with HD with onset before or at age 20 years who carried an abnormal CAG repeat expansion in the HD gene. RESULTS The mean ± SD delay before diagnosis was 9 ± 6 years (range, 0-21 years). The most remarkable signs at onset were severe psychiatric and cognitive disturbances (19 of 29 [65.5%]); rigidity was absent. Unusual signs at onset included myoclonic head tremor in 3 patients, severe isolated drug or alcohol addiction in 2, psychotic disorder in 1, and difficulty writing in 1. One patient had progressive cerebellar signs associated with cerebellar atrophy on cerebral magnetic resonance imaging before signs suggestive of HD appeared. During the course of the disease, psychiatric disturbances were severe, with at least 1 suicide attempt in 7 of 29 patients. Transmission was maternal in 25% of patients. Forty-six percent of patients with JHD had fewer than 60 CAG repeats; 6 of these patients inherited the disease from their father. Anticipation (mean ± SD, 18 ± 9 vs 25 ± 11 years; P = .27) and age at onset (mean ± SD, 17.14 ± 2.2 vs 13.29 ± 5.5 years; P = .09) was similar in patients with maternal compared with paternal transmission, respectively. CONCLUSIONS Patients with JHD started showing disease symptoms through nonspecific features, mostly psychiatric and cognitive difficulties. This led to misdiagnosis or diagnosis delay, especially in cases without a familial history of HD. Maternal transmissions and expansions of fewer than 60 CAG repeats were unexpectedly frequent in this series and should not be considered exceptional.Arch Neurol. 2007;64:813-819 --

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.Arch Neurol. 2007:64;558-564 --