Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 (PMP22), a model of Charcot-Marie-Tooth disease type 1A (CMT1A) associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Adult patients (aged 18-70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 (CMT-TRAUK) and EudraCT 2006-000032-27 (CMT-TRIAAL). We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the ascorbic acid group and 13·9 (4·2) in the placebo group. Mean worsening of CMTNS was 0·2 (SD 2·8, 95% CI -0·3 to 0·7) in the ascorbic acid group and 0·2 (2·7, -0·2 to 0·7) in the placebo group (mean difference 0·0, 95% CI -0·6 to 0·7; p=0·93). We recorded no differences between the groups for the secondary outcomes at 24 months. 21 serious adverse events occurred in 20 patients, eight in the ascorbic acid group and 13 in the placebo group. Ascorbic acid supplementation had no significant effect on neuropathy compared with placebo after 2 years, suggesting that no evidence is available to support treatment with ascorbic acid in adults with CMT1A. Telethon-UILDM and AIFA (Italian Medicines Agency) for CMT-TRIAAL, and Muscular Dystrophy Campaign for CMT-TRAUK.

It is widely agreed that after two or more seizures patients should be given antiepileptic treatment, but there is still controversy about the treatment of patients after a first unprovoked seizure. In a multicenter, randomized, open trial, patients with a first tonic-clonic seizure were randomized to immediate treatment (carbamazepine, phenytoin, phenobarbital, or sodium valproate) or to treatment only after another seizure. Fifty-two (24%) of the 215 patients randomized to immediate treatment and 85 (42%) of the 204 randomized to delayed treatment experienced seizure recurrence during follow-up. Age, acute treatment of the seizure with benzodiazepines, remote etiologic factors, and EEG abnormalities were significant predictors of relapse. Of the immediately treated patients, 87% had no seizures for a year and 68% had no seizures for 2 years, whereas only slightly fewer initially untreated patients (83% and 60%) achieved these endpoints. Patients treated after the first seizure and those treated after seizure relapse had the same time-dependent probability of achieving 1 and 2 seizure-free years. None of the variables that were prognostic predictors of relapse was significantly associated with the probability of having 1 or 2 years of seizure control. Anticonvulsants in patients presenting a first tonic-clonic seizure reduce the risk of relapse; however, 50% of patients who are not treated will never experience a second seizure. Moreover, the probability of long-term remission is not influenced by treatment of the first seizure.

The authors carried out a 1-year, randomized, placebo-controlled trial of idebenone in 29 patients with Friedreich ataxia. They found significant reductions of interventricular septal thickness and left ventricular mass in the idebenone group vs the placebo group, with no improvement in other heart ultrasound measures or neurologic condition. The absolute cardiac changes were modest, but the findings suggest that larger trials should assess whether idebenone reduces ventricular hypertrophy in patients with Friedreich ataxia.

Background: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established. Objective: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial. Methods: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician. Results: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001). Conclusions: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.

OBJECTIVES Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8.5). Patients’ participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patientsv 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.