Iron chelators are a new therapeutical approach for patients with Friedreich's ataxia, on the basis that oxidative cell damage that occurs in these patients is due to the increasing deposits of mitochondrial iron pools. The objective of the study was to evaluate the effects of the combined therapy of idebenone and low oral doses of deferiprone on the neurological signs and cardiac function parameters. This study was designed as a prospective open-label single-arm study. Twenty Friedreich's ataxia patients were treated with idebenone (20 mg/kg/day) and deferiprone (20 mg/kg/day) for 11 months. Patients were evaluated before the start and throughout the study with the International Cooperative Ataxia Rating Scale (ICARS) scores, echocardiographic measurements and MRI (magnetic resonance imaging) techniques to asses brain iron deposits in the dentate nucleus. No significant differences were observed in total ICARS scores when comparing baseline status and the end of the study in the whole group of patients. Posture and gait scores increased significantly after 11 months of therapy (Wilcoxon's test, p = 0.04) and kinetic function improved significantly (Wilcoxon's test, p = 0.015). Echocardiography data showed a significant reduction of the interventricular septum thickness (Wilcoxon's test, p = 0.04) and in the left ventricular mass index (Wilcoxon's test, p = 0.038) after the start of the therapy. The MRI values in the dentate nucleus showed a statistically significant reduction (Wilcoxon's test p = 0.007) between baseline conditions and after 11 months of the therapy. Combined therapy with idebenone and deferiprone in patients with FDRA indicates a stabilizing effect in neurologic dysfunctions due to an improvement in the kinetic functions, with a worsening of gait and posture scores. Heart hypertrophy parameters and iron deposits in dentate nucleus improved significantly. Combined therapy was well tolerated with mild side effects, apart from the risk of neutropenia and progressive reduction of plasma iron parameters.

Objectives: To describe the initial world experience and mid-term follow-up of perimembranous ventricular septal defect (pmVSD) closure with a newly designed occluder. Background: Transcatheter closure of pmVSDs has been associated with a substantial risk of complete heart block, prompting many centers to abandon this intervention. Methods: A prospective multicenter cohort study was conducted on patients with pmVSD undergoing catheter closure using the Amplatzer V R Membranous VSD Occluder 2 in the initial 4 pilot centers. Results: Nineteen patients, median age 6 years (range 1.4-62 years), were enrolled and followed for 14 6 3 months (range 8-20 months). The median weight was 26 kg (range 9.3-96 kg) and the mean Qp/Qs ratio was 1.8 6 0.7. The defect on left ventricular side measured 9.9 6 3.5 mm and the orifice on right ventricular side was 8.1 6 2.8 mm by echocardiography. Mean device size was 9.4 6 2.4 mm (range 5-14 mm). An eccentric device was employed in 9 patients (47%) and a concentric device in 10 (53%). Overall, 18 patients (95%) had successful device implants. Procedural time was 122 6 39 min. There were no procedural complications. Mild residual shunting was initially observed in 14 (78%) patients. At last follow-up, mild residual shunting persisted in only 3 (17%) patients. There was no significant increase in aortic or tricuspid regurgitation. No patient had any degree of AV block, although one developed a transient left anterior fascicular block. Holter evaluation, obtained in all patients, was unremarkable in all. Conclusions: This early cohort experience using a novel adapted transcatheter closure device for pmVSD suggests that the procedure is feasible, safe, and effective. V C 2013 Wiley Periodicals, Inc.