PTC Therapeutics.

Objective. To evaluate the technical feasibility and utility of ultrasonography in the study of diaphragmatic motion at our institution. Methods. The study consisted of 2 parts. For part I, in 23 volunteers we performed 23 studies on 46 hemidiaphragms with excursions documented on M-mode ultrasonography. For part II, in 22 patients we performed 52 studies in 102 hemidiaphragms. In 50 studies both hemidiaphragms were studied, and in another 2 studies only 1 hemidiaphragm was studied. Patients' ages ranged from birth to 66 years (mean, 23 years). There were 16 male and 6 female patients. Indications for the study were (1) suggestion of paralysis of the diaphragm (n = 22); (2) if the diaphragm was already known to be paralyzed, for evaluation of response to phrenic nerve or pacer stimulation (n = 9); and (3) follow-up of previous findings (n = 21). Patients were examined in the supine position in the longitudinal semicoronal plane from a subcostal or low intercostal approach. Motion was documented with real-time ultrasonography and measured with M-mode ultrasonography. Results. Of the 102 clinical hemidiaphragms studied, findings included normal motion (n = 42), decreased motion (n = 22), no motion (n = 6), paradoxical motion (n = 10), positive pacer response (n = 13), negative pacer response (n = 2), positive phrenic stimulation (n = 6), and negative phrenic stimulation (n = 1). There were no failures of visualization. Conclusions. Ultrasonography proved feasible and useful in evaluating diaphragmatic motion. In our practice it has replaced fluoroscopy. Ultrasonography has advantages over traditional fluoroscopy, including portability, lack of ionizing radiation, visualization of structures of the thoracic bases and upper abdomen, and the ability to quantify diaphragmatic motion.

Abstract-Background:The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. Objective: To review available evidence on corticosteroid treatment of boys with Duchenne dystrophy. Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification, and areas for future research are defined. Results: Seven class I studies and numerous less rigorous trials all demonstrated that corticosteroid treatment for 6 months with prednisone (0.75 or 1.5 mg/kg/day) increased muscle strength, performance, and pulmonary function and significantly slowed the progression of weakness. Two class I trials examined the effect of lower dosage of prednisone (0.30 and 0.35 mg/kg/day), demonstrated lesser but similar benefits, and showed a lower frequency of side effects (e.g., weight gain). The only significant side effects in all class I trials were weight gain and development of a cushingoid facial appearance. One longer-term trial of daily prednisone (0.3 to 0.7 mg/kg/day), a class III study, showed prolongation of functional ability and slower progression of weakness in patients during 3 years of treatment. One class IV, open trial of alternate-day prednisone (2 mg/kg for 2 months, then two-thirds dose every other day) extended ambulation by approximately 2 years in treated compared with untreated patients. Deflazacort, a corticosteroid similar in structure to prednisone, produced similar improvement in muscle strength and function with a similar side effect profile. Conclusions: Prednisone has been demonstrated to have a beneficial effect on muscle strength and function in boys with Duchenne dystrophy and should be offered (at a dose of 0.75 mg/kg/day) as treatment. If side effects require a decrease in prednisone, tapering to dosages as low as 0.3 mg/kg/day gives less robust but significant improvement. Deflazacort (0.9 mg/kg/day) can also be used for the treatment of Duchenne dystrophy in countries in which it is available. Benefits and side effects of corticosteroid therapy need to be monitored. The offer of treatment with corticosteroids should include a balanced discussion of potential risks. NEUROLOGY 2005;64:13-20 Duchenne dystrophy (DD), an X-linked, recessive disorder, with onset before age 5 years, is the most common and severe form of childhood muscular dystrophy.1-3 The specific molecular defect is an absence or marked deficiency of dystrophin, a large membrane-associated protein that is part of the dystrophin-glycoprotein complex.1 Affected boys develop neck flexor, anterior abdominal, hip, and shoulder girdle muscle weakness in early childhood, with loss of ambulation between ages 7 and 12. 4,5 Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Death usually occurs in the 20s, with the chance of...

IMPORTANCEAn unmet need remains for safe and efficacious treatments for Duchenne muscular dystrophy (DMD). To date, there are limited agents available that address the underlying cause of the disease.OBJECTIVE To evaluate the safety, tolerability, and efficacy of viltolarsen, a novel antisense oligonucleotide, in participants with DMD amenable to exon 53 skipping. DESIGN, SETTING, AND PARTICIPANTSThis phase 2 study was a 4-week randomized clinical trial for safety followed by a 20-week open-label treatment period of patients aged 4 to 9 years with DMD amenable to exon 53 skipping. To enroll 16 participants, with 8 participants in each of the 2 dose cohorts, 17 participants were screened.

ObjectiveThis study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).MethodsThis prospective, multi‐center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits.ResultsEnrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP‐INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 ± 2.2 mV) was significantly reduced compared to controls (5.5 ± 2.0 mV). Electrical impedance myography (EIM) high‐frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts.InterpretationBy the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit.