Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs

Spinal muscular atrophy (SMA) is an orphan disease characterized by the progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in this study. The median duration of drug treatment was over 20 months. The application of tSCS was performed during physical therapy for 20–40 min per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, and forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both type 2 and 3 SMA participants. The magnitude of functional changes was not associated with participant age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation on SMA

First Use of Non-Invasive Spinal Cord Stimulation in Motor Rehabilitation of Children with Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is characterized by the degeneration of spinal alpha motorneurons. Nusinersen demonstrated good efficacy in the early disease phases. The feasibility of transcutaneous spinal cord stimulation (tSCS) in motor rehabilitation of patients with spinal cord injury has been demonstrated. We hypothesize that tSCS may activate intact and restored by nusinersen motorneurons and slow down the decline in motor activity, and may contribute to the development of motor skills in children with SMA. A case series is presented. Five children (6–13 years old) with SMA type II or III participated in the study. They were treated with nusinersen for ~2 years. Application of tSCS was carried out during physical therapy for 30–40 min per day in the course of 10–14 days. Outcome measures were goniometry of joints with contracture, forced vital capacity (FVC), RULM and HFMSE scales. The participants tolerated the stimulation well. The reduction of the contracture was ≥5 deg. RULM and HFMSE increased by ~1–2 points. Predicted FVC increased by 1–7% in three participants. Each participant expanded their range of active movements and/or learned new motor skills. Spinal cord stimulation may be an effective rehabilitation method in patients treated with nusinersen. More research is needed

First Use of Non-Invasive Spinal Cord Stimulation in Motor Rehabilitation of Children with Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is characterized by the degeneration of spinal alpha motorneurons. Nusinersen demonstrated good efficacy in the early disease phases. The feasibility of transcutaneous spinal cord stimulation (tSCS) in motor rehabilitation of patients with spinal cord injury has been demonstrated. We hypothesize that tSCS may activate intact and restored by nusinersen motorneurons and slow down the decline in motor activity, and may contribute to the development of motor skills in children with SMA. A case series is presented. Five children (6–13 years old) with SMA type II or III participated in the study. They were treated with nusinersen for ~2 years. Application of tSCS was carried out during physical therapy for 30–40 min per day in the course of 10–14 days. Outcome measures were goniometry of joints with contracture, forced vital capacity (FVC), RULM and HFMSE scales. The participants tolerated the stimulation well. The reduction of the contracture was ≥5 deg. RULM and HFMSE increased by ~1–2 points. Predicted FVC increased by 1–7% in three participants. Each participant expanded their range of active movements and/or learned new motor skills. Spinal cord stimulation may be an effective rehabilitation method in patients treated with nusinersen. More research is needed

Identification of genetic variants associated with skeletal muscle function deficit in childhood acute lymphoblastic leukemia survivors

Geneviève Nadeau,1 Erika Ouimet-Grennan,1 Michelle Aaron,1 Simon Drouin,2 Laurence Bertout,2 Albert Shalmiev,2 Patrick Beaulieu,2 Pascal St-Onge,2 Louis-Nicolas Veilleux,3 Frank Rauch,3 Kateryna Petrykey,1,2 Caroline Laverdière,1–2,4 Daniel Sinnett,1–2,4 Nathalie Alos,1–2,5* Maja Krajinovic1–2,4*1Department of Medicine, University of Montreal, Montreal, QC, Canada; 2Sainte-Justine University Hospital Research Centre, Montreal, QC, Canada; 3Division of paediatrics, Montreal Shriners Hospital for Children, Montreal, QC, Canada; 4Division of Hemato-Oncology, Sainte-Justine University Hospital Centre, Montreal, QC, Canada; 5Division of Endocrinology, Sainte-Justine University Hospital Centre, Montreal, QC, Canada *These authors contributed equally to this workBackground: Although 80% of childhood acute lymphoblastic leukemia (ALL) cases are cured with current treatment protocols, exposure to chemotherapeutics or radiation therapy during a vulnerable period of child development has been associated with a high frequency of late adverse effects (LAE). Previous observations suggest important skeletal muscle size, density and function deficits in ALL survivors.Purpose: Given that only a fraction of all patients will suffer from this particular complication, we investigated whether it could be predicted by genetic markers. Patients and methods: We analysed associations between skeletal muscle force (Fmax) and power (Pmax) and germline genetic variants from 1039 genes derived through whole-exome sequencing. Top-ranking association signals retained after correction for multiple testing were confirmed through genotyping, and further analysed through stratified analyses and multivariate models. Results: Our results show that skeletal muscle function deficit is associated with two common single nucleotide polymorphisms (SNPs) (rs2001616DUOX2, P=0.0002 (Pmax) and rs41270041ADAMTS4, P=0.02 (Fmax)) and two rare ones located in the ALOX15 gene (P=0.001 (Pmax)). These associations were further modulated by sex, body mass index and risk groups, which reflected glucocorticoid dose and radiation therapy (P≤0.02). Conclusion: Occurrence of muscle function deficit in childhood ALL is thus strongly modulated by variations in the DUOX2, ADAMTS4 and ALOX15 genes, which could lead to personalized prevention strategies in childhood ALL survivors.Keywords: acute lymphoblastic leukemia, late adverse effects, skeletal muscle deficit, genetic association study, whole exome sequencin