Search

Spinal muscular atrophy (SMA) is one of the most common genetic diseases and was, until recently, a leading genetic cause of infant mortality. Three disease-modifying treatments have dramatically changed the disease trajectories and outcome for severely affected infants (SMA type 1), especially when initiated in the presymptomatic phase. One of these treatments is the adeno-associated viral vector 9 (AAV9) based gene therapy onasemnogene abeparvovec (Zolgensma®), which is delivered systemically and has been approved by the European Medicine Agency for SMA patients with up to three copies of the SMN2 gene or with the clinical presentation of SMA type 1. While this broad indication provides flexibility in patient selection, it also raises concerns about the risk-benefit ratio for patients with limited or no evidence supporting treatment. In 2020, we convened a European neuromuscular expert working group to support the rational use of onasemnogene abeparvovec, employing a modified Delphi methodology. After three years, we have assembled a similar yet larger group of European experts who assessed the emerging evidence of onasemnogene abeparvovec's role in treating older and heavier SMA patients, integrating insights from recent clinical trials and real-world evidence. This effort resulted in 12 consensus statements, with strong consensus achieved on 9 and consensus on the remaining 3, reflecting the evolving role of onasemnogene abeparvovec in treating SMA., Competing Interests: Declaration of competing interest JK has received honoraria for participating in advisory boards and/or symposia by Biogen, Novartis, Roche, and Scholar Rock. His institution receives funding for clinical research from Biohaven, Biogen, Novartis, Roche, and Scholar Rock. GB has received honoraria for participating in advisory boards and/or symposia by Biogen, Novartis, PTC, Pfizer, Roche, and Santhera, and research support from PTC. NB's institution has received funding from Biogen for equipment for the physiotherapy department and for a cough assist machine for patients. LDW has received speaker and consulting fees from Novartis Gene Therapies, Biogen, and Roche, has worked as a principal investigator of SMA studies sponsored by Novartis Gene Therapies, Roche, Scholar Rock, and Biohaven, and has received research grants from Novartis Gene Therapies, Roche, and Biogen. AFV has received honoraria for participating in advisory boards and/or symposia by Biogen, Novartis, and Roche. Her institution has received funding for a SMA registry from Biogen and for a pilot project of newborn screening for SMA from Novartis, Biogen, and Roche. JH has received honoraria for participating to advisory boards and/or symposia by Biogen, Novartis, and Roche. Her institution receives funding for clinical research from Biogen and Roche. TM has received honoraria for participating in meetings, formations and advisory boards from Biogen, Novartis, Roche, PTC, Astellas Gene Therapies, and Pfizer. AK has received honoraria for participating in advisory boards and/or symposia by Biogen, Novartis, Roche. She serves as clinical lead of the Swiss-Reg NMD, that receives funding for clinical research from Biogen, Novartis, and Roche. AKP has received honoraria for advisory boards and for speaking at educational events from Biogen, Novartis, PTC, and Roche; support for congress participation from Biogen, Roche, and Novartis; institutional grant support from Biogen, and support from Roche as principal investigator for SMA studies. EM has received honoraria for participating to advisory boards and/or symposia by Biogen, Novartis, Roche, and Scholar Rock. His institution receives funding for clinical research from Biogen, Novartis, Roche, and Scholar Rock. SQR has received honoraria for participating in advisory boards and giving lectures, as well as travel expenses from Novartis, Biogen, and Roche. TS has received honoraria for lectures or consultancy from Biogen, Novartis, PTC Therapeutics, Sarepta Therapeutics, Roche, Hansa Biopharma, and Sanofi Genzyme. EFT has received support to conduct clinical trials and research on SMA from Biogen and Roche, and has served as consultant to Novartis, Biogen, Biologix, Cytokinetics, Argenx, and Roche. WLP is member of the scientific advisory board of SMA Europe, his employer has received a fee-for-service for scientific advisory boards and participation in educational activities by Novartis, Biogen, and Roche. He was principal investigator for SMA trials sponsored by Novartis, Biogen, and Roche. SW has served as unpaid member on advisory boards for Biogen, Roche, and Novartis. DZ has received honoraria for participating in advisory boards and giving lectures, as well as travel and research grants from Novartis, Biogen, and Roche. AZ has received honoraria for participating in advisory boards and/or symposia by Biogen, Novartis, and Roche. His institution receives funding for clinical research from Biogen. FM has received honoraria for participating in advisory boards and/or symposia by Biogen, Novartis, and Roche. His institution receives funding for clinical trials and the UK SMA REACH registry from Biogen, Novartis, and Roche. LS has received honoraria for participating in advisory boards and/or symposia by Biogen, Novartis, Roche, Scholar Rock, Zentech, Illumina, and BioHaven. His institution receives funding for clinical research and educative events from Biogen, Novartis, Scholar Rock, BioHaven, Zentech, and Roche., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To determine the criterion validity of the SET-ULM (Spatial Exploration Test of Upper Limb Mobility), a functional workspace test., Materials and Methods: A prospective study from July 2017 to November 2018 in 30 children with SMA type 1 or 2. All children underwent assessment with the SET-ULM and the Motor Function Measure (MFM)., Results: We included 30 children. Median (Q1; Q3) MFM D1 (standing ability, ambulation and transfers), D2 (axial and proximal motor function), D3 (distal motor function) scores, Total MFM and Total SET-ULM active score were respectively 2.6% (2.6-3.8); 45.8% (19.9-65.3); 57.7% (36.9-80.9); 35.4% (16.7-43.2) and 70.2% (49.7-97.9). Total SET-ULM active score was strongly correlated with the MFM D2 dimension score (rho 0.82; p  < 001), with the D3 dimension (rho 0.86; p  < 0.001) and with the Total MFM score (rho 0.89; p  < 0.005). Total SET-ULM active score differed between SMA types ( p  < 0.01)., Conclusion: The SET-ULM has good criterion validity for the evaluation of available horizontal active upper limb workspace in children with SMA1 and SMA2. Future studies should evaluate reliability and sensitivity to change during a longitudinal follow-up study, as well as in a longitudinal trial of therapeutic effectiveness., Clinical Trials: NCT03223051IMPLICATIONS FOR REHABILITATIONThe Spatial Exploration Test for Upper Limb Mobility is a useful adjunct to the Motor Function Measure.It provides a precise evaluation of horizontal reaching ability.The Spatial Exploration Test for Upper Limb Mobility will be of great clinical utility for the evaluation of the effects of treatments for spinal muscular atrophy.

Background: Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disorder due to an autosomal recessive mutation in the survival motor neuron 1 gene (SMN1), causing degeneration of the anterior horn cells of the spinal cord and resulting in muscle atrophy. This study aimed to report on the 36-month follow-up of children with SMA treated with nusinersen before the age of 3 years. Changes in motor function, nutritional and ventilatory support, and orthopedic outcomes were evaluated at baseline and 36 months after intrathecal administration of nusinersen and correlated with SMA type and SMN2 copy number., Results: We found that 93% of the patients gained new motor skills during the 3 years-standing without help for 12 of 37 and walking with help for 11 of 37 patients harboring three SMN2 copies. No patients with two copies of SMN2 can stand alone or walk. Patients bearing three copies of SMN2 are more likely to be spared from respiratory, nutritional, and orthopedic complications than patients with two SMN2 copies., Conclusion: Children with SMA treated with nusinersen continue to make motor acquisitions at 3 years after initiation of treatment. Children with two SMN2 copies had worse motor, respiratory, and orthopedic outcomes after 3 years of treatment than children with three copies., Competing Interests: Declaration of Competing Interest JD, CV, MGGB, and UWL received funding as scientific advisory boards member from Biogen. VL, FA, JD, AI, MCN, JBD, CET, MGGB, and UWL received funding as scientific advisory boards member from Novartis. JD, CC, MGGB, and ID received funding as scientific advisory boards member from Roche. ID received funding as scientific advisory boards member from PTC therapeutics. CC, CET, and UWL received funding as scientific advisory boards member from Pfizer. VL, FA, CB, AI, JBD, CS, and ID received compensations for presentation from Novartis. FA, CB, JBD, CV, and CET received compensations for presentation from Biogen. CC received compensations for presentation from Roche. CS received compensations for presentation from PTC therapeutics and Sanofi Adventis. CC and ID received compensations for presentation from Pfizer. JBD is investigator for ongoing Roche clinical trials. MGGB is sub-investigator in SMA studies for Biogen, Novartis, and Roche. SMD, MC, and MB, declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials., Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting., Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources., Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related., Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.

We sought to devise a rational, systematic approach for defining/grouping survival motor neuron-targeted disease-modifying treatment (DMT) scenarios. The proposed classification is primarily based on a two-part differentiation: initial DMT, and persistence/discontinuation of subsequent DMT(s). Treatment categories were identified: monotherapy add-on, transient add-on, combination with onasemnogene abeparvovec, bridging to onasemnogene abeparvovec, and switching to onasemnogene abeparvovec. We validated this approach by applying the classification to the 443 patients currently in the RESTORE registry and explored the demographics of these different groups of patients. This work forms the basis to explore the safety and efficacy profile of the different combinations of DMT in SMA., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To evaluate sensitivity to change and discriminant validity of the 20-item Motor Function Measure (MFM-20) in 2-7-year-old patients with spinal muscular atrophy types 1 (SMA1) or 2 (SMA2) treated with nusinersen., Methods: Children aged 2 to 7 years old with SMA1 or SMA2 treated with nusinersen were assessed at least three times using the MFM-20 over an average follow-up time of 17 months. Evolution of 4-month-standardized MFM-20 scores was calculated for each MFM-20 domain (D1 standing and transfers, D2 axial and proximal, D3 distal) and for the total score (TS)., Results: Included in the study were 22 SMA1 subjects and 19 SMA2 subjects. Baseline MFM scores were significantly lower in patients with SMA1 than SMA2 (TS 29.5% vs. 48.3%, D1 4.5% vs. 10.6%, D2 43.6% vs. 72.6%, D3 51.2% vs. 75.0%). When considering the mean change during nusinersen treatment, standardized over a 4-month period, TS was improved for both SMA1 (+ 4.1%, SRM 1.5) and SMA2 (+ 2.8%, SRM 0.89) patients. For SMA1 patients, considerable changes were observed in D2 (+ 6.2%, SRM 0.89) and D3 (+ 6.0%, SRM 0.72), whereas the change in D1 was small (+ 0.5%, SRM 0.44). In SMA2 2 subjects, D3 was improved to a larger extent (+ 4.2%, SRM 0.53) than D1 (+ 1.8% SRM 0.63) or D2 (+ 3.2%, SRM 0.69)., Conclusion: Our results validate use of MFM-20 to monitor function of young SMA1 and SMA2 subjects treated with nusinersen. Significant motor function improvements following treatment were observed in both SMA1 and SMA2 patients., (© 2022. Fondazione Società Italiana di Neurologia.)

Spinal muscular atrophy is a debilitating neuromuscular disease due to the deletion of the SMN1 gene (SMA). The emergence of innovative targeted therapies changed the natural history of this condition. The French registry of SMA (Registre SMA France) was launched in 2020 to obtain a better knowledge of the pathology. The goal of the register was also to meet the need for real-life data regarding the arrival of these innovative therapies in order to identify the best therapeutic strategies and to improve patient care. The registry collects retrospective and prospective data of all genetically confirmed SMA, treated or not treated, in reference centers belonging to the national neuromuscular network (FILNEMUS). The estimated enrollment is 1,000 patients (50% children). On October 1 st , 666 patients have been enrolled (357 children and 309 adults) by 44 out of 51 open centers of the national network (FILNEMUS) with: 150 type 1 (22%); 278 type 2 (42%), 232 type 3 (35%) and 4 type 4 (1%) respectively., (© 2021 médecine/sciences – Inserm.)

Background: Treatment of spinal muscular atrophy (SMA) scoliosis has evolved in the last decade, with the emergence of fusionless surgical techniques that allow correction of the deformity before the end of growth spurt. These techniques are expected to delay definitive spine fusion and preserve trunk growth., Purpose: The aim was to evaluate long-term clinical, radiologic, and respiratory outcomes of a minimally invasive fusionless surgery (MIFLS) in SMA scoliosis., Methods: All children affected with SMA scoliosis who underwent MIFLS in our department from 2011 to 2019 were included. The instrumentation consisted in a bilateral sliding rod construct from T1 to the sacrum, anchored proximally by double-hook claws and distally by iliosacral screws. Clinical, genetic, respiratory and radiographic data were retrospectively reviewed. A patient's satisfaction survey was performed., Results: A total of 59 children with genetic confirmation of SMA (9SMA1c, 47SMA2, and 3SMA3) underwent MIFLS at a mean age of 11±1.9 years. All of them were nonwalker at the time of surgery. Twenty-six were treated with intrathecal Nusinersen. Mean follow-up was 5.2 years (2 to 9.6 y). Mean major coronal curve improved from 79±15 to 41±16 degrees and pelvic obliquity decreased from 24±11 to 5.9±4 degrees. Mean space available for lung improved from 77% to 93%. Mechanical or infectious complications occurred in 9 patients, with removal of the implant in 1. 6 children required unplanned surgeries. Postoperative bracing was needed in 13 children. Mean gain weight 3 years after the first surgery was 6 kg. 91.5% of patients had a positive satisfaction of the surgery. There was no significant impact in respiratory function postoperatively. Only 30 children required rod lengthening procedures, with a mean interval between procedures of 1.9 years (0.5 to 3.7 y). No arthrodesis was required at last follow-up in any patient., Conclusion: Bipolar MIFLS in SMA preserves spinal and thoracic growth without interference with respiratory function. It provides a significant correction of spinal deformity and pelvic obliquity, having a reduced rate of complications. The correction of spinal deformity was maintained at long term, not requiring definitive fusion at the end of growth., Level of Evidence: Level IV., Competing Interests: L.M. has intellectual property rights with Euros company. S.Q.-R. is consultant and belongs to advisory boards for Biogen, Avexis (Novartis Gene therapies), Roche, Sanofi-Genzyme. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Spinal muscular atrophy (SMA) used to be one of the most common genetic causes of infant mortality. New disease modifying treatments have changed the disease trajectories and most impressive results are seen if treatment is initiated in the presymptomatic phase of the disease. Very recently, the European Medicine Agency approved Onasemnogene abeparvovec (Zolgensma®) for the treatment of patients with SMA with up to three copies of the SMN2 gene or the clinical presentation of SMA type 1. While this broad indication provides new opportunities, it also triggers discussions on the appropriate selection of patients in the context of limited available evidence. To aid the rational use of Onasemnogene abeparvovec for the treatment of SMA, a group of European neuromuscular experts presents in this paper eleven consensus statements covering qualification, patient selection, safety considerations and long-term monitoring., Competing Interests: Declaration of competing interest For the work presented here the authors did not receive any financial or other material support. Outside the submitted work authors declare the following potential conflicts of interest. Janbernd Kirschner received honoraria for participation in advisory boards and educational activities from Avexis, Biogen, Roche, and ScholarRock. He received funding for clinical research from Biogen and AveXis. Nina Butoianu – nothing to disclose. Nathalie Goemans: participated in ad hoc advisory board activities for Biogen, Avexis, Roche and has received speaker's fee for participation in symposia from Roche and Biogen. Jana Haberlova participated in advisory board activities and has received speaker's fee for participation in symposia for Biogen, Novartis and Roche. Anna Kostera-Pruszczyk reports advisory board for Biogen, Avexis/Novartis, Roche, PTC, and grant support from Biogen, travel support from Biogen and Roche. Eduardo F. Tizzano reports grant support to conduct clinical trials on SMA from Ionis/Biogen. Serves as a consultant to AveXis, Biogen, Biologix, Cytokinetics, Roche for participation to scientific advisory boards and participation in educational symposia. Eugenio Mercuri reports acting as a consultant for AveXis, Biogen, Roche, Novartis, Cytokinetics and Scholar Rock; receiving honoraria from AveXis, Biogen, Roche, for participation to scientific advisory boards and participation in educational symposia; receiving investigator grant from Biogen for the iSMAc disease registry; acting as Principal investigator for Ionis/Biogen nusinersen trials; Roche olesoxime and risdiplam trial, Scholar Rock and Avexis zolgesma trials, all in SMA. Susana Quijano-Roy participated in and received honoraria for lectures and advisory board activities for Biogen, Avexis, and Roche. Thomas Sejersen: participated in and received honoraria for lectures and advisory board activities for Biogen, Avexis, and Roche. W. Ludo van der Pol participated in ad hoc advisory board activities for Biogen and Avexis and served as a member of the Data Monitoring Committee for Branaplam (Novartis). Principal investigator for Jewelfish (Roche) and Topaz studies (Scholar Rock) and member of the scientific advisory board for SMA Europe. Andreas Ziegler reports personal fees and scientific funding from Biogen, personal fees from Avexis, outside the submitted work. Laurent Servais reports research support from AveXis, Roche and Biogen, and consultancy fees/board member of Avexis, Biogen, Roche and Cytokinetics. Francesco Muntoni reports serving on the Pfizer Rare Diseases advisory board; acting as a consultant for AveXis, Biogen, Roche, Novartis; receiving honoraria from AveXis, Biogen, Roche, for participation to scientific advisory boards and participation in educational symposia; receiving investigator grant from Biogen for SMA REACH UK registry; acting as Principal investigator for Ionis/Biogen nusinersen trials; Roche olesoxime and risdiplam trial and Avexis zolgesma trials, all in SMA., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord. Nusinersen has been covered by public healthcare in France since May 2017. The aim of this article is to report results after 1 year of treatment with intrathecal nusinersen in children with SMA types 1 and 2 in France. Comparisons between treatment onset (T0) and after 1 year of treatment (Y1) were made in terms of motor function and need for nutritional and ventilatory support. Motor development milestone achievements were evaluated using the modified Hammersmith Infant Neurologic Examination-Part 2 (HINE-2) for patients under 2 years of age and Motor Function Measure (MFM) scores for patients over 2 years of age., Results: Data on 204 SMA patients (type 1 or 2) were retrospectively collected from the 23 French centers for neuromuscular diseases. One hundred and twenty three patients had been treated for at least 1 year and were included, 34 of whom were classified as type 1 (10 as type 1a/b and 24 as type 1c) and 89 as type 2. Survival motor Neuron 2 (SMN2) copy numbers were available for all but 6 patients. Patients under 2 years of age (n = 30), had significantly higher HINE-2 scores at year 1 than at treatment onset but used more nutritional and ventilatory support. The 68 patients over 2 years of age evaluated with the Motor Function Measure test had significantly higher overall scores after 1 year, indicating that their motor function had improved. The scores were higher in the axial and proximal motor function (D2) and distal motor function (D3) parts of the MFM scale, but there was no significant difference for standing and transfer scores (D1). No child in either of the two groups achieved walking., Conclusion: Nusinersen offers life-changing benefits for children with SMA, particularly those with more severe forms of the disorder. Caregiver assessments are positive. Nevertheless, patients remain severely disabled and still require intensive support care. This new treatment raises new ethical challenges.

Background: Dramatic improvements in spinal muscular atrophy (SMA) treatment have changed the prognosis for patients with this disease, leading to important new questions. Gathering representative, real-world data about the long-term efficacy and safety of emerging SMA interventions is essential to document their impact on patients and caregivers., Objectives: This registry will assess outcomes in patients with genetically confirmed SMA and provide information on the effectiveness and long-term safety of approved and emerging treatments., Design and Methods: RESTORE is a prospective, multicenter, multinational observational registry. Patients will be managed according to usual clinical practice. Both newly recruitedSMAtreatment centers and sites involved in existing SMA registries, including iSMAC, Treat-NMD, French SMA Assistance Publique- Hôpitaux de Paris (AP-HP), Cure-SMA, SMArtCARE, will be eligible to participate; de novo; sites already participating in another registry may be included via consortium agreements. Data from patients enrolled in partnering registries will be shared with the RESTORE Registry and data for newly diagnosed patients will be added upon enrollment. Patients will be enrolled over a 5-year period and followed for 15 years or until death. Assessments will include SMA history and treatment, pulmonary, nutritional, and motor milestones, healthcare resource utilization, work productivity, activity impairment, adverse events, quality of life, caregiver burden, and survival.Status:Recruitment started in September 2018. As of January 3, 2020, 64 patients were enrolled at 25 participating sites., Conclusions: The RESTORE Registry has begun recruiting recently diagnosed patients with genetically confirmed SMA, enabling assessment of both short- and long-term patient outcomes.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder characterized by progressive motor and respiratory decline during the first year of life. Early and late-onset cases have recently been reported, although not meeting the established diagnostic criteria, these cases have been genotyped. We thus conducted a national multicenter observational retrospective study to determine the prognosis of children with SMARD1 according to their phenotype. We recorded all known French pediatric cases with mutations identified on the immunoglobulin μ-binding protein 2 gene and the presence of respiratory symptoms. Thirty centers provided 22 observations. A diaphragmatic palsy was diagnosed 1.5 months (p = 0.02) after first respiratory symptoms, and hypotonia preceded areflexia by 4 months (p = 0.02). Early onset of symptoms leading to specialist consultation before the age of 3 months was associated with a significantly worse prognosis (p < 0.01). Among the 6 patients who were still alive, all were tracheostomized. Only one case survived beyond 2 years without artificial ventilation. The remaining patients died at a median age of 7 months. Our results may help pediatricians to provide medical information to parents and improve the decision-making process of setting up life support., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Particular fibroadipose infiltration patterns have been recently described by muscle imaging in congenital and later onset forms of LMNA-related muscular dystrophies (LMNA-RD)., Methods: Scores for fibroadipose infiltration of 23 lower limb muscles in 34 patients with LMNA-RD were collected from heat maps of 2 previous studies. Scoring systems were homogenized. Relationships between muscle infiltration and disease duration and age of onset were modeled with random forests., Results: The pattern of infiltration differs according to disease duration but not to age of disease onset. The muscles whose progression best predicts disease duration were semitendinosus, biceps femoris long head, gluteus medius, and semimembranosus., Discussion: In LMNA-RD, our synthetic analysis of lower limb muscle infiltration did not find major differences between forms with different ages of onset but allowed the identification of muscles with characteristic infiltration during disease progression. Monitoring of these specific muscles by quantitative MRI may provide useful imaging biomarkers in LMNA-RD. Muscle Nerve 58:812-817, 2018., (© 2018 Wiley Periodicals, Inc.)

This is the second half of a two-part document updating the standard of care recommendations for spinal muscular atrophy published in 2007. This part includes updated recommendations on pulmonary management and acute care issues, and topics that have emerged in the last few years such as other organ involvement in the severe forms of spinal muscular atrophy and the role of medications. Ethical issues and the choice of palliative versus supportive care are also addressed. These recommendations are becoming increasingly relevant given recent clinical trials and the prospect that commercially available therapies will likely change the survival and natural history of this disease., (Copyright © 2017. Published by Elsevier B.V.)

Background: Oral salbutamol has shown clinical benefits in spinal muscular atrophy (SMA). We studied its effect on the respiratory muscle strength in children with different types of SMA., Methods: Lung and respiratory muscle functions were assessed in children receiving daily oral salbutamol for at least one year. The respiratory data of age-matched SMA II historical control subjects were compared with data of SMA II patients receiving salbutamol., Results: Seven children (6.4 ± 2.0 years old, range four to ten; one SMA I, five SMA II, and one SMA III) treated with salbutamol (duration 23 ± 8 months) were assessed. Maximal static inspiratory pressure, sniff nasal inspiratory pressure, and slow vital capacity were significantly better in the salbutamol-treated SMA II group compared with control subjects (P < 0.05)., Conclusions: Long-term oral salbutamol showed benefits in respiratory function in children with SMA and appeared to increase the strength of the inspiratory muscles in a small cohort of SMA II patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Assessment of the upper limb strength in non-ambulant neuromuscular patients remains challenging. Although potential outcome measures have been reported, longitudinal data demonstrating sensitivity to clinical evolution in spinal muscular atrophy patients are critically lacking. Our study recruited 23 non-ambulant patients, 16 patients (males/females = 6/10; median age 15.4 years with a range from 10.7 to 31.1 years) with spinal muscular atrophy type II and 7 patients (males/females = 2/5; median age 19.9 years with a range from 8.3 to 29.9 years) with type III. The Brooke functional score was on median 3 with a range from 2 to 6. The average total vital capacity was 46%, and seven patients required non-invasive ventilation at night. Patients were assessed at baseline, 6 months, and 1 year using the Motor Function Measure and innovative devices MyoGrip, MyoPinch, and MoviPlate, which assess handgrip strength, key pinch strength, and hand/finger extension-flexion function, respectively. The study demonstrated the feasibility and reliability of these measures for all patients, and sensitivity to negative changes after the age of 14 years. The younger patients showed an increase of the distal force in the follow-up period. The distal force measurements and function were correlated to different functional scales. These data represent an important step in the process of validating these devices as potential outcome measures for future clinical trials.

The authors present a child affected with diaphragmatic paralysis in the early neonatal period. Although no electroneuromyographic abnormalities were reported, the patient developed dramatic motor and respiratory impairment with impossibility to wean from mechanical ventilation. Repeated electroneuromyographic study at age 4 months revealed severe neurogenic changes and sensory nerve abnormalities with more preserved nerve conduction velocities. Genetic studies identified 2 mutations in the gene IGHMBP2. These results support the consideration of this entity as a form of sensory-motor rapidly progressive polyneuropathy rather than a primary anterior horn disease (IGHMBP2-related neuropathy). A review of the series of mutated patients in the French National Database gives new insights of the incidence of this disease in France.