“Heroic Medicine” in the Management of a Child with Spinal Muscular Atrophy Type 1: A Fair Choice of Treatment?

Medicine is a rapidly changing field. The use of new drugs has given hope for patients’ survival and comfort for the family, especially in cases of children with life-limiting conditions. This has influenced the clinical decision on the options of care and treatment by either the caregivers or healthcare professionals. Medical management for these patients is threaded on many ethical discussions to determine the best choice for these patients. We illustrated a case of a baby with spinal muscular atrophy (SMA) type 1 who was started on a new medication, leading to a renewed hope for the family but a challenging task for the managing team to decide on the highest ceiling of care for the patient.

Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I

Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. Methods: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. Results: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. Conclusions: Our results suggest that early treatment is more important than combined therapy.

Improvement in Fine Manual Dexterity in Children with Spinal Muscular Atrophy Type 2 after Nusinersen Injection: A Case Series

Although nusinersen has been demonstrated to improve motor function in patients with spinal muscular atrophy (SMA), no studies have investigated its effect on fine manual dexterity. The present study aimed to investigate the ability of nusinersen to improve fine manual dexterity in patients with SMA type 2. A total of five patients with SMA type 2 were included. The Hammersmith Functional Motor Scale (expanded version) (HFMSE) and Purdue Pegboard (PP) tests were used to evaluate gross motor function and fine manual dexterity, respectively, until 18 months after nusinersen administration. HFMSE scores improved by 3–10 points (+13–53%) in all patients following nusinersen administration. PP scores also improved in all patients, from 4 to 9 points (+80–225%) in the preferred hand and from 3 to 7 points (+60–500%) in the non-preferred hand. These results suggest that nusinersen treatment improved both gross motor function and fine manual dexterity in children with SMA type 2. Addition of the PP test may aid in evaluating the fine manual dexterity essential for activities of daily living in these patients.