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Background Spinal muscular atrophy type 1 (SMA1) is a motor neuron disease associated with progressive muscle weakness, ventilatory failure, and reduced survival. Objective: To report the evaluation of the nusinersen, an antisense oligonucleotide, on the motor function of SMA1. Methods This was a longitudinal and observational study to assess the outcomes of nusinersen therapy in SMA1 patients using the HINE-2 and CHOP-INTEND scales. Results Twenty-one SMA1 patients (52.4% males) were included; the mean age at first symptoms was 2.7 months (SD =±1.5), and the mean disease duration at first dose was 34.1 (SD =±36.0) months. During posttreatment, the mean gain on the CHOP-INTEND was 4.9, 5.9, 6.6, and 14 points after 6, 12, 18, and 24 months, respectively. Starting medication with a disease duration of less than 12 months and/or without invasive ventilation were predictors of response on CHOP-INTEND. Of the patients, 28.6% acquired a motor milestone or gained at least three points on the HINE-2. The daily time for ventilatory support was reduced after treatment in most of the patients with noninvasive ventilation at baseline. No change in the daytime use of ventilation was observed in most of the patients using invasive ventilation at baseline. Conclusions Nusinersen produces improvements in motor and respiratory functions, even in long-term SMA1 patients. However, patients under invasive ventilation at the beginning of the treatment experience little benefit.

Background Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness and motor disability. Objective This study aims to report the evaluation of nusinersen, an antisense oligonucleotide, on motor function in patients with SMA types 2 and 3. Methods This single-center retrospective observational study assessed nusinersen therapy outcomes, measured by HSMFSE or CHOP-INTEND scales, in patients with SMA types 2 and 3, compared to untreated patients, for at least 24 months. Results In 30 patients with SMA types 2 and 3 (mean age: 10.6 years; 14 with SMA type 2) under nusinersen treatment, the mean change in HFMSE scores was +1.47 points (SD = 0.4) and +1.60 points (SD = 0.6) after 12 and 24 months of treatment, respectively. In contrast, the control group (N = 37) (mean age: 10.2 years; 20 with SMA type 2) presented a mean change of −1.71 points (SD = 0.02) and −3.93 points (SD = 0.55) after 12 and 24 months of follow-up, respectively. The most severe patients (N = 11) showed a change of +2.37 (SD = 1.13) on the CHOP-INTEND scale after 12 months of follow-up. Disease duration at the beginning of treatment was the main predictor of functional improvement. Despite functional gain and motor stabilization, treatment with nusinersen did not prevent the progression of scoliosis. Conclusions Our data provide evidence for the long-term safety and efficacy of nusinersen use in the treatment of later-onset SMA, and patients with shorter disease duration showed better response to treatment.

ObjectiveThe aim of the study was to report the proportion of homozygous and compound heterozygous variants in the survival motor neuron 1 (SMN1) gene in a large population of patients with spinal muscular atrophy (SMA) and to correlate the severity of the disease with the presence of specific intragenic variants in SMN1 and with the SMN2 copy number.MethodsFour hundred fifty Brazilian patients with SMA were included in a retrospective study, and clinical data were analyzed compared with genetic data; the SMN2 copy number was obtained by multiplex ligation-dependent probe amplification and pathogenic variants in SMN1 by next-generation sequencing.ResultsFour hundred two patients (89.3%) presented homozygous exon 7-SMN1 deletion, and 48 (10.7%) were compound heterozygous for the common deletion in one allele and a point mutation in the other allele. Recurrent variants in exons 3 and 6 (c.460C>T, c.770_780dup and c.734_735insC) accounted for almost 80% of compound heterozygous patients. Another recurrent pathogenic variant was c.5C>G at exon 1. Patients with c.770_780dup and c.734_735insC had a clinical phenotype correlated with SMN2 copy number, whereas the variants c.460C>T and c.5C>G determined a milder phenotype independently of the SMN2 copies.ConclusionsPatients with specific pathogenic variants (c.460C>T and c.5C>G) presented a milder phenotype, and the SMN2 copy number did not correlate with disease severity in this group.

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Spinal muscular atrophy (SMA) is genetic and progressive, caused by large bi-allelic deletions in the SMN1 gene, or the association of a large deletion and a null variant. Objective: To evaluate the evidence about cognitive outcomes in spinal muscular atrophy (SMA). Methods: Searches on the PUBMED/Medline, Web of Knowledge and Scielo databases retrieved 26 studies (1989 to 2019, descriptors “spinal muscular atrophy” and “cognition”). Nine studies were selected according to the eligibility criteria: (1) cognition tested in individuals with SMA; (2) written in English or Spanish. The Risk of Bias in Non-Randomized Studies of Interventions was used to describe design, bias, participants, evaluation protocol and main findings. This study was registered on the International prospective register of systematic reviews (PROSPERO). Results: Three studies described normal cognition. In another three studies, cognitive outcomes were above average. Cognitive impairment was found in three studies. Poor cognitive performance was more frequently reported in studies that were recent, included children with SMA type I and that employed visual/auditory attention and executive function tests. Protocols and cognitive domains varied, precluding metanalysis. Conclusion: The severity of motor impairment may be related to cognitive outcomes: studies that included a higher number/percentage of children with SMA type I found cognitive impairment. The establishment of gold-standard protocols is necessary. Further studies should compare the cognitive outcomes of subjects with SMA types I to IV.

O objetivo deste estudo foi verificar se há correlação entre alinhamento postural e desempenho motor em crianças com paralisia cerebral (PC), além de compará-las com crianças de desenvolvimento motor típico. Participaram 14 crianças com PC tipo espástico, entre 4 e 12 anos, classificadas nos níveis III, IV e V no sistema de classificação de função motora ampla (GMFCS); e 20 com idades entre 4 e 8 anos e desenvolvimento motor adequado, que constituíram o grupo controle. Foi avaliado o alinhamento de lordose cervical e cifose torácica na postura sentada por meio de fotometria; o desempenho motor foi avaliado pelo índice de função motora ampla (Gross motor function measure, GMFM) apenas nas dimensões sentar (B) e ficar em pé (D). O subgrupo de PC nível III obteve maiores escores no GMFM do que o dos níveis IV e V, com diferença significativa nas dimensões B (p=0,00) e D (p=0,016). Quanto ao alinhamento postural, os dois subgrupos de PC apresentaram menor angulação da lordose cervical do que o GC, com diferença significativa; também foram medidos ângulos menores da cifose torácica nos subgrupos PC, sendo que o subgrupo dos níveis IV e V apresentou diferença significativa tanto em relação ao outro subgrupo PC quanto ao controle. Foi encontrada correlação positiva (r=0,748) entre o desempenho motor e o alinhamento postural nos subgrupos de PC, mostrando que, quanto melhor o alinhamento postural, melhor o desempenho motor dessas crianças.

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