18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho




Spinal Muscular Amyotrophy (SMA) is a neuromuscular, genetic and hereditary disease, of autosomal and recessive character, characterized by degeneration and loss of motor neurons in the spinal cord and in the brainstem, causing progressive muscle weakness and hypotonia. There are four types of SMA, which are differentiated by the age of onset of symptons and the degree of motor development. In Brazil, there is no curative treatment available, requiring a specific drug that delays its development. Spinraza (nusinersena) is one of the principal drugs indicated in cases of SMA, it is a antisense oligonucleotide drug (ASO), which is capable of synthesizing a biologically active and functional “survival of motor neuron” (SMN) protein.


The study’s objective was to compare the motor functions in children with SMA Type I before and after the application of Spinraza®


Six children diagnosed with SMA Type 1 were analyzed. The data were analysed using IBM SPSS Statistics 22 (2013). The Shapiro-Wilk normality test was performed. The significance level () applied in the test was 5%. The collected data were organized in Microsoft Excel 2010® Software.

Resultados e Conclusões

The mean age was 37.8 months, the study group was composed by 66.7% male and 33.3% female, who underwent treatment with Spinraza, with an average initial age of 21.3 months of life. The results obtained during the experiment showed that the application of the 4th dose presented an increase in the score, compared to the control group. The administration of the 6th dose also pointed improvement in the evaluation (Average 28.00 ± 16.57). Most patients showed a mean improvement of 6.17 points after the sixth dose, and there was a mean improvement of 13 and 6.83 points. The administration of the 4th dose showed no significant difference between children of both genders (p>0.05) and the administration of the 6th dose did not show any significant difference either. Thus, there was a significant improvement in motor skills as the treatment proceeded, without positive interference from sex, age or date of initiation of treatment.

Palavras Chave

Spinal Muscular Amyotrophy; Spinraza; nusinersena; children

Declaração de conflito de interesses de TODOS os autores


Fonte de Fomento (se houver)

Referências (se houver)

ANVISA, Agência Nacional de Vigilância Sanitária. Preços máximos de
medicamentos por princípio ativo, para compras públicas. 2018. Disponível em:
http://portal.anvisa.gov.br/documents/374947/ 2829072/LISTA_CONFORMIDADE_
GOV_2018-09- 25.pdf/b5a4e145-125b-4bb7-9ffcca2a576c77df. Acesso em: 15 nov.
ARAÚJO, A. P.; RAMOS, V. G.; CABELLO, P. H. Dificuldades diagnósticas na
atrofia muscular espinhal. Arq. Neuropsiquiatr. 2005, v. 63, p. 145-9.
ARNOLD, W. D.; KASSAR, D.; KISSEL, J. T. Spinal muscular atrophy: diagnosis and
management in a new therapeutic era. Muscle Nerve. 2015; v. 51, p. 157–67.
Disponível em: http://dx.doi.org/10.1002/mus.24497. Acesso em: 15 fev. 2021.
BEZERRA, M. T. C. Qualidade de vida das crianças com atrofia muscular
Espinhal. Fortaleza. UFF/CE, 2008.
BIOGEN, Brasil Produtos Farmacêuticos LTDA. Spinraza (nusinersena) injeção 12
mg/5 ml: informação completa de bula. 02/2018.
BOWERMAN, M. et al. The UK SMA Research Consortium. Therapeutic strategies
for spinal muscular atrophy: SMN and beyond. Dis Models Mechan. 2017, v. 10, p.
943-54. doi:10.1242/dmm.030148.
BRADFORD, D.S. et al. Moe’s the text book of scoliosis and other deformities.
3. ed. Philadelphia: WB Saunders, 1995.
BRASIL. Ministério da Saúde. Secretária de Atenção Especializada à Saúde.
Portaria Conjunta nº 15, de 22 de outubro de 2019. Aprova o Protocolo Clínico e
Diretrizes Terapêuticas da Atrofia Muscular Espinhal 5q tipo Brasília, DF, 2019.
Disponível em: https://www.in.gov.br/en/web/dou/-/portaria-conjunta-n-15-de-22-deoutubro-de-2019-22331263. Acesso em: 23 fev. 2021
CAMPBELL, P.J. et al. Definition of subtypes of essential thrombocythemia and
relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective
study. Lancet. 2005. dec. 3, n. 366, p. 1945–53.
CHRUN, L. R. et al. Atrofia muscular espinhal tipo I: aspectos clínicos e
fisiopatológicos. Revista de Medicina, [S.L.], v. 96, n. 4, p. 281-286, 22 dez. 2017.
Universidade de Sao Paulo, Agencia USP de Gestão da Informação Acadêmica
(AGUIA). Disponível em: http://dx.doi.org/10.11606/issn.1679-9836.v96i4p281-286.
Acesso em: 15 nov. 2020
CLABORN, M. K. et al. Nusinersen: a treatment for spinal muscular atrophy. Annals
of Pharmacotherapy. Oklahoma, p. 1-9, 2018.
DOMINGOS, E. M.; AGUIAR, A. M. O uso do nusinersen no tratamento da atrofia
muscular espinhal: revisão de literatura. Visão Acadêmica, [S.l.], v. 21, n. 1, may
2020. ISSN 1518-8361. Disponível em:https://revistas.ufpr.br/academica/article/view/70574. Acesso em: 17 fev. 2021.
FINKEL, R. S. et al. Nusinersen versus sham control in infantile-onset spinal
muscular atrophy. New England Journal Of Medicine, [S.L.], v. 377, n. 18, p. 1723-
1732, 2 nov. 2017. Massachusetts Medical Society. Disponível em:
http://dx.doi.org/10.1056/nejmoa1702752. Acesso em: 17 fev. 2021.
FINKEL, R. S. et al. Treatment of infantile-onset spinal muscular atrophy with
nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016; v. 388, p.
3017-26. Disponível em: http://dx.doi.org/10.1016/S0140-6736(16)31408-8. Acesso
em: 17 fev. 2021.
GIDARO, T.; SERVAIS, L. Nusinersen treatment of spinal muscular atrophy: current
knowledge and existing gaps. Developmental Medicine & Child Neurology, [S.L.],
v. 61, n. 1, p. 19-24, 17 set. 2018. Wiley. Disponível em:
http://dx.doi.org/10.1111/dmcn.14027. Acesso em: 20 fev. 2021.
HUA, Y. et al. Antisense masking of an hnRNP A1/A2 intronicsplicing silencer
corrects SMN2 splicing in transgenicmice. Am J Hum Genet. 2008, v. 82, p. 834–48.
LORSON, C. L.; ANDROPHY, E. J. An exonic enhancer is requiredfor inclusion of an
essential exon in the SMA-determininggene SMN. Hum Mol Genet. 2000, v. 9, p.
MENDONÇA, R. H. et al. Real-World data from nusinersen treatment for patients
with later-onset spinal muscular atrophy: a single center experience. Journal Of
Neuromuscular Diseases, [S.L.], v. 8, n. 1, p. 101-108, 1 jan. 2021. IOS Press.
Disponível em: http://dx.doi.org/10.3233/jnd-200551. Acesso em: 20 fev. 2021.
MERCURI E. et al. Longitudinal natural history of type I spinal muscular atrophy: a
critical review. Orphanet J Rare Dis. v. 15, n. 1, p. 84, 2020.
MERCURI E. et al. Patterns of disease progression in type 2 and 3 SMA:
Implications for clinical trials. Neuromuscul Disord. v. 26, p. 126-31, 2016.
MERCURI, E. et al. Diagnosis and management of spinal muscular atrophy: Part 1:
Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care.
Neuromuscul Disord. 2018, v. 28, p. 103-15.
MERCURI, E. et al. Nusinersen versus sham control in later-onset spinal muscular
atrophy. The Journal of Clinical Pharmacology, v. 14, n. 9, p. 1–13, 2017.
OLSSON, B. et al. NFL isamarker oftreatment response inchildren withSMA treated
withnusinersen. Journal of Neurology, v. 76, p. 318–325, May, 2019.
PANE, M.; CORATTI, G.; SANSONE, V. A. Nusinersen in Type 1 Spinal Muscular
Atrophy: Twelve-Month Real-World Data. American Neurological Association. v.
00, p.1–9, 2019.
PASCUAL-PASCUAL, S. I.; GARCÍA-ROMERO, M. Possibilidades de tratamiento en
la atrofia espinal infantil. Rev Neurol. 2017, v. 64, n. 3, p. 19-24. Disponível em:
https://www.neurologia.com/articulo/2017173. Acesso em: 20 fev. 2021.
PECHMANN, A. et al. Evaluation of children with SMA type 1 under treatment with
nusinersen within the expanded access program in Germany. Journal Of
Neuromuscular Diseases, [S.L.], v. 5, n. 2, p. 135-143, 29 abril 2018. IOS Press.
http://dx.doi.org/10.3233/jnd-180315. Acesso em: 23 fev. 2021.
PEREIRA, R; VASCONCELOS, I. de O. Análise comparativa das habilidades
motoras em um paciente com amiotrofia muscular espinhal tipo I antes e após
submissão a tratamento com 5 doses de Spinraza: relato de caso Revista Brasileira
de Reabilitação e Atividade Física, Vitória, v.8, n.1, p. 1-11, ago. 2019. ISSN 2238-
POLIDO, J. G. et al. Matching pairs difficulty in children with spinal muscular atrophy
type I.0 Neuromusc Disord. 2017, v. 27, n. 5, p.:419-27.
RUSSMAN, BS. Spinal muscular atrophy: clinical classifications and disease
heterogeneity. J Child Neurol. 2007, v. 22, p. 946-51.
SHANMUGARAJAN, S. et al. Congenital bone fractures in spinal muscular atrophy:
functional role for SMN protein in bone remodeling. J Child Neurol. 2007, v. 22, p.
SINGH, N. K. et al. Splicing of a critical exon of human Survival Motor Neuron is
regulated by a unique silencer element located in the last intron. Mol Cell Biol
2006, v. 26, p. 1333–46.
TALBOT, K.; TIZZANO, E. F. The clinical landscape for SMA in a new
therapeutic era gene. Gene Ther. 2017, v. 24, n. 9, p. 529-33.
VERHAART, I. E. C. et al. Prevalence, incidence and carrier frequency of 5q–linked
spinal muscular atrophy – a literature review. Orphanet J Rare Dis. 2017, v. 12, -
WANG, C. H. et al. Consensus statement for standard of care in spinal muscular
atrophy. Journal of Child Neurology, v. 22, n. 8, p. 1027-1049, 2007.
WIRTH et al. Mildly affected patients with spinal muscular atrophy are partially
protected by an increased SMN2 copy number. Human Genetics. 2006; v. 119, n. 4,
p. 422–8.
ZERRES, Z.; RUDNIK-SCHÖNEBORN, S. Natural history in proximal spinal
muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification
of existing classifications. Lancet. 1995, May; v. 52, n. 5, p. 18-23.


Doenças neuromusculares