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Article in English | WPRIM | ID: wpr-928588


Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscular weakness and atrophy. SMA, as an inherited disease, is the leading cause of death in infants and young children. Rapid progress has been made in the research field of SMA in recent years, and some related treatment drugs have been successfully approved for marketing. This article reviews the recent research advances in the treatment of SMA.

Child , Child, Preschool , Humans , Infant , Muscular Atrophy, Spinal/genetics
Article in Chinese | WPRIM | ID: wpr-928374


Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron degenerative disease, which is the most common fatal neuromuscular disease in pediatrics with a high carrier frequency and can lead to progressive symmetrical muscle weakness and atrophy of the trunk and limbs. Preimplantation genetic testing (PGT) can be used to prevent the birth of children with SMA effectively. To standardize PGT technologies for SMA, experts from the fields of neurology, pediatrics and reproductive genetics have discussed and drafted this consensus for guiding its clinical application.

Child , Consensus , Genetic Testing , Humans , Muscular Atrophy, Spinal/genetics , Survival of Motor Neuron 1 Protein/genetics
Arq. neuropsiquiatr ; 79(10): 912-923, Oct. 2021. tab, graf
Article in English | LILACS | ID: biblio-1345319


Abstract Background: Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. Objective: This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. Methods: The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. Results: Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. Conclusions: This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.

RESUMO Antecedentes: Atrofia muscular espinhal (AME) de início no adulto representa um grupo de doenças neurodegenerativas hereditárias em expansão na prática clínica. Objetivo: Este artigo de revisão sintetiza os principais aspectos clínicos, genéticos, radiológicos, bioquímicos e neurofisiológicos relacionados às formas clássicas e recentemente descritas de AME proximal do adulto. Métodos: Os autores realizaram uma revisão crítica não sistemática descrevendo as principais apresentações de AME proximal de início no adulto. Resultados: Previamente restrito às apresentações de AME tipo 4 associada ao gene SMN1, este grupo atualmente envolve mais de 15 diferentes condições clínicas que compartilham entre si a presença de comprometimento progressivo e simétrico do neurônio motor inferior se iniciando no adulto ou no idoso. Novos subtipos clínicos e genéticos de AME proximal de início no adulto foram reconhecidas e são alvos atuais de estudos direcionados a aspectos neurorradiológicos, patológicos e genéticos. Conclusões: Este novo grupo complexo de doenças raras tipicamente se apresenta com doença do neurônio motor inferior em associação com outros sinais de comprometimento neurológico ou sistêmico, os quais apresentam padrões relativamente específicos para cada subtipo genético.

Humans , Radiology , Muscular Atrophy, Spinal/genetics , Motor Neuron Disease , Rare Diseases , Neurophysiology
Arq. neuropsiquiatr ; 79(8): 743-747, Aug. 2021. graf
Article in English | LILACS | ID: biblio-1339225


ABSTRACT Over the past 68 years, the Finkel type late-onset adult autosomal dominant spinal muscular atrophy (SMA) that is allelic with amyotrophic lateral sclerosis-8 (ALS8) gained a genotype-phenotype correlation among the motor neuron diseases through the work of groups led by Zatz and Marques Jr.

RESUMO Nos últimos 68 anos, a atrofia muscular espinhal (AME), autossômica dominante, de início tardio, em adultos, conhecida como doença de Finkel, que é alélica com esclerose lateral amiotrófica tipo 8 (ELA8), ganhou uma correlação fenotípica e genotípica dentre as doenças do neurônio motor, a partir da colaboração dos grupos de Zatz e Marques Jr.

Humans , Muscular Atrophy, Spinal/genetics , Amyotrophic Lateral Sclerosis/genetics , Phenotype , Vesicular Transport Proteins/genetics , Mutation
Rev. Hosp. Ital. B. Aires (2004) ; 41(2): 71-78, jun. 2021. tab
Article in Spanish | LILACS | ID: biblio-1254499


Introducción: la atrofia muscular espinal (AME) es la primera causa de origen genético de muerte en la infancia. En los últimos 20 años han sido excepcionales los avances en el conocimiento de su base genética, de su historia natural y se han desarrollado estándares de cuidado y nuevas terapias. Este veloz aumento del conocimiento ha llevado al desarrollo de terapias eficaces para esta devastadora enfermedad, pero el tiempo son neuronas, y esa frase nos lleva a pensar la importancia del diagnóstico precoz y, por qué no, del diagnóstico presintomático mediante pesquisa neonatal. Métodos: revisión de la bibliografía disponible, a través de búsqueda en PubMed y Google para trabajos no indexados o publicaciones de organismos de Salud. Resultados: varios estudios clínicos han mostrado la mayor eficacia del tratamiento en pacientes presintomáticos, por lo que lograrlo en estos pacientes llevaría a cambiar radicalmente la historia de esta enfermedad. Conclusión: es importante analizar y promover el desarrollo de pilotos para pesquisa neonatal en vistas a lograr experiencia para, a partir de ello, pensar en la posibilidad de incorporarlo a programas nacionales. (AU)

Introduction: spinal muscular atrophy (SMA) is the first cause of genetic origin of death in childhood. Throughout the last 20 years, we have witnessed exceptional advances in the knowledge of its genetic base, the history of its nature and several standards of care and new therapies have been developed. This rapid increase in knowledge has led to the development of effective therapies for this devastating disease. However, time is neurons, and that phrase reminds us of the importance of early diagnosis, and, why not, of pre-symptomatic diagnosis by means of neonatal screening. Methods: review of scientific papers searching in Pubmed or Google for non-indexed articles or publications of Health organisms. Results: several clinical studies have shown the greatest effectiveness of treatment in pre-symptomatic patients, so achieving the same in these patients would result in radically changing the history of this disease. Discussion: it is important to analyze and promote the development of pilots for neonatal screening in order to gain experience, so from there on to be able to think about the possibility of incorporating it into national programs. (AU)

Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Muscular Atrophy, Spinal/diagnosis , Neonatal Screening , Muscular Atrophy, Spinal/genetics , Muscular Atrophy, Spinal/therapy , Incidence , Natural History of Diseases , Early Diagnosis
Arq. neuropsiquiatr ; 79(2): 127-132, Feb. 2021. tab, graf
Article in English | LILACS | ID: biblio-1153151


ABSTRACT Background: Spinal muscular atrophy (SMA) is a neurodegenerative disease of lower motor neurons associated with frequent occurrence of spinal deformity. Nusinersen is an antisense oligonucleotide that increases SMN protein level and is administrated by frequent intrathecal lumbar injections. Thus, spinal deformities and previous spinal surgery are important challenges for drug delivery in SMA. Objective: To report imaging methods used for Nusinersen injection in SMA patients. Methods: Nusinersen injection procedures in SMA types 2 and 3 patients who had previous spinal surgery were analyzed retrospectively to describe the imaging and puncture procedures, as well as the occurrence of complications. Results: Nine SMA patients (14 to 50 years old) underwent 57 lumbar punctures for nusinersen injection. Six patients had no interlaminar space available; in five of them, a transforaminal approach was used, and another one underwent a surgery to open a posterior bone window for the injections. Transforaminal puncture was performed using CT scan in three cases and fluoroscopy in the other two, with a similar success rate. One patient in the transforaminal group had post-procedure radiculitis, and another one had vagal reaction (hypotension). In three cases, with preserved interlaminar space, injections were performed by posterior interlaminar puncture, and only one adverse event was reported (post-puncture headache). Conclusion: In SMA patients with previous spinal surgery, the use of imaging-guided intervention is necessary for administering intrathecal nusinersen. Transforaminal technique is indicated in patients for whom the interlaminar space is not available, and injections should always be guided by either CT or fluoroscopy.

RESUMO Introdução: A atrofia muscular espinal (AME) é uma desordem neurodegenerativa dos motoneurônios inferiores frequentemente associada à ocorrência de deformidade da coluna vertebral. Nusinersena é um oligonucleotídeo antisense que aumenta os níveis da proteína SMN, sendo administrado através de injeções lombares intratecais frequentes. Assim, deformidades da coluna vertebral e abordagem cirúrgica prévia são desafios importantes para a administração de medicamentos na AME. Objetivo: descrever os métodos de imagens utilizados para administração do Nusinersena nos pacientes com AME. Métodos: Os procedimentos de administração de nusinersena em pacientes com AME dos tipos 2 e 3 submetidos à cirurgia prévia da coluna foram analisados retrospectivamente para descrever os métodos de imagem e punção, e a ocorrência de complicações. Resultados: Nove pacientes com AME (14 a 50 anos) foram submetidos a 57 punções lombares para administração de nusinersena. Seis pacientes tinham enxerto ósseo ou nenhum espaço interlaminar disponível; em cinco deles foi utilizada uma abordagem transforaminal, e outra paciente foi submetida à abertura cirúrgica de janela óssea para as injeções. A punção transforaminal foi realizada usando tomografia computadorizada (TC) em três casos e fluoroscopia nos outros dois, com taxa de sucesso semelhante. Um paciente no grupo de abordagem transforaminal apresentou radiculite pós-procedimento e outro apresentou reação vagal (hipotensão). Em três casos, com espaço interlaminar preservado, foram realizadas técnica de punção interlaminar posterior e apenas um evento adverso foi relatado (cefaleia pós-punção). Conclusão: Em pacientes com AME e cirurgia prévia, o uso de intervenção guiada por imagem é necessário para a administração de nusinersena. A técnica transforaminal é indicada nos casos onde o espaço interlaminar não está disponível, devendo ser guiada por TC ou técnicas de imagem fluoroscópica.

Humans , Adolescent , Adult , Young Adult , Muscular Atrophy, Spinal/drug therapy , Neurodegenerative Diseases , Oligonucleotides , Retrospective Studies , Middle Aged
Article in English | WPRIM | ID: wpr-922388


OBJECTIVES@#To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA.@*METHODS@#A retrospective analysis was performed on the medical data and survival status of 117 children with SMA.@*RESULTS@#Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (@*CONCLUSIONS@#There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.

Child , Homozygote , Humans , Infant , Muscular Atrophy, Spinal/genetics , Retrospective Studies , Sequence Deletion , Spinal Muscular Atrophies of Childhood/genetics
Article in Chinese | WPRIM | ID: wpr-879556


OBJECTIVE@#To carry out prenatal diagnosis for families with high risk for spinal muscular atrophy (SMA) by using multiplex ligation-dependent probe amplification (MLPA).@*METHODS@#Twenty-one families were enrolled. MLPA was used to detect copy numbers of SMN1 and SMN2 genes. Maternal contamination was excluded by using a short tandem repeat method.@*RESULTS@#For 23 fetuses from the 21 families, 14 were identified as carriers, 1 as SMA patient, and 8 as normal. By linkage analysis of parental samples, three individuals were determined as silent (2+0) carriers.@*CONCLUSION@#MLPA can determine the carrier status of SMA. The identification of three silent (2+0) carriers among the 44 parental samples indicated a risk for such families, for which genetic counseling and reproduction guidance should be provided.

Female , Genetic Counseling , Heterozygote , Humans , Multiplex Polymerase Chain Reaction , Muscular Atrophy, Spinal/genetics , Pregnancy , Prenatal Diagnosis , Survival of Motor Neuron 1 Protein/genetics
Neumol. pediátr. (En línea) ; 16(1): 23-29, 2021. tab
Article in Spanish | LILACS | ID: biblio-1284182


Spinal Muscular Atrophy (SMA) is a disease of the anterior horn of the spinal cord, which causes muscle weakness that leads to a progressive decrease in vital capacity and diminished cough flows. Respiratory morbidity and mortality are a function of the degree of respiratory and bulbar-innervated muscle. The former can be quantitated by the sequential evaluation of vital capacity to determine the lifetime maximum (plateau) and its subsequent rate of decline, progressing to ventilatory failure. SMA types 1 and 2 benefit from non-invasive respiratory care in early childhood and school age, improving quality and life expectancy. This document synthesizes these recommendations with special reference to interventions guided by stages that include air stacking, assisted cough protocols, preparation for spinal arthrodesis and non-invasive ventilatory support, even in those patients with loss of respiratory autonomy, minimizing the risk tracheostomy. Failure to consider these recommendations in the regular assessment of patients reduces the offer of timely treatments.

La Atrofia Muscular Espinal (AME) es una enfermedad genética del asta anterior de la medula espinal, que cursa con debilidad muscular progresiva. La intensidad y precocidad de la debilidad muscular presenta diferentes grados de afectación de los grupos musculares respiratorios, determinando la meseta en la capacidad vital y progresión a la insuficiencia ventilatoria, como también el compromiso de los músculos inervados bulbares. Los AME tipo 1 y 2, se benefician con cuidados respiratorios no invasivos en la infancia temprana y edad escolar, mejorando la calidad y esperanza de vida. Este documento sintetiza dichas recomendaciones, con especial referencia a intervenciones guiadas por etapas, que incluyan apilamiento de aire, protocolos de tos asistida, preparación para la artrodesis de columna y soporte ventilatorio no invasivo, incluso en aquellos pacientes con pérdida de la autonomía respiratoria, minimizando el riesgo de traqueostomía. La no consideración de estas recomendaciones en la valoración regular de los pacientes resta la oferta de tratamientos oportunos.

Humans , Respiratory Therapy/methods , Muscular Atrophy, Spinal/therapy , Muscular Atrophy, Spinal/physiopathology , Vital Capacity/physiology , Noninvasive Ventilation
Rev. Méd. Clín. Condes ; 31(3/4): 358-366, mayo.-ago. 2020. ilus, tab
Article in Spanish | LILACS | ID: biblio-1223786


INTRODUCCIÓN La sobrecarga del cuidador ha sido ampliamente descrita en gerontología, pocos estudios la abordan en niños con enfermedades neuromusculares. El cuidado de pacientes con atrofia muscular espinal (AME), requiere atención continua de un tercero, pudiendo afectar la salud del cuidador y la calidad de atención y bienestar del paciente. El objetivo del estudio fue determinar el nivel de sobrecarga de los cuidadores de pacientes AME, identificando factores protectores y de riesgo asociados MÉTODOS Estudio observacional analítico transversal en padres de pacientes con AME, de un hospital privado de Santiago de Chile. Se analizaron datos demográficos clínicos y encuesta Zarit autoreportada por los padres de los pacientes con AME, realizada entre septiembre de 2017 y febrero de 2018. Se usó estadística descriptiva y regresión logística uni y multivariada para identificar factores asociados a sobrecarga RESULTADOS De los 50 padres encuestados, 14 (28%) eran de pacientes non-sitters, con sobrecarga intensa, mediana de puntaje 59 (37-76), 29 (58%) de pacientes sitters sobrecarga ligera, mediana 48 (32-79) y 7(14%) de pacientes walkers, ausencia de sobrecarga mediana 38 (23-54). Se identificaron como factores protectores de sobrecarga los años de enfermedad OR 0,9 (0,8-0,95) P=0,037 y la mayor edad de los pacientes OR 0,9(08,0,98) p=0,018. Factores de riesgo el uso de silla de ruedas OR 7,2(1,2-4,3) p=0,029 y la vía de alimentación artificial OR 9,2(1-78,8) p=0,040 CONCLUSIÓN Los padres de pacientes con AME tienen un significativo nivel de sobrecarga y existen factores que la aumentan y disminuyen. El equipo multidisciplinario debe integrar la medición periódica del nivel de sobrecarga, para intervenir oportunamente y procurar el cuidado integral de la familia.

Caregiver burden has been widely described in gerontology, few studies address it in children with neuromuscular diseases. The care of patients with spinal muscular atrophy (SMA) requires permanent care from a third person, which may affect the caregiver health, quality of care and well-being of the patient. The aim of the study was to determine the burden of SMA patient's caregivers, identifying associated protective and risk factors METHODS Descriptive cross-sectional analytical study in SMA patient's parents, from a private hospital in Santiago de Chile., demographic Clinical and self-reported Zarit survey data, parents self reported, conducted between September 2017 and February 2018, were analyzed. Descriptive statistics and uni and multivariate logistic regression were used to identify factors associated with overloading RESULTS Parents of non-sitter patients showed a median of 59 (37-76), corresponding to intense burden and those of sitters, a light burden, with a median score of 48 (32-79) Walkers patient's parents, presented a median score of 38 (23-54) that corresponds to an absence of burden. The years of illness and the higher age of the patients were identified as protective factors of overload. As risk factors of burden, the use of a wheelchair and artificial airway. Of the 50 parents surveyed, 14 (28%) were non-sitter patients, with intense overload, median 59(37-76), 29(58%) sitters patients, light overload, median 48 (32-79) and 7(14%) walker patients, absence of overload, median 38 (23-54). Protective factors of overload were years of disease OR 0,9(0,8-0,95) p=0.037 and the patients major age OR 0.9(0.8-0.98) p=0.018. Risk factors were the use of wheelchair OR 7,2(1,2-4,3) p=0.029 and artificial feeding support OR 9,2(1-78.8) p=0.040 CONCLUSION SMA patient's parents have a significant level of overload and there are factors that increase and decrease it. The multidisciplinary team must integrate the periodic measurement of the burden level, to make on time interventions and to ensure the integral care in the family.

Humans , Male , Female , Child , Adult , Muscular Atrophy, Spinal/therapy , Workload/statistics & numerical data , Caregivers , Parents , Logistic Models , Cross-Sectional Studies , Multivariate Analysis , Surveys and Questionnaires , Risk Factors , Protective Factors
Rev. méd. Chile ; 148(6): 875-880, jun. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1139384


Spinal muscular atrophy is an uncommon cause of ketoacidosis, where there is a decrease in muscle mass, an abnormal metabolism of glucose and fatty acids, and changes in neuroendocrine function. These conditions favor the accumulation of keto acids and the development of metabolic acidosis. We report a 26-year-old female, with a history of spinal muscular atrophy type III, consulting for abdominal pain and vomiting lasting one week. She was admitted to the emergency service somnolent and poorly perfused. She had a pH of 6.98, HCO3- of 3.8 mmol/L, pCO2 of 16.4 mmHg, BE of -26 mmol/L, delta ratio of 1.05, anion gap of 31 mEq/L, creatinine of 0.37 mg/dL, sodium of 147 mEq/L, potassium of 3.7 mEq/L, chloride of 112 mEq/L, lactate of 1.2 mmol/L, glucose of 108 mg/dL, albumin of 4.2 g/dL, ketonemia +++, ketonuria +, measured plasma osmolality of 322 mOsm/kg, estimated osmolality of 314 mOsm/kg, toxilab negative, salicylate levels < 3 µg/mL, acetaminophen levels < 1.2 µg/mL. Intravenous hydration and bicarbonate were started, without satisfactory response. Interpreting the clinical picture as a ketoacidosis induced by stress in a patient with spinal muscular atrophy, it was handled with glucose, amino acids, vitamins and trace elements, with a favorable response.

Humans , Female , Adult , Muscular Atrophy, Spinal/complications , Ketosis/etiology , Stress, Physiological , Bicarbonates , Glucose
Article in Chinese | WPRIM | ID: wpr-828319


OBJECTIVE@#To perform carrier screening for spinal muscular atrophy (SMA) among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron (SMN) gene and carrier frequencies.@*METHODS@#Multiplex ligation-dependent probe amplification (MLPA) was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene. Prenatal diagnosis was performed for couples whom were both found to be SMA carriers.@*RESULTS@#In total 62 SMA carriers were identified among the 3049 subjects, which yielded a carrier frequency of 1 in 49 (2.03%). No statistical difference was found in the carrier frequency between males and females (1.91% vs. 2.30%, P>0.05). Respectively, 1.3% (41/3049) and 0.69% (21/3049) of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene. The average copy number for SMN1 alleles was 1.99. Two couples were found to be both as SMA carriers, for whom the birth of an affected fetus was avoided by prenatal diagnosis.@*CONCLUSION@#No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region, which was in keeping to an autosomal recessive inheritance pattern. Determination of the carrier frequency for SMA and SMN gene variants may provide a basis for genetic counseling and prenatal diagnosis for the disease.

China , Female , Genetic Carrier Screening , Genetic Counseling , Genetic Variation , Heterozygote , Humans , Male , Muscular Atrophy, Spinal , Genetics , Pregnancy , Prenatal Diagnosis , Survival of Motor Neuron 1 Protein , Genetics , Survival of Motor Neuron 2 Protein , Genetics
Dement. neuropsychol ; 13(4): 436-443, Oct.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1055998


ABSTRACT 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.

RESUMO A atrofia muscular espinhal (SMA) é genética e progressiva, causada por grandes deleções bi-alélicas no gene SMN1, ou pela associação de uma grande deleção e uma variante nula. Objetivo: Avaliar as evidências sobre o desempenho cognitivo na atrofia muscular espinhal (AME). Métodos: Pesquisas nas bases de dados PUBMED/ Medline, Web of Knowledge e Scielo localizaram 26 estudos (1989 a 2019, descritores "atrofia muscular espinhal" e "cognição"). Nove estudos foram selecionados de acordo com os critérios de elegibilidade: (1) testaram a cognição em pessoas com AME; (2) escritos em inglês/espanhol. A avaliação do risco de viés em estudos com intervenções não-randomizadas foi utilizada para descrever o desenho experimental, viés, amostra, protocolo de avaliação e principais achados. Este estudo foi aprovado no Registro Internacional Prospectivo de Revisões Sistemáticas (PROSPERO). Resultados: Em três estudos, foi registrado que a cognição estava preservada. Em três estudos, o desempenho cognitivo estava acima da média. O comprometimento cognitivo foi encontrado em três estudos. Desempenho cognitivo pobre foi mais frequentemente relatado em estudos recentes, estudos que incluíram crianças com AME tipo I e estudos que incluíram atenção visual/auditiva e testes de função executiva. Protocolos e domínios cognitivos variaram muito, portanto não foi possível a realização de metanálise. Conclusão: A gravidade do comprometimento motor pode estar relacionada ao desempenho cognitivo: estudos que incluíram maior número/porcentagem de crianças com AME tipo I encontraram alterações no desempenho cognitivo. O estabelecimento de protocolos padrão-ouro é necessário. Novos estudos devem comparar o desempenho cognitivo de pessoas com AME tipos I a IV, ou seja, com diferenças no prognóstico e no desempenho motor.

Humans , Muscular Atrophy, Spinal , Child , Cognition , Systematic Review
Rev. Asoc. Argent. Ortop. Traumatol ; 84(4): 393-406, dic. 2019. []
Article in Spanish | LILACS, BINACIS | ID: biblio-1057064


El síndrome de la espalda inclinada o camptocormia es una causa de desequilibrio sagital del tronco no estructurada de difícil manejo médico y quirúrgico. Puede ser secundario a enfermedades del sistema nervioso central o periférico, o de origen primario muscular, como la atrofia aislada de la musculatura paravertebral espinal. El diagnóstico se basa en la evaluación clínica, los estudios por imágenes, la electromiografía y la biopsia muscular. El síndrome de la espalda inclinada, cualquiera fuera su causa, tiene un pronóstico pobre, los síntomas suelen progresar hasta afectar la bipedestación de manera irreversible. Presentamos un análisis retrospectivo de cuatro casos de síndrome de la espalda inclinada tratados en nuestro centro y una revisión de la bibliografía. Nivel de Evidencia: IV

Objectives: Bent spine syndrome (BSS) or camptocormia is a cause of unstructured sagittal imbalance of difficult medical and surgical management. The purpose of this paper is to describe the causes of BSS and how to approach its treatment. Materials and Methods: Retrospective analysis of 4 cases of BSS treated at our center and review of the literature. Results: The 4 patients were women between 60 and 82 years of age. In 3 of them, BSS was due to an isolated atrophy of the paravertebral erector spinae muscles, and in 1 of them, it was due to an inflammatory myopathy. Conclusions: The prognosis of BSS is poor in all cases, so symptoms usually progress to an irreversible difficulty to stand upright. Level of Evidence: IV

Adult , Spinal Curvatures , Muscular Atrophy, Spinal , Postural Balance
Buenos Aires; CONETEC; nov. 2019. tab.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-1025032


INTRODUCCIÓN: La Atrofia Muscular Espinal (AME) es una enfermedad neuromuscular hereditaria caracterizada por la afectación de las células del asta anterior de la médula espinal (neuronas motoras), que cursa con debilidad proximal simétrica y atrofia progresiva de los grupos musculares. Es una patología poco frecuente, altamente discapacitante y con elevada mortalidad en sus formas más graves. Tiene una incidencia aproximada de 1 cada 6.000/10.000 nacidos vivos, y constituye la principal causa de mortalidad infantil por una enfermedad genética. Actualmente, no existe un tratamiento curativo para la AME; sólo se dispone de tratamiento sintomático para retrasar la progresión de la enfermedad y sus efectos discapacitantes, y tratamiento de sostén nutricional, ventilatorio y neuromuscular para mitigar sus complicaciones. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y políticas de cobertura de nusinersen para el tratamiento de la atrofia muscular espinal y el impacto presupuestario de su potencial inclusión en la cobertura del sistema de salud. DESCRIPCIÓN DE LA TECNOLOGÍA: Nusinersen (ISIS-SMNRx o ISIS 396443, SPINRAZANR) es un oligonucleótido antisentido, diseñado para alterar el empalme de ARN mensajero del gen SMN2 y aumentar la síntesis de proteína SMN funcional compensando así la ausencia de proteína SMN protectora, causada por el defecto en el gen SMN1, y la consecuente atrofia muscular. Se encuentra aprobado por FDA (Food and Drug Administration) y EMA (European Medicines Agency) para el tratamiento de AME6. BÚSQUEDA BIBLIOGRÁFICA: Se llevó a cabo una búsqueda bibliográfica utilizando las siguientes palabras claves: nusinersen (all) OR spinraza (all). Se exploraron las siguientes bases de datos: PubMed, Cochrane Library, Biblioteca Virtual en Salud, Biblioteca Central de Medicina (RIMA), Epistemonikos, Tripdatabase, Lilacs, NICE, National Guidelines Clearinghouse, Scielo, Clinical Trials, Orphanet. También se realizó búsqueda manual. Se encontraron 5 estudios8­12, todos ellos financiados por el productor de la tecnología, de los cuales se seleccionaron 2 estudios de fase 3.8,9 Se consideraron además documentos de aprobación de FDA13, EMA14y NHS15.Se revisó información aportada por el fabricante, que solicitó un registro especial. RESULTADOS: Existe evidencia de que el nusinersen para AME tipo I disminuye la mortalidad y el requerimiento de asistencia ventilatoria mecánica, así como también mejora la función motora permitiendo el desarrollo y la adquisición de ciertas habilidades (por ejemplo sentarse, permanecer de pie o caminar) hasta por lo menos los 13 meses de observación. Por otro lado, si bien existe evidencia sobre el uso de nusinersen en pacientes con AME tipo II que muestra una mejora en la función motora a los 15 meses de tratamiento, no se encontró evidencia sobre efectos en la mortalidad, el requerimiento de asistencia ventilatoria mecánica o la calidad de vida. No se encontró evidencia sobre el uso de nusinersen en pacientes con AME de inicio luego de los 20 meses de edad (la mayoría de los pacientes con diagnóstico de AME tipo III y todos los tipo IV). La incidencia global de Efectos Adversos (EAs) resultó similar en los grupos nusinersen y control, al igual que los EAs moderados o graves. Sin embargo, una comunicación de julio de 2018 del productor de la tecnología revela que se han notificado casos de hidrocefalia comunicante no asociada a meningitis ni a hemorragia en pacientes tratados con nusinersen. Varios de estos pacientes fueron tratados mediante la colocación de una Válvula de Derivación Ventriculoperitoneal (VDVP). La eficacia o riesgos de nusinersen tras la implantación de una VDVP se desconocen. No hay información fehaciente más allá del seguimiento publicado y a largo plazo. CONCLUSIONES: Existe evidencia proveniente de un único ensayo clínico aleatorizado con seguimiento a 13 meses que muestra que nusinersen para pacientes con Atrofia Muscular Espinal tipo I disminuye la mortalidad y el requerimiento de asistencia ventilatoria mecánica, así como también mejora la función motora permitiendo el desarrollo y la adquisición de ciertas habilidades (sentarse, permanecer de pie, caminar). Existe evidencia proveniente de un único ensayo clínico sobre la utilización de nusinersen en pacientes con Atrofia Muscular Espinal tipo II, que muestra una mejora en la función motora a los 15 meses de tratamiento en el subgrupo de pacientes con edad de comienzo menor a los 20 meses, aunque no se encontró evidencia sobre efectos en la mortalidad, el requerimiento de asistencia ventilatoria mecánica o la calidad de vida. No se encontró evidencia sobre el uso de nusinersen en pacientes con Atrofia Muscular Espinal de inicio luego de los 20 meses de edad (la mayoría de los AME tipo III y todos los tipo IV).

Humans , Muscular Atrophy, Spinal/drug therapy , Oligonucleotides, Antisense/therapeutic use , Technology Assessment, Biomedical , Cost Efficiency Analysis
Cad. Ibero Am. Direito Sanit. (Impr.) ; 8(3): 48-59, jul.-set. 2019.
Article in Portuguese | LILACS, ColecionaSUS, CONASS | ID: biblio-1022852


Objetivo: discutir o processo regulatório de medicamentos para doenças raras no Brasil, com base no caso Zolgensma®, e avaliar criticamente as evidências disponíveis até o momento sobre a eficácia e a segurança do Zolgensma® no tratamento da atrofia muscular espinhal (AME). Metodologia: estudo descritivo realizado no Núcleo de Avaliação de Tecnologias em Saúde do Hospital Sírio-Libanês (NATS-HSL) em junho de 2019. Resultados: em abril de 2019, o uso do Zolgensma® para AME foi regulamentado nos Estados Unidos com base em dois estudos clínicos abertos (sem mascaramento), sem grupo comparador paralelo (e, portanto, não randomizados). Essas limitações metodológicas aumentam a incerteza nos resultados encontrados. A Agência Nacional de Vigilância Sanitária (Anvisa) aprovou estratégias para regulamentar o processo e os prazos de análise das submissões de registro de novos medicamentos para doenças raras, caso do Zolgensma®. Conclusão: faz-se necessário ampliar o debate em torno do processo de regulamentação e de incorporação de medicamentos órfãos para doenças raras no Brasil. O debate deve incluir as evidências relacionadas aos efeitos ­ benefícios e riscos ­ desses medicamentos, e maior clareza nos critérios para concessão de registro e recomendação de incorporação em sistemas de saúde. (AU).

Objective: to discuss the regulatory process of drugs for rare diseases in Brazil, based on the Zolgensma® case, and to critically evaluate the evidence so far available on the efficacy and safety of Zolgensma® for treating spinal muscular atrophy (SMA). Methods: descriptive study conducted at the Health Technology Assessment Center of the Sírio Libanês Hospital (NATS-HSL) in June 2019. Results: in April 2019, the use of Zolgensma® for SMA was regulated in the United States based on two open-lable (unmasked), non-comparative (and therefore non-randomized) studies. These methodological limitations increase the uncertainty related to study results. The National Agency of Sanitary Surveillance (Anvisa) has approved strategies to regulate the process and specific deadlines for completing the appraisal process of new medicines for rare diseases, such as Zolgensma®. Conclusion: it is necessary to broaden the debate about the process of regulation and incorporation of orphan drugs for rare diseases in Brazil. This debate should include evidence related to the effects (benefits and risks) of these drugs, and greater transparency of the criteria indispensable for granting registration and recommendation of incorporation into health systems. (AU).

Objetivo: analizar el proceso de fármacos reguladores para enfermedades raras en Brasil, con base en el caso Zolgensma, y para evaluar críticamente la evidencia disponible hasta el momento sobre la eficacia y seguridad de Zolgensma® nel tratamiento de atrofia muscular espinal (AME). Métodos: estudio descriptivo realizado en el Centro de Evaluación de Tecnología de Salud del Hospital Sírio-Libanês (NATS-HSL) en junio de 2019. Resultados: en abril de 2019, el uso de Zolgensma® para la AME se reguló en los Estados Unidos basado en dos estudios abiertos (no enmascarados), no comparativos (y por lo tanto no aleatorios). Estas limitaciones metodológicas aumentan la incertidumbre en los resultados encontrados. La Agencia Nacional de Vigilancia Sanitaria en Brasil (Anvisa) ha aprobado estrategias para regular el proceso y los plazos de análisis de las solicitudes de registro de nuevos fármacos para enfermedades raras, el caso de Zolgensma. Conclusión: es necesario ampliar el debate sobre el proceso de regulación e incorporación de medicamentos huérfanos para enfermedades raras en Brasil. Este debate debe incluir evidencia relacionada con los efectos (beneficios y riesgos) de estos medicamentos y una mayor transparencia en los criterios para otorgar el registro y la recomendación de incorporación a los sistemas de salud. (AU).

Muscular Atrophy, Spinal , Genetic Therapy , Rare Diseases , Products Registration , Drugs from the Specialized Component of Pharmaceutical Care
Rev. med. Rosario ; 85(2): 72-76, mayo-ago. 2019. ilus
Article in Spanish | LILACS | ID: biblio-1053263


Las enfermedades de la moto neurona inferior constituyen un grupo heterogéneo de entidades con pronósticos diferentes. El signo radiológico "ojos de serpiente" hace referencia a la hiperintensidad bilateral en el asta anterior de la médula espinal en los cortes axiales de las imágenes por resonancia magnética, generalmente asociada a afecciones como infartos espinales, amiotrofia espondilótica, enfermedad de Hirayama y esclerosis lateral amiotrófica. Se ha descripto recientemente un reducido número de casos de enfermedad de moto neurona inferior asociada a "ojos de serpiente" con características clínicas y pronóstico distintivos. Presentamos dos casos de enfermedad de moto neurona inferior asociada al signo "ojos de serpiente" en pacientes jóvenes. El curso clínico fue progresivo con períodos prolongados de estabilidad clínica y ausencia de compromiso de moto neurona superior durante la evolución. Los pacientes presentaron debilidad segmentaria y asimétrica de miembros superiores con predominio distal en el primer caso y proximal en el segundo. Los casos presentados se corresponden en gran parte con lo comunicado en la literatura, dando apoyo a la existencia de una nueva entidad con pronóstico relativamente benigno denominada enfermedad de moto neurona inferior esporádica con signo de ojos de serpiente en las imágenes por resonancia magnética y cuya identificación debiera obviar tratamientos innecesarios (AU)

Lower motor neuron diseases are a heterogeneous group of entities with different prognosis. The "snake eyes" sign refers to bilateral hyper intensity of the anterior horns on axial magnetic resonance imaging of the spinal cord. It has been associated with ischemia, cervical spondylosis, Hirayama disease, and amyotrophic lateral sclerosis. Recently, a small number of cases of lower motor neuron disease associated with the "snake eyes" sign have been described as having distinctive clinical manifestations and prognosis. Two young patients with "snake eyes" sign associated with lower motor neuron disease had a progressive initial course followed by a stabilization of symptoms without involvement of upper motor neuron. They presented with asymmetric segmental arm weakness with distal predominance in the first a case and proximal predominance in the second. These cases match with those reported in the literature giving support to lower motor neuron disease with "snake eyes" as a pathological entity with a relatively good prognosis. This diagnosis should avoid unnecessary treatments (AU)

Humans , Male , Female , Adult , Magnetic Resonance Spectroscopy , Motor Neuron Disease/diagnostic imaging , Spinal Cord Diseases/diagnostic imaging , Muscular Atrophy, Spinal , Diagnosis, Differential , Amyotrophic Lateral Sclerosis
Rehabil. integral (Impr.) ; 14(1): 30-39, jul. 2019. tab
Article in Spanish | LILACS | ID: biblio-1015959


Introducción: La atrofia muscular espinal (AME) es una enfermedad neuromuscular (ENM) severa caracterizada por la degeneración de las motoneuronas alfa del asta anterior de la médula espinal, generando una debilidad progresiva de la musculatura proximal. La incidencia mundial se estima en 1/6.000-10.000 nacidos vivos. Contamos con escasos datos de las características de los pacientes con AME en la población chilena. Objetivo: Determinar magnitud, características demográficas y clínico funcionales de los pacientes con AME atendidos en el Instituto Teletón Santiago (ITS). Pacientes y Método: Estudio descriptivo transversal, basado en revisión del sistema informático ITS, fichas clínicas y encuesta telefónica. Resultados: Se identificaron 62 pacientes con AME con controles en ITS, 49 (79%), fueron incluidos. 30,6%, 36,7% y 32,7% corresponden a pacientes con AME 1, 2 y 3 respectivamente. Edad promedio 10,6 ± 6,6 años; pérdida de marcha edad mediana de 6,8 años en pacientes AME 3. 67,3% requieren algún tipo de asistencia ventilatoria, 44,9% presentan trastornos de deglución, 75,5% escoliosis, 49,0% subluxación o luxación de cadera, 79,6% retracciones articulares y 65,3% dolor. En participación, el 83% de las actividades de ocio se realizan dentro del hogar, principalmente de tipo tecnológico; 77,5% realiza salidas sociales. Conclusión: Las características clínico funcionales de los pacientes con AME, evidencian un grupo que presenta un alto nivel de dependencia en todos los tipos de la enfermedad, múltiples comorbilidades y alteraciones músculo-esqueléticas secundarias y por ello requiere de un programa de rehabilitación multidisciplinaria tal como lo describe la literatura internacional.

Introduction: Spinal muscular atrophy (SMA) is a severe neuromuscular disease (NMD) characterized by the loss of alpha motor neurons of the anterior horn of the spinal cord, causing progressive weakness of proximal muscles. Global prevalence is estimated to be 1/6,000-10,000 live births. There is limited data on SMA patients in the Chilean population. Objective: To establish the scale, demographics and functional-clinical characteristics of SMA patients attending Instituto Teletón Santiago (ITS). Patients and Method: Cross-sectional, descriptive study based on the review of ITS's data information system, clinical records and telephone surveys. Results: 62 SMA patients were identified attending regular controls at ITS, 49 (79%) were included in the study. 30.6%, 36.7% and 32.7% correspond to SMA 1, 2 or 3, respectively. Average age 10.6 ± 6.6 years; loss of gait at a median age of 6.8 years in SMA 3 patients. 67.3% require some type of breathing assistance, 44.9% have swallowing problems, 75.5% scoliosis, 49% hip dislocation or subluxation, 79.6% contracture of joints and 65.3% pain. In terms of social participation, 83% of recreational activities are carried out indoors, mainly related to the use of technology; and 77.5% go out to take part in social activities. Conclusion: Functional-clinical characteristics of SMA patients show that there is a group with high levels of dependence in all types of the disease, multiple concurrent disorders and secondary musculoskeletal conditions, and therefore, in the necessity to have a multidisciplinary rehabilitation system, as described in international literature.

Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Muscular Atrophy, Spinal/physiopathology , Muscular Atrophy, Spinal/epidemiology , Quality of Life , Activities of Daily Living , Muscular Atrophy, Spinal/rehabilitation , Cross-Sectional Studies
Article in English | WPRIM | ID: wpr-765174


Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive disorder caused by a defect in the immunoglobulin mu binding protein 2 (IGHMBP2) gene, leading to motor neuron degeneration. We identified an infant with SMARD1 by targeted exome sequencing from a consanguineous Syrian family having a history of recurrent infant deaths. The patient initially presented intrauterine growth retardation, poor sucking, failure to thrive, and respiratory failure at the age of two months, and an inborn error of metabolism was suspected at first. Over a period of one month, the infant showed rapid progression of distal muscular weakness with hand and foot contractures, which were suggestive of neuromuscular disease. Using targeted exome sequencing, the mutation in IGHMBP2 was confirmed, although the first report was normal. Targeted exome sequencing enabled identification of the genetic cause of recurrent mysterious deaths in the consanguineous family. Additionally, it is suggested that a detailed phenotypic description and communication between bioinformaticians and clinicians is important to reduce false negative results in exome sequencing.

Carrier Proteins , Contracture , Exome , Failure to Thrive , Fetal Growth Retardation , Foot , Hand , Humans , Immunoglobulins , Infant Death , Infant , Metabolism , Motor Neurons , Muscle Weakness , Muscular Atrophy, Spinal , Neuromuscular Diseases , Respiratory Insufficiency