El difícil camino al diagnóstico del paciente con atrofia muscular espinal / The difficult path to diagnosis of the patient with spinal muscular atrophy

Introducción. Con las nuevas terapias, el diagnóstico temprano de la atrofia muscular espinal (AME) es esencial. El objetivo de este estudio es analizar los distintos componentes que influyen en el retraso diagnóstico. Población y métodos. Se incluyeron pacientes con un diagnóstico molecular de AME tipo I, II y III. Se estudiaron varios parámetros, como la edad al momento de la aparición del primer signo, qué signo fue y el intervalo entre este y el diagnóstico confirmado. Neurólogos especialistas realizaron entrevistas que se complementaron con la revisión de historias clínicas cuando fue necesario. Resultados. Se entrevistaron 112 pacientes. AME I n = 40, AME II n = 48, AME III n = 24. La mediana de edad en meses al momento del reporte del primer signo fue AME I: 1,5 (R 0-7), AME II: 9 (R 2-20), AME III: 18 (R 8-180). Los primeros signos fueron reconocidos por los padres en el 75 % al 85 % de las veces en todos los subtipos. La mediana del tiempo transcurrido entre el primer signo y la primera consulta médica fue menor a un mes en los tres tipos. La mediana de tiempo transcurrido en meses entre el primer signo y el diagnóstico molecular confirmado fue en AME I: 2 (R 0-11), en AME II: 10 (3-46) y en AME III: 31,5 (R 4-288). Conclusiones. Existe un significativo retraso en el diagnóstico de la AME relacionado fundamentalmente a la falta de sospecha clínica. La demora es menor en AME I y mayor en AME III. Otros factores incluyen deficiencias en el sistema de salud.

Introduction. News treatments, make early diagnosis of spinal muscular atrophy (SMA) critical. The objective of this study is to analyze the different factors that influence delay in diagnosis. Population and methods. Patients with a molecular diagnosis of types I, II, and III SMA were included. Several parameters were studied, such as age at onset of first sign, what sign it was, and the time from recognition of first sign to confirmed diagnosis. Neurologists specialized in SMA conducted interviews, supported by the review of medical records when deemed necessary. Results. A total of 112 patients were interviewed. SMA I n = 40, SMA II n = 48, SMA III n = 24. The median age in months at the time of reporting the first sign was SMA I: 1.5 (R: 0­7), SMA II: 9 (R: 2­20), SMA III: 18 (R: 8­180). In all subtypes, first signs were identified by parents from 75% to 85% of the times. The median time from first sign to first medical consultation was less than a month in all 3 types. The median time in months, from first sign to confirmed molecular diagnosis in SMA I was: 2 (R: 0­11), in SMA II: 10 (R: 3­46), in SMA III: 31.5 (R: 4­288). Conclusions. There is a significant delay in SMA diagnosis mainly related to the absence of clinical suspicion. The delay is shorter in SMA I and longer in SMA III. Other factors include deficiencies in the health care system.

Reassessment of fatty infiltration by magnetic resonance ten years after rotator cuff injury repair / Reavaliação da infiltração gordurosa por ressonância magnética após dez anos de reparo de lesão do manguito rotador

ABSTRACT Quantitative assessments of rotator cuff muscle changes after successful tendon repair are scarce. On the other hand, semiquantitative and subjective assessments are more abundant, but their findings are controversial. One hypothesis about this divergence is that there is an immediate decrease in the proportion of fatty infiltration after surgical repair. Objective: Reassess fatty infiltration and muscle trophism of the rotator cuff after ten years of repair. Methods: Prospective comparison study. A total of 10 patients diagnosed with rotator cuff injury underwent repair of the lesion, and MRI of the affected shoulder was performed in the preoperative, immediate postoperative, and late postoperative periods (ten years). A comparative study was performed at every moment. Results: At 5% significance level, the mean of the immediate postoperative period was higher for the variable trophism and true muscle percentage. Fatty infiltration showed no difference in the three periods observed. Conclusion: Fatty infiltration does not change in the three periods evaluated and muscle trophism is greater in the immediate postoperative period. After ten years of rotator cuff repair, muscle trophism and fatty infiltration remain with statistically significantly equal results when compared to the preoperative period. Level of Evidence II, Prospective Comparison Study.

RESUMO Avaliações quantitativas das mudanças musculares do manguito rotador após reparos bem-sucedidos são escassas. Em contrapartida, avaliações semiquantitativas e subjetivas são mais abundantes, porém com achados controversos. Uma hipótese sobre essa discrepância é que a diminuição imediata na proporção de gordura que ocorre logo após o reparo. Objetivo: Reavaliar a infiltração gordurosa e o trofismo muscular do manguito rotador passados dez anos do reparo. Métodos: Estudo prospectivo comparativo realizado com dez pacientes diagnosticados com lesão do manguito rotador que foram submetidos a reparo da lesão e exames de ressonância magnética do ombro acometido no pré-operatório, no pós-operatório imediato e no pós-operatório tardio (dez anos), a fim de comparar as mudanças musculares em cada momento. Resultados: Ao nível de significância de 5%, a média do pós-operatório imediato foi superior para as variáveis trofismo e porcentagem muscular verdadeira. A infiltração gordurosa não apresentou diferença nos três períodos observados. Conclusão: A infiltração gordurosa não se altera nos três períodos avaliados, e o trofismo muscular é maior no pós-operatório imediato. Após dez anos do reparo do manguito rotador, o trofismo muscular e a infiltração gordurosa se mantêm com resultados estatísticos significativamente iguais quando comparados com o pré-operatório. Nível de Evidência II, Estudo Prospectivo Comparativo.

Acompanhamento das funções respiratória e motora de crianças com atrofia muscular espinhal e distrofia muscular de Duchenne: um estudo longitudinal / Monitoring of respiratory and motor functions on children with spinal muscular atrophy and Duchenne muscular dystrophy: a longitudinal study

Objetivo: Realizar o acompanhamento de crianças e adolescentes com Atrofia Muscular Espinhal (AME) e Distrofia Muscular de Duchenne (DMD) em um centro de referência, por meio de avaliações de parâmetros respiratórios e motores. Métodos: Conduziu-se 3 avaliações em um período de 24 meses, em pacientes até 15 anos, com DMD e AME. Avaliações respiratórias incluíram: parâmetros cardiorrespiratórios, força muscular respiratória, pico de fluxo de tosse e espirometria. Analisou-se a função motora por meio de escalas especificas: 1) Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) para crianças até 2 anos; 2) Medida da Função Motora (MFM-32) acima de 6 anos; 3) versão reduzida (MFM-20) para 2 a 6 anos. A análise estatística incluiu o teste de Shapiro-Wilk e utilizou-se ANOVA com Post Hoc de Bonferroni ou Friedman, e aplicou-se os coeficientes de Spearman ou Pearson. Resultados: Participaram 16 pacientes com mediana de idade de 6,5 anos, 12 com AME e 4 DMD. Houve diferença entre dados antropométricos, a frequência de crianças que não realizava fisioterapia reduziu (12,5%X6,3%) e houve aumento na adesão para técnica de empilhamento de ar (37,5%X43,8%). Uso de ventilação não invasiva se manteve igual, assim como parâmetros respiratórios e escalas motoras. Verificou-se forte correlação entre valor predito da capacidade vital forçada e escores MFM-20 e MFM-32. Conclusão: O acompanhamento ambulatorial de crianças com AME e DMD evidenciou relativa manutenção em parâmetros respiratórios e de função motora, o que pode ser atribuído a melhora na adesão de rotinas terapêuticas e aos cuidados em um centro de referência.

Objective: The aim of this study was to monitor children and adolescents with Spinal Muscular Atrophy(SMA) and Duchenne Muscular Dystrophy (DMD) at a referral center, through assessments of respiratory and motor parameters. Methods: 3 evaluations were conducted over a period of 24 months, in patients up to 15 years old, with DMD and SMA. Respiratory assessments included: cardiorespiratory parameters, respiratory muscle strength, peak cough flow and spirometry. Motor function was analyzed using specific scales: 1) Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) for children up to 2 years old; 2) Measurement of Motor Function (MFM-32) over 6 years; 3) reduced version (MFM-20) for 2 to 6 years. The statistical analysis included the Shapiro-Wilk test and ANOVA with Bonferroni or Friedman's Post Hoc was used, and the Spearman or Pearson coefficients were applied. Results: 16 patients with a median age of 6.5 years, 12 with SMA and 4 DMD participated. There was a difference between anthropometric data, the frequency of children who did not undergo physical therapy decreased (12.5%X6.3%) and there was an increase in adherence to the air stacking technique (37.5%X43.8%). Use of non-invasive ventilation remained the same, as did respiratory parameters and motor scales. There was a strong correlation between the predicted value of forced vital capacity and scores MFM-20 and MFM-32. Conclusion: Outpatient follow-up of children with SMA and DMD showed a relative maintenance of respiratory and motor function parameters, which can be attributed to the improvement in adherence to therapeutic routines and care in a reference center.

Diagnóstico tardío de atrofia muscular espinal en paciente con síndrome de Down / Late diagnosis of spinal muscular atrophy in a patient with Down syndrome

El síndrome de Down (SD) es la anomalía cromosómica más frecuente entre los recién nacidos vivos. La atrofia muscular espinal (AME), por su parte, es una enfermedad neuromuscular caracterizada por la degeneración progresiva de las motoneuronas del asta anterior de la médula espinal que produce atrofia muscular, debilidad y parálisis. Presentamos el caso de una niña de 6 años con síndrome de Down derivada a nuestro centro para estudio por cuadro de debilidad muscular generalizada de evolución crónica con falta de adquisición de la marcha. Realizamos una revisión bibliográfica enfocándonos en el compromiso neurológico esperable en el síndrome de Down, la evolución de los hitos del desarrollo motor grueso estipulado para este grupo de pacientes y en los hallazgos que deben sugerir la presencia de una enfermedad neuromuscular.

A case of a 6-year-old girl with Down's syndrome is presented. She was referred to our center due to a history of generalized muscle weakness of chronic evolution, associated to her inability to walk. Her mother claimed that the girl's muscle weakness always called her attention as well as the difficulties to the development of motor skills shown by her daughter compared to other children, whether they were healthy or with Down's syndrome. There was information in her medical record and physical exam that strongly suggested the possibility of suffering a neuromuscular disorder. We asked for a molecular study that confirmed the spinal muscular atrophy diagnosis. We carried out a bibliographical revision focusing on the expected neurological impairment in Down's syndrome, the retardation of the gross motor skills development determined for this kind of patients and on the findings that must suggest a neuromuscular disorder.

Associação entre área de secção transversa do reto femoral e excursão diafragmática com o desmame de pacientes com traqueostomia na unidade de terapia intensiva / Association between rectus femoris cross-sectional area and diaphragmatic excursion with weaning of tracheostomized patients in the intensive care unit

RESUMO Objetivo: Verificar a relação entre área de secção transversa do reto femoral e excursão diafragmática com sucesso no desmame da ventilação mecânica em pacientes críticos crônicos com traqueostomia. Métodos: Este foi um estudo de coorte observacional prospectivo. Incluímos pacientes críticos crônicos (aqueles submetidos à colocação de traqueostomia após 10 dias de ventilação mecânica). A área de secção transversa do reto femoral e a excursão diafragmática foram obtidas por ultrassonografia realizada dentro das primeiras 48 horas após a traqueostomia. Medimos a área de secção transversa do reto femoral e a excursão diafragmática para avaliar sua associação com o desmame da ventilação mecânica, incluindo sua capacidade de prever o sucesso no desmame e a sobrevida durante toda a internação na unidade de terapia intensiva. Resultados: Foram incluídos 81 pacientes. Quarenta e cinco pacientes (55%) foram desmamados da ventilação mecânica. A mortalidade foi de 42% e 61,7% na unidade de terapia intensiva e hospitalar, respectivamente. O grupo que falhou em relação ao grupo que obteve sucesso no desmame apresentou menor área transversa do reto femoral (1,4 [0,8] versus 1,84 [0,76]cm2, p = 0,014) e menor excursão diafragmática (1,29 ± 0,62 versus 1,62 ± 0,51cm, p = 0,019). Quando a área de secção transversa do reto femoral ≥ 1,80cm2 e a excursão diafragmática ≥ 1,25cm era uma condição combinada, apresentava forte associação com sucesso no desmame (RC ajustada de 20,81; IC95% 2,38 - 182,28; p = 0,006), mas não com sobrevida na unidade de terapia intensiva (RC ajustada de 0,19; IC95% 0,03 - 1,08; p = 0,061). Conclusão: O sucesso no desmame da ventilação mecânica em pacientes críticos crônicos foi associado a medidas maiores de área de secção transversa do reto femoral e da excursão diafragmática.

ABSTRACT Objective: To verify the relationship between the rectus femoris cross-sectional area and diaphragmatic excursion with successful weaning from mechanical ventilation in chronic critically tracheostomized patients. Methods: This was a prospective observational cohort study. We included chronic critically ill patients (those who underwent tracheostomy placement after 10 days under mechanical ventilation). The rectus femoris cross-sectional area and diaphragmatic excursion were obtained by ultrasonography performed within the first 48 hours after tracheostomy. We measured rectus femoris cross-sectional area and diaphragmatic excursion to assess their association with weaning from mechanical ventilation, including their potential to predict successful weaning and survival throughout the intensive care unit stay. Results: Eighty-one patients were included. Forty-five patients (55%) were weaned from mechanical ventilation. The mortality rates were 42% and 61.7% in the intensive care unit and hospital, respectively. The fail group in relation to the success group at weaning presented a lower rectus femoris cross-sectional area (1.4 [0.8] versus 1.84 [0.76]cm2, p = 0.014) and lower diaphragmatic excursion (1.29 ± 0.62 versus 1.62 ± 0.51cm, p = 0.019). When rectus femoris cross-sectional area ≥ 1.80cm2 and diaphragmatic excursion ≥ 1.25cm was a combined condition, it had a strong association with successful weaning (adjusted OR = 20.81, 95%CI 2.38 - 182.28; p = 0.006) but not with intensive care unit survival (adjusted OR = 0.19, 95%CI 0.03 - 1.08; p = 0.061). Conclusion: Successful weaning from mechanical ventilation in chronic critically ill patients was associated with higher measurements of rectus femoris cross-sectional area and diaphragmatic excursion.

Hirayama Disease: Case Report / Doença de Hirayama: Relato de caso

Abstract A 26-year-old previously healthy patient who, at the age of 18 years, began progressive loss of distal strength, rest tremor, and muscle atrophy in the left upper limb. Upon examination, the patient presented moderate distal atrophy, degree 4 in muscular strength, and minipolymioclonus. Electromyoneurography revealed (EMNG) chronic preganglionic bilateral involvement of bilateral C7/C8/T1, worse on the left, with signs of active C8/T1 denervation. A cervical spine magnetic resonance imaging (MRI) scan showed spondylodiscal degenerative changes with central protrusions in C4-C5, C6-C7, and right central in C5-C6, which touched the dural sac. The anteroposterior diameter of the medulla in neutral position, in the C5-C6 plane, was of 5.1 mm. There was a reduction of the spinal cord caliber to 4.0 mm after the dynamic maneuver of forced flexion of the spine, as well as signal increase in the anterior horns. The clinical findings and those of the complementary tests were compatible with Hirayama disease (HD), a rare benign motor neuron disease that affects cervical spinal segments and is most prevalent in men, with onset in the early 20s. Unilateral and slowly progressive weakness is typical, but self-limited. Sensory disturbances, and autonomic and upper motor neuron signals are rare. Management is usually conservative, with the use of a soft cervical collar. Although rare, HD should be considered in young patients with focal asymmetric atrophy in the upper limbs. The early diagnosis of HD depends on the degree of suspicion, as well as on the cooperation and communication among the various specialties involved in the investigation.

Resumo Paciente de 26 anos, previamente hígido, que, aos 18 anos, iniciou perda progressiva de força distal, tremor de repouso, e atrofia muscular no membro superior esquerdo. Ao exame, apresentou atrofia moderada, distal, força muscular de grau 4, e minipolimioclonus. A eletroneuromiografia (ENMG) revelou comprometimento pré-ganglionar crônico de C7/C8/T1 bilateral pior à esquerda, com sinais de desnervação ativa em C8/T1. A ressonância magnética (RM) de coluna cervical mostrou alterações degenerativas espondilodiscais com protrusões centrais em C4-C5, C6-C7, e central direita em C5-C6, que tocavam o saco dural. O diâmetro anteroposterior da medula na posição neutra, no plano de C5-C6, era de 5,1 mm. Houve redução do calibre da medula para 4,0 mm após a manobra dinâmica de flexão forçada da coluna, e aumento de sinal nos cornos anteriores. Os achados clínicos e os dos exames complementares eram compatíveis com doença de Hirayama (DH), uma doença benigna rara dos neurônios motores, que afeta os segmentos espinhais cervicais e é mais prevalente em homens e de início próximo aos 20 anos. É típica a fraqueza unilateral e lentamente progressiva, porém autolimitada. Perturbações sensoriais, sinais autonômicos e do neurônio motor superior são raras. O manejo geralmente é conservador, com uso de colar cervical macio. Apesar de rara, a DH deve ser considerada em pacientes jovens que apresentam atrofias assimétricas focais de membros superiores. O diagnóstico precoce de DH depende do grau de suspeição, e da cooperação e comunicação entre as diversas especialidades envolvidas na investigação.

Physical therapy protocols to attenuate skeletal muscle atrophy in critically ill patients: narrative review / Protocolos de terapia física para atenuar la atrofia del músculo esquelético en pacientes críticos: revisión narrativa

SUMMARY: To describe the physical therapy protocols used in critically ill patients to attenuate skeletal muscle atrophy. We conducted a search in PubMed and Embase from inception to November 2020. Observational or experimental studies published in English or Spanish that evaluated the effect of physical therapy protocols on the attenuation of skeletal muscle atrophy in critically ill patients through muscle strength or mass measurement were considered eligible. Studies were only included if they reported a detailed description of the dosing of the interventions. Seventeen studies met the eligibility criteria. We included randomised clinical trials (n = 16) and observational studies (n = 1). The total population of the included studies was 872 critically ill patients. The studies aimed to evaluate the reliability, safety or effectiveness of neuromuscular electrical stimulation (n = 10) protocols, early mobilisation (n = 3), ergometer training (n = 2), transfers in tilt table (n = 1), and blood flow restriction (n = 1). Physical therapy protocols are part of the critically ill patient's integral management. Strategies such as passive mobilisation, in-bed and out-of-bed transfers, gait training, ergometer training, and neuromuscular electrical stimulation substantially impact critically ill patients' prognoses and quality of life after hospital discharge.

RESUMEN: Describir los protocolos de terapia física usados en pacientes críticos para atenuar la atrofia muscular esquelética. Realizamos una búsqueda en PubMed y Embase desde el inicio hasta noviembre de 2020. Se consideraron los estudios observacionales o experimentales publicados en inglés o español que evaluaron el efecto de los protocolos de terapia física en la atenuación de la atrofia del músculo esquelético en pacientes críticos a través de la medición de la fuerza o la masa muscular. Los estudios solo se incluyeron si informaron una descripción detallada de la dosificación de las intervenciones. Diecisiete estudios cumplieron los criterios de elegibilidad. Se incluyeron ensayos clínicos aleatorizados (n = 16) y estudios observacionales (n = 1). La población total de los estudios incluidos fue de 872 pacientes en estado crítico. Los estudios tuvieron como objetivo evaluar la confiabilidad, seguridad o efectividad de los protocolos de estimulación eléctrica neuromuscular (n = 10), movilización temprana (n = 3), entrenamiento con ergómetro (n = 2), transferencias en mesa basculante (n = 1) y restricción del flujo sanguíneo (n = 1). Los protocolos de terapia física forman parte del manejo integral del paciente crítico. Es- trategias como la movilización pasiva, los traslados dentro y fuera de la cama, el entrenamiento de la marcha, el entrenamiento con ergómetro y la estimulación eléctrica neuromuscular tienen un impacto sustancial en el pronóstico y la calidad de vida de los pacientes críticos después del alta hospitalaria.

Gene therapy in neuromuscular disorders / Terapia gênica nas doenças neuromusculares

Abstract Monogenic neuromuscular disorders are potentially treatable through gene therapy. Using viral vectors, a therapeutic transgene aims to restore normal levels of a protein not produced by the defective gene, or to silence a gene whose expression leads to toxic effects. Spinal Muscular Atrophy (SMA) is a good example of a monogenic disease that currently has an AAV9-based vector gene therapy as a therapeutic option. In this review, we intend to discuss the viral vectors and their mechanisms of action, in addition to reviewing the clinical trials that supported the approval of gene therapy (AVXS-101) for SMA as well as neuromuscular diseases that are potentially treatable with gene replacement therapy.

Resumo Doenças neuromusculares monogênicas são potencialmente tratáveis através de terapia gênica. Utilizando-se de vetores virais, um transgene terapêutico objetiva repor os níveis normais de uma proteina não produzida pelo gene defeituoso ou silenciar um gene cuja expressão leva a efeitos tóxicos. A Atrofia Muscular Espinhal (AME) é um bom exemplo de doença monogenica que atualmente tem uma terapia gênica com vetor viral AAV9 como opção terapêutica. Nesta revisão, pretendemos discutir os vetores virais e macanismos de ação utilizados, além de revisar os ensaios clínicos que embasaram a aprovação da terapia gênica (AVXS-101) para AME, assim como doenças neuromusculares potencialmente tratáveis com terapia de reposição gênica.

Caracterización clínica y funcional de pacientes con atrofia muscular espinal en el centro-occidente colombiano / Clinical-functional characterization of patients with spinal muscular atrophy in Central-Western Colombia

Introducción. La atrofia muscular espinal es una enfermedad neurodegenerativa huérfana de origen genético que afecta las neuronas motoras del asta anterior de la médula espinal, y produce atrofia y debilidad muscular. En Colombia, son pocos los estudios publicados sobre la enfermedad y no hay ninguno con análisis funcional. Objetivo. Caracterizar clínica y funcionalmente una serie de casos de atrofia muscular espinal del centro-occidente colombiano. Materiales y métodos. Se hizo un estudio descriptivo transversal, entre el 2007 y el 2020, de pacientes con diagnóstico clínico y molecular de atrofia muscular espinal que consultaron en el centro de atención. La evaluación funcional se realizó con las escalas Hammersmith y Chop Intend. En la sistematización de los datos, se empleó el programa Epi-Info, versión 7.0. Resultados. Se analizaron 14 pacientes: 8 mujeres y 6 hombres. La atrofia muscular espinal más prevalente fue la de tipo II, la cual se presentó en 10 casos. Se encontró variabilidad fenotípica en términos de funcionalidad en algunos pacientes con atrofia muscular espinal de tipo II, cinco de los cuales lograron alcanzar la marcha. La estimación de la supervivencia fue de 28,6 años. Conclusiones. Los hallazgos en el grupo de pacientes analizados evidenciaron que los puntajes de la escala de Hammersmith revisada y expandida, concordaron con la gravedad de la enfermedad.

Introduction: Spinal muscular atrophy is a rare genetic neurodegenerative disorder affecting the motor neurons of the anterior horn of the spinal cord, which results in muscle atrophy and weakness. In Colombia, few studies have been published on the pathology and none with functional analysis. Objective: To characterize clinically and functionally some cases of spinal muscular atrophy patients from Central-Western Colombia. Materials and methods: We conducted a cross-sectional descriptive study between 2007 and 2020 with patients clinically and molecularly diagnosed with spinal muscular atrophy who attended a care center. For the functional assessment we used the Hammersmith and Chop-Intend scales and the data were systematized with the Epi-Info, version 7.0 software. Results: We analyzed 14 patients (42.8 % men). The most prevalent spinal muscular atrophy was type II with 71.4 %. We found phenotypic variability in terms of functionality in some patients with type II spinal muscular atrophy, 37.5 % of whom reached gait. Survival was estimated at 28.6 years. Conclusions: The findings in the group of patients analyzed revealed that the scores of the revised and expanded Hammersmith scales correlated with the severity of SMA.

Case report of gene therapy and nursing care for children with type Ⅱ spinal muscular atrophy / 中国实用护理杂志

Objective:To summarize the nursing care of 3 cases of spinal muscular atrophy (SMA) with intrathecal injection of Nusinersen sodium injections.Methods:From March 2020 to March 2021, 3 children patients with SMA received Nusinersen sodium injections. Multidisciplinary care was applied, the key points of nursing care include: multidisciplinary individualized assessments, multidisciplinary care based on case management model, preoperative and intraoperative care cooperation, and postoperative observations and management of complications.Results:All the three children successfully completed intrathecal injection and were discharged on the second day after surgery. No serious complications occurred.Conclusions:Collaborative multidisciplinary care shows positive significance for children with intrathecal Nusinersen sodium injections.

Lung function of patients with spinal muscular atrophy / 中华实用儿科临床杂志

Objective:To analyze the characteristics of lung function in patients with spinal muscular atrophy (SMA) to provide evidence for multidisciplinary management of SMA.Methods:A total of 30 patients with SMA treated in the SMA multidisciplinary clinic of the Children′s Hospital, Zhejiang University School of Medicine from July 2019 to March 2021 were enrolled, including 1 child with type I, 18 patients with type Ⅱ and 11 children with type Ⅲ.There were 17 males and 13 females; the age ranged from 4 years to 21 years and 10 months old.A retrospective study was conducted to analyze the clinical features, spinal imaging findings and lung functions of patients with different clinical types of SMA and explore the factors influencing the lung functions of patients with SMA.Pulmonary function was measured by forced expiratory flow-volume curve.Forced vital capacity (FVC), forced expiratory volume in one second (FEV 1), FEV 1/FVC and peak expiratory flow (PEF) were measured.The results were expressed as the percentage of the measured value to predicted value.The Cobb angle was measured to evaluate scoliosis. Pearson correlation analysis and multiple linear regression analysis were used to evaluate the relationship between lung function and age and Cobb angle in patients with type Ⅱ SMA. Pearson correlation analysis and univariate linear regression analysis were used to evaluate the relationship between Cobb angle and age in patients with type Ⅱ SMA. Results:Pulmonary function in 1 type I patient showed decreased FVC and FEV 1; Among 18 patients with type Ⅱ, 14 cases had abnormal lung function (77.8%): FVC decreased in 12 patients (66.7%), FEV 1 decreased in 10 patients (55.6%), PEF decreased in 12 patients (66.7%). Among 11 patients with type Ⅲ, one had decreased FVC (9.1%). FVC, FEV 1 and PEF of patients with type Ⅱ were significantly lower than those of patients with type Ⅲ [(62.4±31.8)% vs.(90.8±11.0)%, (66.3±33.3)% vs.(97.8±9.9)%, (65.3±30.1)% vs.(98.6±21.1)%, all P<0.01]. Pearson correlation analysis showed that FVC of patients with type Ⅱ SMA was correlated with age and Cobb angle ( r=-0.864, -0.865, all P<0.001), FEV 1 was correlated with age and Cobb angle ( r=-0.878, -0.863, all P<0.001), PEF was correlated with age and Cobb angle ( r=-0.831, -0.783, all P<0.001), and Cobb angle was related to age ( r=0.922, P<0.001). Multiple linear regression analysis indicated that FVC of patients with type Ⅱ SMA was linearly correlated with Cobb angle ( R2=0.748, P<0.001), FEV 1 was linearly correlated with age ( R2=0.770, P<0.001), PEF was linearly related to age ( R2=0.690, P<0.001). Univariate linear regression analysis revealed that Cobb angle of patients with type Ⅱ SMA was linearly related to age ( R2=0.851, P<0.001). Conclusions:FVC, FEV 1 and PEF may decrease in patients with SMA.The degree of lung function damage is different in different types of SMA patients.With the increase of age, Cobb angle increases and FVC, FEV 1 and PEF decrease in patients with type Ⅱ SMA.Understanding the factors influencing the pulmonary function damage in patients with SMA is conductive to carrying out individual multidisciplinary management.

Experimental study of alendronate sodium in the treatment of denervated skeletal muscle atrophy / 中华骨科杂志

Objective:To observe the effects of alendronate (ALN) on the expression of autophagy signaling pathway related proteins LC3, Beclin-1 and P62 in the muscle tissue of mice with denervated skeletal muscle atrophy, and to explore the potential molecular biological mechanism of ALN in the treatment of skeletal muscle atrophy.Methods:Thirty males C57BL/6 mice were divided into three groups with 10 mices in each group by random number method, including blank control group: sciatic nerve exposed without resection, model group: sciatic nerve exposed and resection, ALN group: sciatic nerve resection +ALN intervention. At the intervention stage, mices were given 1 mg/kg ALN by intragastric administration. The weight of gastrocnemius muscle was weighed by wet weight method. Atpase staining was used to distinguish muscle fiber types. HE staining was used to observe the arrangement and cross-sectional area of gastrocnemius muscle fibers in each group, and further quantitative analysis was performed by Image J 1.48 software. Western blotting and immunohistochemical staining were performed to detect the expressions of MHC and MuRF1 as well as LC3, Beclin-1 and P62 in gastrocnemius tissues of each group.Results:The weight of gastrocnemius muscle in the model group 137±7.80 mg was significantly lower than that in the blank control group 203±10.34 mg, which proved that the denervation muscle atrophy mouse model was successfully established. After intervention, the gastrocnemius muscle weight of ALN group 177±11.65 mg was significantly higher than that of model group, and the muscle mass was significantly improved. HE staining showed that muscle fibers in the model group were loosely arranged and the cross-sectional area was significantly smaller than that in the blank control group, and there were more blue stains among muscle fibers. Atpase staining showed that the distribution of type II muscle fibers in the model group was increased compared with that in the blank control group, and the distribution of type II muscle fibers in the ALN group was decreased compared with that in the model group, but higher than that in the blank control group. The results showed that the most widely distributed muscle fiber cross-sectional area was 600-800μm 2 in the blank control group, 200-400 μm 2 in the model group, and 400-600 μm 2 in the ALN group. The results of quantitative calculation of muscle fiber cross-sectional area by Image J 1.48 showed that the mean value of muscle fiber cross-sectional area in the model group was (352±18) μm 2, which was significantly reduced compared with the blank control group 794±20 μm 2. After ALN treatment, muscle fiber cross-sectional area recovered somewhat. The mean muscle fiber cross-sectional area of ALN group was 578±23 μm 2, which increased muscle fiber cross-sectional area by 29%. Western blotting results showed that the expressions of MHC, LC3 and Beclin-1 in model group were significantly lower than those in blank control group ( P<0.05), while MuRF1 and P62 proteins were significantly higher than those in blank control group ( P<0.05). The MHC, LC3 and Beclin-1 proteins in ALN group were significantly higher than those in model group (0.12±0.01 vs. 0.10±0.003, 0.15±0.02 vs. 0.10±0.02, 0.13±0.03 vs. 0.09±0.04). MuRF1 and P62 proteins in ALN group were significantly lower than those in model group (0.10±0.004 vs. 0.15±0.01, 0.16±0.03 vs. 0.20±0.03). MHC immunohistochemical staining showed that the expression of MHC in gastrocnemius of mice in model group was significantly lower than that in blank control group, and the expression of MHC in gastrocnemius of mice in ALN group was higher than that in model group ( P<0.05). Conclusion:ALN has a therapeutic effect on skeletal muscle atrophy, and its mechanism may be realized by moderately activating the LC3/Beclin-1 autophagy signaling pathway.

Genetic analysis of a case of infant spinal muscular atrophy type 1c / 中国综合临床

Objective:To summarize the genetic characteristics of a case of spinal muscular atrophy type 1c.Methods:The case data of a child with spinal muscular atrophy type 1c was retrospectively analyzed, and the genetic analysis and literature review were carried out.Results:The patient, male, started at the age of 2 months, and showed gross motor development backwardness and low muscular tension. Multiplex connection probe amplification technique showed that the child had homozygous deletion mutation in exon 7-8 of SMN1 gene, and there was duplicate mutation in exon 7-8 of SMN2 gene. The number of copies of exon 7/8 was 3/3. His father was a heterozygous deletion carrier of SMN1 gene, and there was homozygous mutation in exon 8 of SMN2 gene. The number of copies of exon 7/8 was 2/3. His mother did not find abnormal exons of SMN1 gene, and the number of copies of exon 7/8 of SMN2 gene was 1/1.Conclusion:Spinal muscular atrophy lacks specific manifestations in the early stage, and the diagnosis mainly depends on genetic testing. Clinicians need to be vigilant, strengthen the early understanding of the disease, and improve the prognosis.

Frontal and sagittal patterns of neuromuscular spinal deformities based on nosological profile / Padrões frontais e sagitais das deformidades neuromusculares da coluna vertebral, segundo o perfil nosológico / Patrones frontal y sagital de las deformidades neuromusculares de la columna vertebral según el perfil nosológico

ABSTRACT Objective: Reveal frontal and sagittal patterns of spinal deformity depending on neuromuscular nosology for surgery and outcome planning. The characteristics of spinal deformity vary according to the pathology. In cerebral palsy, muscular dystrophies, and spinal muscular atrophy, specific features of deformities are poorly written, especially in the sagittal profile. Methods: The evaluation criteria were age, gender of the patients, the volume of blood loss, duration of hospitalization, measurement of the deformity curve, thoracic and lumbar kyphosis (Cobb angle), pelvic obliquity concerning the horizontal line, the percentage of curve correction. Cobb angle was measured preoperatively before hospital discharge (up to 21 days postoperatively) and one year after surgery. Results: The cohort of 71 patients with spinal deformities due to neuromuscular diseases included four groups: muscular dystrophy (MD), spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD), and cerebral palsy (CP). The most characteristic deformity in the frontal plane was C-shaped thoracolumbar scoliosis with rotation of the pelvis; rotation of the vertebrae increased according to the magnitude of scoliosis. Lumbar hyperlordosis was common in patients with PD, whereas decreased thoracic kyphosis or even thoracic lordosis occurs more frequently in patients with DMD. Moderate correction of scoliosis was observed in all groups. There was no significant improvement in functional status, according to the FIM. Conclusion: The findings showed that rigid hyperlordosis is the main problem of spinal deformities in neuromuscular patients. Scoliosis and pelvic obliquity can be well corrected in NMS by pedicle screw construction with standard maneuvers and pelvic screw fixation. Level of Evidence IV; Lesser quality prospective study.

RESUMO Objetivo: Revelar padrões frontais e sagitais de deformidade espinhal depende da nosologia neuromuscular para cirurgia e planejamento de resultados. As características da deformidade espinhal variam de acordo com a patologia. Na paralisia cerebral, nas distrofias musculares e na atrofia muscular espinhal, as características específicas das deformidades estão mal escritas, especialmente no perfil sagital. Métodos: Os critérios de avaliação foram: idade, sexo dos pacientes, volume de perda de sangue, duração da internação hospitalar, medida da curva de deformidade, cifose torácica e lombar (ângulo Cobb), obliquidade pélvica em relação à linha horizontal, a porcentagem da correção da curva. O ângulo Cobb foi medido no pré-operatório antes da alta hospitalar (até 21 dias de pós-operatório) e um ano após a cirurgia. Resultados: A coorte de 71 pacientes com deformidades espinhais devido a doenças neuromusculares incluiu quatro grupos: distrofia muscular (DM), atrofia muscular espinhal (AME), distrofia muscular de Duchenne (DMD) e paralisia cerebral (PC). A deformidade mais característica no plano frontal era a escoliose toracolombar em forma de C com a rotação da pélvis; a rotação das vértebras aumentou de acordo com a magnitude da escoliose. A hiperlordose lombar era comum em pacientes com DP, enquanto que a diminuição da cifose torácica ou mesmo a lordose torácica ocorre com maior frequência em pacientes com DMD. A correção moderada da escoliose foi observada em todos os grupos. Não houve melhora significativa no status funcional, de acordo com a FIM. Conclusão: Os achados mostraram que a hiperlordose rígida é o principal problema das deformidades espinhais em pacientes neuromusculares. A escoliose e a obliquidade pélvica podem ser bem corrigidas no NMS através da construção de parafusos pediculares com manobras padrão e fixação de parafusos pélvicos. Nível de Evidência IV; Estudo prospectivo de menor qualidade.

RESUMEN Objetivo: La revelación de los patrones frontal y sagital de la deformidad de la columna vertebral depende de la nosología neuromuscular para la planificación de la cirugía y los resultados. Las características de la deformación de la columna vertebral varían según la patología. En la parálisis cerebral, las distrofias musculares y la atrofia muscular espinal, las características específicas de las deformidades están mal escritas, especialmente en el perfil sagital. Métodos: Los criterios de evaluación fueron la edad, el sexo de los pacientes, el volumen de pérdida de sangre, la duración de la hospitalización, la medición de la curva de deformación, la cifosis torácica y lumbar (ángulo de Cobb), la oblicuidad pélvica en relación con la línea horizontal, el porcentaje de corrección de la curva. El ángulo de Cobb se midió antes del alta hospitalaria (hasta 21 días después de la operación) y un año después de la misma. Resultados: La cohorte de 71 pacientes con deformidades espinales debidas a enfermedades neuromusculares incluía cuatro grupos: distrofia muscular (DM), atrofia muscular espinal (AME), distrofia muscular de Duchenne (DMD) y parálisis cerebral (PC). La deformación más característica en el plano frontal era la escoliosis toracolumbar en forma de C con rotación de la pelvis; la rotación de las vértebras aumentaba según la magnitud de la escoliosis. La hiperlordosis lumbar fue común en los pacientes con EP, mientras que la disminución de la cifosis torácica o incluso la lordosis torácica ocurre más frecuentemente en los pacientes con DMD. Se observó una corrección moderada de la escoliosis en todos los grupos. No hubo una mejora significativa del estado funcional según el FIM. Conclusión: Los resultados mostraron que la hiperlordosis rígida es el principal problema de las deformidades de la columna vertebral en los pacientes neuromusculares. La escoliosis y la oblicuidad pélvica pueden corregirse bien en el SMN mediante la construcción de tornillos pediculares con maniobras estándar y la fijación de tornillos pélvicos. Nivel de evidencia IV; Estudio prospectivo de menor calidad.

Advances in drugs on targeting SMN2 for the treatment of spinal muscular atrophy / 药学学报

As one of the most serious hereditary neuromuscular disease, spinal muscular atrophy (SMA) is caused by the loss or mutation of survival motor neuron 1 (SMN1) gene. It leads to a decrease in the level of SMN protein and a consequent loss of alpha neurons and progressive muscle atrophy resulting in the progressive muscle weakness, the significant disability and the shortened lifespan. Up till now, only three drugs have been approved for SMA, including the gene therapy drug onasemnogene abeparvovec. The antisense oligonucleotide drug nusinersen and and the small molecule chemical drug risdiplam were briefly introduced. Some representative samples of the small molecule chemical drugs and antisense oligonucleotide drugs targeting SMN2 in the clinical trial or preclinical research phases were also reviewed.

Nursing of a case of goal-directed pulmonary rehabilitation after spinal cord surgery for type Ⅱ spinal muscular atrophy / 中国实用护理杂志

Objective:To summarize the nursing care measures of a patient after spinal orthopedic surgery for spinal muscular atrophy type Ⅱ.Methods:The patient was provided with a goal-directed pulmonary rehabilitation nursing program during ICU resuscitation by exercise pulmonary function, monitor difficult airway extubation and alleviating anxiety.Results:The patient postoperative pulmonary function recovered well, the difficult airway was extubated smoothly and the anxiety was relieved. The patient was discharged from the hospital on the 17th day after the operation.Conclusions:Goal-directed pulmonary care can help promote pulmonary rehabilitation and improve the quality of patient survival after orthopedic surgery for spinal muscular atrophy typeⅡ.

Research on Syringin protecting C2C12 myotube viability through regulating NF- κB/PPAR γ1 pathway / 国际中医中药杂志

Objective:To discuss the protective effect of Syringin (SYR) on myotube cell atrophy induced by lipopolysaccharide (LPS) and its molecular mechanism.Methods:After C2C12 myoblasts were differentiated into myotubes, they were divided into normal control group, model group and syringin group according to the random number table method. The cultured medium of model group and syringin group were added with LPS with a concentration of 200 ng/ml; the cultured medium of the syringin group was also added with 10 μmol/L syringin for 24 h. CCK8 was used to detect cell viability. In cell supernatant, NO release was detected with Griess and TNF-α level was detected by ELISA kit. The expression of NF-κB, PPAR γ1, MyHC were detected by Western blot.Results:Compared with the model group, the viability of cells [(101.08±8.92)%, (79.53±5.19)% vs. (69.07±7.16)%] in the 10 μmol/L and 100 μmol/L syringin groups were significantly increased ( P<0.01 or P<0.01), of which 10 μmol/L syringin had better effect. Compared with the model group, the level of NO [(2.92±0.33) μmol/L vs. (3.57±0.41) μmol/L] in the syringin group was significantly decreased after 6 hours of intervention ( P<0.01), and the cells in the syringin group after 24 hours of intervention, the level of TNF-α [(2.73±0.29) pg/ml vs. (4.15±0.29) pg/ml] was significantly decreased ( P<0.01), and the protein expression of cellular NF-κB (0.95±0.24 vs. 1.16±0.28) was significantly decreased ( P<0.05), the protein expression of MyHC (0.79±0.15 vs. 0.70±0.16) was increased ( P<0.05). Conclusion:SYR could inhibit the inflammatory response induced by LPS, promote the activity of myotubes, and antagonize the damage of LPS to myotube cells.

Recent research on the treatment of spinal muscular atrophy / 中国当代儿科杂志

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.

Role of autophagy in the maintenance of skeletal muscle mass / 中国骨伤

As an important exercise and energy metabolism organ of the human body, the normal maintenance of skeletal muscle mass is essential for the body to perform normal physiological functions. The autophagy-lysosome (AL) pathway is a physiological or pathological mechanism that is ubiquitous in normal and diseased cells. It plays a key role in the maintaining of protein balance, removing damaged organelles, and the stability of internal environment. The smooth progress of the autophagy process needs to go through multiple steps, which are completed under the coordinated action of multiple factors. Autophagy maintains the muscle homeostasis of a healthy body by removing cell components such as damaged myofibrils and isolated cytoplasmic proteins. Autophagy could also provide the initial energy required for cell proliferation, promote muscle regeneration and remodeling after injury. At the same time, autophagy disorder is also an important cause of age-related skeletal muscle atrophy. Autophagy could affect the response of skeletal muscle to exercise, and increasing the level of basic autophagy is beneficial to improve the adaptive response of skeletal muscle to exercise. This article summarizes the role and pathways of autophagy in the maintenance of skeletal muscle quality, in order to provide effective rehabilitation strategies for clinical prevention and treatment of muscle atrophy.

Reliability of the goutallier classification system in the evaluation of the multifidus muscle / Concordância da classificação de goutallier na avaliação do músculo multífido / Fiabilidad del sistema de clasificación de goutallier en la evaluación del músculo multífido

ABSTRACT Introduction: The paravertebral musculature is essential for the biomechanics and stability of the spine, and its involvement in the pathophysiology of spinal diseases has been demonstrated. Qualitative evaluation of muscle degeneration is usually performed by analyzing the fat infiltration rate proposed by the Goutallier classification system. Objective: The objective of this study is to analyze the intra- and interobserver agreement of the Goutallier Classification for the evaluation of fatty degeneration of the multifidus muscle, using magnetic resonance imaging exams. Methods: The study included 68 patients, all diagnosed with symptomatic disc hernia and indicated for surgery. Preoperative magnetic resonance images were used for the analyses. The images were initially evaluated by two orthopedists and two medical students, and then re-evaluated after two weeks. Intra- and inter-observer reliability analysis was performed using the Fleiss Kappa test and the Landis and Koch criteria. All the analyses were performed using the R statistical environment (R Development Core Team, version 3.3.1, 2016) and the significance level was set at 5%. Results: The percentages of intra- and inter-observer agreement were 86.76% and 61.03%, respectively. The intraobserver agreement was near perfect and the interobserver agreement was moderate. Conclusion: The Goutallier Classification System showed moderate interobserver and intraobserver agreement, being a relevant tool for the evaluation of paravertebral musculature fat replacement. Level of evidence II; Prospective study for diagnostic purposes.

RESUMO Introdução: A musculatura paravertebral é essencial para a biomecânica e estabilidade da coluna e tem sido demonstrado seu envolvimento na fisiopatologia das doenças da coluna vertebral. A avaliação qualitativa da degeneração muscular é usualmente feita pela análise da taxa de infiltração de gordura proposta pelo Sistema de Classificação de Goutallier. Objetivo: O objetivo deste trabalho é analisar a concordância intra e interobservador da Classificação de Goutallier para avaliação da degeneração gordurosa do músculo multífido por meio de exames de ressonância magnética. Métodos: Fizeram parte do estudo 68 pacientes, todos com diagnóstico de hérnia discal sintomática e com indicação cirúrgica. As imagens de ressonância magnética colhidas no pré-operatório foram analisadas por dois ortopedistas e dois estudantes de medicina e foram reavaliadas duas semanas depois. Foi realizada análise de confiabilidade intra e interobservador por meio do teste Kappa de Fleiss e pelos critérios de Landis e Koch. Todas as análises foram realizadas com o auxílio do ambiente estatístico R (R Development Core Team, versão 3.3.1, 2016), e o nível de significância foi fixado em 5%. Resultados: As porcentagens de concordância intra e interobservadores foram, respectivamente, 86,76% e 61,03%. A concordância intraobservador foi quase perfeita e moderada interobservadores. Conclusões: O Sistema de Classificação de Goutallier demonstrou concordância moderada interobservador e intraobservador, sendo uma ferramenta relevante na avaliação da substituição gordurosa da musculatura paravertebral. Nível de evidência II; Estudo prospectivo para fins diagnósticos.

RESUMEN Introducción: La musculatura paravertebral es fundamental para la biomecánica y la estabilidad de la columna y se ha demostrado su intervención en la fisiopatología de las enfermedades de la columna. La evaluación cualitativa de la degeneración muscular se suele realizar analizando la tasa de infiltración de grasa propuesta por el sistema de clasificación de Goutallier. Objetivo: El objetivo de este estudio es analizar la concordancia intra e interobservador de la Clasificación de Goutallier para evaluar la degeneración grasa del músculo multífido mediante resonancia magnética. Métodos: Formaron parte del estudio 68 pacientes, todos con diagnóstico de hernia discal sintomática y con indicación quirúrgica. Se utilizaron imágenes de resonancia magnética preoperatorias para el análisis. Las imágenes fueron evaluadas inicialmente por 02 ortopedistas y 02 estudiantes de medicina y, después de dos semanas, reevaluadas. El análisis de fiabilidad intra e interobservador se realizó mediante la prueba Kappa de Fleiss y los criterios de Landis y Koch. Todos los análisis se realizaron utilizando el entorno estadístico R (R Development Core Team, 2016), versión 3.3.1, y el nivel de significancia se estableció en 5%. Resultados: Los porcentajes de concordancia intra e interobservador fueron, respectivamente, 86,76% y 61,03%. La concordancia intraobservador fue casi perfecta y la concordancia interobservador fue moderada. Conclusión: el Sistema de Clasificación de Goutallier demostró una moderada concordancia interobservador e intraobservador, siendo una herramienta relevante en la evaluación del reemplazo graso de la musculatura paravertebral. Nivel de evidencia II; Estudio prospectivo con fines diagnósticos.