Serum myostatin as a candidate disease severity and progression biomarker of spinal muscular atrophy.

The identification of biomarkers for spinal muscular atrophy is crucial for predicting disease progression, severity, and response to new disease-modifying therapies. This study aimed to investigate the role of serum levels of myostatin and follistatin as biomarkers for spinal muscular atrophy, considering muscle atrophy secondary to denervation as the main clinical manifestation of the disease. The study evaluated the differential gene expression of myostatin and follistatin in a lesional model of gastrocnemius denervation in mice, as well as in a meta-analysis of three datasets in transgenic mice models of spinal muscular atrophy, and in two studies involving humans with spinal muscular atrophy. Subsequently, a case-control study involving 27 spinal muscular atrophy patients and 27 controls was conducted, followed by a 12-month cohort study with 25 spinal muscular atrophy cases. Serum levels of myostatin and follistatin were analysed using enzyme-linked immunosorbent assay at a single centre in southern Brazil. Skeletal muscle gene expression of myostatin decreased and of follistatin increased following lesional muscle denervation in mice, consistent with findings in the spinal muscular atrophy transgenic mice meta-analysis and in the iliopsoas muscle of five patients with spinal muscular atrophy type 1. Median serum myostatin levels were significantly lower in spinal muscular atrophy patients (98 pg/mL; 5-157) compared to controls (412 pg/mL; 299-730) (P < 0.001). Lower myostatin levels were associated with greater disease severity based on clinician-rated outcomes (Rho = 0.493-0.812; P < 0.05). After 12 months, there was a further reduction in myostatin levels among spinal muscular atrophy cases (P = 0.021). Follistatin levels did not differ between cases and controls, and no significant changes were observed over time. The follistatin:myostatin ratio was significantly increased in spinal muscular atrophy subjects and inversely correlated with motor severity. Serum myostatin levels show promise as a novel biomarker for evaluating the severity and progression of spinal muscular atrophy. The decrease in myostatin levels and the subsequent favourable environment for muscle growth may be attributed to denervation caused by motor neuron dysfunction.

Estimated costs for Duchenne muscular dystrophy care in Brazil.

BACKGROUND: The economic burden of rare diseases on health systems is still not widely measured, with the generation of accurate information about the costs with medical care for subjects with rare diseases being crucial when defining health policies. Duchenne Muscular Dystrophy (DMD) is the most common form of muscular dystrophy, with new technologies recently being studied for its management. Information about the costs related to the disease in Latin America is scarce, and the objective of this study is to evaluate the annual hospital, home care and transportation costs per patient with DMD treatment in Brazil. RESULTS: Data from 27 patients were included, the median annual cost per patient was R$ 17,121 (IQR R$ 6,786; 25,621). Home care expenditures accounted for 92% of the total costs, followed by hospital costs (6%) and transportation costs (2%). Medications and loss of family, and patient's productivity are among the most representative consumption items. When disease worsening due to loss of the ability to walk was incorporated to the analysis, it was shown that wheelchair users account for an incremental cost of 23% compared with non-wheelchair users. CONCLUSIONS: This is an original study in Latin America to measure DMD costs using the micro-costing technique. Generating accurate information about costs is crucial to provide health managers with information that could help establish more sustainable policies when deciding upon rare diseases in emerging countries.

Muscle strength, joint range of motion, and gait in children and adolescents with osteogenesis imperfecta.

PURPOSE: To analyze clinical and functional features of children and adolescents with osteogenesis imperfecta (OI). METHODS: A cross-sectional study of 62 participants examined clinical, body structure and function and activity features. RESULTS: A total of 31 participants had OI type I, 9 had type III, and 22 had type IV. Mild (type I) and moderate/severe (types III and IV) OI differed significantly in occurrence of fractures, presence of bone deformities, the use of intramedullary rods, bone mineral density, and bisphosphonate therapy. Age of gait acquisition showed an association with overall joint range of motion and an inverse relationship with overall muscle strength. Level of ambulation was associated with overall muscle strength and inversely associated with overall joint range of motion. CONCLUSIONS: Features vary according to OI type. Moderate and severe forms of OI are associated with greater functional limitation, influenced by fracture history, which negatively affects the acquisition and level of ambulation.

Estimulação elétrica neuromuscular em crianças com paralisia cerebral do tipo diplegia espástica / Neuromuscular electric stimulation in children with spastic diplegia

Nos últimos anos, vários estudos propuseram a utilização da estimulação elétrica como forma de tratamento da paralisia cerebral(PC). Objetivo: Utilizando um delineamento do tipo antes e depois(within-subjects design) buscou-se avaliar os efeitos da estimulação elétrica neuromuscular (EENM) nas habilidades motoras de criançascom PC do tipo diplegia espástica. Material e método: Doze pacientes(8 do sexo masculino, média de idade 6 anos) foram avaliados antese depois de 12 semanas de terapia utilizando EENM. As habilidades motoras foram avaliadas através da escala de função motora grossa(GMFM), parâmetros lineares da marcha e amplitude de movimento(ADM) de fl exão dorsal dos tornozelos. Resultados: A diferença entre as médias dos escores da GMFM foram estatisticamente signifi cativos (P = 0,032) quando comparados antes (73,1 ± 17,2)e depois (76,5 ± 16,3) da intervenção com EENM. Quando ospacientes foram classificados quanto à independência para marcha,o escore da GMFM permaneceu signifi cativo apenas nas crianças dependentes de auxílio para marcha (P = 0,045). O parâmetro decadência da marcha diferiu antes e depois da EENM no grupo decrianças independentes para marcha (P = 0,030). Conclusões: Este estudo demonstrou que a EENM pode ser uma ferramenta complementarno manejo de crianças PC do tipo diplégica espástica.Os mecanismos pelos quais a EENM melhora a função motora nãoestão totalmente esclarecidos.

Introduction: For the last years, several studies have proposed theuse of electric stimulation as a valid therapy for cerebral palsy (CP).Aims: Using a within-subjects design, we set out to determine the effect of neuromuscular electrical stimulation (NMES) on the motorskills of children with spastic diplegic CP. Materials and methods:Twelve patients (8 male, mean age 6 years), were evaluated beforeand after 12 weeks of therapy with NMES. Motor abilities were accomplished by using the gross motor function measure (GMFM),linear parameters of gait, and ankle dorsifl exion range of movement. Results: The mean scores of GMFM were significantly different (P =0.032) before (73.1 ± 17.2) and after (76.5 ± 16.3) the intervention with NMES. When patients were classified for gait dependence, the GMFM scores remained significant only for children dependent ofaid (P = 0.045). The cadence parameter of gait significantly differ before and after NMES in the group of CP children independent forgait (P = 0.030). Conclusions: Th is study demonstrated that NMESmight be a complementary tool for the handling of children with spastic diplegic CP. The mechanisms by which NMES improves themotor function are yet not established.

Estimulação elétrica neuromuscular em crianças com paralisia cerebral do tipo diplegia espástica / Neuromuscular eletric stimulation in children with spastic diplegi cerebral palsy

Nos últimos anos, vários estudos propuseram a utilização da estimulação elétrica como forma de tratamento da paralisia cerebral (PC). Objetivo: Utilizando um delineamentodo tipo antes e depois (a within-subjects design) buscou-se avaliar os efeitos da estimulação elétrica neuromuscular (EENM) nas habilidades motoras de crianças com PC do tipo diplegia espástica. Material e método: Doze pacientes (08 do sexo masculino, média de 06 anos) foram avaliados antes e depois de 12 semanas de terapia utilizando EENM. As habilidades motoras forma avaliadas através da escala de função motora grossa(GMFM), parâmetros lineares da marcha e amplitude de movimento (ADM) de flexão dorsal dos tornozelos. Resultados: A diferença entre as médias dos escores da GMFM foram estatisticamente significativos (P= 0,032) quando comparados antes (73,1 +- 17,2) e depois (76,5 +- 16,3) da intervenção com EENM. Quando os pacientes forma classificados quanto à independência para marcha, o escore da GNMF permaneceu significativo apenas nas crinaças dependentes do auxílio para marcha (P=0,045). O parâmetro de cadência da marcha diferiu antes e depois da EENM no grupo de crianças independentes para marcha (P= 0,030). Conclusões: Este estudo demonstrou que a EENM pode ser uma ferramenta complementar no manejo de crianças PC do tipo diplégica espástica. Os mecanismos pelos quais a EENM melhora a função motora não estão totalmente esclarecidos.

Introduction: For the last years, several studies have proposed the use of eletric stimulation as a valid therapy for cerebral palsy (CP). Aims: Using a within-subjects design , we set out to determine the effect of neuromeuscular eletric stimulation (NMES) on tje motor skills of children with spastic diplegic CP. Materials and methods: Twelve patients (08 male, men age 06 years), were evaluated before accomplished by using the gross motor function measure (GNMF), linear parameters of gait, and ankle dorsiflexion range of moviment. Results: The mean scores of GMFM were significantly different (P= 0,032) before (73,1 =-17,2) and after (76,5 =- 16,3) the intervention with NMES. When patients were classified for gait dependence, the GMFM scores remained significant only for children dependent of aid (p = 0,045). The cadence parameter of gait significantly differ before and after NMES in the group of CP children independent for gait (P = 0,030). Conclusions: This study demonstrated that NMES might be a complementary tool for the handling of children with spadtic diplegic CP. The mechanisms by wich NMES improves the motor function are yet not established.