RESUMEN
McArdle disease results from a lack of muscle glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy. Animal model studies indicate that sodium valproate (VPA) can increase expression of phosphorylase in skeletal muscle affected with McArdle disease. This study was designed to assess whether VPA can modify expression of brain phosphorylase isoenzyme in people with McArdle disease. This phase II, open label, feasibility pilot study to assess efficacy of six months treatment with VPA (20â¯mg/kg/day) included 16 people with McArdle disease. Primary outcome assessed changes in VO2peak during an incremental cycle test. Secondary outcomes included: phosphorylase enzyme expression in post-treatment muscle biopsy, total distance walked in 12 min, plasma lactate change (forearm exercise test) and quality of life (SF36). Safety parameters. 14 participants completed the trial, VPA treatment was well tolerated; weight gain was the most frequently reported drug-related adverse event. There was no clinically meaningful change in any of the primary or secondary outcome measures including: VO2peak, 12 min walk test and muscle biopsy to look for a change in the number of phosphorylase positive fibres between baseline and 6 months of treatment. Although this was a small open label feasibility study, it suggests that a larger randomised controlled study of VPA, may not be worthwhile.
Asunto(s)
Encéfalo/patología , Glucógeno Fosforilasa/metabolismo , Músculo Esquelético/citología , Ácido Valproico/uso terapéutico , Animales , Estudios de Factibilidad , Glucógeno Fosforilasa/farmacología , Humanos , Fibras Musculares Esqueléticas/patología , Fosforilasas/metabolismo , Proyectos Piloto , Calidad de VidaRESUMEN
BACKGROUND: Development of autonomic failure is associated with more rapid disease course and shorter survival in patients with Parkinson's disease and multiple system atrophy. However, autonomic symptoms have not been specifically assessed as a prognostic factor in progressive supranuclear palsy (PSP). We evaluated whether development of autonomic symptoms is associated with disease progression and survival in PSP. METHODS: A retrospective review of clinical data from consecutive patients with autopsy-confirmed PSP from the Queen Square Brain Bank between January 2012 and November 2016 was performed. Time from disease onset to four autonomic symptoms (constipation, urinary symptoms, erectile dysfunction and orthostatic hypotension) were noted. Time from diagnosis to five disease milestones and survival were calculated to assess disease progression, and their risk was estimated through a Cox proportional hazards model. RESULTS: A total of 103 PSP patients were included. Urinary symptoms and constipation were present in 81% and 71% of cases, respectively. Early development of constipation and urinary symptoms were associated with higher risk of reaching the first disease milestone (respectively, HR: 0.88; 95% CI 0.83 to 0.92; p<0.001; and HR: 0.80; 95% CI 0.75 to 0.86; p<0.001) and with a shorter survival in these patients (respectively, HR: 0.73; 95% CI 0.64 to 0.84; p<0.001; and HR: 0.88; 95% CI 0.80 to 0.96; p=0.004). On multivariate analysis, Richardson syndrome phenotype was the other variable independently associated with shorter survival. CONCLUSIONS: Earlier urinary symptoms and constipation are associated with a more rapid disease progression and reduced survival in patients with PSP.
Asunto(s)
Estreñimiento/etiología , Disfunción Eréctil/etiología , Hipotensión Ortostática/etiología , Parálisis Supranuclear Progresiva/complicaciones , Parálisis Supranuclear Progresiva/mortalidad , Trastornos Urinarios/etiología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Parálisis Supranuclear Progresiva/diagnóstico , Tasa de Supervivencia , Evaluación de SíntomasRESUMEN
McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to 'growing pains' and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.
Asunto(s)
Prueba de Esfuerzo/métodos , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Biopsia , Errores Diagnósticos , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Caminata/fisiologíaRESUMEN
McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to ‘growing pains’ and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.
A doença de McArdle é o tipo mais frequente das glicogenoses. A apresentação clínica característica na infância inclui mialgia e intolerância aos esforços/exercício físico. Frequentemente, os sinais e sintomas das crianças não são considerados devidamente, sendo muitas vezes interpretados como “dores do crescimento”, retardando o diagnóstico. Erros diagnósticos não são raros uma vez que outras doenças, como distrofia muscular ou canalopatias musculares, podem apresentar sintomas semelhantes. Entretanto, um simples teste de exercício físico realizado no ambulatório/consultório médico pode ajudar a identificar estes pacientes pois evidencia o fenômeno second wind, patognomônico da doença de McArdle. Aqui é descrito um relato de caso de um paciente ilustrando o valor do simples 12 minutes walk test.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Prueba de Esfuerzo/métodos , Enfermedad del Almacenamiento de Glucógeno Tipo V/patología , Enfermedad del Almacenamiento de Glucógeno Tipo V/fisiopatología , Biopsia , Errores Diagnósticos , Frecuencia Cardíaca/fisiología , Factores de Tiempo , Caminata/fisiologíaRESUMEN
Pediatric normal brachial biceps (14 specimens) and quadriceps muscles (14 specimens) were studied by immunohistochemistry to quantify fiber-type, diameter and distribution, capillary density, presence of inflammatory cells (CD3, CD20, CD68) and expression of neonatal myosin and MHC class 1 proteins. Brachial biceps showed more fast-twitch fibers and lower capillary/fiber ratio than quadriceps. The mean diameter of both fiber types was smaller in biceps than quadriceps. Fast-fibers were smaller than slow-fibers, and capillary/fiber ratio was < 1.0 in both muscles. Fiber size and capillary / fiber ratio increased with age. Normal limits for infiltrating haematopoietic cells were <4 T lymphocytes, or CD68+ cells, very few B cells, < 6 neonatal myosin positive fibers, and no fibers MHC class 1 positive in one x20 field, for both muscles. The present comparison of quantitative findings between brachial biceps and quadriceps may allow standardization of the assessment of pathological changes in both pediatric muscles.