RESUMEN
Spinobulbar muscular atrophy (SBMA) is caused by a trinucleotide repeat expansion in the androgen receptor gene on the X chromosome. There is a toxic effect of the mutant receptor on muscle and neurons resulting in muscle weakness and atrophy. The weakness can be explained by wasting due to loss of muscle cells, but it is unknown whether weakness also relates to poor muscle contractility of the remaining musculature. In this study, we investigated the muscle contractility in SBMA. We used stationary dynamometry and quantitative MRI to assess muscle strength and absolute and fat-free, cross-sectional areas. Specific muscle force (strength per cross-sectional area) and contractility (strength per fat-free cross-sectional area) were compared with healthy controls and their relation to walking distance and disease severity was investigated. Specific force was reduced by 14-49% in SBMA patients compared to healthy controls. Contractility was reduced by 22-39% in elbow flexion, knee extension, ankle dorsi- and plantarflexion in SBMA patients. The contractility decreased with increasing muscle fat content in muscles with affected contractility in SBMA. The decreased muscle contractility in SBMA may relate to motor neuron degeneration and changed fibre type distribution and muscle architecture.
Asunto(s)
Atrofia Bulboespinal Ligada al X/fisiopatología , Neuronas Motoras/fisiología , Contracción Muscular/fisiología , Fuerza Muscular/fisiología , Músculos/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Atrofia Bulboespinal Ligada al X/genética , Cromosomas Humanos X/genética , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dinamómetro de Fuerza Muscular , Debilidad Muscular/genética , Degeneración Nerviosa , Receptores Androgénicos/genética , Expansión de Repetición de Trinucleótido/genéticaRESUMEN
OBJECTIVE: To investigate the phenotypic features, with emphasis on muscle, in 40 patients with spinobulbar muscular atrophy (SBMA) using quantitative MRI, stationary dynamometry, questionnaires, and functional tests. METHODS: Patients with genetically confirmed SBMA were included. MRI was used to describe muscle involvement and quantify muscle fat fractions of arm, back, and leg muscles. Muscle strength was assessed with a stationary dynamometer. All patients were evaluated with the SBMA functional rating scale and the 6-minute walk test among others. MRI and muscle strength results were compared with healthy controls. RESULTS: Forty patients with SBMA were included. The muscle fat content was significantly higher in patients with SBMA than in controls: paraspinal fat fraction was 45% vs 33% in controls, thigh fat fraction 36% vs 14%, calf fat fraction 37% vs 15%, upper arm fat fraction 20% vs 8%, and forearm fat fraction was 20% vs 9%. Muscle strength in patients was reduced to approximately half of that in controls in all muscles. Muscle fat content correlated with muscle strength, SBMA functional rating scale score, and 6-minute walk test distance. CONCLUSIONS: Our results show that there is a diffuse muscle involvement pattern in SBMA. Leg muscles are more vulnerable than arm muscles, especially the posterior flexor muscles. The muscle fat content correlates with muscle function and disease severity.
Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Atrofia Bulboespinal Ligada al X/diagnóstico por imagen , Fuerza Muscular , Músculo Esquelético/diagnóstico por imagen , Adulto , Anciano , Brazo , Músculos de la Espalda/diagnóstico por imagen , Músculos de la Espalda/fisiopatología , Atrofia Bulboespinal Ligada al X/fisiopatología , Estudios de Casos y Controles , Antebrazo , Humanos , Pierna , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Fenotipo , Muslo , Prueba de PasoRESUMEN
OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive disease with weakness of bulbar and extremity muscles. There is no curative treatment for the disease, but several clinical trials have been conducted over the past years. The results from these trials have uncovered a great need to develop quantitative, reliable outcome measures. In this study, we prospectively investigated disease progression over 18 months in 29 patients with genetically confirmed SBMA, using quantitative outcome measures, including Dixon magnetic resonance imaging (MRI). METHODS: We used MRI to assess changes in muscle fat content and stationary dynamometry to assess changes in muscle strength. Disease progression was also investigated with the SBMA functional rating scale, bulbar rating scale, 6-minute walk test, and blood samples, among others. RESULTS: Mean muscle fat content, muscle strength in knee extensors, handgrip strength, walking distance, and creatinine levels changed significantly. Mean muscle fat content increased by 2 ± 1.25%, and knee extension strength decreased from 83 ± 60 to 76 ± 56Nm, handgrip strength from 31 ± 13 to 29 ± 13kg, walking distance from 362 ± 216 to 336 ± 219m, and creatinine level from 58 ± 21 to 54 ± 20 µmol/l. Functional rating scores did not change. INTERPRETATION: The present study demonstrates a slow and steady disease progression in SBMA. Dixon MRI detected increases in muscle fat content in all investigated muscles and is therefore a suitable candidate for an outcome measure in natural history or treatment studies in SBMA. The 6-minute walk test and handgrip strength also seem to be reliable outcome measures for SBMA. Ann Neurol 2018;84:762-773.