Abstract
The aim of this study was to characterize the respiratory function profile of subjects with spinal and bulbar muscular atrophy (SBMA), and to explore the underlying pathological mechanism by comparing the clinical and biochemical indices of this disease with those of amyotrophic lateral sclerosis (ALS). We enrolled male subjects with SBMA (n = 40) and ALS (n = 25) along with 15 healthy control subjects, and assessed their respiratory function, motor function, and muscle strength. Predicted values of peak expiratory flow (%PEF) and forced vital capacity were decreased in subjects with SBMA compared with controls. In SBMA, both values were strongly correlated with the trunk subscores of the motor function tests and showed deterioration relative to disease duration. Compared with activities of daily living (ADL)-matched ALS subjects, %PEF, tongue pressure, and grip power were substantially decreased in subjects with SBMA. Both immunofluorescence and RT-PCR demonstrated a selective decrease in the expression levels of the genes encoding the myosin heavy chains specific to fast-twitch fibers in SBMA subjects. The mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and peroxisome proliferator-activated receptor delta were up-regulated in SBMA compared with ALS and controls. In conclusion, %PEF is a disease-specific respiratory marker for the severity and progression of SBMA. Explosive muscle strength, including %PEF, was selectively affected in subjects with SBMA and was associated with activation of the mitochondrial biogenesis-related molecular pathway in skeletal muscles.
Highlights
Spinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease, is a slowly progressive lower motor neuron and muscular disease characterized by bulbar and limb muscle weakness and elevated levels of serum creatine kinase [1,2,3]
The mean age at examination was higher in subjects with amyotrophic lateral sclerosis (ALS) than in those with SBMA, whereas the mean disease duration was shorter in the ALS subjects than in the SBMA subjects
The difference in %peak expiratory flow (PEF) between SBMA and ALS subjects was significant after adjustment for the ALSFRS-R and %forced vital capacity (FVC) with Analysis of covariance (ANCOVA) (p = 0.002 and 0.002, respectively) (Fig 2). These findings suggest that both %PEF and %FVC are decreased in SBMA patients, as observed in ALS, but the reduction of %PEF is specific to the subjects with SBMA
Summary
Spinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease, is a slowly progressive lower motor neuron and muscular disease characterized by bulbar and limb muscle weakness and elevated levels of serum creatine kinase [1,2,3]. Pneumonia and/or respiratory failure may occur at advanced stages of the disease [7], indicating that the management of swallowing and respiratory function is indispensable for the long-term care of patients with SBMA. In contrast to amyotrophic lateral sclerosis (ALS), another motor neuron disease for which the clinical features of dyspnea have been well documented, respiratory impairment in SBMA has not been well characterized. The aim of this study was to characterize respiratory function in subjects with SBMA both cross-sectionally and longitudinally, and to explore the potential underlying pathological mechanisms of SBMA by comparing the clinical and biochemical indices of this disease with those of ALS
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