Brain Advance Access published online on October 21, 2009
Brain, doi:10.1093/brain/awp258
Clinical features of spinal and bulbar muscular atrophy
1 Neurogenetics Branch, NINDS, NIH, Bethesda, MD, USA 2 Clinical Neurosciences Program, NINDS, NIH, Bethesda, MD, USA 3 EMG Branch, NINDS, NIH, Bethesda, MD, USA 4 Clinical Center Department of Rehabilitation Medicine, NIH, Bethesda, MD, USA 5 Research Service/Geriatrics and Extended Care Service, VA Medical Center, Washington, DC, USA
Correspondence to:
Kenneth Fischbeck, MD, 35-2A1000, 35 Convent Dr., Bethesda, MD 20892-3705, USA E-mail: kf{at}ninds.nih.gov
Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. To characterize the natural history and define outcome measures for clinical trials, we assessed the clinical history, laboratory findings and muscle strength and function in 57 patients with genetically confirmed disease. We also administered self-assessment questionnaires for activities of daily living, quality of life and erectile function. We found an average delay of over 5 years from onset of weakness to diagnosis. Muscle strength and function correlated directly with serum testosterone levels and inversely with CAG repeat length, age and duration of weakness. Motor unit number estimation was decreased by about half compared to healthy controls. Sensory nerve action potentials were reduced in nearly all subjects. Quantitative muscle assessment and timed 2 min walk may be useful as meaningful indicators of disease status. The direct correlation of testosterone levels with muscle strength indicates that androgens may have a positive effect on muscle function in spinal and bulbar muscular atrophy patients, in addition to the toxic effects described in animal models.
Key Words: Kennedy disease; spinal and bulbar muscular atrophy; motor neuron disease; androgens
Abbreviations: ADL, activities of daily living; CI, confidence interval; CMAP, compound motor action potential; IIEF, International Index of Erectile Function questionnaire; MCS, mental component summary of the SF-36v2; MUNE, motor unit nerve estimation; NIH, the National Institutes of Health; PCS, physical component summary of the SF-36v2; QMA, quantitative muscle assessment; SBMA, spinal and bulbar muscular atrophy; SD, standard deviation; SE, standard error; SF-36v2, Medical Outcomes Study 36-item Short Form Version 2 questionnaire; SNAP, sensory nerve action potential
Received June 11, 2009. Revised August 13, 2009. Accepted August 31, 2009.