Clinical features of spinal and bulbar muscular atrophy.
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.
Neurogenetics Branch, NINDS, NIH, Bethesda, MD, USA.
Lindsay E
LE
Rhodes
Brandi K
BK
Freeman
Sungyoung
S
Auh
Angela D
AD
Kokkinis
Alison
A
La Pean
Cheunju
C
Chen
Tanya J
TJ
Lehky
Joseph A
JA
Shrader
Ellen W
EW
Levy
Michael
M
Harris-Love
Nicholas A
NA
Di Prospero
Kenneth H
KH
Fischbeck
D000200:Action Potentials / Q000502:physiology; D000203:Activities of Daily Living; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000728:Androgens / Q000627:therapeutic use; D055534:Bulbo-Spinal Atrophy, X-Linked / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology*; D004568:Electrodiagnosis; D004576:Electromyography / Q000379:methods; D007172:Erectile Dysfunction / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D017079:Exercise Tolerance / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000502:physiology; D018908:Muscle Weakness / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000503:physiopathology; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000032:analysis / Q000097:blood; D013997:Time Factors
D000728:Androgens; D013739:Testosterone