Autonomic dysfunction in Machado-Joseph disease.
OBJECTIVE
Machado-Joseph disease is an autosomal dominant spinocerebellar ataxia with expanded trinucleotide repeats. Although autonomic nervous system degeneration was documented in postmortem reports, the autonomic dysfunction in patients with Machado-Joseph disease, either in clinical analysis or electrophysiological investigations, has not yet been studied in detail.


METHODS
Fifteen patients with genetically confirmed Machado-Joseph disease and 34 healthy subjects were studied. The study design included a detailed questionnaire, R-R interval variation on deep breathing or Valsalva maneuver, and sympathetic skin response evoked by electrical stimulation of the median nerve or magnetic stimulation of the neck.


RESULTS
Sixty-seven percent of patients had at least 3 symptoms involving different aspects of autonomic functions. Voiding problems and thermoregulatory disturbance were the most common symptoms. Ten (71%) of 14 patients had abnormal R-R interval variation with a significant reduction of the mean ratio. Prolonged latency or absence of sympathetic skin response to electrical stimulation was identified in 73% of patients and to magnetic stimulation, in 53%. R-R interval variation and sympathetic skin response showed good correlation with the functional stage. Electrical stimulation revealed the highest sensitivity, specificity, and positive predictive value compared with other tests.


CONCLUSIONS
The present investigation documents that autonomic dysfunction is not uncommon in patients with Machado-Joseph disease and might be related to the clinical progression.
Yeh
Tu-Hsueh
TH
First Department of Neurology and Human Molecular Genetic Laboratory, Chang Gung Memorial Hospital, Taipei, Taiwan.
Lu
Chin-Song
CS
Chou
Yah-Huei Wu
YH
Chong
Chok-Chean
CC
Wu
Tony
T
Han
Nai-Hui
NH
Chen
Rou-Shayn
RS
D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D001833:Body Temperature Regulation / Q000235:genetics; D003080:Cold Temperature / Q000009:adverse effects; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D012867:Skin / Q000294:innervation / Q000503:physiopathology; D011795:Surveys and Questionnaires; D017779:Sympathetic Fibers, Postganglionic / Q000503:physiopathology; D001750:Urinary Bladder, Neurogenic / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D014661:Vasoconstriction / Q000502:physiology