Autonomic Dysfunction in Machado-Joseph Disease

Abstract

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. Conclusion: The present investigation documents that autonomic dysfunction is not uncommon in patients with Machado-Joseph disease and might be related to the clinical progression.

Altered Heart Rate Control in Response to Postural Change in Patients with Machado–Joseph Disease (SCA3)

“…In our study, however, HUT-induced BP and cerebral oxyhemoglobin did not fall except in one patient who showed neurally mediated syncope. In previous studies [5,6,12], the incidence of orthostatic hypotension was not extremely high in MJD patients (13-26%), as in our study, and this incidence seems relatively low in spite of the incidence of postural dizziness. A reduced initial HR response to arising suddenly and an excessive HR rise during HUT may account for the high incidence of postural symptoms without orthostatic hypotension.…”

“…Previous studies also indicated that postural symptoms were common (26-47%) in genetically diagnosed MJD patients [5,6]. In our study, however, HUT-induced BP and cerebral oxyhemoglobin did not fall except in one patient who showed neurally mediated syncope.…”

“…Some previous studies have reported autonomic dysfunction in genetically diagnosed MJD patients [4][5][6]. Heart rate (HR) variability at rest, which is a sensitive index to detect cardiac autonomic dysfunction, has been reported to be reduced in MJD patients [6,7].…”

“…Heart rate (HR) variability at rest, which is a sensitive index to detect cardiac autonomic dysfunction, has been reported to be reduced in MJD patients [6,7]. On the other hand, measurement of the initial HR response to the subjects' arising suddenly, where the heart rate rise is usually bimodal in healthy subjects and occurs within about 30 s ( Fig.…”

Machado–Joseph disease in a Nigerian family: mutational origin and review of the literature

“…Sequeiros and Coutinho 4 reported difficulty in sphincter control in 5.8% of 143 Portuguese patients. The nationwide epidemiological survey in Japan 14 revealed voiding dysfunction in 31.3% of 66 patients, whereas Yeh et al 15 in Taiwan reported that 53% of their patients had urinary disturbance (nocturia and/or incontinence) and more than half of the patients had abnormal sudomotor function.…”