Autonomic Symptoms in Huntington’s Disease – Current Understanding and Perspectives for the Future

European Neurological Review, 2010;5(2):46-48

Abstract:

Huntington’s disease (HD) is a fatal hereditary neurodegenerative disorder caused by an expanded cytosine-adenine-guanine (CAG) repeat sequence in the first exon of the huntingtin (HTT) gene. The disease is characterised by motor impairment, cognitive deterioration, behavioural problems and progressive weight loss. Although less well-known, autonomic nervous system dysfunction can also accompany HD. In this article, we delineate the characteristics and correlates of autonomic symptoms in HD. In addition, we provide an overview of autonomic defects that have been found thus far by means of standardised autonomic function tests in HD, discuss their pathophysiological meaning and point to perspectives for future research in this area. In conclusion it can be stated that autonomic symptoms are highly prevalent in HD patients and may even precede the onset of motor signs. Moreover, autonomic dysfunction appears to be related to functional disability and depression in HD. Therefore, increased clinical awareness and adequate management of autonomic symptoms may lead to a considerable improvement in quality of life.

Acknowledgement: This work was supported by The Netherlands Organization for Scientific Research (grant number 017.003.098 to NAA).
Keywords: Huntington’s disease, autonomic nervous system, symptoms and signs, premanifest mutation carrier, disability, depression
Disclosure: The authors have no conflicts of interest to declare.
Received: September 01, 2010 Accepted October 25, 2010 Citation European Neurological Review, 2010;5(2):46-48
Correspondence: N Ahmad Aziz, Leiden University Medical Centre, Department of Neurology, K-05-Q 110, PO Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands. E: N.A.Aziz@lumc.nl

Huntington’s Disease

Huntington’s disease (HD) is an autosomal-dominantly inherited neurodegenerative disorder. It has a prevalence of 5–7 per 100,000 people in European and North American populations.1 The first symptoms typically appear between the ages of 35 and 45 years and include minor uncontrollable movements and personality changes such as depression and irritability.1

Initially, motor symptoms mainly involve the small distal muscles, but later on the larger postural muscles also become affected, resulting in the characteristic choreatic movements. Over the years, cognitive functions gradually deteriorate leading to impairments in memory and attention. Progressive weight loss and muscle wasting, despite sustained or even increased caloric intake, are also hallmarks of the disease.2–4 The end stage of the disease is characterised by rigidity, dystonia, dementia and cachexia. In most cases, HD results in death about 15–20 years after clinical onset. HD is caused by an expanded sequence of a cytosine-adenine-guanine (CAG) repeat located near the 5’ end of the first exon of the huntingtin (HTT) gene.5 Healthy individuals typically have fewer than 36 CAG repeats, and repeats of 40 or more cause HD with complete penetrance.5 Individuals with 36–39 CAG repeats are at risk of developing HD, but penetrance is often incomplete.6 There is an inverse association between the length of the mutant CAG expansion and age of onset, which is modulated by the size of the CAG repeat tract in the normal allele,7 as well as by other genetic and environmental factors.8,9

Autonomic Symptoms in Huntington’s Disease

Although less well-known, autonomic nervous system (ANS) dysfunction can also accompany HD.2 Indeed, vegetative symptoms indicative of ANS dysfunction have repeatedly been reported in patients with HD and include hyperhydrosis, micturition and swallowing difficulties,10–12 sexual dysfunction13 and complaints suggestive of orthostatic intolerance.14,15 Vegetative symptoms are most prominent in the advanced stages of the disease,16,17 but autonomic complaints such as dizziness following standing up, excessive perspiration and tachycardia can occur even in mildly disabled HD patients (i.e. Shoulson and Fahn stages I and II), as well as in otherwise asymptomatic gene carriers.18–20

References:
  1. Walker FO, Lancet, 2007;369(9557):218–28.
  2. Aziz NA, et al., Rev Neurosci, 2007;18(3–4):223–51.
  3. Aziz NA, et al., Neurology, 2008;71(19):1506–13.
  4. Trejo A, et al., Nutrition, 2004;20(2):192–6.
  5. The Huntington’s Disease Collaborative Research Group, Cell, 1993;72(6):971–83.
  6. McNeil SM, et al., Hum Mol Genet, 1997;6(5):775–9.
  7. Aziz NA, et al., Neurology, 2009;73(16):1280–5.
  8. Gayan J, et al., Genet Epidemiol, 2008;32(5):445–53.
  9. Wexler NS, et al., Proc Natl Acad Sci USA, 2004;101(10): 3498–503.
  10. Bruyn GW, Huntington’s chorea: historical, clinical and laboratory synopsis. In: Vinken PJ, Bruyn GW (eds), Diseases of the basal ganglia, Amsterdam: North-Holland Publishing Co., 1968;298–378.
  11. Kagel MC, Leopold NA, Dysphagia, 1992;7(2):106–14.
  12. Leopold NA, Kagel MC, Arch Neurol, 1985;42(1):57–60.
  13. Fedoroff JP, et al., J Neuropsychiatry Clin Neurosci, 1994;6(2):147–53.
  14. . Aminoff MJ, Gross M, Clin Sci Mol Med, 1973;45(3):20P.
  15. Aminoff MJ, Gross M, J Neurol Sci, 1974;21(1):33–8.
  16. Kirkwood SC, et al., Arch Neurol, 2001;58(2):273–8.
  17. Nance MA, Sanders G, Mov Disord, 1996;11(5):542–8.
  18. Kobal J, et al., Eur J Neurol, 2004;11(12):842–8.
  19. Kobal J, et al., Acta Neurol Scand, 2010;121(6):392–9.
  20. Aziz NA, et al., Eur J Neurol, 2010;17(8):1068–74.
  21. Sassone J, et al., Exp Neurol, 2009;219(2):385–97.
  22. Low PA, Mayo Clin Proc, 1993;68(8):748–52.
  23. Verbaan D, et al., Neurology, 2007;69(4):333–41.
  24. Davidson J, Turnbull CD, Br J Psychiatry, 1986;148:442–6.
  25. Den Heijer JC, et al., Arch Neurol, 1988;45(3):309–12.
  26. Andrich J, et al., J Neurol Neurosurg Psychiatry, 2002;72(6):726–31.
  27. Sharma KR, et al., Arch Neurol, 1999;56(10):1248–52.
  28. Bar KJ, et al., Eur J Neurol, 2008;15(8):869–71.
  29. Benarroch EE, Mayo Clin Proc, 1993;68(10):988–1001.
  30. van der Burg JM, et al., Neurobiol Dis, 2008;29(1):41–51.
  31. Politis M, et al., Brain, 2008;131(11):2860–9.
  32. Aziz A, et al., Brain Pathol, 2008;18(4):474–83.
  33. Rosas HD, et al., Neurology, 2005;65(5):745–7.
  34. Klein CM, Semin Neurol, 2008;28(2):195–204.
  35. Zesiewicz TA, et al., Neurology, 2010;74(11):924–31.
Keywords: Huntington’s disease, autonomic nervous system, symptoms and signs, premanifest mutation carrier, disability, depression
Customize This