Brain, Vol. 126, No. 4, 965-973,
April 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg073
Muscle cramp in Machado–Joseph disease
Altered motor axonal excitability properties and mexiletine treatment
Department of Neurology, Chiba University School of Medicine, Chiba, Japan
Correspondence to: Satoshi Kuwabara MD, Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260–8670, Japan E-mail: kuwabara{at}med.m.chiba-u.ac.jp
Machado–Joseph disease is one of the most common hereditary spinocerebellar degenerative disorders with a wide range of clinical manifestations. Pathology studies have shown mild to moderate loss of anterior horn cells and, in terms of spinal pathology, Machado–Joseph disease is regarded as a type of lower motoneuron disease. Muscle cramps are often associated with lower motoneuron disorders, but features of cramps in Machado–Joseph disease patients have never been studied. We investigated the incidence and nature of muscle cramps in Machado–Joseph disease patients, the excitability properties of motor axons [strength–duration time constant (
SD), threshold electrotonus, refractoriness and supernormality] using threshold tracking and the effects of mexiletine hydrochloride on those cramps. Of 20 consecutive patients, 16 (80%) had frequent, severe muscle cramps in the legs, trunk or arms that disturbed their daily activities. The frequency of pathological muscle cramps was similar to that for patients with amyotrophic lateral sclerosis (68%) and higher than those for patients with spinal muscular atrophy (33%) or peripheral axonal neurophathy (24%). Threshold-tracking studies showed that SD, which in part reflects Na+ conductance at the resting membrane potential, was significantly greater in the Machado–Joseph disease patients than in normal subjects; severe muscle cramps were associated with a longer SD. Threshold electrotonus, refractoriness and supernormality were not significantly different between Machado–Joseph disease patients and normal subjects. Eight Machado–Joseph disease patients with severe cramps, who received mexiletine treatment, experienced nearly complete relief with a partial normalization of SD (P = 0.08). Muscle cramps are a very frequent and disabling factor in Machado–Joseph disease. Pathological muscle cramps responded well to mexiletine treatment, and this is consistent with the hypothesis that they are caused by an increase in persistent Na+ conductance, possibly associated with axonal regeneration or collateral sprouting.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. C. Franca Jr, A. D'Abreu, A. Nucci, and I. Lopes-Cendes Muscle Excitability Abnormalities in Machado-Joseph Disease Arch Neurol, April 1, 2008; 65(4): 525 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vucic and M. C. Kiernan Pathophysiologic insights into motor axonal function in Kennedy disease Neurology, November 6, 2007; 69(19): 1828 - 1835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vucic and M. C. Kiernan Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease Brain, September 1, 2006; 129(9): 2436 - 2446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kanai, S. Kuwabara, S. Misawa, N. Tamura, K. Ogawara, M. Nakata, S. Sawai, T. Hattori, and H. Bostock Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage Brain, April 1, 2006; 129(4): 953 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Krishnan, R. K. S. Phoon, B. A. Pussell, J. A. Charlesworth, H. Bostock, and M. C. Kiernan Altered motor nerve excitability in end-stage kidney disease Brain, September 1, 2005; 128(9): 2164 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Krishnan and M. C. Kiernan Altered nerve excitability properties in established diabetic neuropathy Brain, May 1, 2005; 128(5): 1178 - 1187. [Abstract] [Full Text] [PDF]
|
|