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Prodromal muscle cramps predict rapid motor functional decline in amyotrophic lateral sclerosis
  1. Kazumoto Shibuya,
  2. Sonoko Misawa,
  3. Yukari Sekiguchi,
  4. Minako Beppu,
  5. Hiroshi Amino,
  6. Tomoki Suichi,
  7. Yo-ichi Suzuki,
  8. Atsuko Tsuneyama,
  9. Satoshi Kuwabara
  1. Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
  1. Correspondence to Dr Satoshi Kuwabara, Department of Neurology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; kuwabara-s{at}

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Muscle cramps are a common and annoying symptom in patients with amyotrophic lateral sclerosis (ALS). A previous study reported that 95% of patients with ALS experience muscle cramps during the disease course.1 Up to 20% of patients have severe and frequent (more than once/day) cramps, and sleeping is disturbed in 50%.

The origin of muscle cramps is uncertain, but distal motor axons potentially contribute to ectopic burst activity and thereby muscle cramps. Nerve excitability measurements have disclosed hyperexcitable state of motor nerve in patients with ALS.2 Hyperexcitability leads to fasciculations and muscle cramps, and potentially enhances motor neuron death, via glutamate-induced excitotoxicity and increased oxidative stress and metabolic demand.

In line with this view, patients with ALS with hyperexcitable motor nerve, measured by nerve excitability measurements, have shorter survival.2 The relationship between muscle cramps and ALS progression has not been elucidated. The aim of this study was to reveal characteristics of muscle cramps and their relationship with disease progression.

Materials and methods


Forty-three consecutive patients with sporadic ALS (29 men), who fulfilled the Awaji diagnostic criteria for definite or probable ALS, with sporadic ALS (29 men) were included in this study. They were evaluated according to ALS Functional Rating Scale-Revised (ALSFRS-R) at first visit.3 Initial weakness, including …

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  • Contributors KS and SK designed the study. KS, SM, YS, MB, HA, TS, YS and AT collected clinical data. KS and SK drafted the manuscript. KS performed statistical analyses. SK supervised the study.

  • Funding KS, SM, YS and SK receive research support from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. SK receives Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labour and Welfare of Japan.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval This study was approved by the Ethics Committee of Chiba University School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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