Pathophysiology of Muscle Cramps
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Cornell Campus. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.
Synopsis: Patients will benefit from further studies to better define the pathophysiology of muscle cramps and to find more effective medications with fewer side-effects.
Source: Miller TM, Layzer RB. Muscle Cramps. Muscle Nerve. 2005;32;431-442.
Cramps, sudden painful muscle contractions lasting seconds to minutes and usually relieved by stretching, are common, occurring in up to 60% of the elderly and up to 95% of young exercise enthusiasts. Electromyography of a cramp discharge demonstrates high frequency, repetitive, motor unit potential firing, preceded and followed by fasciculation potentials, suggesting that cramp discharges arise in motor nerves, rather than muscle. Disease of the lower motor neuron, but not muscle, is associated with cramps, further supporting this localization. Whether the nerve, in turn, is provoked more proximally from the central nervous system, or generates its discharge independently, remains unclear, with evidence supporting both scenarios.
Multiple etiologies are recognized. Disease of the lower motor neuron, including amyotrophic lateral sclerosis, radiculopathy, or neuropathy are associated with cramps, as are metabolic perturbations, as seen in pregnancy, uremia, cirrhosis, hypothyroidism, or hypoadrenalism. Volume depletion precipitated by perspiration, dialysis, diarrhea, or diuretics may provoke cramps, and medications, including statins, beta-adrenergic agonists, and clofibrate may cause myopathy and myalgia, though the occurrence of true cramps remains questionable. Nocturnal leg cramps occur with no underlying pathology, particularly in the elderly, as do exercise-related cramps, and the benign cramp-fasciculation syndrome may also be a form of idiopathic cramps associated with muscle twitching, again with no identifiable cause. Generalized muscle cramps may occur in an autosomal-dominant hereditary pattern within families, possibly neurogenic in origin, with one family demonstrating myopathic features on muscle biopsy. Satoyoshi syndrome encompasses a usually childhood onset of painful muscle cramps, alopecia, diarrhea, and skeletal abnormalities due to an apparent autoimmune etiology. Muscle cramps should be differentiated from myalgias, muscle pain without contractions, with or without muscle weakness, which have a separate, broad, and varied differential.
Treatment is best addressed at the underlying cause that, however, is often irreversible or unidentifiable. In such instances, treatment includes non-pharmacologic steps, including muscle lengthening, stretching, or foot splints; the latter specifically for nocturnal foot cramps or pharmacologic agents, including carbamazepine or phenytoin, either of which is nearly always effective. Gabapentin, creatine, verapamil, or vitamin E are other options which have demonstrated benefit, albeit some in open-label, unblinded trials. Quinine sulfate, an old favorite, has recently (1995) fallen out of favor for cramps by the FDA due to reported health issues, including thrombocytopenia, cinchonism (quinine toxicity, manifested by fever, nausea, vomiting, diarrhea, dizziness, and visual and hearing disturbances), and even death. Primum non nocere.
Commentary
For fellow sufferers reading this abstract, there are 5 good ways to prevent painful nocturnal leg cramps (Harvard Health Letter. 2004,30:6). Proper footwear is rule #1, so wear good shoes during the day. Flat feet predispose to the problem, and correct footwear allows you to fight back. Do not sleep under snug covers, especially if you sleep on your back, as this tends to foreshorten muscles and provoke cramping. Hanging the feet over the edge of the bed further allows for better muscle relaxation. Muscle stretches before bedtime and being well hydrated, perhaps with a glass of tonic water which contains a small, safe amount of quinine, will also aid in cramp prevention.
Patients will benefit from further studies to better define the pathophysiology of muscle cramps and to find more effective medications with fewer side-effects.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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