Leg Cramps Peak in Summer, Dip in Winter

Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta EdmontonMedicalResearch.com Interview with:
Scott R. Garrison MD PhD

Associate Professor, Department of Family Medicine
Director, Pragmatic Trials Collaborative
Faculty of Medicine University of Alberta Edmonton

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Garrison: Nocturnal leg cramps (also called rest cramps) are painful muscle tightenings, most often in the legs or feet, that are brought on by rest and often wake the sufferer from sleep. They are very common in older adults and can also occur during pregnancy. Having read anecdotal mention that the rest cramps of pregnancy appeared to be worse in summer we sought cohort level evidence to determine whether the more common presentation of age-related rest cramps was also seasonal. To do this we primarily looked at new quinine starts in the province of British Columbia over a period of several years. British Columbia has a publicly funded health care system and maintains electronic records on all health services, including prescription drugs, provided to its roughly 4.2 million residents. Quinine is approved for the treatment of acute malaria in Canada but is instead almost exclusively used off-label to prevent rest cramps. As such, new quinine starts are an excellent marker for new or escalating cramp burden. We also looked at Internet searches, geographically limited to the USA, for the term “leg cramps” (reflecting public interest) obtained from the Google Trends Search Volume Index Tool. Seasonality for both of these indicators of cramp burden was assessed by determining how well a least squares minimizing sinusoidal model predicted variability.

We found that quinine starts and “leg cramp” related Internet queries were both strikingly sinusoidal with a 365-day periodicity (mid-summer high, mid-winter low) and a peak-to-peak variability that is approximately 2/3 of the mean. Seasonality accounted for 88% of the observed monthly variability (p < 0.0001) in quinine starts, and 70% of the observed variability (p < 0.0001) in “leg cramp” related internet searches.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Garrison: These data suggest that cramp burden roughly doubles in the peak of summer, compared to the mid-winter low. From the perspective of someone suffering from frequent cramping, understanding why exacerbations are happening and that they are temporary is helpful in learning to cope with them. In addition, quinine carries risk of toxicity (most notably thrombocytopenia and cardiac rhythm disturbances) and its use for rest cramp prevention has been discouraged by multiple drug regulatory bodies such as the American FDA. Patients currently taking quinine despite these warnings may find that they are able to reduce their quinine use by taking a quinine holiday during the 6 colder months of the year when their symptom burden may be lower.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Garrison: The seasonality effect we have observed is stronger than the effect of most therapeutics. Any meaningful evaluation of cramp therapies will certainly require a control group and, ideally, some measure of how balanced each group is with respect to month of enrolment. An effective therapy introduced in the spring may struggle to show benefit, while an ineffective therapy introduced as the summer wanes may look like a winner simply because the cramp burden was about to lessen anyway.

And from a basic science point of view – why would a disorder of motor neurons display such strong seasonality? Could some basic property of motorneuron physiology be seasonal? Consider the example of vitamin D. Vitamin D is known to be a potent regulator of neurotrophins and to potentiate axon regeneration in a rat model of transected peripheral nerve. Given Vitamin D can be expected to vary seasonally according to the availability and intensity of daylight, it is conceivable that growth and repair of peripheral motoneurons might also undergo some seasonal modulation. Although the exact mechanism behind muscle cramping remains obscure, some of the conditions associated with muscle cramps (e.g. aging, ALS, radiculopathy) have in common loss of, or injury to, peripheral motor neurons. Theoretically, the process of axonal outgrowth or axonal sprouting might in some way facilitate muscle cramping and, if such a process were itself seasonal, a seasonal manifestation of cramp burden might be observed. Whether this is the case or not, the possibility that some aspect of motor neuron physiology is seasonal is worth exploring.


Seasonal effects on the occurrence of nocturnal leg cramps: a prospective cohort study

Scott R. Garrison, Colin R. Dormuth, Richard L. Morrow, Greg A. Carney, and Karim M. Khan
CMAJ cmaj.140497; published ahead of print January 26, 2015, doi:10.1503/cmaj.140497

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