Resources

  1. Ann Fam Med 2018;16:296-301. https://doi.org/10.1370/afm.2238.










Transcript

Dr. Frank Domino:

Anthony is a 72-year-old male who has been in your practice for the last 20 years. He has happily retired, stone mason, who lives with his wife and has children and grandchildren, all within an hours drive. He only smoked during his three years in the Navy. He currently walks two miles a day and is happy to report he takes no medications, unlike most of his friends who are in his age group. On review of symptoms, he reports that about three times a week, he wakes up during the middle of the night with lower leg cramps. "They can be on either side", he says. They never happen when he walks or goes about his daily activities, which is annoying to him, because it wakes him out of a sound sleep. He thinks he takes pretty good care of himself. He asks you if he needs a vitamin to fix these leg cramps but his wife is worried that this is something serious.

Hi, this is Frank Domino, Professor in the Department of Family Medicine and Community Health at the University of Massachusetts Medical School. And joining me today is Alan Ehrlich, Associate Professor in the Department of Family Medicine and Community Health at the University of Massachusetts Medical School and Executive Editor at DynaMed. Hi, Alan.

Alan Ehrlich:

Hi, Frank.

Dr. Domino:

Well, this is certainly a common problem. Can you tell us about the causes of nocturnal leg cramps?

Alan Ehrlich:

Well, nocturnal leg cramps are a bane of many of our seniors existence. They wake them up, they're very annoying. And when you look into the literature, the differential diagnosis about the ideology of that, of nocturnal leg cramps, are quite broad. Obvious things like renal disease or liver disease can have a great role, as can peripheral vascular disease. Any cardiovascular disease can increase the risk of leg cramps. Diabetes can in seniors, spinal stenosis can, even obstructive sleep apnea, all run the risk of inducing nocturnal leg cramps. If we talk about medications, the list is varied. Things like estrogen replacement therapy, anti-inflammatories, in particular, naproxen, diuretics, long-acting beta agonists, inhalers can do it, as well as alcohol and many other causes. So the differential is quite large, and many of the things we do in managing our patients other problems can actually increase that risk.

Dr. Domino:

So Anthony seems pretty healthy. Is idiopathic a typical cause?

Alan Ehrlich:

Absolutely, idiopathic is probably the most common cause, although we probably don't realize either what we prescribe or what the patients may take over the counter can be a cause.

Dr. Domino:

So what kind of work-up would you suggest for a patient with nocturnal leg cramps?

Alan Ehrlich:

Well, I think the first thing to do is generate the differential and look at maybe what prescriptions he might be taking or what over the counter agency he might be using. If everything seems pretty clear that it's not something exogenous, it's not unreasonable to do a comprehensive metabolic profile. Looking at his LFTs, to see if he has any liver disease, looking at his electrolytes, albumin/creatinine, to see if he has any abnormality with his kidney function. Think about peripheral neuropathies, so B12 would not be unreasonable, a thyroid. If you have any risk factors for peripheral vascular disease, an ankle brachial index is something to certainly consider. And if he reports snoring, daytime fatigue, his wife reports that he falls asleep easily driving, etcetera, consider a sleep study for obstructive sleep apnea.

Dr. Domino:

You know, when you were talking about the various medication causes and other types of things similar, you mentioned alcohol. What's the data on that? Is that really something that we should be concerned about?

Alan Ehrlich:

So it's very interesting. A recent publication came out that tried to help answer this very question. This was a case control study done in the Alsace region of France. And they looked at ambulatory patients over age 60, across a wide spectrum of general practices. And they looked for correlations of what people took in and how they related to the occurrence of nocturnal leg cramps. And it turned out that regular use of alcohol, dramatically, by a factor of over six, increased the risk of nocturnal leg cramps. But what's most interesting was that it had no correlation with the amount or in some cases even the frequency. So using alcohol, even once a week, increased the risk of nocturnal leg cramps, even if it was just one drink a week. It wasn't that people who abused or took in large amounts of alcohol or binge drank, or had a regular heavy consumption of alcohol, had greater risk. The correlation that was best found using both a review of medications, as well as a food frequency questionnaire, was regular consumption of alcohol.

Dr. Domino:

So Frank, help us. This is a case-control study, and yes, there's an increased odds ratio but how do we translate that clinically?

Alan Ehrlich:

Okay. The first thing is I think if someone has nocturnal leg cramps, telling them to stop drinking is not the solution. The presence of a risk factor helps you generate a differential diagnosis and devise a treatment plan, but it doesn't necessarily require you to change behavior. If I were counseling Anthony today, I'd probably suggest that if his work-up was negative and I could not find any other clues as to what was causing it, was to maybe abstain from alcohol for a week or two. And look at the frequency of his nocturnal leg cramps. If they resolve after two, three weeks off of alcohol, well then he can feel very comfortable that his leg cramps may be related to the alcohol, and choose to drink or not drink alcohol. This would also relieve his wife's anxiety that something bad is wrong. On the other hand, if he chooses to continue to drink, there's probably a very low risk in someone who's not a vasculopath or someone who's got severe risk factors that these nocturnal leg cramps are implying some other physiologic condition that needs to be diagnosed and evaluated.

Dr. Domino:

So in other words, if you've done a work-up and you've ruled out some fairly simple, straightforward causes based on routine lab tests, and you can certainly offer the alcohol cessation as a therapeutic trial, but ultimately, it may come down to the patient deciding, "Okay, maybe I don't mind the leg cramps that much, and I'm still gonna enjoy wine or whatever."

Alan Ehrlich:

I think that's exactly right. The other thing that I thought was very fascinating is that things we commonly consider for interventions to treat nocturnal leg cramps are probably of no benefit. For example, anti-inflammatories were something that we used to consider in the past as sort of a first-line treatment, also the use of quinine.

Dr. Domino:

Yeah, many people [chuckle] might interpret this as, "Well, I'll have a gin and tonic because alcohol maybe makes it all worse and quinine maybe makes it a little better." What's the story with quinine?

Alan Ehrlich:

So quinine, first of all, he should have the gin and tonic if he so chooses and it sounds like a fine idea to me. What we do know is that quinine supplementation does not lower the risk of nocturnal leg cramps any better than placebo. And so in many patients, they like using tonic water or something, some pill formulation that might contain quinine, but we know it's probably no more effective than placebo. And a gin and tonic might be the perfect placebo to help control his nocturnal leg cramps.

Dr. Domino:

Yeah. And I believe the quinine pills, the FDA put the kibosh on that many years ago.

Alan Ehrlich:

Yeah. My take away from this study is that when you have patients with nocturnal leg cramps, you need to take a very good review of symptoms. Review their meds, review their both prescription and over-the-counter usages of different agents, broadly think about the differential diagnosis. And if it comes down to maybe alcohol is their only risk factor, a brief trial of cessation. And then let the patient decide, because without a risk of peripheral vascular disease or spinal stenosis, the morbidity and mortality of nocturnal leg cramps are primary around disrupted sleep.

Dr. Domino:

Sounds good. Thanks a lot, Frank.

Alan Ehrlich:

Thank you, Alan.

Dr. Domino:

Practice pointer; When evaluating patients with nocturnal leg cramps, consider both over-the-counter as well as prescription medications in your differential diagnosis.