Restless Leg Syndrome and Parkinson's Disease
by J. Steven Poceta, MD
Restless Legs Syndrome (RLS) is a neurologic and sleep-related condition characterized by an irresistible urge to move the legs. There are certain features that make this condition a unique and specific disorder. First, the hallmark of the condition is the feeling of restlessness, usually in the legs. The restlessness is often accompanied by additional sensations such as tingling or creepycrawly feelings, usually located in the legs. The exact location in the legs is usually not restricted to the toes or feet, as in peripheral neuropathy, but rather more generally in the legs, often the calves or thighs. A second feature of RLS is the fact that the restlessness is worse when the person is at rest or not moving. This feature makes it hard for people with RLS to sit still in order to read, relax, or do desk work. The third feature of RLS is that symptoms are improved with moving, particularly walking. Unfortunately, the relief lasts only as long as the movement continues, which makes some people "pace the floor" for hours when the condition is severe. Besides walking, sometimes providing other stimuli to the legs is helpful, such as rubbing or massage, or stretching.
Lastly, and most intriguing—as well as the reason that RLS is a sleep disorder—is that RLS symptoms only occur in the evening and night, and are absent in the daytime. This circadian (24-hour) pattern makes RLS one of the most unique conditions in all of medicine. Unfortunately, we do not know why this occurs, but again, it is a feature that must be present in order for a doctor to diagnosis RLS (or if the symptoms are present in the daytime, the intensity of the restlessness must be much worse in the evening and night). Most people with the condition have the onset of the feeling in the hours after dinner and before bedtime. The restlessness might impede the onset of sleep or cause the person to wake up frequently, but usually the restlessness goes away during the latter portion of the night and is gone by morning. Besides these four features, other typical features include repetitive leg movements during sleep, the occurrence in family members, and an association with certain metabolic conditions such as diabetes and anemia.
The link between RLS and Parkinson's: dopamine agonists
Although the cause of RLS remains unknown, we know that RLS runs in families in about one-half of the cases, and that some families have an abnormality on chromosome 12. Because RLS is well treated by medications that also treat Parkinson's disease, it is likely that some aspect of brain dopamine function is altered in RLS. However, unlike in Parkinson's disease, in which the deficit in substantia nigra dopamine-producing cells can be proven in many ways, no such abnormality has been shown in RLS. For example, studies show that there is no major deficit on PET or other imaging studies of the brain, as is there is in PD. The spinal fluid is normal in RLS, but shows low dopamine in PD.
Lastly, RLS does not progress to cause other major symptoms such as tremor, gait disorder, or loss of taste or smell, and does not progress to PD. In fact, one of the leading possibilities as the cause of RLS and for which there is good scientific evidence and much research is a form of iron-transport abnormality in the brain. In effect, RLS patients may have low levels of iron in brain nerve cells—just the opposite of some portions of the brain in PD.
Thus, although RLS and PD share the same treatments—and no other common disorder is treated with these dopamine agents— RLS and PD do not appear to share a common brain defect. RLS affects as much as 10% of the US adult population, and is practically a household word now. This is because an effective new medication has been approved by the FDA and is being marketed directly to the public, as well as to the medical profession. It is reassuring that on almost every test, RLS patients are like normal control patients and not like PD patients; and it is reassuring for those of us interested in RLS over the last 20 years or so that we have not observed large numbers of RLS patients developing PD. But what about the other possibility? Do patients with PD have RLS, and how often? Is it the same RLS as the person without PD has, or is it different?
This question has been difficult to answer. Of course, since PD affects about 2% of the elderly, and RLS about 10%, there will be some coincidental overlap. In addition to this chance, however, patients with PD can have RLS symptoms when their dose of dopamine medication is wearing off, and RLS is one of the symptoms during "off spells" in patients with advanced PD. This type of RLS is probably not the same as typical RLS because of the lack of a circadian (24-hour) pattern, but it is consistent with the "low dopamine" hypothesis of the cause of RLS. Also, as many as 80% of patients with PD have the "periodic limb movements in sleep," just like RLS patients, but this is a non-specific finding. That means that these leg movements do not make the diagnosis of RLS, and in fact can be considered normal even in healthy elderly. Studies of patients with PD that assess for RLS and compare to a control group are few, and are hindered by the fact that the majority of patients with significant PD are under treatment with medications that affect RLS. Despite the fact that many neurologists and sleep specialists have the impression that RLS is more common in PD, research has not proven this. There have been three recent and fairly large studies that interviewed PD patients about RLS. One study did not show an increase in RLS compared to a control group, and two studies did show an increase in the diagnosis of RLS. However, the percentage of PD patients with RLS was in the 10 to 15% range, and the control group in the 2% range (very low), and these studies were not conducted in the United States. Thus, it remains unclear whether or not true RLS is more common in patients with PD.
Despite this uncertainty, however, for patients with PD who have sleep disturbances characterized by restlessness, excessive muscular twitching, abnormal dreams, or acting-out of dreams, taking medications such as those for RLS can sometimes be helpful. We know that dopamine agonists such as ropinerole (Requip®) and pramipexole (Permax®) can decrease muscle activity during both REM sleep and nonREM sleep. Some patients with PD benefit from doses of these medications at bedtime, not only for this reason, but also to decrease typical PD symptoms overnight. Caution is in order, of course, because in some patients with PD, especially older or more advanced patients, these medications can cause confusion and hallucinations and are thus not well-tolerated. Nonetheless, trying to address sleep issues such as Restless Legs Syndrome in patients who have sleep complaints can be an important aspect of maximizing therapy for Parkinson's disease.
Dr. Poceta is a Consultant in Neurology and Sleep Disorders in the Division of Neurology, Scripps Clinic, La Jolla, and the Scripps Clinic Sleep Center. His current interests include organized medicine and Internet medicine. (Article printed with permission from the Parkinson's Disease Association of San Diego, April-May 2006 issue "Parkinson Post").
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