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Restless Legs Syndrome

Restless Legs Syndrome

Restless Legs Syndrome (RLS) and Periodic Leg Movements during Sleep (PLMS) should not be confused with each other. Indeed, Restless Legs syndrome is a neurological disorder with established effects on the quality of life and health. In contrast, Periodic Leg Movements during Sleep is a polysomnographic finding of unknown clinical significance. While the majority of RLS patients also have PLMS witnessed during nocturnal polysomnography, but in contrast, many patients with PLMS do not have RLS.

Restless Legs Syndrome (RLS)

RLS is increasingly recognized as an important neurological disorder. It is about twice more common in women versus men and increases with aging. Awareness has come from public education efforts by the RLS Foundation and the realization by the pharmaceutical industry that a significant part of the population is affected by RLS (3% severely affected). In spite of these efforts, however, the disorder is often not considered by neurologists, academia and funding agencies as an important condition.

RLS symptoms can range from the very mild or transient (for example a few times during pregnancy) to severe, occurring every evening and being excruciatingly painful. The following symptoms are characteristic of RLS:

Patients may displays one or more of the following symptoms:

  • A strong urge to move the legs, which may be irresistible.
  • Uncomfortable sensations in the legs. Words used to describe these sensations include: painful, creeping, itching, pulling, creepy-crawly, tugging, or gnawing.
  • RLS symptoms start or become worse when resting. The longer patients are resting, the greater the chance the symptoms will occur and the more severe they are likely to be.
  • RLS symptoms are worse in the evening especially when lying down.
  • RLS symptoms get better when the patient move the legs. The relief can be complete or only partial but generally starts very soon after starting an activity (for example walking). Relief persists as long as the motor activity continues.
  • RLS can cause difficulty in falling or staying asleep which can be one of the chief complaints of the syndrome.

A substantial number of people who have RLS also have periodic limb movements of sleep (PLMS). These are jerks that occur every 20 to 30 seconds on and off throughout the night. This can cause partial awakenings that disrupt sleep. Typically, these movements affect the legs but may also affect the entire body. Poor sleep can seriously impact work, relationships, and health.

Cause of Restless Legs Syndrome

Research in the area of RLS has advanced over the last few years. First, there has been a growing realization that low brain iron metabolism may be a critical pathway in the pathophysiology of RLS. Blood ferritin levels are often lower in RLS patients (typically below 50 µg/L), and iron deficiency seems to be most pronounced when measured in the brain or CSF. Iron deficiency can also produce anemia (Low hemoglobin and red blood cell count) and fatigue. If iron deficiency is discovered, it is important to establish its cause.

The cause of RLS also likely involved abnormal Dopamine. Dopamine is an important neurochemical in the brain that is involved in sleep, movements (for example low dopamine is partially responsible for Parkinson’s disease), and the control of pleasurable emotions. For this reason some of the treatment used for Parkinson’s diseases called Dopaminergic agonist can be effective in the treatment of RLS, although they should be used with caution (see below).

Genetic factors are strong predictors of RLS. First, RLS commonly runs in family, especially when it is severe and start early in life. DNA changes in five genes have been associated with RLS. These genes are MEIS1, BTBD9, MAP2K5/LBXCOR1, and PTPRD. Interestingly, these genes are mostly DNA binding factors and some are highly expressed in the spinal cord. Although unproven, it is likely that polymorphisms at the level of these genes modulate how the spinal cord process sensory inputs and/or regulate spinal cord motor reflexes. This disturbance would also explain the association of RLS with Periodic Leg Movements during sleep (PLMS).

Environmental factors and other medical problems are also associated with RLS. Most notably, RLS is frequently exacerbated or may start during pregnancy. Second, in addition to iron deficiency, RLS can be caused or exacerbated by renal/kidney failure, spinal cord/back pain issue, and is likely more frequent in people who have damaged peripheral nerves ending, such as in those with peripheral neuropathy (for example in patients with long term diabetes).

RLS may be associated with other conditions, and has been suggested to predispose to depression and heart disease.

Diagnosing Restless Legs Syndrome

The diagnosis of RLS is primarily clinical, and sleep studies are generally not needed. To meet criteria for RLS, the urge to move and abnormal leg sensation must be worse in the evening and at rest, and must be relieved with movement such as walking or stretching the legs. These criteria differentiate RLS from other neurological problems such as those involving peripheral nerve damage. The major issue in RLS is to sufficiently severe and frequent to require treatment.

Stanford Sleep Specialists may elect to conduct a nocturnal polysomnogram to evaluate for the presence of Periodic Leg Movements during Sleep (PLMS, also called nocturnal myoclonus). The polysomnogram continuously records brain waves during sleep, as well as a number of nerve and muscle functions during nighttime sleep. During the test, 90% of RLS patients with have a high number of PLMs during sleep and even while awake. Typically a Periodic Leg Movement Index per hour of Sleep (PLMS) and wake (PLMW) is reported. A PLMS index higher than 5 per hour is generally supportive of a diagnostic of RLS. Importantly, however, many people have PLMs (especially with increased age) without RLS. The significance of PLMs without RLS is unclear at this time, and may represent a normal variant.

RLS can affect children and may be difficult to diagnose in this population. RLS symptoms in children may include ”growing pains” or problems with “attention and hyperactivity disorders”.

As mentioned above, a work up of RLS requiresmeasuring blood ferritin level and a CBC, if not done prior to the visit to the sleep clinic. A careful medical and drug history is also needed to exclude confounding/exacerbating factors or associated problems.

Treating Restless Leg Syndrome

Sleep specialists normally treat RLS with a combination of pharmacological treatments and behavioral advices. The Restless Legs Foundation provides patient education and support.

Non-drug treatment may include: Iron and vitamin supplementation (especially if anemia or iron deficiency), removing treatments that can make RLS worse (for example neuroleptic, antihistamine, antidepressants), eliminating alcohol or caffeine intake, exercise, walking, stretching, taking a hot or cold bath, massaging, acupressure, or relaxation/mind engagement techniques.

Drug treatments may include: Dopaminergic agents (L-DOPA or Dopaminergic agonists drugs also used for Parkinson’s disease), gabapentin and opiates. Other sleeping aids, anticonvulsants, and pain relievers may also be used. Treatment duration varies and could require frequent adjustment of medications to get the best response. Although dopaminergic stimulants such as ropinirole and pramipexole are the only drugs approved by the Food and Drug Administration for the treatment RLS, the other treatments are also effective. All these drugs may produce side effects and must be prescribed by a doctor.

The decision to treat RLS should not be taken lightly, especially if a Dopaminergic drug is prescribed, as chronic treatment with L-DOPA or Dopaminergic agonists can lead to a worsening of RLS called augmentation. If augmentation occurs, the usual dose of a dopaminergic agent will relieve symptoms helping to sleep at night, but eventually, the unpleasant sensations will develop earlier in the day. Augmentation of RLS symptoms may occur after an initial period of relief with dopaminergic agents, and unfortunately, increasing your dosage will probably worsen your symptoms. Once Augmentation has occurred, it is difficult to stop the drug, as it typically exacerbates the symptoms. If augmentation occurs, you and your doctor must work together to find a new drug regimen that will work for you.

Periodic Leg Movements of Sleep (PLMS)

PLMs are limb movements of 0.5-5 sec duration that typically occur in batches of 30 minutes or more with a periodicity of 5-90 minutes during the night. These are recorded during Nocturnal Polysomnography using anterior tibialis Electromyogram (EMG) recordings (limb electrodes).

It is important to distinguish periodic legs movements from leg movements that do occur if patients are waking up for other reasons, for example because of sleep apnea. A series of four or more PLM's with an interval between 5 and 90 sec between the onset of each limb movement is considered periodic. It is also helpful to note whether the periodic movement are leading to an arousal, and disturbing sleep. As mentioned above, a PLM index (PLMI) above 5/hour may be supportive of RLS. Although a PLMI above 5/hour is not considered a formal disease in isolation of RLS symptoms, some authors have suggested it is part of the same disease continuum (PLM disease, or “PLMD” if associated with significant sleep disruption). Indeed, several of the genes associated with RLS, notably MEIS1, BTBD9 are also associated with PLMS independently of RLS.


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