Restless Legs SyndromeEtiologyA Swe

Restless Legs Syndrome
Etiology
A Swedish neurologist, Karl A. Ekbom, described a disorder characterized by sensory symptoms and
motor disturbance of the limbs, mainly during rest in the 1940’s and he named the condition “restless legs
syndrome” (RLS), also known as Ekbom’s Syndrome. More than sixty years has passed yet RLS is often
unrecognized or misdiagnosed by physicians and misunderstood by sufferers and their families.
An expert in sleep disorders and author of “The Promise of Sleep”, Dr. William Dement, has referred to
RLS sufferers as one of the most sleep-deprived patients seen in his practice and possibly one of the biggest
completely un-addressed healthcare priorities in America. Awareness and education about RLS is a necessary first
step in helping those who suffer from this debilitating disorder. RLS is classified as a neurologic movement
and/or sensorimotor disorder that inflicts from 5% to 15% of Americans according to the National Institute of
Health. The cause of RLS is currently unknown, although researchers are making significant advances in
understanding this disorder. At the present time, researchers believe that RLS is probably due to a subcortical
brain dysfunction involving the dopaminergic system. Onset of RLS may begin at any age, even infancy, but most
patients who are severely affected are middle-aged or older. There are three known types of RLS, which are
categorized as primary, secondary, or idiopathic.
1. Primary RLS is inherited/familial. Primary RLS inheritance seems to follow an autosomal dominant
pattern based on frequent findings of RLS in children of affected individuals and the nearly equal appearance in
both sexes. Genetic studies are now underway in an attempt to identify the gene responsible for Primary RLS, if
this indeed is a genetic disorder. Recent studies have suggested that patients with RLS and associated conditions
who develop symptoms at a later age are less likely to have affected family members than are patients with
idiopathic RLS.
2. Secondary RLS is usually a reversible form of the disorder seen in patients with iron deficiency, such as
gastrointestinal bleeding, pregnancy, malabsorption, or iron-poor diets. Iron deficiency produces dopamine
abnormalities in animals similar to those seen in RLS patients. Iron has a direct influence on dopamine because
iron is a co-factor for tyrosine, the enzyme required to metabolize dopamine. During late pregnancy, up to 15%
of women develop RLS. Treatment may involve dietary changes or intermittent low-potency pain medications.
After delivery, the symptoms usually disappear. The management of secondary RLS (excluding pregnancy) is
treating the underlying disorder that is causing the iron deficiency and giving the patient iron replacement therapy.
Treatment with iron usually improves or even resolves all RLS symptoms. However, oral treatment may take
several months to be effective and for some patients may be poorly tolerated.
3. Idiopathic RLS is when the disorder develops in a patient with no family history of RLS and there is no
underlying or associated conditions causing the disorder.
Symptoms
Fatigue is often the chief clinical complaint for which most patients initially seek treatment and it is at this
point that a misdiagnosis (such as insomnia) can occur unless the clinician or physician delves further into the
cause of the fatigue. A distinctive characteristic of RLS is that rest, quiet activities, or attempts to sleep evoke
unpleasant sensory and motor symptoms most commonly of the legs and sometimes the arms. Individuals
typically describe their symptoms as worse when sitting or lying down, with a tendency to be more prominent at
night. Sensations range from mild to intolerable combined with a need to move the legs. Patients might describe
their sensations as pulling, prickly, or electric.
Individuals with RLS have a sleep-onset difficulty because lying down and/or sitting activates their
symptoms. In addition to experiencing a prolonged time in falling asleep, patients may have difficulty with sleep
maintenance. A contributory factor can be periodic limb movements while awake. Typically, these are brisk
movements that occur most commonly in the legs. Once sleep is obtained, there is relief, unless the patient is
aroused and the cycle repeats itself. In severe cases, patients may have a total sleep time of only a few hours per
night, which produces extreme daytime fatigue or tiredness. This extreme fatigue does affect an individual’s
performance, functioning, and mental status, but does not cause the sleepiness seen when falling asleep while
driving or in patients with narcolepsy. However, symptoms progress over time in about two-thirds of patients and
may be severe enough to be disabling. Travel by plane, train, or as a passenger in a car can become extremely
unpleasant, as do many other activities that involve prolonged sitting, such as dining, going to the theater,
watching television, or just reading a book.
The RLS Study Group developed a rating scale known as the International RLS that is used to gather
information on the severity of symptoms. Patients rate 10 symptom factors on a scale of 0 (no symptoms) to 4
(most severe). Five of the rating factors pertain to symptom frequency and intensity, and the other five factors
address the effect of the symptom on sleep and daytime function. The patients are then asked to rate the
symptom severity for the preceding week, overall as one of the following:
Assessment and Diagnosis
Restless legs syndrome is diagnosed most often in people in their middle age years and effects females
more than males. Many individuals with RLS, particularly those with primary RLS, can trace their symptoms back
to childhood. These symptoms may have been called “growing pains” or attributed to being “hyperactive”. The
diagnosis is based primarily on the patient’s history and assessment. The physical assessment, laboratory, and
diagnostic testing must rule out other disorders prior to making a diagnosis of RLS. The physical examination is
usually normal in patients with RLS. A serum ferritin level to rule out a ferritin deficiency and a chemistry profile
to rule out uremia and diabetes are routine lab tests. A sleep study (polysomnography) is not routinely indicated
because RLS is diagnosed on the basis of history and clinical findings. The following are particular areas usually
ruled-out.
 Peripheral neuropathy. Causes leg symptoms that are different from RLS and are usually not associated
with motor restlessness or helped by movement, and do not worsen in the evening or nighttime. Sensory
complaints are typically numbness, tingling or pain. Small fiber sensory neuropathies, as seen in diabetes,
can often be confused with RLS.
 Intermittent claudication. This is pain in the legs from poor arterial circulation and most often occurs
during activity and is relieved with rest.
 Nocturnal leg cramps. Nocturnal leg cramps are typically painful, palpable, involuntary muscle
contractions that are most often focal. In addition, they are usually unilateral and have a sudden onset.
 Varicose veins. The examination of the lower extremities usually rules out this disorder. In addition, the
pain with varicose veins most often occurs with increased pressure as seen in the standing position and is
relieved when lying down.
Treatment
The goal for treatment of RLS is to alleviate symptoms – particularly the ones that cause sleep
disturbances and discomfort. The selection of treatment modalities depends on the age of the patient, severity,
duration and frequency of symptoms, and comorbid illnesses, including pregnancy. Life style changes, nutrition,
and iron supplements are first step interventions, however, in many cases, symptoms of RLS progress so that
relief is insufficient with these methods.
There are several medications that can be prescribed to help relieve the symptoms of RLS, but they
currently do not have U.S. Food and Drug Administration approval for the treatment of RLS. Several drugs (that
have FDA approval for other disorders) have been evaluated in the treatment of RLS. The most commonly used
are classified into four categories:
1. Dopaminergic agents
2. Sedatives/Benzodiazepines
3. Opioids
4. Anticonvulsants.
1. Dopaminergic agents
First-line therapy for primary or idiopathic RLS is with dopamine agonists such as pramipexole (Mirapex),
pergolide (Permax), and ropinirole (Requip), as they stimulate dopamine receptors in the body and are useful in
moderate to severe RLS. Although dopaminergic agents are used to treat Parkinson’s disease, RLS is not a form
of Parkinson’s disease. All of these drugs should be started at low subtherapeutic doses and increased slowly to a
level that obtains an optimum effect. This approach is used in order to decrease potential side effects. A side
effect that often results in patients discontinuing the therapy with these agents is hallucinations, seen in 5% to
10% of cases. Other common side effects include nausea, hypotension, syncope, and somnolence. Recent
reports indicate a high efficacy of dopamine agonists, but the role of their long-term use in treating RLS is
unknown.
Of the dopamine precursors, carbidopa-levodopa (Sinemet, Atamet) has been used the longest, but it has
recently been found to cause augmentation, a serious problem in the majority of patients who take it for the
treatment of RLS. Augmentation is when symptoms worsen during drug therapy and may become more severe,
start earlier in the day, and may spread to different parts of the body (from the lower extremities to the upper
extremities). Augmentation can develop shortly after therapy is initiated or may occur years later. Clinicians
should be aware that research is investigating whether or not the dopamine agonist medications might also cause
augmentation. Another important issue with Carbidopa-levodopa, is that it should not be taken within two hours
after eat

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