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Restless Legs Syndrome

Restless Legs Syndrome (RLS) – Causes – Symptoms – Treatment – Treatment Complications – Augmentation – Iron Deficiency – Inheritance – Pregnancy

Symptoms of Restless Legs Syndrome

Restless legs syndrome (RLS) is characterized by an urge to move the legs while being at rest caused by unpleasant sensation in the legs. It should not be confused with habitual foot tapping or an urge to move without any leg discomfort.

The majority of patients experience unpleasant sensations in the legs relieved by walking or by leg movements. There are no cramps. The sensation in the legs is often described as tingly, achy, crawly or similar. The most common location of the leg discomfort is in the cuff area, typically on both legs.

The symptoms are worse at rest, no matter sitting or lying down. Long trips by car or by plane are challenging. The discomfort is the worst at night and evening hours, at least initially.

A disturbed night sleep due to pain in the legs is very common. Unpleasant sensation in the legs leads to frequent awakening. The patients often get out of bed, walk around, and then go back to sleep.

In severe cases of restless legs syndrome the symptoms may spread to the upper body or appear in the morning hours. Over years, the relief brought up by walking may lessen.

Leg discomfort does not have to be symmetrical. Some patients have symptoms in one leg and the sides may switch from time to time.
There are multiple disorders that may mimic restless legs syndrome: leg cramps, arthritis, neuropathy or swelling of the legs.

Cause of Restless Legs Syndrome

Iron deficiency is common. There is a scientific evidence of low iron depot in some brain areas (basal ganglia). Abnormalities of iron transport to the brain might be responsible for the disease because iron supplementation alone does not always relieve the symptoms.

Another problem is a low sensitivity of some brain areas to dopamine, which pretty much explains the benefit of dopaminergic drugs in restless legs syndrome.

Recent blood loss and pregnancy are well-known precipitating factors of RLS. Some medications, such as antidepressants, antihistamines, and neuroleptics may bring up the symptoms restless legs syndrome.

Diagnosis of Restless Legs Syndrome

There is no confirmatory diagnostic testing for restless legs syndrome. The diagnosis is based exclusively on neurological examination and detailed medical history. Worsening of leg discomfort towards the end of the day and during rest is the most striking feature of RLS.

It always makes sense to obtain blood levels of ferritin, iron-binding capacity and percent of transferrin saturation. Statistically, about 40% of patients with restless legs syndrome have evidence of iron deficiency.

All other diagnostic tests are meant to rule out other disorders that imitate RLS.

Prognosis of Restless Legs Syndrome

Restless legs syndrome is present in 1.5 to 3.0 % of the population. It is more common in women. Frequency of this disorder is increasing with age. Over 50% of patients have family history of restless legs syndrome.

The intensity of RLS symptoms varies from daily to occasional. Severity of the symptoms often progresses over years. Remissions for a few months are not uncommon.

Moderate to severe RLS significantly degrades the quality of life. Fifty to eighty five percent of patients report difficulty falling and staying asleep. Studies also show an increased frequency of anxiety and depression.

Treatment of Restless Legs Syndrome

Iron supplementation is a reasonable treatment approach for the patients with iron deficiency. Iron supplementation works well in RLS due to recent blood loss and during pregnancy. Iron supplementation effect is suboptimal at best in patients with chronic and inherited varieties of this condition.

The most effective medications are Mirapex (pramipexole), Requip (ropinirole), and Neupro (rotigotine) patch. All these medications imitate actions of dopamine and are originally marketed for the treatment of Parkinson’s disease. This class of medications is called Dopaminergic Medications.

Doses administered for RSL are much lower than those for treatment of Parkinson’s. Low doses of those medications are generally well tolerated.

Long term use is limited by side effects. The main problem is Augmentation which occurs in 42% of the patients. Augmentation has to be suspected when RLS symptoms shift to the morning hours or spread to the upper half of the body. Higher doses may alleviate the symptoms for some time but worsening augmentation may eventually necessitate a discontinuation of treatment.
Impulse Control Disorder develops in about 15% of patients on dopaminergic drugs after 9 months on average. The symptoms of impulse control disorder are pathologic gambling, compulsive shopping and hypersexuality. These side effects resolve promptly after the drug is discontinued.
An excessive daytime sleepiness develops in about 50% of people on these drugs.

Gabapentin at relatively high doses has been shown to be effective for restless legs syndrome without causing augmentation. Most common side effects are sleepiness, dizziness, lack of balance, weight gain and edema.

Opioids (narcotics) are very efficient for restless legs syndrome. The best option is probably Methadone, which has been shown to stay effective for many years without developing tolerance.
Narcotics, however, have to be reserved for severe cases of RLS due to high risk of dependence.

Benzodiazepines, such as Clonazepam, were among the first drugs tried for RLS. They probably help by improving sleep rather than by alleviating the actual symptoms of restless legs syndrome.

Restless Legs Syndrome during Pregnancy

Restless legs syndrome is the most common movement disorder during pregnancy. It affects between 10% and 26% of pregnant women, which is 2 to 4 times of the incidence in general population. Genetic forms of RLS may first present or get worse during pregnancy. Pregnancy associated RLS typically starts in the second or third trimester and resolves after delivery.

Treatment during pregnancy is complicated by the fact that Ropinirole (Requip) has been associated with fetal growth retardation, birth defects, and fetal death in animals.

The first step is a blood test for iron deficiency. Iron supplements are OK when the deficiency is present. On the other hand, iron supplementation trials during pregnancy are not recommended without documented iron deficiency.

Levodopa is believed to be an acceptable option during pregnancy, but it has to be reserved for severe cases. Normally, Levodopa is only rarely used for restless legs syndrome treatment because of very high rate of augmentation phenomenon (see above).

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