Restless Leg Syndrome

Restless legs syndrome (RLS) is characterized by unpleasant sensations of the legs that are worse in the evening and at night, and that are relieved by movement. Most patients with RLS also have movements of the legs that occur periodically at 20- to 30-second intervals for minutes to hours during sleep. Although the term nocturnal myoclonus sometimes is used to describe these movements, they usually are not sudden lightning-like movements. Rather, they typically last for about 1 second and consist of extension of the great toe with variable degrees of ankle extension, knee extension, and hip extension or flexion.

PLMS (previously called nocturnal myoclonus) is a disorder in which repetitive, brief, and stereotyped limb movements occur during sleep, usually about every 20 to 40 seconds. Dorsiflexions of the big toe, ankle, knee, and sometimes the hip are involved. Periodic movements occur during sleep but the unpleasant evening and nighttime sensations are absent. Arousals associated with the PLMs may lead to complaints of insomnia or daytime sleepiness, or the disorder may be asymptomatic (Without Symptoms).

Features of Periodic Limb Movements in Sleep

Leg kicks every 20-40 s
Duration of 0.5-5 s
Complaints of;

  • Insomnia
  • Excessive sleepiness
  • Restless legs
  • Cold or hot feet
  • Uncomfortable sensations in legs

Individuals with PLMS are reported to sleep about an hour less per night than control subjects without PLMS. Interestingly, the prevalence of PLMS is not higher in insomniac patients than in those without insomnia. Complaints of excessive daytime sleepiness increase in individuals with PLMS, probably consequent to the numerous sleep interruptions. The psychiatrist may find it useful to talk with a bed partner, who will often describe kicking and leg twitches during sleep in individuals with PLMS.

The myoclonic movements are not related to seizure disorder but should be distinguished from seizures. Because complaints of insomnia and daytime sleepiness are not uncommon, other insomnias, sleep apnea, and narcolepsy should be ruled out.

Symptoms

Questioning of the patient or bed partner often yields reports of restlessness, kicking, cold feet, disrupted and torn bedclothes, un-refreshing sleep, insomnia, or excessive daytime sleepiness. Patients may be unaware of these pathological leg movements or arousals, although their bed partners may be all too aware of the kicking, frequent movements, and restlessness.

Patients with RLS complain of a gradual buildup of a subcutaneous crawling, pulling, itching, aching, or pins-and-needles sensation that affects the muscles or bones of the calves and thighs. As the sensation builds, the associated urge to move gradually becomes irresistible and movement provides temporary relief. Most patients have insomnia with difficulty getting to sleep and frequent awakenings during which they may flex and extend the legs, repeatedly turn over in bed, or get out of bed and walk. About 80 to 90 percent of patients with RLS have PLMs, usually during light NREM sleep, that contribute to awakenings and arousals.

During the day and especially during attempts to remain still, many patients fidget, swing their legs, or have movements that are similar to the extensor movements during sleep. Apart from the movements, neurological examination is usually normal.

In PLM disorder, the condition is associated with arousals that lead to sleep disruption and complaints of insomnia or daytime sleepiness, but the sensory symptoms and waking dyskinesias that accompany RLS do not occur. Although severely affected patients may produce movements throughout sleep, PLMs may also be entirely asymptomatic, causing no disruption of sleep patterns, and are sometimes brought to medical attention either as an incidental finding on a polysomnogram or because the spouse is unable to sleep owing to the leg jerks and kicks.

Tests

If these disorders are strongly suspected, the patient should probably be referred to a sleep disorders laboratory for evaluation. The following tests should be performed:

  • Overnight Polysomnogram with Tibial Electromyograms
  • EEG
  • CBC
  • Serum Iron and Ferritin Levels
  • Renal Function Tests
  • EMG and Nerve Conduction studies (In selected individuals)
  • Fasting glucose
  • Electrolytes – Sodium, Potassium, Calcium and Mg Levels
  • B12, folate levels
  • BUN, Creatinine

Causes

Unknown; hereditary factors are involved in some patients

In the elderly

Many medications have been associated with this disorder, especially tricyclic antidepressants, and elimination of all potentially psychoactive drugs should be the first therapeutic approach. In REM sleep behavior disorders, the usual sharply reduced motor tone characteristic of REM sleep is replaced by a tendency to act out dreams, sometimes in very dramatic fashion. As opposed to sleepwalking, which occurs in sleep stages 3 and 4, when individuals are very hard to arouse, patients with REM disorders remember the dream content, which is often very frightening. Not surprisingly, these episodes can be mistaken for manifestations of dementia.

Pathogenesis and Pathophysiology

Although the pathophysiological basis for RLS and PLMs is unknown, disinhibition of a CNS pacemaker that affects reticular excitability may contribute. The similarity of PLMs to the extensor response to plantar stimulation (Babinski’s sign) or to a triple flexion response suggests that pyramidal or dorsal reticulospinal tract dysfunction is involved. Functional dopamine or opiate insufficiency, perhaps related to abnormal iron metabolism, may also play a role. Abnormal sensory input may be a factor in some patients.

Some studies suggest that the movements arise subcortically from the brain or spinal cord; others suggest subclinical peripheral neuropathy.

Who Gets RLS and PLMS?

The prevalence of RLS is about 2 to 5 percent for the adult population and increases with age, but many patients report having had the same sensations as adolescents and even as children. . Men and women are affected equally, and symptoms begin after age 40 in most patients. About one third to one half of patients report that other family members are affected, and in some families, the syndrome occurs in a pattern consistent with an autosomal dominant inheritance. Periodic limb movements without waking symptoms of RLS occur in about 5 percent of persons between ages 30 and 50 years and in 30 to 45 percent or more of persons older than 65 years of age.

Whereas almost all patients with restless legs syndrome have PLMS, not all patients with PLMS have restless legs syndrome. Restless legs syndrome may be frequent in patients with uremia and rheumatoid arthritis or in pregnant women.

In sleep disorders clinic populations, about 11% of those complaining of insomnia are diagnosed with PLMS.

The prevalence of PLMS in older populations has been estimated to be 44%. This disorder, therefore, may account for many of the complaints reported by elderly people about difficulty in falling asleep. In the elderly, however, this condition is extremely common; more than 40% have at least five leg kicks per hour of sleep.

Risk Factors

Peripheral neuropathy may be a factor in some cases, although peripheral nerve function is clinically normal in most affected patients. Symptoms occur in 10 to 20 percent of pregnant women and usually resolve postpartum. Other disorders that may be associated with PLMs or RLS include venous disease, degenerative CNS disorders, and vitamin deficiency.

RLS and PLMs may be induced or aggravated by a variety of conditions. The list below summarizes these conditions:

Chemical agents

  1. Caffeine
  2. Antidepressants (Trazadone & Nefazadone are exceptions)
  3. Dopamine Antagonists
  4. Metoclopramide
  5. Calcium Channel Blockers
  6. Theophylline
  7. Adrenergics
  8. Withdrawal from Sedatives/Narcotics can augment symptoms.

Diseases

  1. Peripheral Neuropathy
  2. Radiculopathies
  3. Neurodegenerative Diseases
  4. Movement Disorders – Parkinson’s
  5. Diabetes
  6. Anemia
  7. Electrolyte Deficiencies which may involve Potassium, Calcium or Magnesium -Low normal values may indicate a low tissue level
  8. Chronic Renal Failure

Treatment

Because the pathogenesis of PLMS is usually unknown, treatment is often symptomatic. Walking about, rubbing or moving the limbs briefly relieves the symptoms. Other interventions for RLS and PLMS include eliminating aggravating factors:

  • Removal of caffeine containing foods, beverages, and OTC drugs can often result in improvement.
  • Avoidance of most antidepressants (Serzone and Trazodone excepted)
  • Avoidance of dopamine blocker antipsychotics, metoclopramide (Reglan), and calcium channel blockers.
  • Supplement essential minerals: K, Ca, Mg, if indicated – being careful not to overtreat (especially in presence of K-sparing diuretics).
  • Ferrous sulfate in individuals with a ferritin level of 50 mcg/ml or less
  • Regular sleep habit with adequate 7 1/2-8 hrs sleep time
  • Mild to moderate regular exercise is particularly helpful to RLS/PLMS patients

Medications Include:

  • Levodopa – Sinemet (Beginning with 25/100, 30 minutes before bedtime) (Suggesting that the dopamine system may be involved)
  • Opiates (Tylenol with codeine)
  • Gabapentin
  • Carbamazepine
  • Baclofen
  • Clonidine
  • Benzodiazepines are commonly given, not because they eliminate the abnormal movements but because they enable the patient to sleep through the movements without awakening.
  • Sinemet (Beginning with 25/100, 30 minutes before bedtime)
  • Bromocriptine (2.5-7.5 mg a few hours before sleep)
  • Clonazepam may be useful

Each type of treatment has its advantages and disadvantages, and the benefit-to-risk ratio of long-term treatment is unresolved.

Evening and bedtime doses of levodopacarbidopa or dopaminergic agonists provide the most benefit in RLS and PLM disorder. Some patients require additional doses during the night or controlled-release formulations. Unfortunately, some patients develop tolerance and require increasing doses, whereas others develop increased daytime symptoms of restless legs. If necessary, levodopa-carbidopa can be given around the clock to such patients. Temporary withdrawal and reinstitution of therapy a few weeks later may improve efficacy.

Benzodiazepines, particularly clonazepam, can be used either alone or in combination with dopaminergic agents for RLS and for PLM disorder. Daytime sedation, tolerance, and loss of efficacy are the major problems encountered with these drugs. Opiates such as propoxyphene, codeine, and hydrocodone also reduce the unpleasant sensations and can be used alone or in combination with dopaminergic agents and benzodiazepines. Clonidine, baclofen, carbamazepine, and gabapentin are sometimes helpful.

For patients with PLMs without RLS, it may be difficult to determine the extent to which PLMs contribute to daytime symptoms. The decision to treat PLMs depends on the frequency of movements and associated arousals and on the clinical assessment of the degree to which other sleep disorders contribute to symptoms.

Differential Diagnosis

The diagnosis of RLS is based on the history. The essential elements are the urge to move associated with sensory phenomena in the legs, motor restlessness, and exacerbation at rest and in the evening and night. The differential diagnosis may include akathisia, peripheral neuropathy, claudication, and leg cramps. With akathisia caused by phenothiazines, there is restlessness of the body and a compulsion to move, but the sensory component is less than with RLS and it is usually not exacerbated at night. Neuropathic dysesthesias are usually more distal than proximal, are felt more on the surface than in deeper structures, and are not relieved by movement. Claudication is brought on by exercise and relieved by rest, which is the reverse of the pattern with RLS. Leg cramps are associated with palpable tightness of muscles that does not occur with RLS.

Differential diagnosis of PLMs includes sleep starts and a variety of other movements during sleep. Sleep starts are vigorous myoclonic jerks of the extremities or trunk that occur at sleep onset but do not recur periodically. Most other types of movements and behaviors during sleep are not periodic.

Prognosis and Future Perspectives

RLS has a variable course. Some patients have long periods of relative stability, whereas others worsen with age. Permanent remissions are rare.

For more information on RLS

Be sure to visit the official foundation for Restless Legs Syndrome. Yes there is one! They have a website full of up to date information on RLS. They also have a newsletter called Nightwalkers.

The Restless Legs Syndrome Foundation, Inc

Recommended reading for those of you suffering with RLS

Sleep Thief, Restless Legs Syndrome
Author: Wilson, Virginia N.
Editor: Walters, Arthur S.

References

Tasman: Psychiatry, 1st ed., Copyright ? 1997 W. B. Saunders Company Pages 1234-1235

Goetz: Textbook of Clinical Neurology, 1st ed . , Copyright ? 1999 W. B. Saunders Company 1114-1115

Goldman: Cecil Textbook of Medicine, 21st ed., Copyright ? 2000 W. B. Saunders Company Page 2031

Duthie: Practice of Geriatrics, 3rd ed., Copyright ? 1998 W. B. Saunders Company Page 240,

Dambro: Griffith’s 5-Minute Clinical Consult, 2001 ed . , Copyright ? 2001 Lippincott Williams & Wilkins Page 938

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