Restless Legs Syndrome
Periodic Limb Movement Disorder
Periodic Limb Movement Disorder (PLMD) involves excessive movement during sleep. Polysomnography reveals stereotyped limb movments that are >.5 sec, at least 4 movements, separated by >5 sec, < 90 sec. PLMD > 15/hr adults or >5/hr pediatric patients is considered to be significant especially if they are associated with disturbed sleep or resulting in daytime sleepiness or fatigue.
Treatment or PLMD is sometimes necessary and I typically use Dopa-agonists such as Mirapex, or benzodiazepines such as Clonazepam. PLMS can be seen in 80-90% of PSG in patients with a history of RLS but is not synonymous with RLS. Likewise, PLMS is not necessary for the diagnosis of RLS
Restless Legs Syndrome
Originally described in 1652 by Sir John Willis as “Night-Crawler Syndrome”, it was later described by Ekbom who coined the term RLS in 1950’s. Ekbom produced extensive publications, and predicted an incidence of 5-15% of population, as well as correlated it with iron deficiency, which still rings true today.
4 cardinal symptoms or RLS (“URGE”): Urge to move legs associated with unpleasant sensation, Worsening of symptoms with Rest, Improvement of symptoms with movement or Getting up, and that Symptoms tend to increase in Evening and night. However, symptoms can also include creepy-crawly, burning/tingling, aching and arms can be affected too! It has been suggested that RLS can be “tested” by using the Immobilization Test (SIT). The SIT test is a Polysomnogram format during day for 1 hour. The subject sits comfortably awake and upright in bed with legs outstretched. RLS is supported in more than 40 PLMW occur per hour.
Other things can appear similar to RLS. I consider EMG/Nerve conduction testing for peripheral neuropathy if appropriate. Overnight Polysomnography in a Sleep Lab sometimes but rarely needed. Labs such as Iron (% saturation), Ferritin should be perfomed in everyone with RLS. It is also associated with Thyroid Disease, Peripheral Neuropathy, Lumbar Radiculopathy, ADHD and Fibromyalgia.
Approximately 10%-15% of Northern European Population suffers from RLS. Accurate demographics in other populations not yet clear. Treatment usually begins after 4th decade. It is slightly more common in women. Family History of RLS in 50% of patients. It can occur sporadically or with an autosomal dominant pattern. Early onset (before age 45) usually is a familial pattern.
Causes of RLS
Iron deficiency is a common cause of “secondary” RLS. Brain Iron Deficiency may be a cause of “primary” RLS. Patients with low serum Ferritin levels will respond to Iron replacement oral or I.V. Iron is a co-factor for tyrosine hydroxylase, the rate limiting reaction for dopamine synthesis. Iron deficiency may decrease the number of DA-D2 receptor binding sites. Post-mortem studies have shown abnormalities in the substantia nigra (reduced Ferritin and iron transporters). Iron abnormalities may cause problems with dopamine metabolism. This helps explain why Dopamine agents help RLS and why Dopamine antagonists worsen RLS.
A number of genes such as Chromosome 12q (French families), Chromosome 14q (Italian families), and Chromosome 9p (American families) have been linked to RLS. Pregnancy, Gastric surgery, Iron deficiency anemia , End-Stage Renal Disease are all considered secondary forms of RLS. RLS symptoms are more common in smokers, obese patients, and in those who exercise less than 3 hours per month.
Treatment
Quinine can be beneficial in some (now only available in Tonic water). Magnesium in higher doses (500-1000 mg per day) can also be helpful. Exercise can help. Iron replacement should always be perfomed if ferritin/iron saturation are low. The most commonly used medications for RLS include Benzodiazepines (Klonopin), AED’s: Depakote, Topamax, Narcotics (Vicodin) and Dopa Agonists (Mirapex, Requip). Levodopa/Carbidopa may encourage “anticipation” and is not considered first line therapy at this time. Requip may require higher dosages and hence S/E can include syncope, hypotension, nausea, sleep attacks. Mirapex is usually effective at 0.125 mg nightly though some patients need higher doses or more frequent dosing.
Many medications can exacerbate RLS including Antihistamines (OTC sleep aids, allergy meds), TCA’s (Elavil, Pamelor), SNRI’s (Effexor, Cymbalta), SSRI’s (Zoloft, Paxil) and Dopamine antagonists (Seroquel, Zyprexa).
