Restless legs syndrome (RLS) afflicts individuals of all ages. Insufficient public awareness and lack of clinician knowledge result in many untreated patients. A high index of suspicion, appropriate diagnostic tests, and careful selection of treatment regimens usually result in significant clinical improvement and patient satisfaction.
Demographics
RLS affects children, adolescents, and adults. Prevalence ranges from 1%-15%, with most studies showing equal involvement of males and females. The mean age of onset ranges from the late 20s to the early 40s. As many as 38%-45% of patients develop RLS-related symptoms before age 20 years, but the incidence clearly increases with age.
When RLS affects children, it may be confused with attention-deficit disorder. No racial or ethnic differences have been noted. Up to 50% of cases may be familial. Preliminary studies have documented a linkage to the 12q and 14q chromosomes in some families.1,2
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Clinical presentation
At onset, the symptoms may be intermittent. Initially, RLS presents with nighttime complaints as the patient reclines to go to sleep. Primary symptoms involve motor and/or sensory systems. Motor symptoms include jumping or moving, stretching, or bending of the legs. More common are the sensory symptoms of tingling, formication (ants walking on skin), crawling, itching, pulling, overt pain, stinging, nervousness of the legs, electrical sensation, or burning. These symptoms are most prominent distal to the knees but can occur more proximally. The complaints may be unilateral or bilateral in the early stages but almost always become bilateral. Much less common is involvement of the upper extremities. Spontaneous remissions, which occur in some patients, last from months to years.
Although some patients will present with the symptoms previously described, others will complain of excessive daytime somnolence, “tiredness,” or fatigue. Other patients present with difficulty falling or remaining asleep, i.e., disorders of initiating or maintaining sleep. For many women, the first presentation may be disturbed sleep in pregnancy. Often the bed partner will complain about inability to sleep because of the patient’s excessive movements or getting out of bed. Some patients will present with leg pains, such as cramps, aching, jolting sensations, or even “growing pains.”
The International Restless Legs Syndrome Study Group has defined a set of essential and non-essential criteria. Diagnosis requires the presence of all four essential criteria.
Classification
Primary RLS occurs without any underlying condition, while secondary RLS is associated with another condition.
Pregnancy: Symptoms often begin in the second or third trimester and worsen as the pregnancy progresses. Typically, the symptoms abate in the first two postpartum months.
Anemia: Many patients have low serum ferritin levels that may fall before the complete blood count reflects anemia. Although the lower limit of normal for ferritin is 12 ng/mL, patients with symptoms of RLS whose levels are <50 should be considered at risk. An associated inflammatory process (infection, rheumatologic disorder, etc.) can cause an increased ferritin level even in the face of anemia. Therefore, the clinician must interpret the results carefully.
Lyme disease: One patient with myelitis from Lyme disease also had symptoms of RLS.3
Metabolic conditions: Uremia resulting from chronic renal failure is the most common metabolic cause of RLS. Less common are folate deficiency and hypomagnesemia. The mechanism(s) by which these may result in RLS are unknown.
Neurologic states: Polyneuropathy, especially when caused by diabetes, is common. However, the association may not be true in adolescents with type 1 diabetes.
Parkinson’s disease (PD) has many associated sleep disturbances, with RLS being one of the more common. A recent case control study found RLS in 7% of patients with PD versus only about 0.7% of normal case controls.4 The association with PD and the amelioration by the same medications is intriguing, suggesting a role for the dopaminergic pathways. The motor restlessness that characterizes PD may be a source of diagnostic confusion. A careful history can usually differentiate these two conditions. Patients with PD-related motor restlessness have no sensory symptoms and lack diurnal variation.
Isolated case reports document a possible association with other conditions, such as Charcot-Marie-Tooth disease type II,5 chronic demyelinating polyneuropathy,6 hepatitis C with polyneuropathy,7 and cryoglobulinemia with neuropathy, although some patients also had other rheumatologic conditions8 or spinocerebellar atrophy (SCA type 3).9
Medications: Some medications are associated with RLS. Withdrawal of analgesic medications, such as tramadol, may also cause RLS.
Other possible associations: The prevalence of RLS in fibromyalgia and rheumatoid arthritis is estimated to be 31% and 30%,10 respectively; the mechanism is unknown. RLS may also be associated with depression. As in fibromyalgia, the incidence of sleep problems is increased, although the exact prevalence is unknown.
