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Restless Legs Syndrome
Diagnosis Associated Features Associated features of RLS include that those are frequently found in affected individuals but are not specific to the diagnosis of RLS (Table 3). Table 3
Modified from Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4(2):101-119. The natural clinical course of RLS is dependent upon whether the RLS is a primary or a secondary form of the disorder. As mentioned previously, in primary RLS, the onset of symptoms typically occurs at a younger age, is insidious and slowly progressive, and is not related to any secondary etiology. The onset of symptoms in secondary RLS typically begins after age 40 years. The course is one of more-rapid onset and escalation of symptoms coinciding with the causative factor, i.e., ESRD, pregnancy, neuropathy, and iron deficiency—with or without anemia. The second associated feature of RLS—the disturbance of sleep onset and maintenance of sleep—reflects both the circadian and quiescegenic features of RLS. As the primary precipitating event leading patients to seek treatment, the negative impact of RLS on sleep is at least partially responsible for the reduced quality of life in patients with RLS.2,3,112,145-149 Finally, unless the RLS is related to a secondary condition, the findings on physical examination are typically normal. Identifying and treating relevant secondary causes of RLS will assist in guiding treatment and lead to improved outcome. The diagnosis of RLS is based upon the history obtained from the patient and physical examination, with history confirming the four required diagnostic criteria. The differential includes a variety of neurologic, vascular, and other sensory conditions (Table 5). Table 5
Elicitation of the history should focus on factors related to family history, gross or microscopic blood loss, and the use of or exposure to medications or substances that are known to be associated with an increase in RLS symptomatology (Table 6). Antidepressant medications have been clinically reported to exacerbate RLS, thereby worsening sleep problems.150 Paradoxically, some patients report benefit from the use of these medications.151 Although no studies have clearly addressed these issues, the treating physician should be aware of the potential of tricyclic antidepressants and serotonin reuptake inhibitors to worsen the symptoms of RLS. Table 6
As mentioned in the section on associated features, the examination is typically normal in patients with primary RLS. Findings on physical examination in patients with secondary RLS are most often those related to the associated condition and guide the clinician in obtaining additional testing. Although no standardized tests reveal the diagnosis of RLS, laboratory measures of anemia status, iron stores (e.g., ferritin, total iron-binding capacity, and percentage of transferrin saturation) and serum glucose levels may be warranted. Nerve conduction studies and electromyography may be appropriate for patients with evidence on physical examination of neuropathy. In patients who have symptoms of a sleep disorder other than RLS, polysomnography may be necessary, and results may help to clarify clinical challenges.153,154 
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