Melody Ryan; John T. Slevin


Am J Health Syst Pharm. 2006;63(17):1599-1612. 

In This Article


It was the consensus opinion of the Workshop that four essential criteria are required to make the diagnosis of RLS.[3] In uncertain clinical cases, three additional features may support, but are not essential for, the diagnosis. Finally, in addition to identifying essential and supportive criteria, the Workshop outlined associated features of RLS (Appendix A). A distinction between intermittent and daily RLS has been made by the Medical Advisory Board of the Restless Legs Syndrome Foundation, which is helpful for treatment decisions.[51] Intermittent RLS is defined as RLS that is troublesome enough to require treatment but that does not occur frequently enough to necessitate daily therapy. The authors defined daily RLS as RLS that is frequent and troublesome enough to require daily therapy.[51]

PLMS have been quantified in the sleep laboratory; five or more PLMS per hour of sleep are considered abnormal and warrant a diagnosis of PLMD.[3] Although PLMS and PLMD are not specific to RLS, 80% of patients with RLS have five or more PLMS per hour of sleep, suggesting that the diagnosis of RLS should be made with caution in those individuals who do not meet this criterion. Clinical tests such as actigraphy and polysomnography (Appendix B) may help in the assessment of RLS and PLMS.

Other illnesses that may be confused with RLS include nocturnal recumbancy leg cramps and akathisia. The former are painful, palpable, and involuntary muscular contractions that occur suddenly and are often focal and unilateral.[52] Since the introduction of neuroleptic drugs in the mid-20th century, akathisia has been used to describe the sense of restlessness and need to move that is reported by many of the patients taking these drugs. Akathisia does not correlate with rest or time of day.[53] Some evidence, generally from case reports, indicates that RLS symptoms can be induced or exacerbated by medications. In particular, the D2-receptor antagonist metoclopramide and the nonselective opioid antagonist naloxone have been shown to blunt treatment effects of dopamine agonists and opioids, respectively. However, in at least one study, i.v. administration of either metaclopramide or naloxone in untreated patients failed to cause deterioration in the sensory or motor symptoms of RLS.[54]

Other medications reported to increase symptoms of RLS include the selective serotonin reuptake inhibitor (SSRI) fluoxetine,[55] caffeine,[56] and lithium.[57] The adverse effects of fluoxetine, and by extension all SSRIs, may relate to the enhancement of serotonin transmission, which results in inhibition of dopaminergic neurons.[58] Animal studies indicate that chronic lithium treatment decreases presynaptic dopamine release and postsynaptic D2-receptor numbers[59,60]; the effects of both would be expected to produce RLS symptoms. The decreased dopamine release caused by chronic lithium intake has been measured in rat nucleus accumbens and linked to stimulation of serotonin 1A receptors by serotonergic dorsal raphe neurons,[61] suggesting a common mechanism for SSRI-induced and lithium-induced RLS symptoms.

Peripheral neuropathies, especially those affecting predominantly small unmyelinated fibers such as occur in diabetes, can be confused with RLS. However, patients with sensory neuropathies typically describe numbness, tingling, and pain that are not usually associated with restlessness, helped by movement, or confined to evening and nighttime.[62] Because vascular disease, such as deep venous thrombosis, may produce symptoms that mimic RLS, a peripheral vascular examination for peripheral pulses, hair distribution over the legs, and the presence of ulcers should be performed.[37]


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