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during treatment to evaluate treatment benefit. This wellvalidated scale has been used in treatment studies, 27 and up-dated versions of the scale are available online from the MAPI Research Institute (www.mapi-research-inst.com). RLS and Periodic Limb Movements in Sleep (PLMS) and Waking (PLMW) Many RLS patients also experience periodic limb movement disorder (PLMD), which may be manifested as periodic limb movements in sleep (PLMS) and in waking (PLMW). 1 Approximately 85% of RLS patients also experience PLMS, 4 and the finding of PLMS supports a diagnosis of RLS. PLMS, however, also commonly occurs independently, especially in the elderly. Characteristics of PLMS include the following: 6 Table 2. Key Questions for Patients Who May Have RLS ✦ Do you feel an urge to move your legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs? ✦ Does this urge to move begin or worsen when you lie down, rest, or are inactive? ✦ Is the urge to move partially or totally relieved by walking or stretching, as long as the movement continues? ✦ Are your symptoms worse in the evening or at night, or do they only occur during the evening or the night? ✦ Involuntary, stereotypic, slow leg and hip movements (0.5 to 5 seconds in duration) while asleep ✦ Movements occur periodically (usually every 20 to 40 seconds) ✦ Movements can be associated with awakenings and arousal ✦ PLMS are nonspecific and may occur in isolation or with narcolepsy, REM (rapid eye movement) sleep behavior disorder, or sleep apnea PLMW may also occur for RLS patients. These movements are less common for elderly patients and are therefore more specific for the diagnosis of RLS. However, the sensitivity of this measure is not known. PLMW may occur during the night, when the patient lies awake in bed, or in the evening, when the patient is lying down or seated with legs outstretched. Treatment Options Iron Supplementation. Patients with RLS often have a decreased level of ferritin and an elevated level of transferrin in their cerebrospinal fluid. 17 Furthermore, a low serum ferritin level (
These dopaminergic agents may be recognized by primary care providers as the gold standard for treatment of Parkinson’s disease, in which relatively large doses are administered to control motor abnormalities caused by loss of nigrostriatal dopaminergic neurons. In contrast, relatively small doses of these agents are used to treat RLS, thus minimizing the side effects. It is therefore important that primary care providers not base their decisions to use these agents for RLS solely on their prior experience using them for Parkinson’s disease. Long-term use of levodopa, and possibly the dopamine agonists, promotes augmentation of RLS symptoms. With augmentation, symptoms begin to appear progressively earlier in the day and may become more severe. Augmentation has been reported in approximately 80% of patients who take levodopa, 31 although the process appears to be associated much less frequently with dopamine agonists. 27, 32-34 It must be noted, however, that the dopamine agonists have not been investigated as fully as levodopa in long-term clinical trials. Table 3. Drugs Used to Treat RLS 28 Levodopa’s rapid onset of action (15 to 20 minutes) makes it ideal for intermittent usage when symptoms occur only occasionally, as augmentation is unlikely in this scenario. For patients with daily symptoms, however, a dopamine agonist is suggested as first-line treatment. Sedative-Hypnotic Agents. This class of drugs represents an option if dopaminergic agents are unsuitable. However, at present, there are few data to evaluate the efficacy of these agents for RLS. Sedative-hypnotic agents may be used in combination with the aforementioned agents if sleep initiation remains problematic despite relief of the sensory symptoms of RLS. It must be noted that these agents mask the symptoms of RLS but do not treat the underlying causes of the disease. There are no data available that demonstrate augmentation with sedative-hypnotic agents, although tolerance may develop. The potential for abuse, morning drowsiness, and an increased risk of falls during the night should be considered when prescribing these medications for RLS. Agent Initial Dose Recommended Maximum Daily Dose Serum Half-life Common Side Effects (at levels indicated for Parkinson’s Disease) Dopaminergic Agents Levodopa (Dopar ® , Larodopa ® ) Ropinirole* (Requip ® ) Pergolide* (Permax ® ) Pramipexole* (Mirapex ® ) Sedative-Hypnotic Agents Clonazepam (Klonopin ® ) Oxazepam (Serax ® ) Zaleplon (Sonata ® ) Zolpidem (Ambien ® ) Triazolam (Halcion ® ) 50 mg 0.25 mg 0.025 mg 0.125 mg 0.25 mg 10 mg 5 mg 5 mg 0.125 mg 200 mg at bedtime 4 mg in divided doses (evening and bedtime) 0.5 mg in divided doses (evening and bedtime) 1.5 mg in divided doses (evening and bedtime) 2 mg at bedtime 40 mg at bedtime 20 mg at bedtime 20 mg at bedtime 0.5 mg at bedtime 1.5-2 h 6-8 h † 2-16 h 8-10 h ‡ 30-40 h 5-10 h 1 h † 1.6 h † 2-4 h Nausea, vomiting, augmentation of symptoms, sedation Same as for levodopa, plus nasal congestion and fluid retention Same as for ropinirole Same as for ropinirole Tolerance, sedation Tolerance, sedation Tolerance, sedation Tolerance, sedation Tolerance, sedation 7
Page 1 and 2: RESTLESS LEGS SYNDROME: Diagnosis a
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