RESTLESS LEGS SYNDROME

Etiologies

†††† This condition afflicts persons of all age groups but is seen more commonly in persons who are middle-aged and older.† According to the International Restless Legs Syndrome Study Group, four criteria must be fulfilled in order to establish the diagnosis:† (1) a desire to move the limbs, often associated with paresthesia or dysesthesia, (2) symptoms are exacerbated by rest and relieved with activity, (3) motor restlessness, and (4) nocturnal worsening of symptoms.† Other associated symptoms include: periodic movements of the limbs during sleep, periodic limb movements while awake, and sleep disturbance secondary to limb discomfort or jerking movements.

     This syndrome may be secondary to idiopathic disease or may be a manifestation of an underlying disease state.  Symptoms are common during pregnancy and generally resolve in the postpartum period without treatment.  Iron deficiency, peripheral neuropathy, folate deficiency, diabetes mellitus, Lyme disease, hypomagnesemia, and chronic renal failure are common causes of secondary disease and should be excluded in the work-up.† Measurement of the serum ferritin, iron and total iron-binding capacity should be performed in all patients, as this may be an initial presentation of iron deficiency.† In fact, iron deficiency need not be present as symptoms may occur despite a normal ferritin level.† If the ferritin is less than 45 micrograms/L, a trial of iron supplementation should be instituted and the response to therapy should be noted.† The goal is to increase the serum ferritin to approximately 50-60 microgram/L.† A complete workup to determine the etiology of the iron deficiency should also be instituted.† Also, remember to question patients if they are recurrent blood donors, as this may be the underlying etiology of their iron deficiency.† Medication side effect should always be considered, and a careful review of the patientís medications should be undertaken.† A trial of discontinuation of any medication which may be causing restless legs syndrome should be instituted when appropriate.† Common medications which aggravate this condition include tricyclic antidepressants, serotonin reuptake inhibitors, and dopaminergic antagonists.

†††† Patients without an identifiable etiology should be advised to avoid caffeine, alcohol and nicotine.† Various physical treatment modalities include hot or cold baths, whirlpool baths, massage therapy of the limbs, or vibratory/ electrical stimulation of the feet and toes.† When there are associated varicose veins, the injection of sclerosing agents to ablate the varicosities may also cure the symptoms of restless legs.

†††† Pharmacologic management includes ropinirole (0.25 2-3 hours before bed with food and titrated up to 3.0 mg/day as tolerated or until symptom resolution), pramipexole (0.125 mg taken 2-3 hours before bed with food and titrated up to 0.5 mg as tolerated or until symptoms resolution), carbidopa/levodopa immediate release or SR (levodopa/carbidopa 25/100 mg tablet taken 1 to 2 hours before sleep and titrated up to effect), Permax (0.05mg before bedtime and increased in increments of 0.05 mg until relief-usually 0.1 to 0.75 mg but may require up to 1.5 mg), Parlodel (1.25 mg at bedtime increased in 1.25 mg increments with a usually therapeutic dose of 5 to 15 mg), klonopin, opioids, clonidine hydrochloride (0.1 mg before bedtime and increased weekly by 0.1 mg with a maximum dose of 1 mg), and gabapentin (starting dose of 100 to 300 mg at bedtime and increase in increments of 100 to 300 mg until effect or a maximum of 2,400 mg/day).† In general, all medications should be started at the lowest possible dose and titrated up to the lowest effective dosage.† They should be administered one to two hours prior to the patientís bedtime, and the patient should be instructed to take additional doses if symptoms awaken the patient during the night.† Once tolerance to one medication develops, the patient should then be rotated to another effective therapy.† In fact, monthly rotation between several agents that are effective at controlling symptoms may help prevent the development of tolerance.† In secondary disease, treatment of the underlying condition may resolve the restless legs syndrome.