Symptoms may resolve with correction of coexisting iron-deficiency anemia and often respond to dopamine agonists, levodopa, diazepam, clonazepam, gabapentin, or opiates. Dopaminergic therapy is the preferred treatment for restless legs syndrome and should be initiated with long-acting dopamine agonists (eg, pramipexole 0.125–0.75 mg or ropinirole 0.25–4.0 mg once daily) or with the rotigotine skin patch to avoid the augmentation that may be associated especially with carbidopa-levodopa (25/100 or 50/200 taken about 1 hour before bedtime). Augmentation refers to the earlier onset or enhancement of symptoms; earlier onset of symptoms at rest; and a briefer response to medication. When augmentation occurs with levodopa, a dopamine agonist should be substituted. If it occurs in patients receiving an agonist, the daily dose should be divided, another agonist tried, or other medications substituted. Dopamine agonist therapy may be associated with development of impulse control disorders. Gabapentin is effective in reducing the severity of restless legs syndrome and is taken once or twice daily (in the evening and before sleep). The starting dose is 300 mg daily, building up depending on response and tolerance (to approximately 1800 mg daily). Oral gabapentin enacarbil (600 or 1200 mg once daily) may also be helpful. A recent study suggests that pregabalin, a related drug, is also effective at a daily total dosage of 150–300 mg, taken in divided doses. Clonazepam, 1 mg daily, is also sometimes helpful, especially for those with intermittent symptoms. When opiates are required, those with long half-lives or low addictive potential should be used. Oxycodone is often effective; the dose is individualized.
A recessively inherited (13q14.3–q21.1) disorder of copper metabolism, Wilson’s disease is characterized biochemically by reduced serum copper and ceruloplasmin concentrations, pathologically by markedly increased concentration of copper in the brain and viscera, and clinically by signs of hepatic and neurologic dysfunction. Neurologic signs include tremor, choreiform movements, rigidity, hypokinesia, and dysarthria and dysphagia. Siblings of affected patients should be screened for asymptomatic Wilson’s disease.
Treatment involves the removal of excess copper, followed by maintenance of copper balance. Dietary copper should also be kept below 2 mg daily. Penicillamine (dimethylcysteine) has been used for many years as the primary agent to remove copper. It is a chelating agent that forms a ring complex with copper (see Chapter 57). It is readily absorbed from the gastrointestinal tract and rapidly excreted in the urine. A common starting dose in adults is 500 mg three or four times daily. After remission occurs, it may be possible to lower the maintenance dose, generally to not less than 1 g daily, which must thereafter be continued indefinitely. Adverse effects include nausea and vomiting, nephrotic syndrome, a lupus-like syndrome, pemphigus, myasthenia, arthropathy, optic neuropathy, and various blood dyscrasias. In about 10% of instances, neurologic worsening occurs with penicillamine. Treatment should be monitored by frequent urinalysis and complete blood counts.