Chorea Coexisting with Restless Legs Syndrome improvement after 2 weeks. Consequently, carbamazepine and topiramate were replaced with tramadol 150 mg, while maintaining haloperidol 1.5 mg, citalopram 20 mg, and clonazepam 0.5 mg. After the first administration of tra- madol, the pain, dysesthetic restlessness, difficulty in initi- ating sleep, frequent awakenings, and difficulty in falling back to sleep after an awakening slightly improved, and then gradually improved further, followed by improvements in the depressed mood, lethargy, markedly decreased volition and appetite, and feelings of hopelessness. DISCUSSION Peripheral neuropathy is a disorder that needs to be dif- ferentiated from RLS because both conditions include some similar symptoms; however, it is also a main cause of sec- ondary RLS (3). The patient’s dysesthetic sensations in the present case improved with movement but worsened in the evening. The pain continued regardless of movement or time. The findings in his nerve conduction test also supported the presence of peripheral polyneuropathy. As a result, he was thought to have both disorders. Although its pathophysiology is not completely under- stood, circumstantial evidence exists for the role of the dopa- minergic system in the pathophysiology of RLS (4). A positron emission tomography (PET) (5) study and a single-photon emission computed tomography (SPECT) (6) study show- ed significantly decreased striatal D2 receptor activity. Also, there is circumstantial evidence for the role of iron in the pathophysiology of RLS (7). Tyrosine hydroxylase is the rate- limiting enzyme in the production of dopamine and requires iron as a cofactor for hydroxylation of tyrosine (8). Therefore, iron deficiency may reduce dopamine production in the brain indirectly, while dopaminergic agents are effective in thera- py for idiopathic RLS (9). The patient had conditions that would cause RLS, such as end-stage renal disease, iron defi- ciency, and peripheral neuropathy, and then to make mat- ters worse, he was injured in the basal ganglia and thalamus by hypoglycemia. Following the hemodialysis treatment for the end-stage renal disease, his symptoms of RLS were aggra- vated, and after the brain injury, choreic movements devel- oped and symptoms of RLS became extremely severe. In this case, iron deficiency due to ESRD with hemodialysis and poor nutrition might lead to decreased production of dopa- mine, and it would have caused RLS. In addition, the injury of the basal ganglia might have raised a further decrease of dopamine, aggravating RLS. Chorea results from various dysfunctions within the com- plex neural network interconnecting the basal ganglia-tha- lamus-motor cortex (10). In the present case, the choreic movements developed after injuries to the basal ganglia and thalamus and decreased as the injuries recovered, although the movements remained owing to the thalamic infarct. 535 Because anti-dopaminergic drugs are used to treat chorea, dopaminergic agents for RLS could not be used in this case. Gabapentin was prescribed, but the chorea grew worse. Most studies have reported that gabapentin improved pain and dysesthetic sensations without the risk of dyskinesia, but some studies found that gabapentin induced dyskinesia or even chorea. These reports hypothesized that increased gaba- nergic input may precipitate more motor facilitation through the thalamus (11), augment dopaminergic activity in the striatum (12), or indirectly raise the concentration of sero- tonin (13). The patient experienced alleviation of his pain, dysesthet- ic sensations, and insomnia after being prescribed tramadol, which produces both opioid and non-opioid analgesic effects. Tramadol acts on the central nervous system and is known to have an effect on opioid receptors, especially the μrecep- tor, and serotonergic and noradrenergic transporters. The positive pharmacological response to an opioid and the exac- erbation of RLS by the opiate receptor blocker naloxone sup- port the hypothesis that dysfunction of the endogenous opi- ate system is connected to the pathophysiology of RLS (14). Few studies have examined the effect of tramadol on RLS (15). The present case was remarkable because of the risk associated with using dopaminergic or gabanergic drugs given the patient’s complicated medical condition and the observation that tramadol was an effective treatment. The positive effect of tramadol may originate not only from its action on opioid receptors but also through increased activi- ties of dopamine, serotonin, and noradrenalin. However, not only the effect of tramadol but also the recovery from the injury of the basal ganglia, iron supplement, and improve- ment of depression may contribute to the alleviation of the symptoms of RLS. This case suggests that the dopaminergic system participates intricately with the opioid, serotonergic, and noradrenergic systems in the pathophysiology of RLS and pain and indirectly of depression and insomnia. REFERENCES 1. Cardoso F, Seppi K, Mair KJ, Wenning GK, Poewe W. Seminar on choreas. Lancet Neurol 2006; 5: 589-602. 2. American Academy of Sleep Medicine. International classification of sleep disorders, 2nd ed: Diagnostic and coding manual. Westch- er, IL: American Academy of Sleep Medicine 2005; 81-6. 3. Polydefkis M, Allen RP, Hauer P, Earley CJ, Griffin JW, McArthur JC. Subclinical sensory neuropathy in late-onset restless legs syn- drome. Neurology 2000; 55: 1115-21. 4. Allen RP, Earley CJ. Restless legs syndrome. A review of clinical and pathophysiologic features. J Clin Neurophysiol 2001; 18: 128-47. 5. Turjanski N, Lees AJ, Brooks DJ. Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology 1999; 52: 932-7. 6. Michaud M, Soucy JP, Chabli A, Lavigne G, Montplaisir J. SPECT