Amantadine as Treatment for Levodopa-Induced Dyskinesia

BACKGROUND: Dyskinesia is a common side effect complicating long-term levodopa therapy for Parkinson's disease. However, the pathogenesis of dyskinesia has not been completely understood. In recent animal studies, it has been reported that a NMDA (N-methyl-D-aspartate) antagonist reduced levodopa-induced dyskinesia. These findings suggest that the hyperfunction of NMDA receptors on striatal efferent neurons contributed to the pathogenesis of dyskinesia. Amantadine has also been recently shown to antagonize central NMDA receptors. In the present study, we observed amantadine efficacy in levodopa-induced dyskinesia in parkinsonian patients. METHODS:Twenty-two parkinsonian patients with levodopa-induced dyskinesia participated in a placebo-controlled, cross-over study. We prescribed 100 mg amantadine daily as a starting dose, which was built up every four days and titrated up to 400 mg a day. After two weeks of a wash-out period, a placebo was given with the same schedule. The doses of levodopa and other antiparkinsonian drugs were unchanged during this period. We assessed the duration and disability of dyskinesia (UPDRS part IV, item 32 and 33) based on diary and interview. RESULTS: Amantadine was superior to placebo in reducing the duration of dyskinesia in 9 patients (42.9%) and the disability of dyskinesia in 11 patients (52.4%). The reduction of the duration and disability of dyskinesia was correlated with the dose of amantadine. CONCLUSIONS These findings suggest that amantadine can improve levodopa induced dyskinesia and supports the view that the hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa induced dyskinesia.

A Case of Familial Writer's Cramp

Writer's cramp is one of the most frequent type of task-related dystonia. It is primarily defined by the appearance of involuntary muscle contractions soon after one begins to write and often co-exists with postural tremor. The cause of writer's cramp as well as other focal dystonia is still a matter of debate. Although the genetic background of some dys-tonia was well known, there have been few cases of writer's cramp that involve other family members. We experienced one family with writer's cramp and postural tremor. A 42-year-old man noted handwriting difficulty of gradual onset which began with postural tremor at the age of 25. When he wrote certain letters or numbers, he automatically had to press hard or hold the pen tightly, experiencing tremor as well as dystonia. His mother and four siblings also had simi-lar disabilities. All were right-handed, and had a postural tremor, prominent in their right hands. They noted the onset of symptoms between the age of 20 and 40. The symptoms had slowly progressed over a period of years and no patient described a remission of symptoms. Two of them eventually no longer attempted to write due to writer's cramp. Two members could write but barely readable and the other two had minimal distress. Alcohol somewhat relieved the cramp in only one of them. Levodopa was no beneficial to the cramp and baclofen relieved the cramp minimally. We report this rare case with familial writer's cramp and postural tremor that suggests autosomal dominant inheritance.

Electrophysiologic Study for Estimating the Clinical Severity of Hemifacial Spasm

BACKGROUND AND PURPOSE: Hemifacial spasm(HFS) is a chronic and often progressive disorder characterized by unilateral irregular clonic and tonic contractions of one or more muscles of facial expression. Many previous electrophysiologic studies showed characteristic features of HFS differentiating from other involuntary movements of the face. However, there has been no electrophysiologic study for estimating the clinical severity of HFS. This study was prospectively designed to evaluate the relationships between electrophysiologic findings and clinical severity of HFS. METHODS: The authors performed direct facial nerve stimulation, blink reflex, and lateral spread response in 62 patients with HFS, and compared the results of affected side with those of unaffected each other. Clinical severity was graded into seven groups (0-6) by questionnaire and confirmed by a neurologist. RESULTS: The results were as following. 1) The total number of subjects were 62, the number of patients in group 2 was 3 (4.8%), group 3 was 12 (19.3%), group 4 was 25 (40.3%), group 5 was 21 (33.9%), and group 6 was 1(1.6%). 2) The mean age was 54.5+/-9.1years old, the mean duration of the illness was 6.4+/-4.9years, male was 11(17.7%) and female was 51(82.3%), and involved sites were right in 26(41.9%) and left in 36(58.1%) patients. 3) Direct stimulation of facial nerve showed no differences between affected and unaffected sides in HFS. 4) The results of blink reflex showed more increased latencies and larger amplitudes of R1 & R2 responses in affected sides than in unaffected sides of HFS, but no differences among the groups. 5) The lateral spread responses were found in 45 of 62 (72.6%) patients by stimulation of zygomatic branch and recording in mentalis muscle, 26 of 62 (41.9%) patients by stimulation of mandibular branch and recording in orbicularis oculi muscle on affected side. 6) There was a linear correlation between the presence of lateral spread response with zygomatic or mandibular stimulation and the grade of clinical severity. CONCLUSION: We suspected that the lateral spread response was a significant electrophysiological test for estimating the clinical severity of HFS.