Perampanel as an Effective Treatment for Cortical Reflex Myoclonus in Juvenile Huntington's Disease

Perampanel has not been previously reported as a treatment for cortical myoclonus in juvenile Huntington's disease (HD). We report a patient with juvenile HD with cortical reflex myoclonus who was successfully treated with perampanel. A 20-year-old right-handed woman with a normal perinatal and developmental history had bilateral hand tremors since the age of 16 years. She had been diagnosed and treated as essential tremor. Her symptoms gradually worsened for 4 years, and she was admitted to our hospital. She had no family history of neurodegenerative disease including Huntington's disease. She showed slow eye movements, moderate myoclonus predominantly in the right upper extremity at rest, chorea-like movements in both upper extremities, and moderate wide-based gait (Video 1). Myoclonus was easily evoked to auditory and tactile stimuli and myoclonus scale1 of 2 points. Blood examination indicated slightly low serum ceruloplasmin level (18.8 mg/dL, reference value 21–37 mg/dL), no acanthocytes in the blood smear, and lactic and pyruvic acid within normal range. Cerebrospinal fluid examination showed no abnormalities. Electroencephalogram (EEG) demonstrated generalized polyspikes. Polyspikes were immediately followed by myoclonus of the right upper extremity (Fig. 1A). Giant somatosensory evoked potentials (SEPs)2 to the right median nerve stimulation were recorded (P25 amplitude: 17.7 μV, N35 amplitude: 24.0 μV) (Fig. 1B), and long-loop reflexes (Fig. 1C) to the left and right median nerve stimulation were observed. Head magnetic resonance imaging showed a mild diffuse brain atrophy, especially in the bilateral caudate nuclei (Fig. 1D). After obtaining informed consent, a genetic test was conducted, which demonstrated an abnormal expansion of CAG repeats (57 repeats) in the Huntingtin (HTT) gene, confirming a diagnosis of HD. Perampanel was started for cortical reflex myoclonus as a steady dose of 2.0 mg/day. The frequency of myoclonus moderately decreased, and the myoclonus scale decreased from 2 to 1 point. The SEP amplitudes decreased (right median nerve stimulation, P25 amplitude from 17.7 to 8.5 μV, N35 amplitude from 24.0 to 10.7 μV), and generalized polyspikes disappeared on EEG. We encountered a patient of genetically diagnosed HD with slowly progressive myoclonus, chorea, and ataxia. Based on neurophysiological findings, the myoclonus was diagnosed as cortical reflex myoclonus2 and was moderately improved by perampanel. Myoclonus has been reported in 30% to 50% of patients with juvenile HD.3 Few electrophysiological studies on myoclonus in HD have reported EEG spikes preceding myoclonus and long-loop reflexes, suggesting cortical hyperexcitability and hyperreflexivity.3, 4 However, giant SEPs, also suggestive of cortical reflex myoclonus, have been reported in only one patient5 of juvenile HD. The present patient showed a generalized polyspike on EEG preceding myoclonus, a long-loop reflex, and giant SEPs, which clearly indicated cortical reflex myoclonus. Symptoms of HD, including myoclonus, are usually intractable.6 Perampanel suppresses cortical hyperexcitability.7 As previous studies have reported in patients other than juvenile HD, perampanel was moderately effective for cortical reflex myoclonus and decreasing the amplitudes of giant SEPs in this patient. This is the first report of perampanel treatment for cortical reflex myoclonus in HD. Cortical reflex myoclonus is infrequently present in HD, and perampanel would be one of the optimal treatment options. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. K.Y.: 1A, 1B, 1C, 2A, 2B, 3A, 3B. M.T.: 1A, 1B, 2A, 2B, 3B. E.N.: 1A, 1C. T.A.: 1C. R.T.: 1B. A.I.: 1A, 1B, 3B. R.M.: 1B. K.Y. and T.A. report no conflicts of interest. M.T. received grants from JSPS KAKENHI (22 K20855 and 23 K14774) and honoraria from Ono Pharmaceutical Co., Ltd. E.N. received consulting fees from Kyowa Kirin Co., Ltd.; honoraria from AbbVie GK, Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Viatoris Pharmaceuticals; and a subcontracting fee from Takeda Pharmaceutical Co., Ltd. R.T. received consultancies from Eisai Co., Ltd.; grants/research support from Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., Boehringer Ingelheim Co., Ltd., and SUNWELS Co., Ltd.; grants from Japan Agency for Medical Research and Development, JSPS, and Ministry of Education Culture, Sports, Science and Technology Japan; and honoraria from Sumitomo Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Novartis Pharma, Co., Ltd., Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., and SUNWELS Co., Ltd. A.I. received grants from Eli Lilly Japan K.K. and UCB Japan Co., Ltd., and honoraria from Eisai Co., Ltd. and UCB Japan Co., Ltd. R.M. received honoraria from Eisai Co., Ltd. and UCB Japan Co., Ltd. The data that support the findings of this study are available from the corresponding author upon reasonable request.