Gironell Alexandre, Marin-Lahoz Juan
Movement Disorders Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Catalonia, Spain.
Tremor Other Hyperkinet Mov (N Y). 2016 Jul 13;6:378. doi: 10.7916/D8FQ9WN0. eCollection 2016.
T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated.
Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score.
Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients' subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment.
The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET.
T型钙通道激活被认为是橄榄小脑系统节律性的基础,而这种节律性与特发性震颤(ET)有关。乙琥胺可降低T型钙电流,并能在两种ET动物模型中抑制震颤。我们在一项开放标签试验中,使用临床量表和加速度计记录测量方法,探讨了乙琥胺对ET患者的影响。我们最初计划招募15名患者进行试验,但由于缺乏疗效且不良反应发生率高,在7名患者参与后试验停止。
7名被诊断为ET的患者纳入研究。乙琥胺剂量为每日500毫克(分两次服用)。主要结局指标为:1)震颤临床评分量表(TCRS)评分,2)加速度计记录,3)自我报告的残疾量表评分。
5名患者完成研究,2名因不良反应退出。运动任务表现(TCRS 1 + 2)、日常生活活动(TCRS 3)的临床评分,或患者的主观评估(TCRS 4)和整体评估均无显著变化。加速度计数据或残疾量表评分也无差异。两名患者在服用乙琥胺时报告出现焦虑、紧张、头痛和头晕,导致他们停止试验。没有患者愿意继续乙琥胺治疗。
我们的探索性研究结果表明,乙琥胺不是治疗ET的有效药物。