Abstract：
BACKGROUND: Task-specific dystonia (TSFD) is a disabling movement disorder. Effective treatment options are currently limited. Zolpidem was reported to improve primary focal and generalized dystonia in a proportion of patients. The mechanisms underlying its therapeutic effects have not yet been investigated.
METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers\' Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability - active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo.
RESULTS: Zolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo.
CONCLUSIONS: Zolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.
METHODS: We conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers\' Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability - active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo.
RESULTS: Zolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo.
CONCLUSIONS: Zolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.
摘要：
背景：任务特异性肌张力障碍（TSFD）是一种致残运动障碍。目前有效的治疗方案有限。据报道，唑吡坦可改善一部分患者的原发性局灶性和广泛性肌张力障碍。其治疗作用的潜在机制尚未得到研究。
方法：我们进行了随机，双盲,安慰剂对照,单剂量唑吡坦在24例TSFD患者中的交叉试验。使用Burke-Fahn-Marsden肌张力障碍量表（BFMDRS）对患者进行临床评估，作家抽筋评分量表(WCRS)，和视觉模拟评分（VAS），在接受安慰剂和唑吡坦之前和之后。对安慰剂和唑吡坦进行经颅磁刺激，以比较皮质脊髓兴奋性-活动和静息运动阈值（AMT和RMT），静息和主动输入/输出曲线和皮质内兴奋性-皮质沉默期(CSP)，短间隔皮质内抑制曲线（SICI），长间隔皮质内抑制（LICI）和皮质内促进（ICF）。8例患者接受了唑吡坦和安慰剂的脑FDG-PET成像。
结果：唑吡坦治疗可改善TSFD。唑吡坦与安慰剂平缓休息和主动输入/输出曲线相比，ICF降低，并与右小脑的低代谢和左顶叶下小叶和左扣带的高代谢有关。发现WCRS上肌张力障碍严重程度的变化与活动输入/输出曲线和脑代谢的变化之间存在相关性。分别。RMT较低的患者，与安慰剂相比，更高的休息和主动输入/输出曲线对唑吡坦的反应更好。
结论：唑吡坦通过减少皮质运动输出并影响高阶感觉和运动网络中的关键节点来改善TSFD。
方法：我们进行了随机，双盲,安慰剂对照,单剂量唑吡坦在24例TSFD患者中的交叉试验。使用Burke-Fahn-Marsden肌张力障碍量表（BFMDRS）对患者进行临床评估，作家抽筋评分量表(WCRS)，和视觉模拟评分（VAS），在接受安慰剂和唑吡坦之前和之后。对安慰剂和唑吡坦进行经颅磁刺激，以比较皮质脊髓兴奋性-活动和静息运动阈值（AMT和RMT），静息和主动输入/输出曲线和皮质内兴奋性-皮质沉默期(CSP)，短间隔皮质内抑制曲线（SICI），长间隔皮质内抑制（LICI）和皮质内促进（ICF）。8例患者接受了唑吡坦和安慰剂的脑FDG-PET成像。
结果：唑吡坦治疗可改善TSFD。唑吡坦与安慰剂平缓休息和主动输入/输出曲线相比，ICF降低，并与右小脑的低代谢和左顶叶下小叶和左扣带的高代谢有关。发现WCRS上肌张力障碍严重程度的变化与活动输入/输出曲线和脑代谢的变化之间存在相关性。分别。RMT较低的患者，与安慰剂相比，更高的休息和主动输入/输出曲线对唑吡坦的反应更好。
结论：唑吡坦通过减少皮质运动输出并影响高阶感觉和运动网络中的关键节点来改善TSFD。
