Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease A Randomized Clinical Trial
Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease A Randomized Clinical Trial
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DOI：
10.1001/jamaneurol.2017.3098
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发表时间：
2017-12-01
期刊：
影响因子：
29
通讯作者：
Elias, W. Jeffrey
中科院分区：
文献类型：
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作者：
Bond, Aaron E.;Shah, Binit B.;Elias, W. Jeffrey
临床试验已经证实了聚焦超声（FUS）丘脑切开术治疗原发性震颤的有效性，但其治疗震颤显性帕金森病（TDPD）的有效性和安全性尚不清楚。帕拉;&帕拉;目的评估单侧FUS丘脑切开术治疗TDPD患者的安全性和有效性，并考虑安慰剂反应。帕拉，设置，和参与者的326例患者确定从内部数据库中，53例患者同意进行筛选。26例不合格，27例从2012年10月18日至2015年1月8日在2家中心随机（2：1）接受FUS丘脑切开术或假手术。最常见的不合格原因是退出（8人[31%]）和非药物难治性（8人[31%]），使用意向治疗分析分析数据，并通过主要结局进行双盲评估。干预20例患者随机接受单侧FUS丘脑切开术，7例接受假手术。假手术组在揭盲后接受开放标签治疗。帕拉;&帕拉;主要结局和指标预定义的主要结局是安全性和3个月时来自震颤临床评定量表（CRST）的药物治疗手震颤分项评分的组间改善差异。次要结果包括统一帕金森病评定量表（UMRS）评分和生活质量测量的描述性结果。结果27例患者中，26例（96%）为男性，中位年龄为67.8岁（四分位距[IQR]，62.1-73.8岁）。FUS丘脑切开术后，药物治疗中位震颤评分较基线17分（IQR，10.5-27.5）改善62%（IQR，22%-79%），假手术后较基线23分（IQR，14.0-27.0）改善22%（IQR，-11%至29%）;组间差异显著（Wilcoxon P = 0.04）。在FUS丘脑切开术后，药物治疗中位WARS运动评分较基线23分（IQR，15.5-34.0）改善8分（IQR，0.5-11.0），假手术后较基线25分（IQR，15.0-33.0）改善1分（IQR，-5.0至9.0）。在研究早期，内囊加热导致2例（8%）轻度轻偏瘫，这改善并提示在磁共振测温期间监测额外的轴。其他持续的不良事件是口面感觉异常（4起事件[20%]），手指感觉异常（1起事件[5%]）和共济失调（1起事件[5%]）。帕拉;&帕拉;结论和相关性TDPD患者的聚焦超声丘脑切开术通过CRST评估证明了药物难治性震颤的改善，即使在安慰剂反应的情况下。
IMPORTANCE Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown.& para;& para;OBJECTIVE To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD.& para;& para;DESIGN, SETTING, AND PARTICIPANTS Of the 326 patients identified from an in-house database, 53 patients consented to be screened. Twenty-six were ineligible, and 27 were randomized (2:1) to FUS thalamotomy or a sham procedure at 2 centers from October18, 2012, to January 8,2015. The most common reasons for disqualification were withdrawal (8 persons [31%]), and not being medication refractory (8 persons [31%]), Data were analyzed using intention-to-treat analysis, and assessments were double-blinded through the primary outcome.& para;& para;INTERVENTIONS Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding.& para;& para;MAIN OUTCOMES AND MEASURES The predefined primary outcomes were safety and difference in improvement between groups at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor (CRST). Secondary outcomes included descriptive results of Unified Parkinson's Disease Rating Scale (UPDRS) scores and quality of life measures.& para;& para;RESULTS Of the 27 patients, 26 (96%) were male and the median age was 67.8 years (interquartile range [IQR], 62.1-73.8 years). On-medication median tremor scores improved 62% (IQR, 22%-79% ) from a baseline of 17 points (IQR, 10.5-27.5) following FUS thalamotomy and 22% (IQR, -11% to 29%) from a baseline of 23 points (IQR, 14.0-27.0) after sham procedures; the between-group difference was significant (Wilcoxon P =.04 ). On-medication median UPDRS motor scores improved 8 points (IQR, 0.5-11.0) from a baseline of 23 points (IQR, 15.5-34.0) following FUS thalamotomy and 1 point (IQR, -5.0 to 9.0) from a baseline of 25 points (IQR, 15.0-33.0) after sham procedures. Early in the study, heating of the internal capsule resulted in 2 cases (8%) of mild hemiparesis, which improved and prompted monitoring of an additional axis during magnetic resonance thermometry. Other persistent adverse events were orofacial paresthesia (4 events [20%]), finger paresthesia (1 event [5%]), and ataxia (1 event [5%]).& para;& para;CONCLUSIONS AND RELEVANCE Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response.