Bond Aaron E, Shah Binit B, Huss Diane S, Dallapiazza Robert F, Warren Amy, Harrison Madaline B, Sperling Scott A, Wang Xin-Qun, Gwinn Ryder, Witt Jennie, Ro Susie, Elias W Jeffrey
Department of Neurosurgery, University of Virginia Health Science Center, Charlottesville.
Department of Neurology, University of Virginia Health Science Center, Charlottesville.
JAMA Neurol. 2017 Dec 1;74(12):1412-1418. doi: 10.1001/jamaneurol.2017.3098.
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.
To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD.
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.
Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding.
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.
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%]).
Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response.
ClinicalTrials.gov identifier NCT01772693.
临床试验已证实聚焦超声丘脑切开术对特发性震颤有效，但其治疗以震颤为主的帕金森病（TDPD）的有效性和安全性尚不清楚。
评估TDPD患者单侧聚焦超声丘脑切开术在12个月随访时的安全性和有效性，并考虑安慰剂反应。
设计、地点和参与者：从内部数据库中识别出的326例患者中，53例患者同意接受筛查。26例不符合条件，27例于2012年10月18日至2015年1月8日在2个中心随机分组（2:1）接受聚焦超声丘脑切开术或假手术。不合格的最常见原因是退出研究（8人[31%]）和对药物治疗无效（8人[31%]）。采用意向性分析进行数据分析，通过主要结局进行双盲评估。
20例患者随机接受单侧聚焦超声丘脑切开术，7例接受假手术。假手术组在揭盲后接受开放标签治疗。
预定义的主要结局是安全性以及治疗3个月时两组之间震颤主导型帕金森病临床评定量表（CRST）中用药侧手部震颤子评分改善情况的差异。次要结局包括统一帕金森病评定量表（UPDRS）评分的描述性结果和生活质量测量指标。
27例患者中，26例（96%）为男性，中位年龄为67.8岁（四分位间距[IQR]，62.1 - 73.8岁）。聚焦超声丘脑切开术后，用药时的中位震颤评分从基线的17分（IQR，10.5 - 27.5）改善了62%（IQR，22% - 79%），假手术后从基线的23分（IQR，14.0 - 27.0）改善了22%（IQR， - 11%至29%）；组间差异显著（Wilcoxon P = 0.04）。聚焦超声丘脑切开术后，用药时的中位UPDRS运动评分从基线的23分（IQR，15.5 - 34.0）改善了8分（IQR，0.5 - 11.0），假手术后从基线的25分（IQR，15.0 - 33.0）改善了1分（IQR， - 5.0至9.0）。在研究早期，内囊受热导致2例（8%）轻度偏瘫，症状改善，并促使在磁共振热成像期间监测另一个轴。其他持续性不良事件为口面部感觉异常（4例[20%]）、手指感觉异常（1例[5%]）和共济失调（1例[5%]）。
对于TDPD患者，聚焦超声丘脑切开术经CRST评估显示，即使在存在安慰剂反应的情况下，对药物难治性震颤也有改善。
ClinicalTrials.gov标识符NCT01772693。
