ImportanceUnilateral magnetic resonance–guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option.ObjectiveTo evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy.Design, Setting, and ParticipantsThis prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category).InterventionA focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation.Main Outcomes and MeasuresTremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months.ResultsThe mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient.Conclusions and RelevanceStaged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient.Trial RegistrationClinicalTrials.gov Identifier NCT04112381.

中文翻译：

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分期双侧聚焦超声丘脑切除术治疗特发性震颤的安全性和有效性


重要性单侧磁共振引导聚焦超声消融丘脑腹中间核治疗原发性震颤可减少一侧震颤，但未经治疗的对侧或中线症状对某些患者来说仍然有限。从历史上看，双侧损伤会产生不可接受的风险，并被深部脑刺激所取代。对单侧聚焦超声损伤的接受度不断提高，引起了人们对双侧选择的兴趣。目的评估分阶段、双侧聚焦超声丘脑切除术的安全性和有效性。设计、设置和参与者这项前瞻性、开放标签、多中心试验治疗患有原发性震颤的患者2020年7月至2021年10月，在美国7个学术医疗中心进行了12个月的随访。在入组前至少 9 个月接受过单侧聚焦超声丘脑切除术的 62 名患者中，11 名被排除，51 名接受治疗。资格标准包括患者年龄（22 岁及以上）、药物难治性、震颤严重程度（震颤临床评定量表 [CRST] A 部分对于姿势性或运动性震颤评分≥2）和功能障碍（CRST C 部分任何一项评分≥2）。干预与磁共振成像接口的聚焦超声系统可以将热成像图与解剖结构实时对齐。阈下超声处理允许在进行消融之前对疗效和脱靶效应进行目标询问。主要结果和测量治疗后 3 个月时治疗侧的震颤/运动评分（CRST A 和 B 部分）是主要结果测量，次要评估是疗效和安全性持续至 12 个月。结果 人群平均年龄 (SD) 为 73 (13.9) 岁，44 名参与者 (86.3%) 为男性。 3 个月时，平均 (SD) 震颤/运动评分从 17.4（5.4；95% CI，15.9-18.9）改善至 6.4（5.3；95% CI，4.9 至 7.9）（CRST A 和 B 部分评分改善 66%） ；95% CI，59.8-72.2；平均 (SD) 姿势性震颤（从 2.5 [0.8]；95% CI，2.3 至 2.7 至 0.6 [0.9]；95% CI，0.3 至 0.8；P < .001）和平均 (SD) 均有显着改善残疾评分（从 10.3 [4.7]；95% CI，9.0-11.6 到 2.2 [2.8]；95% CI，1.4-2.9；P < .001）。 12 名参与者出现了轻度（研究定义的）共济失调，其中 6 名参与者在 12 个月时持续存在这种症状。最常见的不良事件（188 例中的 159 例 [85%] 为轻度，188 例中的 25 例为中度 [13%]，以及 1 例严重尿路感染），最常见的不良事件包括麻木/刺痛（总共 n = 17 例；12 个月时 n = 8 例）、构音障碍（总共 n = 15 例；12 个月时 n = 7 例）、共济失调（总共 n = 12 例；12 个月时 n = 6 例）、不稳定/不平衡（总共 n = 10 例；12 个月时 n = 0）和味觉障碍（总共 n = 7；12 个月时 n = 3）。言语困难，包括发声、发音和吞咽困难，通常是轻微的（被评为无临床意义，没有参与者在所有 3 项测量中出现恶化）和短暂的。结论和相关性分期、双侧聚焦超声丘脑切除术显着降低了震颤严重程度和功能障碍评分。言语、吞咽和共济失调的不良事件大多是轻微且短暂的。试验注册ClinicalTrials.gov 标识符 NCT04112381。