MR-guided focused ultrasound pallidotomy for Parkinson's disease: safety and feasibility
MR-guided focused ultrasound pallidotomy for Parkinson's disease: safety and feasibility
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DOI：
10.3171/2020.6.jns192773
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发表时间：
2021-09-01
影响因子：
4.1
通讯作者：
Fishman, Paul S.
中科院分区：
文献类型：
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作者：
Eisenberg, Howard M.;Krishna, Vibhor;Fishman, Paul S.
目的：立体定向射频苍白球切开术已证明可改善帕金森病（PD）患者的运动波动，特别是左旋多巴（L-dopa）引起的运动障碍。作者的目的是确定单侧苍白球切开术与磁共振引导聚焦超声（MRgFUS）是否可以安全地提高PD患者的统一运动障碍评定量表（UDysRS，主要结果测量指标）评分高于基线评分。方法20例PD伴左旋多巴反应、不对称运动体征和运动波动（包括运动障碍）的患者参加了一项为期1年的多中心开放标签试验，该试验采用MRgFUS单侧消融内苍白球。结果20例患者均成功完成超声检查。mrgfus相关的不良神经事件通常是轻微和短暂的，包括视野障碍（n = 1），构音障碍（n = 4, 2轻度和2中度），认知障碍（n = 1），精细运动障碍（n = 2）和面部无力（n = 1）。虽然有3个不良事件（AE）被评为严重（2例短暂超声相关疼痛，1例恶心/呕吐），但没有一个AE符合美国FDA的严重不良反应标准。主要结局指标总UDysRS在治疗后改善了59%（基线平均评分36.1,95% CI 4.88； 3个月时14.2,95% CI 5.72, p < 0.0001），并在整个研究过程中持续（12个月时20.5,95% CI 7.39, 43%改善，p < 0.0001）。在“停药”状态下，治疗侧运动体征的严重程度（运动障碍学会版联合帕金森病评定量表[MDS-UPDRS]第三部分）也显著改善（基线平均评分20.0,95% CI 2.4； 3个月时评分10.6,95% CI 1.86, 44.5%改善，p < 0.0001； 12个月时评分10.4,95% CI 2.11, 45.2%改善，p < 0.0001）。绝大多数患者在UDysRS的损伤部分或UPDRS的运动部分表现出具有临床意义的改善水平，而1例患者在第3个月UPDRS表现出具有临床意义的恶化。结论：本研究支持MRgFUS苍白球切开术治疗PD伴运动波动（包括运动障碍）患者的可行性和初步疗效。这些初步数据支持继续调查，一项安慰剂对照的盲法试验正在进行中。
OBJECTIVE Stereotactic radiofrequency pallidotomy has demonstrated improvement in motor fluctuations in patients with Parkinson's disease (PD), particularly levodopa (L-dopa)-induced dyskinesias. The authors aimed to determine whether or not unilateral pallidotomy with MR-guided focused ultrasound (MRgFUS) could safely improve Unified Dyskinesia Rating Scale (UDysRS; the primary outcome measure) scores over baseline scores in patients with PD.METHODS Twenty patients with PD and L-dopa responsiveness, asymmetrical motor signs, and motor fluctuations, including dyskinesias, participated in a 1-year multicenter open-label trial of unilateral MRgFUS ablation of the globus pallidus internus.RESULTS The sonication procedure was successfully completed in all 20 enrolled patients. MRgFUS-related adverse neurological events were generally mild and transient, including visual field deficit (n = 1), dysarthria (n = 4, 2 mild and 2 moderate), cognitive disturbance (n = 1), fine motor deficit (n = 2), and facial weakness (n = 1). Although 3 adverse events (AEs) were rated as severe (transient sonication-related pain in 2, nausea/vomiting in 1), no AE fulfilled US FDA criteria for a Serious Adverse Effect. Total UDysRS, the primary outcome measure, improved 59% after treatment (baseline mean score 36.1, 95% CI 4.88; at 3 months 14.2, 95% CI 5.72, p < 0.0001), which was sustained throughout the study (at 12 months 20.5, 95% CI 7.39, 43% improvement, p < 0.0001). The severity of motor signs on the treated side (Movement Disorder Society version of the United Parkinson's Disease Rating Scale [MDS-UPDRS] part III) in the "off" medication state also significantly improved (baseline mean score 20.0, 95% CI 2.4; at 3 months 10.6, 95% CI 1.86, 44.5% improvement, p < 0.0001; at 12 months 10.4, 95% CI 2.11, 45.2% improvement, p > 0.0001). The vast majority of patients showed a clinically meaningful level of improvement on the impairment component of the UDysRS or the motor component of the UPDRS, while 1 patient showed clinically meaningful worsening on the UPDRS at month 3.CONCLUSIONS This study supports the feasibility and preliminary efficacy of MRgFUS pallidotomy in the treatment of patients with PD and motor fluctuations, including dyskinesias. These preliminary data support continued investigation, and a placebo-controlled, blinded trial is in progress.