丘脑下核生理学与深部脑刺激的运动和非运动结果相关

Mikael Levy, Mika Zurawel, Vincent d’Hardemare, Anan Moran, Fani Andelman, Yael Manor, Jacob Cohen, Moshe Meshulam, Yacov Balash, Tanya Gurevich, Itzhak Fried, Hagai Bergman
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摘要

丘脑下核(STN)深部脑刺激(DBS)是特发性帕金森病的常用治疗方法。尽管已知在运动评分方面有所改善,但在手术后,情感、认知、声音和语言功能可能会恶化。最近的研究将运动结果与术中微电极记录(MER)联系起来。然而,目前还没有基于mer的工具对综合运动和非运动症状的长期预后具有预测价值。我们对2015-2016年在特拉维夫苏拉斯基医疗中心(Tel Aviv, Israel)接受STN-DBS治疗的特发性帕金森病患者的预后进行了回顾性分析。48例患者(女性19例,男性29例;平均年龄(58±8岁),植入STN-DBS装置的患者接受术前和术后的运动、神经心理、语音和言语症状评估。所有患者的所有运动症状(轴向体征除外)和左旋多巴当量日剂量均有显著改善。脑后相关的神经心理功能(言语记忆、视觉记忆和组织)有轻度改善,而额叶功能(人格改变、执行功能和语言流畅性)有轻度恶化。伴随而来的言语清晰度的下降是轻微的,而且只是部分的,可能与神经心理学语言流畅性的结果一致。声学特性受影响最小,保持在正常值范围内。运动、神经心理和声音评分的维度降低呈现了六个主要组成部分,反映了主要的临床方面:震颤-显性vs僵硬-运动迟缓-显性运动-症状,额神经心理缺陷vs后神经心理缺陷,声学特征vs言语可理解性异常。对STN穗状活性的MER进行了离线分析,并与原始分数和主成分结果进行了相关性分析。基于198个MER轨迹,我们建议术中STN- dbs评分,这是三个MER特性的简单总和:归一化神经元活动,STN宽度和STN背外侧振荡区的相对比例。阈值STN- dbs评分>2.5(优先由归一化均方根>1.5, STN宽度> 3mm和背侧振荡区/STN宽度比>1/3组成)预测更好的运动和非运动长期预后。本文提出的算法基于MER优化DBS接触定位的术中决策,旨在改善长期(>1年)的运动、神经心理和声音症状。
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Subthalamic nucleus physiology is correlated with deep brain stimulation motor and non-motor outcomes
Abstract Subthalamic nucleus (STN) deep brain stimulation (DBS) is commonly indicated for symptomatic relief of idiopathic Parkinson’s disease. Despite the known improvement in motor scores, affective, cognitive, voice and speech functions might deteriorate following this procedure. Recent studies have correlated motor outcomes with intra-operative microelectrode recordings (MER). However, there are no MER-based tools with predictive values relating to long-term outcomes of integrative motor and non-motor symptoms. We conducted a retrospective analysis of the outcomes of patients with idiopathic Parkinson’s disease who had STN-DBS at Tel Aviv Sourasky Medical Centre (Tel Aviv, Israel) during 2015-2016. Forty-eight patients (19 women, 29 men; mean age, 58±8 years) who were implanted with a STN-DBS device underwent pre- and post-surgical assessments of motor, neuropsychological, voice and speech symptoms. Significant improvements in all motor symptoms (except axial signs) and levodopa equivalent daily dose were noted in all patients. Mild improvements were observed in more posterior-related neuropsychological functions (verbal memory, visual memory and organization) while mild deterioration was observed in frontal functions (personality changes, executive functioning and verbal fluency). The concomitant decline in speech intelligibility was mild and only partial, probably in accordance with the neuropsychological verbal fluency results. Acoustic characteristics were the least affected and remained within normal values. Dimensionality reduction of motor, neuropsychological and voice scores rendered six principal components that reflect the main clinical aspects: the tremor-dominant vs the rigidity-bradykinesia-dominant motor-symptoms, frontal vs posterior neuropsychological deficits and acoustic characteristics vs speech intelligibility abnormalities. MER of STN spiking activity were analysed off-line and correlated with the original scores, and with the principal component results. Based on 198 MER trajectories we suggest an intraoperative STN-DBS score which is a simple sum of three MER properties: normalized neuronal activity, the STN width and the relative proportion of the STN dorsolateral oscillatory region. A threshold STN-DBS score >2.5 (preferentially composed of normalized root mean square >1.5, STN width >3 mm and a dorsolateral oscillatory region/STN width ratio >1/3) predicts better motor and non-motor long-term outcomes. The algorithm presented here optimizes intraoperative decision-making of DBS contact localization based on MER with the aim of improving long-term (>1 year) motor, neuropsychological and voice symptoms.
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