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帕金森病患者丘脑底核深部脑刺激1年随访期间纹状体多巴胺转运体可用性与个体临床病程

Striatal dopamine transporter availability and individual clinical course within the 1-year follow-up of deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease.

作者信息

Löser Julia, Luthardt Julia, Rullmann Michael, Weise David, Sabri Osama, Meixensberger Jürgen, Hesse Swen, Winkler Dirk

机构信息

Departments of1Nuclear Medicine.

2Neurosurgery, and.

出版信息

J Neurosurg. 2021 Feb 19;135(5):1429-1435. doi: 10.3171/2020.8.JNS192740. Print 2021 Nov 1.

Abstract

OBJECTIVE

Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of this study was therefore to evaluate whether 1) DAT availability changes within 1 year of STN-DBS and 2) the clinical outcome can be predicted based on preoperative DAT availability.

METHODS

Twenty-seven PD patients (mean age 62.7 ± 8.9 years; mean duration of illness 13.0 ± 4.9 years; PD subtypes: akinetic-rigid, n = 11; equivalence, n = 13; and tremor-dominant, n = 3) underwent [123I]FP-CIT SPECT preoperatively and after 1 year of STN-DBS. DAT availability as determined by the specific binding ratio (SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side.

RESULTS

Unified Parkinson's Disease Rating Scale (UPDRS) III scores improved significantly (mean preoperative on medication 25.6 ± 12.3, preoperative off medication 42.3 ± 15.2, postoperative on medication/off stimulation 41.4 ± 13.2, and postoperative on medication/on stimulation 16.1 ± 9.4; preoperative on medication vs postoperative on medication/on stimulation, p = 0.006), while the levodopa-equivalent daily dose was reduced (mean preoperative 957 ± 440 mg vs postoperative 313 ± 189 mg, p < 0.001). The SBR did not differ significantly before and 1 year after DBS, regardless of PD subtype. Preoperative DAT availability was not related to the change in UPDRS III score, but the change in DAT availability was significantly correlated with the change in UPDRS III score (contralateral head of the caudate VOI, p = 0.014; contralateral putamen VOI, p = 0.018).

CONCLUSIONS

Overall, DAT availability did not change significantly after 1 year of STN-DBS. However, on an individual basis, the improvement in UPDRS III score was associated with an increase in DAT availability, whereas DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of preoperative DAT availability can become a reliable predictor of successful STN-DBS must be evaluated in larger study cohorts.

摘要

目的

投射至纹状体的黑质中多巴胺能神经元变性是帕金森病(PD)运动症状的病因。丘脑底核(STN)的深部脑刺激(DBS)是一种已确立的用于缓解晚期PD这些症状的方法。然而,其作用机制,尤其是STN-DBS对作为黑质纹状体神经细胞功能标志物的纹状体多巴胺转运体(DAT)可用性的影响,在很大程度上仍不清楚。因此,本研究的目的是评估:1)STN-DBS 1年内DAT可用性是否变化;2)能否根据术前DAT可用性预测临床结局。

方法

27例PD患者(平均年龄62.7±8.9岁;平均病程13.0±4.9年;PD亚型:运动不能-强直型,n = 11;混合型,n = 13;震颤为主型,n = 3)在术前及STN-DBS 1年后接受[123I]FP-CIT单光子发射计算机断层扫描(SPECT)。通过对临床受累更严重一侧同侧及对侧尾状核和壳核进行感兴趣区(VOI)分析,以特异性结合率(SBR)确定DAT可用性。

结果

统一帕金森病评定量表(UPDRS)III评分显著改善(平均术前服药时25.6±12.3,术前未服药时42.3±15.2,术后服药/关闭刺激时41.4±13.2,术后服药/开启刺激时16.1±9.4;术前服药时与术后服药/开启刺激时比较,p = 0.006),而左旋多巴等效日剂量减少(平均术前957±440 mg与术后313±189 mg比较,p < 0.001)。无论PD亚型如何,DBS前和1年后SBR无显著差异。术前DAT可用性与UPDRS III评分变化无关,但DAT可用性变化与UPDRS III评分变化显著相关(对侧尾状核头部VOI,p = 0.014;对侧壳核VOI,p = 0.018)。

结论

总体而言,STN-DBS 1年后DAT可用性无显著变化。然而,个体上,UPDRS III评分的改善与DAT可用性增加相关,而STN-DBS手术前的DAT可用性不能预测临床结局。术前DAT可用性的亚型特异性模式能否成为STN-DBS成功的可靠预测指标,必须在更大的研究队列中进行评估。

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