Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Parkinsonism Relat Disord. 2019 Jul;64:235-241. doi: 10.1016/j.parkreldis.2019.04.006. Epub 2019 Apr 16.
Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease the striatal vesicular monoamine transporter (VMAT2), secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical cerebral metabolism.
PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4-6 months of STN stimulation in seven PD patients (mean age 67 ± 7).
The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism.
The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.
深部脑刺激（DBS）是治疗帕金森病（PD）的一种已确立的方法。尽管通过丘脑底核（STN）DBS 改善了大多数患者的运动症状，并且其应用广泛，但神经生物学机制仍不完全清楚。本研究的目的是阐明 STN 刺激对 PD 患者的纹状体多巴胺系统和神经回路的影响，采用高分辨率正电子发射断层扫描（PET）成像。测试的假设是 STN DBS 会降低纹状体囊泡单胺转运蛋白（VMAT2），这是由于多巴胺浓度增加所致，并且会降低纹状体脑代谢并增加皮质脑代谢。
在 7 名 PD 患者（平均年龄 67±7 岁）进行 DBS 手术前和 STN 刺激后 4-6 个月进行囊泡单胺转运蛋白（VMAT2）和脑葡萄糖代谢的 PET 成像。
STN DBS 后，患者的运动和神经精神症状均有显著改善。在尾状核、壳核和联合纹状体以及额皮质、顶皮质和边缘皮质区域观察到 VMAT2 减少。在纹状体亚区观察到脑葡萄糖代谢减少，在颞叶和顶叶皮质以及小脑观察到脑葡萄糖代谢增加。纹状体 VMAT2 减少与纹状体减少和皮质增加相关。抑郁症状的改善与纹状体和纹状体外区域 VMAT2 的减少以及纹状体减少和皮质增加相关。
本研究结果支持进一步研究 VMAT2 的作用，以及在 PD 中 STN DBS 改善运动和非运动症状的神经回路中的相关变化。
