Moss J, Ryder T, Aziz T Z, Graeber M B, Bain P G
Electron Microscopy Unit, Department of Histopathology, Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London, UK.
Brain. 2004 Dec;127(Pt 12):2755-63. doi: 10.1093/brain/awh292. Epub 2004 Aug 25.
Deep brain stimulation (DBS) is used to treat a variety of severe medically intractable movement disorders, including Parkinson's disease, tremor and dystonia. There have been few studies examining the effect of chronic DBS on the brains of Parkinson's disease patients. Most of these post mortem studies concluded that chronic DBS caused mild gliosis around the lead track and did not damage brain tissue. There have been no similar histopathological studies on brains from dystonic patients who have undergone DBS. In this study, our objective was to discover whether tissue would be attached to DBS electrodes removed from patients for routine clinical reasons. We hoped that by examining explanted DBS electrodes using scanning (SEM) and/or transmission (TEM) electron microscopy we might visualize any attached tissue and thus understand the electrode-human brain tissue interaction more accurately. Initially, SEM was performed on one control DBS electrode that had not been implanted. Then 21 (one subthalamic nucleus and 20 globus pallidus internus) explanted DBS electrodes were prepared, after fixation in 3% glutaraldehyde, for SEM (n = 9) or TEM (n = 10), or both (n = 2), according to departmental protocol. The electrodes were sourced from two patients with Parkinson's disease, one with myoclonic dystonia, two with cervical dystonia and five with primary generalized dystonia, and had been in situ for 11 and 31 months (Parkinson's disease), 16 months (myoclonic dystonia), 14 and 24 months (cervical dystonia) and 3-24 months (primary generalized dystonia). Our results showed that a foreign body multinucleate giant cell-type reaction was present in all TEM samples and in SEM samples, prewashed to remove surface blood and fibrin, regardless of the diagnosis. Some of the giant cells were >100 microm in diameter and might have originated from either fusion of parenchymal microglia, resident perivascular macrophage precursors and/or monocytes/macrophages invading from the blood stream. The presence of mononuclear macrophages containing lysosomes and sometimes having conspicuous filopodia was detected by TEM. Both types of cell contained highly electron-dense inclusions, which probably represent phagocytosed material. Similar material, the exact nature of which is unknown, was also seen in the vicinity of these cells. This reaction was present irrespective of the duration of implantation and may be a response to the polyurethane component of the electrodes' surface coat. These findings may be relevant to our understanding of the time course of the clinical response to DBS in Parkinson's disease and various forms of dystonia, as well as contributing to the design characteristics of future DBS electrodes.
深部脑刺激（DBS）用于治疗各种严重的药物难治性运动障碍，包括帕金森病、震颤和肌张力障碍。很少有研究探讨慢性DBS对帕金森病患者大脑的影响。这些尸检研究大多得出结论，慢性DBS会导致电极轨迹周围出现轻度胶质增生，且不会损伤脑组织。对于接受过DBS治疗的肌张力障碍患者的大脑，尚未有类似的组织病理学研究。在本研究中，我们的目的是确定是否会有组织附着在因常规临床原因从患者体内取出的DBS电极上。我们希望通过使用扫描电子显微镜（SEM）和/或透射电子显微镜（TEM）检查取出的DBS电极，能够观察到任何附着的组织，从而更准确地了解电极与人类脑组织的相互作用。最初，对一根未植入的对照DBS电极进行了SEM检查。然后，根据部门协议，将21根（1根丘脑底核和20根内侧苍白球）取出的DBS电极在3%戊二醛中固定后，分别用于SEM（n = 9）或TEM（n = 10）检查，或两者都用（n = 2）。这些电极取自两名帕金森病患者、一名肌阵挛性肌张力障碍患者、两名颈部肌张力障碍患者和五名原发性全身性肌张力障碍患者，植入时间分别为11个月和31个月（帕金森病）、16个月（肌阵挛性肌张力障碍）、14个月和24个月（颈部肌张力障碍）以及3 - 24个月（原发性全身性肌张力障碍）。我们的结果表明，无论诊断如何，在所有TEM样本以及预先冲洗以去除表面血液和纤维蛋白的SEM样本中均存在异物多核巨细胞型反应。一些巨细胞直径大于100微米，可能起源于实质小胶质细胞、常驻血管周围巨噬细胞前体和/或从血流侵入的单核细胞/巨噬细胞的融合。通过TEM检测到含有溶酶体且有时具有明显丝状伪足的单核巨噬细胞的存在。这两种类型的细胞都含有高度电子致密的内含物，可能代表吞噬的物质。在这些细胞附近也可见到类似的物质，其确切性质尚不清楚。无论植入时间长短，这种反应均存在，可能是对电极表面涂层的聚氨酯成分的一种反应。这些发现可能有助于我们理解帕金森病和各种形式肌张力障碍对DBS临床反应的时间进程，也有助于未来DBS电极的设计特点。
