Postmortem analysis following 71 months of deep brain stimulation of the subthalamic nucleus for Parkinson disease

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Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective neurosurgical treatment for Parkinson disease. Tissue reaction to chronic DBS therapy and the definitive location of active stimulation contacts are best studied on a postmortem basis in patients who have undergone DBS. The authors report the postmortem analysis of STN DBS following 5 years and 11 months of effective chronic stimulation including the histologically verified location of the active contacts associated with bilateral implants. They also describe tissue response to intraoperative test passes with recording microelectrodes and stimulating semimacroelectrodes. The results indicated that 1) the neural tissue surrounding active and nonactive contacts responds similarly, with a thin glial capsule and foreign-body giant cell reaction surrounding the leads as well as piloid gliosis, hemosiderin-laden macrophages, scattered lymphocytes, and Rosenthal fibers; 2) there was evidence of separate tracts in the adjacent tissue for intraoperative microelectrode and semimacroelectrode passes together with reactive gliosis, microcystic degeneration, and scattered hemosiderin deposition; and 3) the active contacts used for ~ 6 years of effective bilateral DBS therapy lie in the zona incerta, just dorsal to the rostral STN. To the authors' knowledge, the period of STN DBS therapy herein described for Parkinson disease and subjected to postmortem analysis is the longest to date.

Abbreviations used in this paper: DBS = deep brain stimulation; PD = Parkinson disease; STN = subthalamic nucleus.

Article Information

Address correspondence to: Peter E. Konrad, M.D., Ph.D., Department of Neurological Surgery, Vanderbilt University Medical Center, T-4224 Medical Center North, Nashville, Tennessee 37232-2380. email: peter.konrad@vanderbilt.edu.

© AANS, except where prohibited by US copyright law.

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    Photograph (A) showing decreased pigmentation in the patient's brain. Photomicrographs (B and C) demonstrating Lewy Body formation in the substantia nigra. H & E (B) and alpha-synuclein (C). Original magnification × 40.

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    Photomicrographs revealing a histopathological comparison between chronic DBS lead implantation (A, B, and C) and a test electrode pass during surgery (D, E, and F). A: Left active DBS lead location (arrow) dorsal to the STN border (arrowheads). Note the increased neuronal density within the STN (below the border). B: Hemosiderinladen macrophages, microcystic degeneration, glial capsule with piloid gliosis, and Rosenthal fibers (black arrows) associated with chronic DBS lead implantation. C: Reactive astrocytosis of the DBS lead capsule. D: Parallel residual tract from a test electrode pass during surgery (outlined arrow) within the STN. Again, the left active DBS electrode location (black arrow) is dorsal to the STN border (arrowheads). E: Residual tract from a parallel electrode pass demonstrating microcystic degeneration, increased cellularity due to gliosis, and scattered hemosiderin deposition; a glial capsule and Rosenthal fibers are lacking. F: Reactive astrocytosis in a residual tract from a parallel electrode pass. H & E (A, B, D, and E) and GFAP (C and F). Original magnification × 4 (A and D), 10 (C and F), and 20 (B and E).

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