The national DBS brain tissue network pilot study: need for more tissue and more standardization

Abstract

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Glial responses to implanted electrodes in the brain

“…Subsequently, the role of glia as a cellular target of DBS treatment 118–120 has emerged among several candidate mechanisms. Gliosis is commonly observed in post-mortem brain tissue from DBS patients 121,122 and can be more pronounced when surrounding active devices 123 (Fig. 1).…”

“…e , Histology from a primate with Utah array implanted, with microglia labelled (IBA1, red) 65 , at 17 weeks. f , Human DBS lead implant at ~38 months, with labelled astrocytes (GFAP, magenta; white arrowheads), microglia (IBA1, cyan; white arrows) and all cell nuclei (CyQUANT, yellow) 121 . Scales bars: a , d , f , 100 µm; b , 1 mm; c , 2 mm; e , 28 µm.…”

“…By approximately four to six weeks, they begin to form a dense scar around the device that can last for years 26,65,121 .…”

A pilot study of human brain tissue post-magnetic resonance imaging: Information from the National Deep Brain Stimulation Brain Tissue Network (DBS-BTN)

“…Tissue blocks were cut and prepared using standard paraffin embedding. Paraffin blocks sectioned at 5 μm were stained using the standard hematoxylin-eosin (H&E) tissue staining method (Vedam-Mai et al, 2010).…”

“…from the University of Florida Institutional Review Board (IRB) approved DBS-BTN study was then performed (Vedam-Mai et al, 2010). Clinical notes directly proceeding and following the MRI procedures were examined for signs established as clinical criteria for MRI-induced damage (problems with subsequent device programming, dystonic movements, ballistic movements, hyperkinetic movements, or any clinical worsening) (Rezai et al, 2004;Spiegel et al, 2003).…”