Neuropathology of Cervical Dystonia

• Type of Material: Article
• Authors: C.N. Prudente, Emory University; C.A. Pardo, Johns Hopkins University; J. Xiao, University of Tennessee; John Hanfelt, Emory University; Ellen Hess, Emory University; M.S. LeDoux, University of Tennessee; Hyder A Jinnah, Emory University
• Language: English
• Date: 2013-03
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.expneurol.2012.11.019
• Title of Journal or Parent Work: Experimental Neurology
• ISSN: 0014-4886
• Volume: 241
• Start Page: 95
• End Page: 104
• Grant/Funding Information: Human tissue for cervical dystonia cases was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland in Baltimore MD, contract HHSN275200900011C, #N01-HD-9-0011.
• Keywords: DYT6; Marinesco bodies; autopsy study; THAP1; spasmodic torticollis
• Research Categories: Biology, Neuroscience

Abstract

The aim of this study was to search for neuropathological changes in postmortem brain tissue of individuals with cervical dystonia (CD). Multiple regions of formalin-preserved brains were collected from patients with CD and controls and examined with an extensive battery of histopathological stains in a two-stage study design. In stage one, 4 CD brains underwent a broad screening neuropathological examination. In stage two, these 4 CD brains were combined with 2 additional CD brains, and the subjective findings were quantified and compared to 16 age-matched controls. The initial subjective neuropathological assessment revealed only two regions with relatively consistent changes. The substantia nigra had frequent ubiquitin-positive intranuclear inclusions known as Marinesco bodies. Additionally, the cerebellum showed patchy loss of Purkinje cells, areas of focal gliosis and torpedo bodies. Other brain regions showed minor or inconsistent changes. In the second stage of the analysis, quantitative studies failed to reveal significant differences in the numbers of Marinesco bodies in CD versus controls, but confirmed a significantly lower Purkinje cell density in CD. Molecular investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD. The findings suggest that subtle neuropathological changes such as lower Purkinje cell density may be found in primary CD when relevant brain regions are investigated with appropriate methods.