The Neuropathology of Huntington’s Disease: Classical Findings, Recent Developments and Correlation to Functional Neuroanatomy

Udo Rüb, Jean Paul G. Vonsattel, Helmut Heinsen, Horst-Werner Korf

The historical survey of the evolution of the knowledge in neuropathological HD research provided in this monograph shows that the stepwise scientific progress made during a time period of more than one century (1) has considerably changed the traditional, reductionistic pathoanatomical, and pathophysiological concepts of the polyglutamine disease HD, which were unilaterally based on the well-known degeneration of the striatum and (2) have paved the way for basic research aimed at elucidation of the pathogenic mechanisms leading to HD. The focused efforts and progress in neuropathological HD research led to the development, establishment, and international appreciation of a simple, but reliable grading system of the chronological and topographical progression and severity of the HD-related degeneration in the striatum. They form the empirical base for the implementation of the cerebral allo- and neocortex as additional main targets of the disease process of HD (Figs. 1.4 , 2.1 , 2.2 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 3.1 , 3.2 , and 3.3 ) and favor the view that the consistent degeneration of the pallidum, select thalamic nuclei, cerebellum, and brainstem also represents inherent features of the HD brain pathology (Figs. 2.10 , 2.11 , 4.4 , 4.5 , 5.2 , 5.3 , 5.4 , 5.5 , 6.4 , and 6.5 ) (see Chaps. 1 , 2 , and 3 ) (Atkin and Paulson 2014; Borrell-Pagès et al. 2006; Braak and Braak 1992a, b; Bruyn et al. 1979; De la Monte et al. 1988; Estrada-Sanchez and Rebec 2013; Fennema-Notestine et al. 2004; Ferrante et al. 1987; Finkbeiner and Mitra 2008; Hedreen et al. 1991; Heinsen et al. 1992, 1994, 1996, 1999; Heinsen and Rüb 1997; Imarisio et al. 2008; Lange 1981; Lange and Aulich 1986; Lange et al. 1976; Li and Conforti 2013; Margolis and Ross 2003; Myers et al. 1988; Rosas et al. 2003; Rüb et al. 2009, 2013a, 2014a, b; Schulte and Littleton 2011; Selemon et al. 2004; Sotrel et al. 1991; Valera et al. 2005; Vonsattel 2008; Vonsattel and DiFiglia 1998; Vonsattel et al. 1985; Walker 2007a, b).