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

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

The involvement of the brainstem is still not among the established degenerative features of HD (Bruyn et al. 1979; Koeppen 1989; Lange and Aulich 1986; Oyanagi et al. 1989; Rüb et al. 2014a; Vonsattel and DiFiglia 1998; Vonsattel et al. 1985). Although some of the unexplained HD disease symptoms (e.g., oculomotor dysfunctions) also suggested degeneration of select brainstem nuclei, damage to the brainstem and its possible clinical relevance in HD has been controversially discussed for many decades (see Sects. 6.2, 6.5, and 6.6). Previous assumptions that select nuclei of the brainstem may also undergo neurodegeneration during HD (i.e., dopaminergic and GABAergic substantia nigra, auditory superior olive, lateral vestibular nucleus, precerebellar inferior olive) (Figs. 1.4, 7.1, 7.2, and 7.3) have not been revisited or taken into account by current researchers (see Chap. 1) (Bruyn et al. 1979; Bollen et al. 1986; Koeppen 1989; Kremer et al. 1992; Lange and Aulich 1986; Lange et al. 1976; Lasker and Zee 1997; Leigh et al. 1983, 1985; Oyanagi et al. 1989; Rüb et al. 2009, 2014a; Vonsattel 2008; Vonsattel and DiFiglia 1998; Vonsattel et al. 1985; Walker 2007a, b). These assumptions, however, were confirmed by recent systematic pathoanatomical investigations of serial brainstem sections stained for neuronal Nissl material (with Darrow red) and lipofuscin pigment (with aldehyde-fuchsin) of clinically diagnosed and genetically confirmed HD patients that suffered from chorea, cognitive decline, and personality changes and also showed disease signs possibly related to brainstem damage (i.e., broad-based gait, gait imbalance, dysphagia, slowed horizontal saccades, inability to start horizontal saccades without initial head thrust, slowed and saccadic smooth pursuits, falls) (Rüb et al. 2014a).