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 autosomal dominantly inherited polyglutaminopathy causing Huntington's disease (HD) is a currently untreatable and rare neuropsychiatric disorder with an estimated prevalence in Europe and the USA of 4-8:100,000 (Andrew et al. 1993; Finkbeiner and Mitra 2008; Harper 1992; Labbadia and Morimoto 2013; Margolis and Ross 2003; Ortega et al. 2007; Rüb et al. 2009; Schapira et al. 2014; Schulte and Littleton 2011; Tanner and Goldman 1994; Vonsattel and DiFiglia 1998; Walker 2007a, b). The symptoms of adult-onset HD commonly begin around the age of 40 years with progressive cognitive impairments and motor symptoms often designated as clumsiness, tremor, balance trouble, or jerkiness. Although choreatic movements may also be among the early and progressive HD symptoms, they plateau and disappear in the advanced clinical stages. During the late clinical stage, additional somatomotor (i.e., bradykinesia, akinesia, dystonia, hypotonia, rigidity, dysarthria, dysphagia) and oculomotor symptoms, visual and executive dysfunctions, personality changes, psychiatric disturbances (e.g., depression, schizophrenia-like symptoms), electrophysiological abnormalities, and an unintended, severe, and unexplained weight loss may occur (Andrew et al. 1993; Aziz et al. 2008; Borrell-Pages 2006; Bruyn et al. 1979: Deuschl et al. 1989; Ellenberger et al. 1978; Gil and Rego 2008; Heinsen et al. 1994; Hennerici et al. 1985; Imarisio et al. 2008; Jossiasen et al. 1994; Knikou 2008; Kremer et al. 1992; Lasker and Zee 1997; Leigh and Zee 2006; Li and Conforti 2013; Margolis and Ross 2003; McLeod 1969; Misiaszek 2003; Myers 2004; Petersen et al. 2005; Ross and Tabrizi 2011; Rüb et al. 2009, 2013a, 2014a, b; The Huntington's disease Collaborative Research Group 1993; Vonsattel 2008; Vonsattel and DiFiglia 1998; Vonsattel et al. 1985; Walker 2007a, b).