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

This monograph describes the progress in neuropathological HD research made during the last century, the neuropathological hallmarks of HD and their pathogenic relevance. Starting with the initial descriptions of the progressive degeneration of the striatum as one of the key events in HD, the worldwide practiced Vonsattel HD grading system of striatal neurodegeneration will be outlined. Correlating neuropathological data with results on the functional neuroanatomy of the human brain, subsequent chapters will highlight recent HD findings: the neuronal loss in the cerebral neo-and allocortex, the neurodegeneration of select thalamic nuclei, the affection of the cerebellar cortex and nuclei, the involvement of select brainstem nuclei, as well as the pathophysiological relevance of these pathologies for the clinical picture of HD. Finally, the potential pathophysiological role of neuronal huntingtin aggregations and the most important and enduring challenges of neuropathological HD research are discussed.

1. Introduction. - 2. The neuropathological grading of Huntington disease. - 3. The cerebral cortex in Huntington s disease. - 4. Degeneration of select motor and limbic nuclei of the thalamus in Huntington s disease. - 5. Consistent and widespread degeneration of the cerebellum in Huntington s disease. - 6. Elucidation of the role of the premotor oculomotor brainstem nuclei in the pathogenesis of oculomotor dysfunctions in Huntington s disease. - 7. Widespread brainstem neurodegeneration in Huntington s disease. - 8. Intraneuronal transport and defense mechanisms with possible pathogenetic relevance in Huntington s disease. - 9. The disease protein huntingtin and neuronal protein aggregations in Huntington s disease. - 10. Pathological nerve cell alterations in Huntington s disease (HD) and their possible role for the demise of nerve cells. - 11. Conclusions and outlook.