Pathology of Huntingtonʼs Chorea

Huntington's disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain

“…In his famous essay “On chorea” from 1872 the American physician George Huntington (1850–1916) provided a detailed description of the clinical picture of adult chorea, its hereditary transmission and the relentless clinical progress of this neurological disease. Although this widely known essay by George Huntington was preceded by earlier clinical descriptions of adult‐onset hereditary chorea (such as those of Waters, Lund and Lyon), hereditary chorea has been called Huntington's disease (HD) since the late 1880s .…”

“…Recent neuropathological HD research, however, led to the rediscovery and confirmation of many of the initial, groundbreaking postmortem findings. On account of the results of these recent re‐investigations, the oversimplified concept of HD as a neurodegenerative disease predominantly affecting the striatum was replaced by the current view of HD as a multisystem degenerative disease of the human brain (Figures ) . The early descriptions of macroscopical brain alterations (reduced brain weight and brain atrophy) and widespread visible microscopical degenerative changes in the striatum, thalamus, pallidum, brainstem and circumscribed regions of the cerebral cortex (Figures ) in patients suffering from Huntington's chorea by both well‐known ( Alois Alzheimer, Gerbrandus Jelgersma, Cécile and Oskar Vogt) and less prominent neuroscientists ( Ewald Stier) were already compatible with the currently favored view of HD as a multisystemic neurodegenerative disease.…”

“…Cécile and Oskar Vogt, in their classic comprehensive work on the human striatum and its diseases in 1920 confirmed the disease‐specific histopathological feature of striatal neurodegeneration in HD (differential vulnerability of small and large nerve cells of the striatum in the degenerative process) which was initially delineated by James Ramsey Hunt in 1917. However, Cécile and Oskar Vogt had already questioned the attribution of the occurrence of involuntary choreatic and incoordinated movements to striatal degeneration, as suggested by Gerbrandus Jelgersma in 1908 and by Alois Alzheimer in 1911 .…”

“…Recent investigation in HD, however, has shown that all four cerebral lobes undergo thinning of their cortical mantles along with a severe atrophy, and it has demonstrated layer‐specific neuronal loss in various areas of the cerebral allocortex and neocortex (Figures , , and ). These findings have sounded the death knell of the traditional, reductionistic pathoanatomical and pathophysiological concepts of the polyglutamine disease HD as a selective disease of the striatum and they have resulted in the definitive appreciation of the cerebral neocortex and allocortex as the main targets of the HD disease process (Figures −6 and ) . The layer‐specific neuronal loss in the neocortical and allocortical targets of the destructive process of HD is now regarded as the most important morphological correlate of the psychiatric symptoms, neuropsychological deficits, cognitive decline and neurophysiological abnormalities (ie, alterations of the somatosensory and visual evoked potentials) of affected HD patients and some at‐risk gene carriers.…”

“…Degeneration of the thalamus of HD patients (eg, global atrophy and volume loss of the thalamus; thalamic astrogliosis; diminished density of microneurones in the precerebellar ventrolateral nucleus; reactive astrogliosis in the thalamic centromedian and parafascicular nuclei; shrinkage of the centromedian nucleus and its nerve cells) was described in some early neuropathological HD reports. In the period that follow the involvement of this large diencephalic nuclear complex in HD patients, however, it experienced only minor attention (Figures and ) . Recent re‐investigations applying modern stereological methods, however, have demonstrated that thalamic neurodegeneration is not confined to the cerebellar territory of the thalamus (ie, motor ventrolateral nucleus), but also occurs in the thalamic centromedian‐parafascicular complex and mediodorsal nucleus .…”