Comparison to Neuropathology and to Other Basal Ganglia Disorders

Marked striatal atrophy has been demonstrated post mortem repeatedly [11] and was most prominent in the head of the caudate nucleus, in putamen and pallidum. The substantia nigra was also affected. This loss of tissue appears to be neurodegenerative

(a) Case One - Left Caudate

(a) Case One - Left Caudate

Posterior — > Anterior

Posterior — > Anterior

(b) Case One - Right Caudate

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Slice: Posterior —> Anterior

Fig. 5 Caudate volume/shape in two previously described male and female ChAc patients [18, 21] (black lines), compared with age-matched controls (grey lines); (a) left and (b) right caudate volumes of a 33-year-old man with OCD onset at the age of 10, who developed seizures at 21 and chorea at 25

Slice: Posterior —> Anterior

Fig. 5 Caudate volume/shape in two previously described male and female ChAc patients [18, 21] (black lines), compared with age-matched controls (grey lines); (a) left and (b) right caudate volumes of a 33-year-old man with OCD onset at the age of 10, who developed seizures at 21 and chorea at 25

in origin, with severe neuronal loss and gliosis in the caudate and, to a lesser degree, the putamen and pallidum [26]. Neuropathologic investigations using a stereologi-cal technique for cell counting [2] support this, again demonstrating marked striatal atrophy with a predilection for the caudate nucleus. Additionally, in contrast to former studies, the group of Arzberger also found a more distinct and diffuse cortical cell loss suggesting more diffuse cerebral involvement of the neurodegenerative process. Thus, we would expect future neuroimaging studies to show selective

Fig. 5 (continued) (c) left and (d) right caudate volumes of a 38-year-old woman who developed OCD at 16, her first seizure at 21 and choreiform movements at 27

regional loss in the striatum, but also to show cortical volume loss, possibly with a predilection for frontal cortical regions, as might be expected given the pattern of neuropsychological impairments and behavioural disturbances.

In Huntington's disease (HD), global brain parenchyma reduction seems to be an early feature. In VBM studies brain parenchymal fractions in early HD patients (stage I and II according to Shoulson et al. [23]) were significantly reduced compared to age-matched controls [16]. Regional volume loss was found bilaterally in striatal areas as well as in the hypothalamus and the opercular cortex, and unilaterally in the right paracentral lobule [17] as well in dorsal midbrain and bilateral intra-parietal sulcus [24]. The topography of striatal changes in HD correspond to the dorso-medial to ventro-lateral gradient of neuronal loss that was found in neu-

ropathological studies [27]. Additionally a correlation between cerebral grey matter loss with clinical severity and CAG repeat length was found in this study.

In comparison to HD, the small number of available ChAc patients limits extended morphometric studies. The present data suggest a greater total reduction of striatal volume with differential involvement of striatal subregions in comparison to HD. The ventrocaudal to dorsolateral gradient described in HD, has not been found. Additionally the caudate nucleus seems to be more involved than the putamen, whereas in HD the whole striatum shows marked pathology. Adequately powered studies are needed in the future to directly compare these two groups, as well as other relevant patient groups (e.g. McLeod syndrome, Huntington disease like-2, and obsessive-compulsive disorder), to reveal their differential effects on striatal and extra-striatal regions. Eventually, genotype-phenotype and structure-function correlations may be further clarified. Neuroimaging studies in general, and volumetric studies in particular, are able to at least partly provide "missing links." Understanding the progression of pathology from genome to proteome, through microstructure and macrostructure, to clinical phenotype and illness course, will ultimately allow for the nature of the illness to be more fully understood, and for future treatments to be tailored and introduced appropriately to ChAc patients.

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