Basic Neuropathology

In vivo, neurodegeneration can be observed by MRI scans, which show a special vulnerability of the head of the caudate nucleus [13] in ChAc. FDG-PET scans reveal a marked decrease in neuronal glucose metabolism in striatal structures [17, 20], whereas the cortex show regular glucose uptake. Postmortem macroscopic findings in ChAc reveal a significant degeneration of the caudate nucleus, the putamen and minor atrophy of the globus pallidus and the substantia nigra [1, 3, 10, 22]. These findings are very similar to those found in Huntington's disease (HD). On histological and immunohistochemical examination, there was loss of 90% of striatal neurons, accompanied by a striking astroglial and oligodendroglial proliferation as well as microglial activation as shown in Fig. 1 [1, 3, 22]. This results in an increased striatal glial index (number of striatal astroglial and oligodendroglial cells divided by the number of striatal neurons) in ChAc of 46.9 (two cases) compared to 22.9 in HD (five cases) and 3.4 in non-affected controls (five controls). Gliosis was also found in

Fig. 1 Immunohistochemistry of the putamen in ChAc (x200 enlargement). (a) Staining for glial fibrillary acidic protein (GFAP) shows numerous reactive astrocytes, (b) staining for CD68 shows many activated microglial cells or macrophages

Fig. 2 Postmortem brain section of a 35-year-old male ChAc patient at the level of the anterior striatum. Gallocyanin staining was applied to the tissue to highlight neuronal areas. The cutout in the big picture is shown in the left enlargement. For comparison, an enlargement of approximately the same region of a HD-affected brain is shown in the right enlargement. cc, corpus callosum; cd, caudate nucleus; put, putamen

Fig. 2 Postmortem brain section of a 35-year-old male ChAc patient at the level of the anterior striatum. Gallocyanin staining was applied to the tissue to highlight neuronal areas. The cutout in the big picture is shown in the left enlargement. For comparison, an enlargement of approximately the same region of a HD-affected brain is shown in the right enlargement. cc, corpus callosum; cd, caudate nucleus; put, putamen thalamic regions [22], together with moderate atrophy of the anterior and centromedian nuclei [1]. Compared to HD, pathology of the corpus callosum in ChAc was only mild at best.

Figure 2 shows a post mortem brain section of a 35-year-old male ChAc patient at the level of the anterior striatum. An impressive reduction of the mediolateral diameter of the caudate nucleus to 4 mm can be observed. Brains were embedded in celloidin, cut and stained with gallocyanin [12]. In contrast to HD, there was no apparent atrophy of the corpus callosum (Fig. 1). Three-dimensional reconstructions of striatal structures in HD and ChAc from postmortem sections also demonstrate a dramatic atrophy in both neurodegenerative diseases compared to healthy controls (Fig. 3).

Stereological investigations [3] estimated the total number of astroglial, oligodendroglial and neuronal cells within the striatum of two post mortem ChAc brains compared to HD brains and non-affected control brains (Fig. 3). In ChAc, the number of glial cells (astroglial and oligodendroglial cells) is markedly increased relative to the decrease of neurons. This effect is even more striking than

Control Morbus Huntington Chorea-Acanthocytosis

Fig. 3 3D reconstructions of the striatum from digitalized consecutive 440 |lm coronal brain sections of healthy controls (control), HD (Morbus Huntington) and ChAc. cd, caudate nucleus, light grey; put, putamen, dark grey

Control Morbus Huntington Chorea-Acanthocytosis

Fig. 3 3D reconstructions of the striatum from digitalized consecutive 440 |lm coronal brain sections of healthy controls (control), HD (Morbus Huntington) and ChAc. cd, caudate nucleus, light grey; put, putamen, dark grey in five HD patients. Hence, the striatal glia index in ChAc is 2.1 times higher than in HD, and 14 times higher than in non-affected controls (Fig. 4).

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