Degeneration of the thalamic nuclei in X-chromosome-linked copper malabsorption (Menkes' kinky hair disease)

Neuropathological examination of five autopsied cases of X-chromosome-linked copper malabsorption (X-cLCM), Menkes' kinky hair disease, revealed thalamic degeneration with characteristic topographical distribution in all cases. Among the thalamic nuclei, those in the formatio paraventricularis, intralamellaris and extralamellaris were always spared. The nuclei ventralis posterior, dorsalis anterior and dorsalis posterior and the formatio medialis, as well as the lateral and medial geniculate bodies, inevitably showed almost complete neuronal loss with severe fibrillary gliosis. The lateral part of the pulvinar was similarly degenerated, while its medial portion was either normal or only slightly depopulated. The nuclei ventralis anterior and ventralis oralis were much less affected than the other nuclei of the formatio lateralis. The formatio anterior and the nucleus dorsalis superficialis, its caudal extension, were normal in three cases and mildly depopulated in two. As a whole, thalamic nuclei without direct thalamo-cortical projection were spared and those sending their axons to the agranular cortics were less affected than those with thalamo-cortical fibers to the granular cortices, the latter nuclei being always nearly completely degenerated in this condition. Thalamic afferents were intact except for degeneration of the red nucleus. Cerebral cortical lesions, consisting of focal necrotic lesions caused by either generalized ischemia or compression due to the chronic subdural hematoma, and of more diffuse loss of cortical neurons without evident cortical laminar predilection, varied case to case and usually were less marked than thalamic degeneration. Clinical as well as neuropathological significance of thalamic degeneration and the pathogenesis of it are discussed.