Thalamic degeneration in X‐chromosome–linked copper malabsorption

Abstract

Thalamic degeneration was present in 5 autopsied cases of X-chromosome-linked copper malabsorption (X-cLCM), Menkes' kinky hair disease. Among the thalamic nuclei, those in the formatio paraventricularis, intralamellaris, and extralamellaris were spared. The nuclei projecting to the granular cortices had severe neuronal depopulation. The thalamic nuclei that send axons to the agranular cortices were less often and less severely involved. The thalamic afferent system was intact except for degeneration of the red nucleus. Cerebral cortical lesions varied from case to case and usually were less marked than thalamic neuronal changes.

Cytochrome C Oxidase Deficiency and Neuronal Involvement in Menkes' Kinky Hair Disease: Immunohistochemical Study

“…Because the cytoarchitecture in both of these areas was well preserved, it is possible that functional impairment preceded neuropathological changes. Furthermore, the severe and diffuse COX alterations detected in the frontal cortex could represent the functional basis for a transsynaptic retrograde degeneration of the thalamic nuclei, as Iwata and co-workers have proposed (11). In the cerebellum, the reduction of COX I1 and IV immunoreactivity affected especially Purkinje cells and cells of the granular layer.…”

“…The clinical presentation is typically neonatal onset with hypothermia, inadequate feeding, poor weight gain, seizures, mental retardation and abnormal hair in association with significantly reduced levels of serum ceruloplasrnin and copper (1)(2)(3)(4)(5)(6)(7). The main neuropathological features are widespread neuronal loss and gliosis; Purkinje cell changes (somatic sprouts and abnormal dendritic arborization) are particularly prominent (1)(2)(3)(5)(6)(7)(8)(9)(10)(11)(12).…”

Neuronal and vascular disorders of the brain and spinal cord in Menkes kinky hair disease

“…However, in approximately 10% of reported cases, neural damage was unassociated with vascular abnormalities. Copper deficiency may cause diverse metabolic responses and may induce neuronal degeneration without any vascular abnormality [Iwata et al, 1978;Yoshimura and Kudo, 1982;Martin and Leroy, 19851. Although autopsy examination in each reported case was by no means complete, involvement of the spinal cord was rather low, about 30% in 37 autopsied cases. The lesions in the spinal cord in these cases varied greatly from minor neuronal loss to systemic demyelination of the lateral column combined with marked loss of neurons [Garnica et al, 1977;Martin et al, 1978;Aguilar et al, 1966;Ghatak et al, 1972;Erdohazi et al, 1976;Barnard et al, 1978;Grover et al, 19781.…”

“…Danks et al [1972b] first postulated that the vascular abnormality in Menkes disease was the primary cause of the neural damage; since then most cases (more than 70%) have shown various degrees of vascular change recognized either at autopsy or by radiological examination [Vagn-Hansen et al, 1973;Hara et al, 1979;Camakaris and Danks, 1981;Farrelly et al, 19841. However, in approximately 10% of reported cases, neural damage was unassociated with vascular abnormalities. Copper deficiency may cause diverse metabolic responses and may induce neuronal degeneration without any vascular abnormality [Iwata et al, 1978;Yoshimura and Kudo, 1982;Martin and Leroy, 19851. Although autopsy examination in each reported case was by no means complete, involvement of the spinal cord was rather low, about 30% in 37 autopsied cases. The lesions in the spinal cord in these cases varied greatly from minor neuronal loss to systemic demyelination of the lateral column combined with marked loss of neurons [Garnica et al, 1977;Martin et al, 1978;Aguilar et al, 1966;Ghatak et al, 1972;Erdohazi et al, 1976;Barnard et al, 1978;Grover et al, 19781. In the present case, both the ascending (spinocerebellar) and the descending (corticospinal) tracts were severely demyelinated from the cervical to the sacral levels.…”