Summary
The brain from a clinically typical case of the Zellweger malformation, dying at 5 weeks of age, is studied in general histologic preparations and in Bielschowsky impregnations. Cytoarchitectonic abnormalities, typical of previously described cases and unique to the Zellweger malformation, are observed in the cerebral hemispheres, the cerebellum and the inferior olivary complex. Neocortical malformation is associated with neuronal heterotopia. The impediment to neuronal migration has affected, principally, neurons destined for the outer cortical layers. The impediment to migration appears to be only partially effective in that a portion of neurons destined for cortical layers II and III are in their normal laminar positions whereas others lie in heterotopic intra-cortical and subcortical positions. The cerebellar cortex in this malformation is distinctive for large Purkinje cell heterotopias, subjacent to intact Purkinje and granule cell cortical laminae. Bielschowsky preparations identify multiple primary dendritic processes extending from the somata of heterotopic Purkinje cells. Finally, there are laminar discontinuities, unique to this malformation, in the principal nucleus of the inferior olivary complex. By analogy with the cerebellar cortical malformation in the weaver mutant mouse, the Zellweger cortical malformation may result from incomplete disruption of neuronal migration caused by circulating toxic metabolites.
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This study was supported in part by USPHS Grant 1 RO1 NS12005-02, National Institutes of Health, Bethesda, Maryland, U.S.A.
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Evrard, P., Caviness, V.S., Prats-Vinas, J. et al. The mechanism of arrest of neuronal migration in the Zellweger malformation: An hypothesis based upon cytoarchitectonic analysis. Acta Neuropathol 41, 109–117 (1978). https://doi.org/10.1007/BF00689761
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DOI: https://doi.org/10.1007/BF00689761