The isolated human cortex. A Golgi analysis of Krabbe's disease.

The clinical course of a child with Krabbe's leukodystrophy was characterized by clinical seizures, startle myoclonus, and paroxysmal activity recorded by EEG. At autopsy in the fourth year, myelinated subcortical axons were destroyed, virtually completely. Despite isolation from major subcortical and interhemispheric connections, the cell and fiber pattern of the cortex appeared remarkably normal in routine histologic preparations. The normal range of pyramidal and stellate interneurons were also present in rapid Golgi impregnations. The dendritic arbors of pyramidal neurons appeared to be normally formed and were richly invested with spinous postsynaptic specializations. The near-normal morphology of neurons isolated in the neocortex by the myelinoclastic process illustrates the sustaining influence of local intracortical synaptic connections. Alterations of cortical neuronal circuits resulting from synaptic remodeling of local interneuronal connections may account for cortical hyperexcitability as seen in cases of leukodystrophy.