Developmental neuropathology and impact of perinatal brain damage. III: Gray matter lesions of the neocortex

The evolving neuropathology of primarily undamaged conical regions adjacent to the injured site has been studied in 36 infants who survived a variety of perinatally acquired encephalopathies (microgyrias, ulegyrias, multicyst ic encephalopathies, porencephalies, and hydranencephalies) and later died of unrelated causes. Their survival times range from hours, days, weeks, or months, to several years. Ten of these children developed epilepsy, 2 deve loped cerebral palsy, and several were neurologically and mentally impaired . In all cases studied, the undamaged colter adjacent to the injured site s urvives, retains its intrinsic vasculature, and is capable of continuing di fferentiation. However, its postinjury development is characterized by prog ressive alterations compatible with acquired cortical dysplasia that affect s the structural and functional differentiation of its neurons, synaptic pr ofiles, fiber distribution, glial elements, and vasculature. The synaptic p rofiles of many neurons are transformed by an increased number of intrinsic loci that replace extrinsic ones vacated by the destruction of afferent fi bers. The intrinsic fibers of layer I and some Cajal-Retzius cells survive even in severe lesions and may be capable of interconnecting cortical regio ns that have lost other type of connections. Some intrinsic neurons undergo postinjury structural and functional hypertrophy, acquire new morphologic and functional features, and achieve a large size (meganeurons). Probably, these meganeurons acquire their structural and functional hypertrophy by pa rtial endomitotic DNA and/or RNA reduplication (polyploidy). These postinju ry alterations are not static but ongoing processes that continue to affect the structural and functional differentiation of the still developing cort ex and may eventually influence the neurologic and cognitive maturation of affected children. This study proposes that, in acquired encephalopathies, the progressive postinjury reorganization of the undamaged cortex and its c onsequences (acquired cortical dysplasia), rather than the original lesion, represent the main underlying mechanism in the pathogenesis of ensuing neu rological sequelae, such as, epilepsy, cerebral palsy, dyslexia, cognitive impairment, and/or poor school performance.