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[Pathology and pathogenesis of secondary epilepsy to hypoxic-ischemic encephalopathies]
1Department of Pathology, Dartmouth Medical School, Hanover, NH 03755, USA.
Insights
Brain injury from perinatal hemorrhages and hypoxic-ischemic events alters gray matter development. These specific neuropathological changes are linked to neurological issues like epilepsy and cerebral palsy in children.
Area of Science:
- Neuropathology
- Developmental Neuroscience
- Pediatric Neurology
Background:
- Perinatal encephalopathies, including hemorrhagic and hypoxic-ischemic injuries, can lead to significant neurological sequelae in surviving children.
- Understanding the long-term effects on brain development is crucial for managing conditions like epilepsy and cerebral palsy.
Purpose of the Study:
- To investigate the specific neuropathological changes in gray matter following perinatal brain lesions.
- To elucidate how these alterations in gray matter development contribute to post-natal neurological deficits.
Main Methods:
- Histopathological examination of brain tissue from children with a history of perinatal lesions.
- Utilizing immunohistochemical techniques and Golgi's method to analyze neuronal and neuropil changes.
- Correlation of neuropathological findings with clinical outcomes, including epilepsy and cerebral palsy.
Main Results:
- Subpial hemorrhages lead to cortical scarring and leptomeningial heterotopia, transforming pyramidal cells into 'star cells'.
- Infarcts in white matter alter gray matter development, causing projection neurons to become short-axon cells and leading to irregular neuropil expansion.
- Neuronal hypertrophy with increased dendritic spines was observed in affected gray matter areas.
Conclusions:
- Post-natal gray matter development is specifically altered by perinatal subpial hemorrhages and hypoxic-ischemic infarcts.
- These structural and functional changes in gray matter are implicated in the pathogenesis of epilepsy and infantile cerebral palsy.
- The study highlights the critical link between early brain injury neuropathology and long-term neurodevelopmental outcomes.
Abstract:
The neuropathology of haemorrhagic and hypoxic-ischaemic perinatal encephalopathies and their effect on the post-natal development of the brain, has been studied in children who survived with these lesions (for days, weeks, months and even years). Eventually some children developed neurological sequelae, including epilepsy and cerebral palsy. In this paper it is emphasized that the post-natal development of the grey matter next to these lesions in altered in a specific manner. The post-natal resolution (scarring) of the subpial haemorrhage causes structural changes in the superficial layers of the cortex and permanent leptomeningial heterotopia. The pyramidal cell of layers II and III whose apical dendrites had been partially amputated by haemorrhage became star cells. The grey matter often survived an infarct of the subjacent white matter, since its circulation remained intact. However its post-natal development was altered in a specific way. The post-natal development of this grey matter (partly deprived of sensory information because of the destruction of afferent fibres and with contact lost because on the destruction of efferent fibres) is inevitably different. Projection pyramidal cells (long axon) axotomized by the subjacent lesion, survive the insult and post-natally are changed into intracortical short axon cells. The intrinsic neuropile of the grey matter (partially isolated) increases in an irregular manner which can be seen using immunohistochemical techniques and Golgi's method: areas with a great increase in fibres alternate with areas with few fibres. The presence of large neurones (Golgi's method) with long drendites covered with spines (acquired neuronal hypertrophy) is frequent. In this paper it is suggested that these changes in the grey matter secondary to subpial haemorrhage and hypoxic-ischaemic perinatal infarcts are accompanied by functional changes which may play and important role in the pathogenesis of epilepsy (infantile spasm) and in infantile cerebral palsy.