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Developmental neuropathology and impact of perinatal brain damage. II: white matter lesions of the neocortex
1Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Insights
Infants surviving perinatal brain damage show altered gray matter development over white matter lesions. These gray matter changes, including neuronal transformation and hypertrophy, are linked to neurological issues like epilepsy and cerebral palsy.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neuropathology
Background:
- Perinatal brain damage can cause acute, subacute, and chronic white matter lesions.
- Infants surviving these lesions exhibit significant neuropathology and developmental impacts.
- Gray matter overlying extensive white matter lesions can survive due to intact vascular supply.
Purpose of the Study:
- To investigate the neuropathology and developmental impact of white matter lesions in surviving infants.
- To understand the structural and functional alterations in gray matter following perinatal brain injury.
- To correlate post-injury gray matter changes with the pathogenesis of neurological sequelae.
Main Methods:
- Study of infants surviving perinatal brain damage with white matter lesions.
- Analysis of neuropathology and developmental outcomes over varying survival periods (days to years).
- Correlation of observed gray matter alterations with neurological sequelae, such as epilepsy.
Main Results:
- Gray matter overlying extensive white matter lesions (e.g., multicystic encephalopathy) survives due to unaffected leptomeningeal and intrinsic vasculature.
- Post-injury, surviving gray matter undergoes significant structural and functional alterations.
- These include transformation of pyramidal neurons into local-circuit interneurons and hypertrophy of interneurons and intracortical neuropil.
Conclusions:
- Neurological sequelae, including epilepsy and cerebral palsy, following perinatal white matter lesions are proposed to result directly from these post-injury gray matter transformations.
- The study highlights the critical role of gray matter adaptation in the development of neurological deficits after white matter injury.
- Understanding these transformations is key to addressing the long-term consequences of perinatal brain damage.
Abstract:
The neuropathology and developmental impact of acute, subacute, and chronic white matter lesions has been studied in infants who survived (days, weeks, months, or years) this type of perinatal brain damage. The study emphasizes the survival of the developing gray matter overlying extensive white matter lesions (multicystic encephalopathy, porencephaly, and hydranencephaly ex-vacuo). Although partially isolated from afferent inputs (corticipetal fiber destruction) and unable to reach other cortical centers (corticofugal fiber destruction), this overlying gray matter is able to survive because neither its independent leptomeningeal blood supply nor its intrinsic anastomotic vasculature are affected by the underlying lesion. Moreover, the postinjury structural and functional development of this partially isolated gray matter is altered. Some of its axotomized pyramidal neurons are transformed into local-circuit interneurons, some of its interneurons are structurally and functionally enlarged (hypertrophy), and its intracortical neuropil (deprived of afferent synaptic terminals) increases by an expansion of intrinsic terminals (hypertrophy). An attempt has been made to correlate these postinjury alterations with the pathogenesis of the ensuing neurologic sequelae (7 infants develop epilepsy). The study proposes that neurological sequelae (e.g. epilepsy and cerebral palsy) following perinatal white matter lesions are a direct consequence of the postinjury gray matter transformations.