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White matter injury and neurodevelopmental disabilities: A cross-disease (dis)connection

Elisa Cainelli¹, Filippo Arrigoni², Luca Vedovelli³

¹Department of General Psychology, University of Padova, Padova, Italy.

Progress in Neurobiology

|June 8, 2020

Insights

Subtle white matter (WM) injuries in early life, often overlooked, significantly impact cognitive development and neurodevelopmental disorders. This review explores their role, mechanisms, and potential interventions.

Area of Science:

Neuroscience
Developmental Biology
Pediatrics

Background:

White matter (WM) injury, previously associated mainly with preterm newborns, is now recognized in a diffused, non-necrotic form across various early-life diseases.
Despite medical advances reducing severe outcomes, subtle brain injuries contribute to persistent cognitive and psychopathological impairments with lifelong consequences.
WM's role in coordinating neuronal activity through myelination is crucial; even mild structural alterations can disrupt cognitive performance as learning demands increase.

Purpose of the Study:

To review and synthesize evidence on how diffused WM injuries contribute to neurodevelopmental disorders.
To explore potential common mechanisms underlying WM abnormalities across different perinatal diseases and insults.
To discuss neuroimaging, biomarkers, and neuroprotective strategies for addressing these injuries.

Main Methods:

Systematic review of existing literature on white matter injury in early-life diseases.
Organization of evidence linking diffused WM injuries to neurodevelopmental disorders.
Analysis of potential shared pathophysiological pathways and therapeutic approaches.

Main Results:

Diffused white matter injuries are implicated in neurodevelopmental disorders stemming from prematurity, intrauterine growth restriction, congenital heart defects, and hypoxic-ischemic encephalopathy.
Mild WM alterations can interfere with cognitive development, explaining late-appearing impairments in children with perinatal insults.
WM abnormalities are also observed in neuropsychiatric disorders like autism and schizophrenia.

Conclusions:

Diffused white matter injuries represent a critical factor in subtle early-life brain insults, leading to long-term neurodevelopmental and cognitive deficits.
Understanding the common mechanisms across various perinatal conditions is key to developing effective interventions.
Further research into neuroimaging, biomarkers, and neuroprotective strategies is warranted to mitigate the impact of these injuries.

Read full analysis

Abstract:

White matter (WM) injury, once known primarily in preterm newborns, is emerging in its non-focal (diffused), non-necrotic form as a critical component of subtle brain injuries in many early-life diseases like prematurity, intrauterine growth restriction, congenital heart defects, and hypoxic-ischemic encephalopathy. While advances in medical techniques have reduced the number of severe outcomes, the incidence of tardive impairments in complex cognitive functions or psychopathology remains high, with lifelong detrimental effects. The importance of WM in coordinating neuronal assemblies firing and neural groups synchronizing within multiple frequency bands through myelination, even mild alterations in WM structure, may interfere with the cognitive performance that increasing social and learning demands would exploit tardively during children growth. This phenomenon may contribute to explaining longitudinally the high incidence of late-appearing impairments that affect children with a history of perinatal insults. Furthermore, WM abnormalities have been highlighted in several neuropsychiatric disorders, such as autism and schizophrenia. In this review, we gather and organize evidence on how diffused WM injuries contribute to neurodevelopmental disorders through different perinatal diseases and insults. An insight into a possible common, cross-disease, mechanism, neuroimaging and monitoring, biomarkers, and neuroprotective strategies will also be presented.

Keywords:

Connectivity Myelin Neurodevelopment White matter

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