Bihemispheric alterations in myelination in children following unilateral perinatal stroke
Sabrina Yu1, Helen L Carlson2, Aleksandra Mineyko3
1Calgary Pediatric Stroke Program, University of Calgary, Calgary, AB, Canada.
Insights
Perinatal stroke impairs myelination in both affected and unaffected brain hemispheres, impacting brain development. Further research is needed to understand the clinical significance of these myelination changes.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatric Neurology
Background:
- Perinatal stroke is a major cause of brain injury in newborns, leading to conditions like cerebral palsy and epilepsy.
- The underlying biological mechanisms for variable outcomes after perinatal stroke remain unclear.
- Altered developmental myelination is a known factor in preterm brain injury but has not been studied in perinatal stroke.
Purpose of the Study:
- To investigate and characterize myelination patterns in children with arterial perinatal stroke.
- To determine if ipsilesional (on the same side as the stroke) myelination is impaired.
- To explore the correlation between the degree of myelination impairment and clinical outcomes.
Main Methods:
- A retrospective, controlled cohort study using data from the Alberta Perinatal Stroke Project (APSP).
- Inclusion criteria: MRI-confirmed unilateral arterial perinatal stroke, T1-weighted MRI after 6 months, no other neurological disorders, and assessed neurological outcomes.
- FreeSurfer software was used to measure hemispheric asymmetry in myelination intensity, with validation using ImageJ software.
Main Results:
- Twenty children with stroke and 27 controls were analyzed.
- Participants with stroke showed significantly reduced myelination in the ipsilesional hemisphere (p < 0.0001).
- Myelination was reduced in perilesional, ipsilesional remote, and contralesional homologous regions compared to controls, indicating widespread effects.
Conclusions:
- Perinatal stroke leads to decreased myelination in both ipsilesional and contralesional hemispheres, even in areas not directly affected by the lesion.
- These myelination deficits appear to spread outwards from the stroke site.
- Further investigation is required to establish the clinical significance of these findings.
Background:
Stroke is a leading cause of perinatal brain injury with variable outcomes including cerebral palsy and epilepsy. The biological processes that underlie these heterogeneous outcomes are poorly understood. Alterations in developmental myelination are recognized as a major determinant of outcome in preterm brain injury but have not been explored in perinatal stroke. We aimed to characterize myelination in hemiparetic children after arterial perinatal stroke, hypothesizing that ipsilesional myelination would be impaired, the degree of which would correlate with poor outcome.
Methods:
Retrospective, controlled cohort study. Participants were identified through the Alberta Perinatal Stroke Project (APSP), a population-based research cohort (n > 400). Inclusion criteria were: 1) MRI-confirmed, unilateral arterial perinatal stroke, 2) T1-weighted MRI after 6 months of age, 3) absence of other neurological disorders, 4) neurological outcome that included at least one of the following tests - Pediatric Stroke Outcome Measure (PSOM), Assisting Hand Assessment (AHA), Melbourne Assessment (MA), neuropsychological evaluation (NPE), and robotic sensorimotor measurements. FreeSurfer software measured hemispheric asymmetry in myelination intensity (primary outcome). A second method using ImageJ software validated the detection of myelination asymmetry. A repeated measures ANOVA was used to compare perilesional, ipsilesional remote, and contralesional homologous region myelination between stroke cases and typically developing controls. Myelination metrics were compared to clinical outcome measures (t-test, Pearson's correlation).
Results:
Twenty youth with arterial stroke (mean age: 13.4 ± 4.2yo) and 27 typically developing controls (mean age: 12.5 ± 3.7yo) were studied in FreeSurfer. Participants with stroke demonstrated lower myelination in the ipsilesional hemisphere (p < 0.0001). Myelination in perilesional regions had lower intensity compared to ipsilesional remote areas (p < .00001) and contralesional homologous areas (p < 0.00001). Ipsilesional remote regions had decreased myelination compared to homologous regions on the contralesional hemisphere (p = 0.016). Contralesional myelination was decreased compared to controls (p < 0.00001). Myelination metrics were not strongly associated with clinical motor, robotic sensorimotor, or neuropsychological outcomes though some complex tests requiring speeded responses had moderate effect sizes.
Conclusion:
Myelination of apparently uninjured brain in both the ipsilesional and contralesional hemispheres is decreased after perinatal stroke. Differences appear to radiate outward from the lesion. Further study is needed to determine clinical significance.
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