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Arterial Tortuosity: An Imaging Biomarker of Childhood Stroke Pathogenesis?
Background and purposeArteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.MethodsChildren (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test).ResultsOne hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P=0.998), meningitis (1.348±0.052; n=11; P=0.989), and cardioembolic (1.379±0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70).ConclusionsIn children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke
Segmental Diffusion Properties of the Corticospinal Tract and Motor Outcome in Hemiparetic Children With Perinatal Stroke
Bihemispheric alterations in myelination in children following unilateral perinatal stroke
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. Keywords: Perinatal stroke, Myelination, White matter, Developmental plasticity, Cerebral pals