Abstract

Objectives: To investigate correlations between infarct topography on acute diffusion weighted MRI, using voxel-based lesion-symptom mapping (VLSM), and later development of cerebral palsy (CP) and neurological impairments, in neonatal arterial ischaemic stroke (AIS). Methods: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language or cognitive-behavioural impairments were assessed using the Pediatric Stroke Outcome Measure dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using axial DWI images, and coregistered to the Melbourne Children’s Regional Infant Brain 2.0 atlas. All lesions were projected to the left hemisphere to obtain binary union masks. VLSM was conducted using MATLAB SPM12 toolbox. A generalised linear model was used to correlate the lesion mask with outcomes. Voxel-wise t test statistics were calculated, and corrected for multiple comparisons using family-wise error rate (FWE). Results: 85 newborns (55 male) met inclusion criteria. Infarct lateralization was left hemisphere in 62%, right in 8% and bilateral in 29%. At median age 2.1 years (IQR1.9-2.6), 34% developed CP and 42% had neurological impairments. 54 ROIs were correlated with CP (t>4.33; FWE <0.05); the 12 highest correlated ROIs were the superior corona radiata, putamen, anterior corona radiata, insula, thalamus, external capsule, pars triangularis, caudate, lateral orbitofrontal cortex, superior temporal cortex, pars opercularis and precentral cortex. (Figure) No significant correlations were found for poor language or cognitive-behavioural outcomes. Conclusions: Cerebral palsy following neonatal AIS correlates predominantly with regions of acute infarction directly involved in motor control, or in functionally connected regions. Brain regions associated with language or cognitive-behavioural impairment are less clear.

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