The influence of perinatal arterial ischemic stroke on contralesional brain volumes

Abstract

Perinatal arterial ischemic stroke (PAIS) is associated with long-term neurological sequelae, like cerebral palsy, epilepsy and cognitive deficits. It is hypothesized that plasticity of the contralesional hemisphere may play a role in developmental outcomes. This study aimed to explore the effects of stroke volume and location on contralesional brain volumes at 2-3 months of age in infants with PAIS. We included near term-born infants (>36 weeks of gestation) with primary unilateral PAIS, admitted to the University Medical Center Utrecht between 2008-2023. All patients underwent a neonatal diagnostic MRI, and a follow-up MRI performed ≥45 weeks postmenstrual age (PMA). We assessed the arterial territory of the stroke and involvement of several brain areas. We segmented the neonatal and follow-up T2-weighted MRIs with the developing Human Connectome Project (dHCP) pipeline, and we extracted total contralesional hemispheric volumes and several tissue volumes. An in-house segmentation method was applied to segment the stroke area based on neonatal T2 and DW images. Infants with poor quality tissue segmentations were excluded (n = 17). We excluded ventricular and cerebrospinal fluid volumes, and corrected neonatal and follow-up contralesional brain volumes for post-menstrual age (PMA) at scanning. Multiple linear regression analyses and ANCOVAs were performed to correlate stroke characteristics with contralesional volumes at follow-up, with neonatal contralesional brain tissue volumes as a covariate. The final cohort consisted of 86 infants (52% male, n = 45), with a median [IQR] gestational age of 40+1 [1+6] weeks, and a birth weight of 3433 [653] grams. Median stroke volume was 5.6 [6.2] % of total brain volume. Stroke volume and arterial territory did not correlate to follow-up contralesional hemispheric and tissue volumes at a median of 53 weeks PMA. Stroke volume did not correlate to several contralesional lobar volumes, contralesional white matter, deep and cortical grey matter, or cerebellar volumes. However, contralesional white matter volume significantly differed across arterial territories (p = .01). No associations between affected brain areas and contralesional homologous volumes were found. Stroke volume and location did not correlate to contralesional brain tissue volumes 2-3 months after PAIS, suggesting contralesional development is preserved in the first months. Future research should examine the impact of PAIS on other contralesional morphometric parameters at later timepoints, and relate contralesional development to functional outcome.