Maja Steinlin

Background and ObjectivesCardiac abnormalities are among the most common and complex risk factors of pediatric acute ischemic stroke (AIS). Although endovascular treatment (EVT) is increasingly use...

BACKGROUND: Growing evidence for reperfusion therapies in pediatric acute ischemic stroke (AIS) increases the importance of timely diagnosis within treatment windows. We therefore aimed to describe 24-year trends and associated factors of diagnostic delay. METHODS: We conducted a nationwide retrospective cross-sectional study including 314 children aged 28 days to 16 years from the Swiss Neuropediatric Stroke Registry (2000–2023). The primary outcome was time from stroke onset to diagnosis (TOD). Trends for diagnoses beyond intravenous thrombolysis (≥4.5 hours) and thrombectomy (≥24 hours) windows were assessed with multivariable logistic regression, and for continuous TOD with robust linear regression. Prespecified covariates were retained in multivariable models if associated with the outcome in univariable analyses. Analyses were stratified by AIS onset location (out-of-hospital and in-hospital). RESULTS: Median TOD was 26.9 hours (interquartile range, 10.1–91.5) between 2000 and 2023. During this period, the proportion diagnosed beyond the thrombolysis window decreased significantly in the overall cohort from 90.9% to 77.5% (adjusted odds ratio per calendar year 0.94 [95% CI, 0.88–1.00]) and in out-of-hospital AIS from 88.1% to 74.1% (adjusted odds ratio, 0.91 [0.84–1.00]). No significant change was observed beyond the thrombectomy window diagnoses. Continuous TOD decreased significantly only in in-hospital AIS (β=−4.3 [−7.2 to −1.5]). Older age (β=−1.8 [−2.9 to −0.8]), higher pediatric National Institutes of Health Stroke Scale (β=−1.2 [−2.1 to −0.4]), and facial palsy (β=−19.4 [−30.2 to −8.5]) were associated with shorter TOD, and nonspecific symptoms (β=110.0 [72.5–147.5]) with longer TOD. Out-of-hospital TOD was shorter when patients presented to a stroke center compared with other presentation sites. Posterior-stroke symptoms were associated with diagnoses beyond the thrombolysis window. CONCLUSIONS: Despite decreasing proportions of beyond-thrombolysis window diagnoses in out-of-hospital AIS and decreasing TOD in in-hospital AIS, most diagnoses occur beyond reperfusion windows. Goals to decrease delay include raising awareness of posterior-stroke signs and AIS in younger children, and strengthening direct-to-stroke center pathways.

BACKGROUND: Predicting the development of cerebral palsy after neonatal stroke remains challenging. This study aimed to identify novel acute brain functional connectome-based correlates of cerebral palsy after neonatal stroke. METHODS: Stroke lesions were segmented from routine clinical diffusion images of a cohort of term-born neonates with symptomatic arterial ischemic stroke, recruited to Swiss (from 2000 to 2013) and Australian (from 2003 to 2014) pediatric stroke registries. Lesions and 3-Tesla resting-state functional magnetic resonance imaging scans of term-born newborns from the developing Human Connectome Project were coregistered to a template. A neonatal stroke functional connectome was created by computing voxel-wise correlations between lesions and gray matter regions. Linear regressions compared functional connections to lesions between participants who did and did not develop cerebral palsy. RESULTS: From the total N=199 recruited participants, 85 newborns with stroke were included (65% male; median age at magnetic resonance imaging of 4 days), of which 33% developed cerebral palsy at a median age of 2.1 years. Multiple gray matter regions were more highly functionally correlated to lesions in participants who developed cerebral palsy (1721 voxels; t : 5.4–7.4; all P <0.05, family-wise error rate–corrected). These regions included the basal ganglia, thalamus, cerebellum, frontal regions (inferior and orbital frontal and superior frontal), temporal regions (pole, superior, and mesial temporal, including hippocampus and amygdala), and the insula. CONCLUSIONS: This study identified functional networks related to the development of cerebral palsy after neonatal stroke. Building on prior individual lesion-based studies, this work suggests that the development of cerebral palsy after neonatal stroke is related to disruptions of broader functional networks involving motor and extramotor regions, as opposed to only lesions in motor regions.

Background: Predicting development of cerebral palsy following neonatal stroke remains challenging. This study aimed to identify novel acute brain functional connectome-based correlates of cerebral palsy following neonatal stroke. Methods: Stroke lesions were segmented from routine clinical diffusion images of a cohort of term-born neonates with symptomatic arterial ischemic stroke, recruited to Swiss and Australian pediatric stroke registries. Lesions, and 3T resting state functional MRIs of term-born newborns from the developing Human Connectome Project, were co-registered to a template. A neonatal stroke functional connectome was created by computing voxel-wise correlations between lesions and gray matter regions. Linear regressions compared functional connections to lesions between participants who did and did not develop cerebral palsy. Results: Eighty-five newborns with stroke were included (64% male; median age at MRI of 4 days), of which 33% developed cerebral palsy at a median age of 2.1 years. Multiple gray matter regions were more highly functionally correlated to lesions in participants who developed cerebral palsy (1721 voxels; t : 5.4-7.4; all p <0.05, family-wise error rate corrected). These regions included the basal ganglia, thalamus, cerebellum, frontal regions (inferior and orbital frontal and superior frontal), temporal regions (pole, superior, and mesial temporal including hippocampus and amygdala) and the insula. Conclusions: This study identified functional networks related to the development of cerebral palsy following neonatal stroke. Building on prior individual lesion-based studies, this work suggests that development of cerebral palsy after neonatal stroke is related to disruptions of broader functional networks involving motor and extramotor regions, as opposed to only lesions in motor regions.

BACKGROUND: Inflammatory type focal cerebral arteriopathy (FCA-i) in the anterior circulation (AC) is well characterized, and the focal cerebral arteriopathy severity score (FCASS) reflects the severity of the disease. We identified cases of FCA-i in the posterior circulation (PC) and adapted the FCASS to describe these cases. METHODS: In this comparative cohort study, patients from the Swiss NeuroPaediatric Stroke Registry with ischemic stroke due to FCA-i between January 2000 and December 2018 were analyzed. A comparison between PC and AC cases regarding pediatric National Institutes of Health Stroke Scale score and pediatric stroke outcome measure and FCASS was performed. We estimated infarct size by the modified pediatric Alberta Stroke Program Early Computed Tomography Score in children with AC stroke and the adapted Bernese posterior diffusion–weighted imaging score in the PC. RESULTS: Thirty-five children with a median age of 6.3 (interquartile range, 2.7–8.2 [95% CI, 0.9–15.6]; 20 male; 57.1%) years with FCA-i were identified. The total incidence rate was 0.15/100 000/year (95% CI, 0.11–0.21). Six had PC-FCA-i. Time to final FCASS was longer in the PC compared with AC; the evolution of FCASS did not differ. Initial pediatric National Institutes of Health Stroke Scale score was higher in children with FCA-i in the PC with a median of 10.0 (interquartile range, 5.75–21.0) compared with 4.5 (interquartile range, 2.0–8.0) in those with AC-FCA-i. Different from the anterior cases, PC infarct volume did not correlate with higher discharge, maximum, or final FCASS scores (Pearson correlation coefficient [r], 0.25, 0.35, and 0.54). CONCLUSIONS: FCA-i also affects the PC. These cases should be included in future investigations into FCA-i. Although it did not correlate with clinical outcomes in our cohort, the modified FCASS may well serve as a marker for the evolution of the arteriopathy in posterior FCA-i.