Pediatric arterial ischemic stroke: Epidemiology, risk factors, and management.

Pediatric arterial ischemic stroke (AIS) is an uncommon but important cause of neurologic morbidity in neonates and children, with consequences including hemiparesis, intellectual disabilities, and epilepsy. The causes of pediatric AIS are unique to those typically associated with stroke in adults. Familiarity with the risk factors for AIS in children will help with efficient diagnosis, which is unfortunately frequently delayed. Here we review the epidemiology and risk factors for AIS in neonates and children. We also outline consensus-based practices in the evaluation and management of pediatric AIS. Finally we discuss the outcomes observed in this population. While much has been learned in recent decades, many uncertainties sill persist in regard to pediatric AIS. The ongoing development of specialized centers and investigators dedicated to pediatric stroke will continue to answer such questions and improve our ability to effectively care for these patients.

Pediatric Cortical Vein Thrombosis: Frequency and Association With Venous Infarction.

BACKGROUND AND PURPOSE: Cortical vein thrombosis (CVT) is an uncommon site of involvement in cerebral sinovenous thrombosis. Few reports have described pediatric CVT, and none has differentiated its unique attributes. This study assessed the clinical features and radiographic outcome of a cohort of children with cerebral sinovenous thrombosis, comparing those with CVT to those without CVT. METHODS: Children diagnosed with cerebral sinovenous thrombosis were retrospectively reviewed and separated into 2 groups based on the presence or absence of cortical vein involvement. RESULTS: Fifty patients met inclusion criteria, including 12 with CVT. The CVT group was more likely to present with seizure (P=0.0271), altered mental status (P=0.0271), and a family history of clotting disorder (P=0.0477). Acute imaging of the CVT group more commonly demonstrated concurrent superior sagittal sinus thrombosis (P=0.0024), parenchymal hemorrhage (P=0.0141), and restricted diffusion (P<0.0001). At follow-up, the CVT group more commonly showed headache, seizure, and focal neurological deficit (P=0.0449), and venous infarction (P=0.0007). CONCLUSIONS: In our cohort, CVT was significantly associated with seizures at presentation, hemorrhage and restricted diffusion on acute imaging, as well as neurological disability and venous infarction at follow-up. Involvement of cortical veins in cerebral sinovenous thrombosis is associated with an increased risk of infarction and adverse outcome in children.

Hemispheric lateralization of verbal and spatial working memory during adolescence.

Adult functional magnetic resonance imaging (fMRI) literature suggests that a left-right hemispheric dissociation may exist between verbal and spatial working memory (WM), respectively. However, investigation of this type has been obscured by incomparable verbal and spatial WM tasks and/or visual inspection at arbitrary thresholds as means to assess lateralization. Furthermore, it is unclear whether this hemispheric lateralization is present during adolescence, a time in which WM skills are improving, and whether there is a developmental association with laterality of brain functioning. This study used comparable verbal and spatial WM n-back tasks during fMRI and a bootstrap analysis approach to calculate lateralization indices (LIs) across several thresholds to examine the potential of a left-right WM hemispheric dissociation in healthy adolescents. We found significant left hemispheric lateralization for verbal WM, most notably in the frontal and parietal lobes, as well as right hemisphere lateralization for spatial WM, seen in frontal and temporal cortices. Although no significant relationships were observed between LI and age or LI and performance, significant age-related patterns of brain activity were demonstrated during both verbal and spatial WM. Specifically, increased adolescent age was associated with less activity in the default mode brain network during verbal WM. In contrast, increased adolescent age was associated with greater activity in task-positive posterior parietal cortex during spatial working memory. Our findings highlight the importance of utilizing non-biased statistical methods and comparable tasks for determining patterns of functional lateralization. Our findings also suggest that, while a left-right hemispheric dissociation of verbal and spatial WM is apparent by early adolescence, age-related changes in functional activation during WM are also present.

The impact of sex, puberty, and hormones on white matter microstructure in adolescents.

BACKGROUND: During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. METHODS: White matter microstructure was examined in 77 adolescents (ages 10-16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, and their interaction, controlling for age. Follow-up analyses determined if sex steroids predicted microstructural characteristics in sexually dimorphic and pubertal-related white matter regions, as well as in whole brain. RESULTS: Boys had higher FA in white matter carrying corticospinal, long-range association, and cortico-subcortical fibers, and lower MD in frontal and temporal white matter compared with girls. Pubertal development was related to higher FA in the insula, while a significant sex-by-puberty interaction was seen in superior frontal white matter. In boys, testosterone predicted white matter integrity in sexually dimorphic regions as well as whole brain FA, whereas estradiol showed a negative relationship with FA in girls. CONCLUSIONS: Sex differences and puberty uniquely relate to white matter microstructure in adolescents, which can partially be explained by sex steroids.

Treatment and outcome of childhood cerebral sinovenous thrombosis.

OBJECTIVE: To test our hypothesis that anticoagulation is associated with better neurologic outcomes in childhood cerebral sinovenous thrombosis (CSVT), we analyzed treatment and outcomes in a population of 410 children from the International Pediatric Stroke Study (IPSS). METHODS: We included patients enrolled in the IPSS registry with a diagnosis of CSVT at age >28 days with radiologic confirmation, in isolation or with concomitant arterial ischemic stroke. The primary outcome was the neurologic status at discharge. We defined unfavorable outcome as severe neurologic impairment or death at discharge. The Pediatric Stroke Outcome Measure was used for long-term outcome in those with follow-up. Predictors of anticoagulation use and outcome were analyzed by logistic regression. RESULTS: Most children (95%) had identifiable risk factors, and 82% received anticoagulation. Shift analysis demonstrated better outcomes at discharge in children who were anticoagulated, and this persisted with longer-term outcomes. In multivariable analysis, anticoagulation was significantly associated with favorable outcomes (adjusted odds ratio [aOR] unfavorable 0.32, p = 0.007) whereas infarct was associated with unfavorable outcome (aOR unfavorable 6.71, p < 0.001). The trauma/intracranial surgery was associated with a lower odds of anticoagulation use (aOR 0.14, p < 0.001). CONCLUSIONS: Within the IPSS registry, children with risk factors of trauma or intracranial surgery were less likely to receive anticoagulation for CSVT. Anticoagulation was associated with a lower odds of severe neurologic impairment or death at hospital discharge, but this finding is limited and needs further confirmation in randomized, controlled, prospective studies.

A different outlook on time: visual and auditory month names elicit different mental vantage points for a time-space synaesthete.

Synaesthesia is a fascinating condition whereby individuals report extraordinary experiences when presented with ordinary stimuli. Here we examined an individual (L) who experiences time units (i.e., months of the year and hours of the day) as occupying specific spatial locations (January is 30 degrees to the left of midline). This form of time-space synaesthesia has been recently investigated by Smilek et al. (2007) who demonstrated that synaesthetic time-space associations are highly consistent, occur regardless of intention, and can direct spatial attention. We extended this work by showing that for the synaesthete L, her time-space vantage point changes depending on whether the time units are seen or heard. For example, when L sees the word JANUARY, she reports experiencing January on her left side, however when she hears the word "January" she experiences the month on her right side. L's subjective reports were validated using a spatial cueing paradigm. The names of months were centrally presented followed by targets on the left or right. L was faster at detecting targets in validly cued locations relative to invalidly cued locations both for visually presented cues (January orients attention to the left) and for aurally presented cues (January orients attention to the right). We replicated this difference in visual and aural cueing effects using hour of the day. Our findings support previous research showing that time-space synaesthesia can bias visual spatial attention, and further suggest that for this synaesthete, time-space associations differ depending on whether they are visually or aurally induced.

The ups and downs (and lefts and rights) of synaesthetic number forms: validation from spatial cueing and SNARC-type tasks.

Typically, numbers are spatially represented using a mental 'number line' running from left to right. Individuals with number-form synaesthesia experience numbers as occupying specific spatial coordinates that are much more complex than a typical number line. Two synaesthetes (L and B) describe experiencing the numbers 1 through 10 running vertically from bottom to top, 10-20 horizontally from left to right, 21-40 from right to left, etc. We investigated whether their number forms could bias their spatial attention using a cueing paradigm and a SNARC-type task. In both experiments, the synaesthetes' responses confirmed their synaesthetic number forms. When making odd-even judgments for the numbers 1, 2, 8, and 9, they showed SNARC-compatibility effects for up-down movements (aligned with their number form), but not left-right (misaligned) movements. We conceptually replicated these biases using a spatial cueing paradigm. Both synaesthetes showed significantly faster response times to detect targets on the bottom of the display if preceded by a low number (1, 2), and the top of the display if preceded by a high number (8, 9), whereas they showed no cueing effects when targets appeared on the left or right (misaligned with their number forms). They were however reliably faster to detect left targets following the presentation of numbers 10 and 11, and right targets following numbers 19 and 20 (since 10-20 runs from left to right). In sum, cueing and SNARC tasks can be used to empirically verify synaesthetic number forms, and show that numbers can direct spatial attention to these idiosyncratic locations.