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Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub‐nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross‐sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right‐handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school‐age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization. [ABSTRACT FROM AUTHOR]

Abbreviation PABAK prevalence and bias adjusted kappa Cerebral palsy (CP) is a group of permanent disorders of movement and posture development, causing activity limitation that can be attributed to non-progressive disturbances that occurred in the fetal or infant brain.1 It is the most common form of physical disability in childhood with lifelong neurological disability. Collected data included sociodemographic variables, pre-, peri-, and neonatal CP risk factors, CP functional outcomes including GMFCS, and CP-related comorbidities. Previously we have shown that the GMFCS is associated with comorbidities.11 Higher burden of CP-related comorbidities such as seizures, the need for nasogastric tube feeding, and certain CP subtypes were associated with incremental increase of GMFCS level.11 Thus, we hypothesize that factors such as CP subtype and the presence of CP-related comorbidities may therefore influence the GMFCS stability. Our unadjusted logistic regression analyses showed that the likelihood of change in GMFCS level was related to the initial GMFCS level, CP subtype, and cognitive impairment. [Extracted from the article]

Brain stimulation combined with intensive therapy may improve hand function in children with perinatal stroke‐induced unilateral cerebral palsy (UCP). However, response to therapy varies and underlying neuroplasticity mechanisms remain unclear. Here, we aimed to characterize robotic motor mapping outcomes in children with UCP. Twenty‐nine children with perinatal stroke and UCP (median age 11 ± 2 years) were compared to 24 typically developing controls (TDC). Robotic, neuronavigated transcranial magnetic stimulation was employed to define bilateral motor maps including area, volume, and peak motor evoked potential (MEP). Map outcomes were compared to the primary clinical outcome of the Jebsen–Taylor Test of Hand Function (JTT). Maps were reliably obtained in the contralesional motor cortex (24/29) but challenging in the lesioned hemisphere (5/29). Within the contralesional M1 of participants with UCP, area and peak MEP amplitude of the unaffected map were larger than the affected map. When comparing bilateral maps within the contralesional M1 in children with UCP to that of TDC, only peak MEP amplitudes were different, being smaller for the affected hand as compared to TDC. We observed correlations between the unaffected map when stimulating the contralesional M1 and function of the unaffected hand. Robotic motor mapping can characterize motor cortex neurophysiology in children with perinatal stroke. Map area and peak MEP amplitude may represent discrete biomarkers of developmental plasticity in the contralesional M1. Correlations between map metrics and hand function suggest clinical relevance and utility in studies of interventional plasticity. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) motor mapping is a safe, non‐invasive method that can be used to study corticomotor organization. Motor maps are typically acquired at rest, and comparisons to maps obtained during muscle activation have been both limited and contradictory. Understanding the relationship between functional activation of the corticomotor system as recorded by motor mapping is crucial for their use clinically and in research. The present study utilized robotic TMS paired with personalized neuro‐navigation to examine the relationship between resting and active motor map measures and their relationship with motor performance. Twenty healthy right‐handed participants underwent resting and active robotic TMS motor mapping of the first dorsal interosseous to 10% maximum voluntary contraction. Motor map parameters including map area, volume, and measures of map centrality were compared between techniques using paired sample tests of difference and Bland–Altman plots and analysis. Map area, volume, and hotspot magnitude were larger in the active motor maps, while map center of gravity and hotspot locations remained consistent between both maps. No associations were observed between motor maps and motor performance as measured by the Purdue Pegboard Test. Our findings support previous suggestions that maps scale with muscle contraction. Differences in mapping outcomes suggest rest and active motor maps may reflect functionally different corticomotor representations. Advanced analysis methods may better characterize the underlying neurophysiology of both types of motor mapping. [ABSTRACT FROM AUTHOR]

Aim: To explore clinical factors associated with perinatal arterial ischemic stroke (AIS) and periventricular venous infarction (PVI) in infants who develop unilateral cerebral palsy (CP). Method: This was a case–control study. Data current to 2019 was extracted from the Canadian Cerebral Palsy Registry (CCPR). Cases were infants born at term with confirmed unilateral CP. Magnetic resonance images were stratified by expert review of reports as definitive perinatal stroke (AIS or PVI). Controls with common data elements were recruited from a population‐based study in Alberta. Multivariable regression analyses were performed to estimate associations expressed as odds ratios with 95% confidence intervals. Results: Of 2093 cases from the CCPR, 662 had unilateral CP, of whom 299 (45%) had perinatal stroke: AIS 169 (57%) and PVI 130 (43%). Median age at diagnosis for AIS was 11.9 months (interquartile range: 6.2–25.7mo; range 0.17–104.1mo), and 58.6% were male. Median age at diagnosis for PVI was 25.3 months (interquartile range: 14.5–38mo, range 0.7–114.7mo) and 57.7% were male. Independent associations for both AIS and PVI on multivariable analysis were chorioamnionitis, illicit drug exposure, diabetes, gestational age, and maternal age. Variables associated with AIS alone were low Apgar score and prolonged rupture of membranes. Variables associated with PVI alone were small for gestational age and primigravida. Interpretation: Controlled analysis of disease‐specific unilateral CP may offer unique perspectives on its pathophysiology. Acute intrapartum factors are mainly associated with AIS, while in utero factors are associated with PVI. This original article is commented by Ganesan on page 9 of this issue. [ABSTRACT FROM AUTHOR]

Aim: To explore the feasibility and possible effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the supplementary motor area (SMA) on tic severity and motor system neurophysiology in children with Tourette syndrome.Method: Ten children with Tourette syndrome (eight males, two females; 9-15y) participated in this open-label, phase 1 clinical trial. Treatment consisted of 1800 low-frequency (1Hz) neuronavigated robotic rTMS (100% resting motor threshold) to the SMA, bilaterally for 15 sessions. The primary outcome was a change in Yale Global Tic Severity Scale (YGTSS) total score from baseline to posttreatment. Secondary outcome measures included changes in magnetic resonance spectroscopy metabolite concentrations, TMS neurophysiology measures, TMS motor maps, and clinical assessments (anxiety, depression) from baseline to the end of treatment.Results: The YGTSS score decreased from baseline after treatment (p<0.001; Cohen's d=2.9). All procedures were well-tolerated.Interpretation: Robot-driven, neuronavigated bilateral rTMS of the SMA is feasible in children with Tourette syndrome and appears to reduce tic severity. What this paper adds Repetitive transcranial magnetic stimulation (rTMS) is feasible to use in children with Tourette syndrome. rTMS is tolerated by children with Tourette syndrome. Precise targeting of the supplementary motor area using functional magnetic resonance imaging is also feasible in these children. [ABSTRACT FROM AUTHOR]

Aim: To determine whether inequities in health outcomes for Indigenous Canadians are also present in cerebral palsy (CP) by comparing CP profiles between Indigenous and non‐Indigenous children. Method: Using the Canadian Cerebral Palsy Registry, we conducted a cross‐sectional study. CP motor subtype, gross motor severity, comorbidities, perinatal adversity, preterm birth, and parental education were compared between 94 Indigenous (53 males, 41 females) and 1555 non‐Indigenous (891 males, 664 females) children (all >5y). Multivariate analysis was done to analyze adverse CP factors, defined as CP gross motor severity and comorbidities. CP etiologies, either prenatal/perinatal or postnatal, were also compared. Results: Indigenous children with CP have higher odds of having low parental education (odds ratio [OR] 6.15, 95% confidence interval [CI] 3.36–11.3) and comorbidities (OR 4.46, 95% CI 1.62–12.3), especially cognitive (OR 4.52, 95% CI 2.27–9.05), communication (OR 2.66, 95% CI 1.54–4.61), and feeding (OR 2.25, 95% CI 1.33–3.83) impairment. Indigenous children also have higher CP gross motor severity (p=0.03). Indigenous children are also more likely to have non‐accidental head injury (n=4; OR 8.18, 95% CI 1.86–36.0) as the cause of their postnatal CP. Interpretation: Indigenous populations have worse health outcomes as a result of intergenerational impacts of colonization. Our study shows that Indigenous children with CP have increased comorbidities and higher CP gross motor severity, reinforcing the need for a multidisciplinary approach to management. Furthermore, targeted prevention programs against preventable causes of CP, such as non‐accidental head injury, may be beneficial. What this paper adds: Indigenous children with cerebral palsy (CP) have more severe motor impairment and more comorbidities.Non‐accidental head injury is a significant cause of postnatal CP. What this paper adds: Indigenous children with cerebral palsy (CP) have more severe motor impairment and more comorbidities.Non‐accidental head injury is a significant cause of postnatal CP. This article is commented on by King on page 500 of this issue. [ABSTRACT FROM AUTHOR]

Aim: To explore relationships between category classifications for children's rehabilitation goals, outcomes, and participant characteristics. Method: Children with hemiparetic cerebral palsy due to perinatal stroke rated self‐selected goals with the Canadian Occupational Performance Measure (COPM) and completed the Assisting Hand Assessment (AHA) and Box and Block Test (BBT), at baseline and 6 months, in a randomized, controlled 10‐day neuromodulation rehabilitation trial using repetitive transcranial magnetic stimulation. Goals were classified with the Canadian Model of Occupational Performance and Engagement and the International Classification of Functioning, Disability and Health. Analysis included standard linear regression. Results: Data for 45 participants (mean age 11y 7mo, SD 3y 10mo, range 6–19y, 29 males, 16 females) on 186 goals were included. Self‐care goal percentage corresponded with baseline BBT by age (standardized ß=–0.561, p=0.004). Leisure goal percentage corresponded with baseline BBT (standardized ß=0.419, p=0.010). AHA change corresponded with productivity goals (standardized ß=0.327, p=0.029) and age (standardized ß=0.481, p=0.002). COPM change corresponded with baseline COPM and age by AHA change (p<0.05). Interpretation: Younger children with lower motor function were more likely to select self‐care goals while those with better function tended to select leisure goals. Functional improvement corresponded with older age and productivity goals. COPM change scores reflected functional improvement among older children. Children chose functionally and developmentally appropriate goals. Consequently, children should be free to set goals that matter to them. What this paper adds: Children in a brain stimulation trial chose divergent upper extremity functional goals.Younger children with lower ability chose more self‐care goals.Children with higher ability chose more leisure goals.Older children's goal ratings reflected objective functional motor gains.Children chose goals appropriate to their function and level of development. What this paper adds: Children in a brain stimulation trial chose divergent upper extremity functional goals.Younger children with lower ability chose more self‐care goals.Children with higher ability chose more leisure goals.Older children's goal ratings reflected objective functional motor gains.Children chose goals appropriate to their function and level of development. [ABSTRACT FROM AUTHOR]

Introduction: Transcranial magnetic stimulation (TMS) motor mapping can characterize the neurophysiology of the motor system. Limitations including human error and the challenges of pediatric populations may be overcome by emerging robotic systems. We aimed to show that neuronavigated robotic motor mapping in adolescents could efficiently produce discrete maps of individual upper extremity muscles, the characteristics of which would correlate with motor behavior. Methods: Typically developing adolescents (TDA) underwent neuronavigated robotic TMS mapping of bilateral motor cortex. Representative maps of first dorsal interosseous (FDI), abductor pollicis brevis (APB), and abductor digiti minimi (ADM) muscles in each hand were created. Map features including area (primary), volume, and center of gravity were analyzed across different excitability regions (R100%, R75%, R50%, R25%). Correlations between map metrics and validated tests of hand motor function (Purdue Pegboard Test as primary) were explored. Results: Twenty‐four right‐handed participants (range 12–18 years, median 15.5 years, 52% female) completed bilateral mapping and motor assessments with no serious adverse events or dropouts. Gender and age were associated with hand function and motor map characteristics. Full motor maps (R100%) for FDI did not correlate with motor function in either hand. Smaller excitability subset regions demonstrated reduced variance and dose‐dependent correlations between primary map variables and motor function in the dominant hemisphere. Conclusions: Hand function in TDA correlates with smaller subset excitability regions of robotic TMS motor map outcomes. Refined motor maps may have less variance and greater potential to quantify interventional neuroplasticity. Robotic TMS mapping is safe and feasible in adolescents. [ABSTRACT FROM AUTHOR]

Preterm germinal matrix-intraventricular hemorrhage (GMH-IVH) grading can be applied to fetuses. Almost all the currently known risk factors for GMH-IVH pertain to the extra-uterine environment and its effect on the immature brain, and studying in utero GMH-IVH presents a unique opportunity to better understand the pathophysiology of GMH-IVH distinct from the stressors imposed by preterm delivery. Exclusion criteria Cases were excluded if they were duplicates, had a postnatal diagnosis of GMH-IVH only, intraventricular hemorrhage (IVH) secondary to extension of parenchymal hemorrhage or tumor, or insufficient information to confirm GMH-IVH such as specification only of intracranial hemorrhage without specifying the site. Grade III was defined as GMH-IVH with hydrocephalus or ventricular dilatation as described by the authors; it was not always possible to distinguish between acute dilatation that is a criteria for grade III hemorrhage, and post-hemorrhagic ventricular dilation which can occur after any grade of hemorrhage. Term defined as 37 weeks gestational age or greater. gl Hydrocephalus and postnatal surgical intervention Hydrocephalus was present in 0 out of 27 out of those with grade I/II GMH-IVH, 100 out of 100 of those with grade III, and 89 out of 93 (96%) of those with PVHI. [Extracted from the article]

Aim: To characterize fatigue in children with hemiparesis with perinatal stroke and explore associations with measures of motor performance and corticospinal excitability.Method: Forty-five children (16 females, 29 males), aged 6 to 18 years (mean [SD] 12y [4]), with magnetic resonance imaging-confirmed perinatal stroke participated. Associations between fatigue (Pediatric Quality of Life Inventory Version 3.0 cerebral palsy module fatigue subscale), motor performance (Assisting Hand Assessment [AHA], Box and Blocks Test, grip strength), and excitability of corticospinal projections to both hands were examined using ranked tests of correlation, robust regression, and the Mann-Whitney U test.Results: Nearly half of the participants (n=21) reported experiencing fatigue in the previous month. Function in the less affected hand (Box and Blocks Test, grip strength) was correlated with fatigue scores. Participants with preserved ipsilateral projections to the more affected hand had less fatigue, and scores correlated with the excitability of these projections. Fatigue scores were not associated with age, sex, or AHA score.Interpretation: Fatigue is common in children with hemiparesis with perinatal stroke and is associated with motor performance and the presence and excitability of ipsilateral corticospinal projections from the contralesional hemisphere to the more affected hand.What This Paper Adds: Fatigue is common in children with hemiparesis with perinatal stroke. Fatigue was associated with motor performance and strength in the less affected, but not the more affected, hand. Fatigue was associated with the presence and excitability of ipsilateral corticospinal projections from the contralesional hemisphere. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Perinatal stroke causes lifelong disability, particularly hemiparetic cerebral palsy. Arterial ischemic strokes (AIS) are large, cortical, and subcortical injuries acquired near birth due to acute occlusion of the middle cerebral artery. Periventricular venous infarctions (PVI) are smaller, subcortical strokes acquired prior to 34 weeks gestation involving injury to the periventricular white matter. Both stroke types can damage motor pathways, thus, we investigated resulting alterations in functional motor networks and probed function. We measured blood oxygen level dependent (BOLD) fluctuations at rest in 38 participants [10 arterial patients (age = 14.7 ± 4.1 years), 10 venous patients (age = 13.5 ± 3.7 years), and 18 typically developing controls (TDCs) (age = 15.3 ± 5.1 years)] and explored strength and laterality of functional connectivity in the motor network. Inclusion criteria included MRI‐confirmed, unilateral perinatal stroke, symptomatic hemiparetic cerebral palsy, and 6–19 years old at time of imaging. Seed‐based functional connectivity analyses measured temporal correlations in BOLD response over the whole brain using primary motor cortices as seeds. Laterality indices based on mean z‐scores in lesioned and nonlesioned hemispheres explored laterality. In AIS patients, significant differences in both strength and laterality of motor network connections were observed compared with TDCs. In PVI patients, motor networks largely resembled those of healthy controls, albeit slightly weaker and asymmetric, despite subcortical damage and hemiparesis. Functional connectivity strengths were not related to motor outcome scores for either stroke group. This study serves as a foundation to better understand how resting‐state fMRI can assess motor functional connectivity and potentially be applied to explore mechanisms of interventional therapies after perinatal stroke. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Perinatal stroke is the leading cause of hemiparetic cerebral palsy (CP), resulting in life‐long disability. In this study, we examined the relationship between robotic upper extremity motor impairment and corticospinal tract (CST) diffusion properties. Thirty‐three children with unilateral perinatal ischemic stroke (17 arterial, 16 venous) and hemiparesis were recruited from a population‐based research cohort. Bilateral CSTs were defined using diffusion tensor imaging (DTI) and four diffusion metrics were quantified: fractional anisotropy (FA), mean (MD), radial (RD), and axial (AD) diffusivities. Participants completed a visually guided reaching task using the KINARM robot to define 10 movement parameters including movement time and maximum speed. Twenty‐six typically developing children underwent the same evaluations. Partial correlations assessed the relationship between robotic reaching and CST diffusion parameters. All diffusion properties of the lesioned CST differed from controls in the arterial group, whereas only FA was reduced in the venous group. Non‐lesioned CST diffusion measures were similar between stroke groups and controls. Both stroke groups demonstrated impaired reaching performance. Multiple reaching parameters of the affected limb correlated with lesioned CST diffusion properties. Lower FA and higher MD were associated with greater movement time. Few correlations were observed between non‐lesioned CST diffusion and unaffected limb function though FA was associated with reaction time (R = −0.39, p < .01). Diffusion properties of the lesioned CST are altered after perinatal stroke, the degree of which correlates with specific elements of visually guided reaching performance, suggesting specific relevance of CST structural connectivity to clinical motor function in hemiparetic children. [ABSTRACT FROM AUTHOR]

Perinatal stroke causes most hemiparetic cerebral palsy, resulting in lifelong disability. We have demonstrated the ability of robots to quantify sensory dysfunction in hemiparetic children but the relationship between such deficits and sensory tract structural connectivity has not been explored. It was aimed to characterize the relationship between the dorsal column medial lemniscus (DCML) pathway connectivity and proprioceptive dysfunction in children with perinatal stroke. Twenty-nine participants (6-19 years old) with MRI-classified, unilateral perinatal ischemic stroke (14 arterial, 15 venous), and upper extremity deficits were recruited from a population-based cohort and compared with 21 healthy controls. Diffusion tensor imaging (DTI) defined DCML tracts and five diffusion properties were quantified: fractional anisotropy (FA), mean, radial, and axial diffusivities (MD, RD, AD), and fiber count. A robotic exoskeleton (KINARM) tested upper limb proprioception in an augmented reality environment. Correlations between robotic measures and sensory tract diffusion parameters were evaluated. Lesioned hemisphere sensory tracts demonstrated lower FA and higher MD, RD, and AD compared with the non-dominant hemisphere of controls. Dominant (contralesional) hemisphere tracts were not different from controls. Both arterial and venous stroke groups demonstrated impairments in proprioception that correlated with lesioned hemisphere DCML tract diffusion properties. Sensory tract connectivity is altered in the lesioned hemisphere of hemiparetic children with perinatal stroke. A correlation between lesioned DCML tract diffusion properties and robotic proprioceptive measures suggests clinical relevance and a possible target for therapeutic intervention. Hum Brain Mapp 38:2424-2440, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Perinatal stroke causes hemiparetic cerebral palsy and lifelong motor disability. Bilateral motor cortices are key hubs within the motor network and their neurophysiology determines clinical function. Establishing biomarkers of motor cortex function is imperative for developing and evaluating restorative interventional strategies. Proton magnetic resonance spectroscopy (MRS) quantifies metabolite concentrations indicative of underlying neuronal health and metabolism in vivo. We used functional magnetic resonance imaging (MRI)-guided MRS to investigate motor cortex metabolism in children with perinatal stroke. Children aged 6-18 years with MRI-confirmed perinatal stroke and hemiparetic cerebral palsy were recruited from a population-based cohort. Metabolite concentrations were assessed using a PRESS sequence (3T, TE = 30 ms, voxel = 4 cc). Voxel location was guided by functional MRI activations during finger tapping tasks. Spectra were analysed using LCModel. Metabolites were quantified, cerebral spinal fluid corrected and compared between groups (ANCOVA) controlling for age. Associations with clinical motor performance (Assisting Hand, Melbourne, Box-and-Blocks) were assessed. Fifty-two participants were studied (19 arterial, 14 venous, 19 control). Stroke participants demonstrated differences between lesioned and nonlesioned motor cortex N-acetyl-aspartate [NAA mean concentration = 10.8 ± 1.9 vs. 12.0 ± 1.2, P < 0.01], creatine [Cre 8.0 ± 0.9 vs. 7.4 ± 0.9, P < 0.05] and myo-Inositol [Ins 6.5 ± 0.84 vs. 5.8 ± 1.1, P < 0.01]. Lesioned motor cortex NAA and creatine were strongly correlated with motor performance in children with arterial but not venous strokes. Interrogation of motor cortex by fMRI-guided MRS is feasible in children with perinatal stroke. Metabolite differences between hemispheres, stroke types and correlations with motor performance support functional relevance. MRS may be valuable in understanding the neurophysiology of developmental neuroplasticity in cerebral palsy. Hum Brain Mapp 38:1574-1587, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim: To determine epilepsy risk factors after pediatric stroke.Method: A cohort of children with arterial ischemic stroke (birth-18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression.Results: Among 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1-year follow-up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7-13). Patients with more than 10 acute seizures had a 30-fold increased epilepsy risk (OR 30, 95% CI 2.9-305).Interpretation: Pediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Aim Structural, functional, and metabolic changes in the dorsolateral prefrontal cortex ( DLPFC) are implicated in the pathogenesis of major depressive disorder ( MDD). We used proton magnetic resonance spectroscopy (1 H-MRS) to examine the metabolite choline (glycerophosphocholine plus phosphocholine), which is used as an index of membrane integrity in the left DLPFC, in adolescents and young adults with MDD who were treatment-resistant and had a positive family history compared to healthy controls. Differences in the choline resonance indicate an imbalance between synthesis and degradation activity of neuronal and glia membrane phospholipids. Methods Seventeen adolescents with MDD and 11 healthy controls underwent 1 H-MRS. A short echo point-resolved spectroscopy ( echo time = 30 ms, repetition time = 2000 ms) protocol was used with a voxel (4.5cm3, 128 averages) placed within the left DLPFC. Results There were significantly increased choline ( P = 0.04) and creatine concentrations ( P = 0.005) in the left DLPFC of the MDD group compared to controls. In MDD participants, choline concentration correlated with scores on the Beck Depression Inventory ( r = 0.41, P = 0.03). Conclusion Increased left DLPFC choline and creatine levels in depressed adolescents may be biomarkers for the disorder. The increased choline levels may indicate abnormalities in neuronal membrane integrity, and the increased creatine could be reflective of altered energy demands and metabolism. [ABSTRACT FROM AUTHOR]

Aim Brain plasticity mechanisms are probably different in children but remain poorly understood. Paired afferent stimulation ( PAS) combines peripheral sensory stimulation with transcranial magnetic stimulation ( TMS) of primary motor cortex to induce rapid, reversible, topographically specific increases in primary motor cortex excitability suggestive of long-term potentiation in adults. Our aim was to determine frequency, characteristics, age effects, and reproducibility of PAS in school-age children. Method Typically developing right-handed children (6-18y) were recruited. Median nerve stimulation was delivered 25ms before suprathreshold primary motor cortex stimulation (0.2Hz, 7.5min). Primary outcome was changed in the amplitude of motor evoked potentials ( MEPs) at five time points after PAS (0, 15, 30, 45, 75min) expressed as area under the curve. Reproducibility was evaluated. Secondary outcomes included stimulus response curves and safety/tolerability. Results Of 28 children (20 males, mean age 12y), 64% demonstrated PAS effects (11 definite, seven probable). PAS effects were sustained across all time points to 75min ( p=0.004). Stimulus response curve scores increased after PAS ( n=9, p=0.02). PAS effect and age were not correlated. PAS was highly reproducible ( p=0.925, r=0.283). Tolerability was favorable without adverse events. Interpretation PAS effects are present and reproducible in children. Pediatric PAS paradigms appear safe and tolerable. PAS may provide insight into endogenous developmental plasticity, informing future studies in children with cerebral palsy and other motor disorders. [ABSTRACT FROM AUTHOR]

Autosomal recessive cutis laxa (ARCL) is a clinically and genetically heterogeneous group of disorders characterized by loose, inelastic skin and variable systemic involvement and severity. Mutations in the FBLN4 gene are associated with ARCL1B. Fibulin-4 is important in elastic fiber formation and smooth muscle cell differentiation. We describe herein an 8-year-old boy who presented with severe aortic root dilatation and arterial tortuosity at 1 year of age which required surgical repair. His parents were consanguineous and there was a family history of three brothers who died early in life with an unknown type of connective tissue disorder in the 1960s. Both parents of the patient reported here were related to these three boys. We used a homozygosity mapping strategy with a 900K SNP array and identified FBLN4 as a candidate gene in an extended region of homozygosity. We sequenced this gene in the patient and identified a homozygous non-synonymous mutation at c.376G>A (p.Glu126Lys) in exon 5 that was predicted to be damaging. ARCL1B has most typically been associated with early demise but our report suggests that long-term survival is possible. With this longer term survival we are learning more about the natural history of this disorder, which includes baroreceptor reflex failure and low bone mineral density in this patient. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective Perinatal stroke commonly causes childhood neurological morbidity. Presumed perinatal ischemic stroke (PPIS) defines children presenting outside a normal perinatal period with chronic, focal infarction on neuroimaging. Infarcts are assumed to represent arterial strokes, but recent evidence suggests the periventricular venous infarction (PVI) of infants born preterm may also occur in utero and present as PPIS. Using the largest published cohort, we aimed to define arterial and PVI PPIS syndromes and their outcomes. Methods A PPIS consecutive cohort was identified (SickKids Children's Stroke Program, 1992-2006). Systematic neuroradiological scoring executed by blinded investigators included previously defined arterial stroke syndromes. PVI criteria included unilateral injury with at least four of the following conditions: (1) focal periventricular encephalomalacia, (2) internal capsule T2 prolongation, (3) cortical and (4) relative basal ganglia sparing, and (5) remote hemorrhage. Arterial and PVI classifications were validated and correlated with neurological outcomes (Pediatric Stroke Outcome Measure). Results In 59 PPISs (64% male), 94% of lesions fell within potential middle cerebral artery territories. Although arterial proximal M1 infarction was most common (n = 19; 35%), venous PVI was second (n = 12; 22%) and accounted for 75% of subcortical injuries. Motor outcomes (mean follow-up, 5.3 years) were predicted by basal ganglia involvement including leg hemiparesis, spasticity, and need for assistive devices ( p < 0.01). Nonmotor outcomes were associated with cortical involvement, including cognitive/behavioral outcomes, visual deficits, and epilepsy ( p < 0.01). Classification interrater reliability was excellent (correlation coefficients > 0.975). Interpretation Recognizable PPIS patterns predict long-term morbidity and may guide surveillance, therapy, and counseling. PVI is an underrecognized cause of PPIS and congenital hemiplegia. Ann Neurol 2008 [ABSTRACT FROM AUTHOR]

This commentary is on the letter to the editor by Debillon et al. on pages 980–981 of this issue. [ABSTRACT FROM AUTHOR]

COVER ILLUSTRATION A stylistic impression of task fMRI sensorimotor activations created by combining an fMRI‐derived activation map with a painting by Vassilios Antonakos via a neural network algorithm (www.deepart.io). [ABSTRACT FROM AUTHOR]

This commentary is on the original article by Ecury‐Goossen et al. on pages 49–56 of this issue. [ABSTRACT FROM AUTHOR]

This commentary is on the original article by van der Aa et al on pages 707–712 of this issue. [ABSTRACT FROM AUTHOR]