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Most cases of hemiparetic cerebral palsy are caused by perinatal stroke, resulting in lifelong disability for millions of people. However, our understanding of how the motor system develops following such early unilateral brain injury is increasing. Tools such as neuroimaging and brain stimulation are generating informed maps of the unique motor networks that emerge following perinatal stroke. As a focal injury of defined timing in an otherwise healthy brain, perinatal stroke represents an ideal human model of developmental plasticity. Here, we provide an introduction to perinatal stroke epidemiology and outcomes, before reviewing models of developmental plasticity after perinatal stroke. We then examine existing therapeutic approaches, including constraint, bimanual and other occupational therapies, and their potential synergy with non-invasive neurostimulation. We end by discussing the promise of exciting new therapies, including novel neurostimulation, brain-computer interfaces and robotics, all focused on improving outcomes after perinatal stroke. [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]

Background: Studies using clinical measures have suggested that proprioceptive dysfunction is related to motor impairment of the upper extremity following adult stroke. We used robotic technology and clinical measures to assess the relationship between position sense and reaching with the hemiparetic upper limb in children with perinatal stroke.Methods: Prospective term-born children with magnetic resonance imaging-confirmed perinatal ischemic stroke and upper extremity deficits were recruited from a population-based cohort. Neurotypical controls were recruited from the community. Participants completed two tasks in the Kinarm robot: arm position-matching (three parameters: variability [Varxy], contraction/expansion [Areaxy], systematic spatial shift [Shiftxy]) and visually guided reaching (five parameters: posture speed [PS], reaction time [RT], initial direction error [IDE], speed maxima count [SMC], movement time [MT]). Additional clinical assessments of sensory (thumb localization test) and motor impairment (Assisting Hand Assessment, Chedoke-McMaster Stroke Assessment) were completed and compared to robotic measures.Results: Forty-eight children with stroke (26 arterial, 22 venous, mean age: 12.0 ± 4.0 years) and 145 controls (mean age: 12.8 ± 3.9 years) completed both tasks. Position-matching performance in children with stroke did not correlate with performance on the visually guided reaching task. Robotic sensory and motor measures correlated with only some clinical tests. For example, AHA scores correlated with reaction time (R = - 0.61, p < 0.001), initial direction error (R = - 0.64, p < 0.001), and movement time (R = - 0.62, p < 0.001).Conclusions: Robotic technology can quantify complex, discrete aspects of upper limb sensory and motor function in hemiparetic children. Robot-measured deficits in position sense and reaching with the contralesional limb appear to be relatively independent of each other and correlations for both with clinical measures are modest. Knowledge of the relationship between sensory and motor impairment may inform future rehabilitation strategies and improve outcomes for children with hemiparetic cerebral palsy. [ABSTRACT FROM AUTHOR]

• Patients with ESES show significantly higher pre-diagnosis spike-frequency than those without ESES. • Stroke patients with ESES show significantly lower pre-diagnosis delta power than those without ESES. • Using spike-frequency, clinicians may be able to identify patients at risk of developing ESES. Continuous spike and wave in slow-wave sleep (CSWS), an epileptic encephalopathy, occurs after perinatal stroke where it is associated with cognitive decline. CSWS features a distinct EEG pattern, electrical status epilepticus in sleep (ESES). Biomarkers for the prediction of ESES have not been identified but will facilitate earlier diagnosis and treatment. We hypothesized that spike-frequency and differences in power spectra would be predictive of subsequent ESES. A cross-sectional study comparing EEG spike-frequency and Power before the development of ESES in patients with perinatal stroke, patients with focal epilepsy, and appropriate controls. 43 patients met the inclusion criteria; 11 stroke-ESES, 10 stroke controls, 14 epilepsy-ESES, 8 epilepsy controls. ESES patients had higher pre-diagnosis mean spike-frequency (24.0 ± 24 versus 6.6 ± 9.1 SW/min, p = 0.002) than patients that did not develop ESES; these differences present ~ 3 years before ESES diagnosis. Pre-diagnosis, normalized delta power (1–4 Hz) was higher in the stroke-ESES group (105.7 ± 58 dB/Hz) compared to stroke controls (57.4 ± 45 dB/Hz, p = 0.036). Spike-frequency and delta power may represent EEG biomarkers of the risk of developing ESES in children with perinatal stroke. EEG biomarkers may be used by clinicians to assess which patients are more at-risk for ESES. Using spike-frequency, clinicians may be able to identify patients at risk of developing ESES. [ABSTRACT FROM AUTHOR]

Background: Pediatric cerebral sinovenous thrombosis is a treatable cause of brain injury, acute symptomatic seizures, and remote epilepsy. Our objective was to prospectively study epilepsy and outcomes in neonates and children one year after cerebral sinovenous thrombosis diagnosis.Methods: Patients with cerebral sinovenous thrombosis were enrolled prospectively from 21 international sites through the Seizures in Pediatric Stroke Study. Clinical data, including acute symptomatic seizures and cerebral sinovenous thrombosis risk factors, were collected at diagnosis. A neuroradiologist who was unaware of the diagnosis reviewed acute imaging. At one year, outcomes including seizure recurrence, epilepsy diagnosis, antiepileptic drug use, and modified Engel score were collected. Outcomes were assessed using the modified Rankin score and the King's Outcome Scale for Childhood Head Injury.Results: Twenty-four participants with cerebral sinovenous thrombosis were enrolled (67% male, 21% neonates). Headache was the most common presenting symptom in non-neonates (47%, nine of 19). Nine (37.5%) presented with acute symptomatic seizures. Six (25%; 95% confidence interval, 10% to 47%) developed epilepsy by one-year follow-up. No clinical predictors associated with epilepsy were identified. King's Outcome Scale for Childhood Head Injury and modified Rankin scores at one year were favorable in 71%. Half of the patients who developed epilepsy (three of six) did not have infarcts, hemorrhage, or seizures identified during the acute hospitalization.Conclusion: Our study provides a prospective estimate that epilepsy occurs in approximately one-quarter of patients by one year after diagnosis of cerebral sinovenous thrombosis. Later epilepsy can develop in the absence of acute seizures or parenchymal injury associated with the acute presentation. [ABSTRACT FROM AUTHOR]

Aim: We aimed to characterize the phenotype and outcome of children with bilateral, large vessel perinatal arterial ischemic stroke.Methods: Patients with bilateral, large vessel perinatal arterial ischemic stroke were identified from a large, population-based cohort (Alberta Perinatal Stroke Project). Subjects were included if stroke involving a major cerebral artery territory was documented in both cerebral hemispheres on magnetic resonance imaging. Standardized variables were extracted from charts including clinical presentations, associated potential risk factors, and outcomes. Outcome measures included the Pediatric Stroke Outcome Measure, Gross Motor Function Classification System, and epilepsy frequency score. Electroencephalographies were reviewed for sleep, epileptiform activity, and background.Results: Of 174 children with perinatal arterial ischemic stroke, eight (5%) had bilateral large artery infarcts. Patients were followed for a mean of 9.7 years (range 1.8 to 14.6 years). One child died. All children had a total Pediatric Stroke Outcome Measure of ≥2 (median 8, range 2 to 10) and Gross Motor Function Classification System ≥ II. Seven of eight (88%) children had a history of epilepsy.Conclusions: Children with bilateral, large vessel perinatal stroke are at high risk of severe cognitive and motor sequelae. Epilepsy may also be more common than unilateral strokes. Cautious discussions with families regarding prognosis are recommended. [ABSTRACT FROM AUTHOR]

As a focal injury in an otherwise healthy child, perinatal stroke provides a clinical model of developmental brain plasticity. In this study, we report evidence that children with perinatal periventricular venous infarcts perform as well as control children on a video game that tests navigation abilities. In addition, children with a history of perinatal arterial strokes overcame initial deficits in navigation performance after additional practice. These findings lend support to the hypothesis that a complex cognitive skill dependent on a distributed neural network with prolonged maturation, such as navigation, may demonstrate resilience after early brain injury. [ABSTRACT FROM PUBLISHER]

Background: Pediatric arterial ischemic stroke remains incompletely understood. Population-based epidemiological data inform clinical trial design but are scant in this condition. We aimed to determine age-specific epidemiological characteristics of arterial ischemic stroke in neonates (birth to 28 days) and older children (29 days to 18 years).Methods: We conducted a 16-year, prospective, national population-based study, the Canadian Pediatric Ischemic Stroke Registry, across all 16 Canadian acute care children's hospitals. We prospectively enrolled children with arterial ischemic stroke from January 1992 to December 2001 and documented disease incidence, presentations, risk factors, and treatments. Study outcomes were assessed throughout 2008, including abnormal clinical outcomes (stroke-related death or neurological deficit) and recurrent arterial ischemic stroke or transient ischemic attack.Results: Among 1129 children enrolled with arterial ischemic stroke, stroke incidence was 1.72/100,000/year, (neonates 10.2/100,000 live births). Detailed clinical and radiological information were available for 933 children (232 neonates and 701 older children, 55% male). The predominant clinical presentations were seizures in neonates (88%), focal deficits in older children (77%), and diffuse neurological signs (54%) in both. Among neonates, 44% had no discernible risk factors. In older children, arteriopathy (49% of patients with vascular imaging), cardiac disorders (28%), and prothrombotic disorders (35% of patients tested) predominated. Antithrombotic treatment increased during the study period (P < 0.001). Stroke-specific mortality was 5%. Outcomes included neurological deficits in 60% of neonates and 70% of older children. Among neonates, deficits emerged during follow-up in 39%. Overall, an initially decreased level of consciousness, a nonspecific systemic presentation, and the presence of stroke risk factors predicted abnormal outcomes. For neonates, predictors were decreased level of consciousness, nonspecific systemic presentation, and basal ganglia infarcts. For older children, predictors were initial seizures, nonspecific systemic presentation, risk factors, and lack of antithrombotic treatment. Recurrent arterial ischemic stroke or transient ischemic attack developed in 12% of older children and was predicted by arteriopathy, presentation without seizures, and lack of antithrombotic treatment. Emerging deficit was predicted by neonatal age at stroke and by cardiac disease.Conclusions: This national data set provides a population-based disease incidence rate and demonstrates the protective effect of antithrombotic treatment in older children, and frequent long-term emerging deficits in neonates and in children with cardiac disorders. Further clinical trials are required to develop effective age-appropriate treatments for children with acute arterial ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Diffusion-weighted imaging magnetic resonance imaging may detect changes in brain structures remote but connected to stroke consistent with neuropathological descriptions of diaschisis. Early diffusion-weighted imaging demonstrates restriction in corticospinal pathways after arterial ischemic stroke of all ages that correlates with motor outcome. Aim/hypothesis: We hypothesized that cerebral diaschisis is measurable in childhood arterial ischemic stroke and explored associations with outcome. Methods: This sub-study of the validation of the Pediatric NIH Stroke Scale study prospectively enrolled children with acute arterial ischemic stroke and both acute and early follow-up (5-14 days) diffusion-weighted imaging. Inclusion criteria were (1) unilateral middle cerebral artery arterial ischemic stroke, (2) acute and subacute diffusion-weighted imaging (b=1000), and (3) 12 month neurological follow-up (Pediatric Stroke Outcome Measure). A validated method using ImageJ software quantified diffusion-weighted imaging diaschisis in anatomically connected structures. Diaschisis measures were corrected for infarct volume, compared to age, imaging timing, and outcomes (Chi square/Fisher, Mann-Whitney test). Results: Nineteen children (53% male, median 8.1 years) had magnetic resonance imaging at medians of 21 and 168 h post-stroke onset. Diaschisis was common and evolved over time, observed in one (5%) on acute but eight (42%) by follow-up diffusion-weighted imaging. Thalamic and callosal diaschisis were most common (5, 26%). Estimates of perilesional diaschisis varied (54±18% of infarct volume). Children with diaschisis tended to be younger (7.02±5.4 vs. 11.82±4.3 years, p=0.08). Total diaschisis score was associated with poor cognitive outcomes (p=0.03). Corticospinal tract diaschisis was associated with motor outcome (p=0.004). Method reliability was excellent. Conclusions: Diffusion-weighted imaging diaschisis occurs in childhood arterial ischemic stroke. Mistaking diaschisis for new areas of infarction carries important clinical implications. Improved recognition and study are required to establish clinical relevance. [ABSTRACT FROM AUTHOR]

Summary Stroke occurs across the lifespan with unique issues in the fetus, neonate, and child. The past decade has seen substantial advances in paediatric stroke research and clinical care, but many unanswered questions and controversies remain. The pathobiology of perinatal stroke needs to be better understood if prevention strategies are to be realised. Similarly, enhanced understanding of the mechanisms underlying childhood stroke, including cerebral arteriopathies, could inform the development of mechanism-specific treatments. Emerging clinical trials, including studies of neonatal sinovenous thrombosis and childhood arterial stroke, offer the hope of evidence-based treatment options in the near future. Early recognition of stroke in children is a key educational target for both the public and health-care professionals, and has translational potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after stroke onset, improving outcomes and quality of life for affected children and their families. [ABSTRACT FROM AUTHOR]

Introduction: Large/medium vessel vasculitis is an important etiology of childhood stroke. Early research suggests vessel wall enhancement on postcontrast MRI may be a marker of intracranial vasculitis yet no systematic descriptions of normal periarterial enhancement exist in the literature. The aim was to describe normal periarterial enhancement in the pediatric population. Methods: We included all children who had an MR scan between January 2007 and December 2010, with normal parenchymal imaging, no clinical concern of vasculopathy, and axial and coronal postcontrast fat-saturated T1-weighted images with 3-mm slice thickness. Intensity of periarterial enhancement was graded on a three-point scale by two investigators for all intracranial large and medium arteries. Results: A total of 44 patients aged 4 months to 16 years were included. Inter- and intra-rater reliability in enhancement grading was high (all kappa >0.65). Thin, linear, noncircumferential periarterial enhancement was common and usually symmetrical. It was most commonly prominent in the cavernous and petrous segments of the internal carotid artery and the M1 segment of the middle cerebral artery. Periarterial enhancement was rarely observed at segments surrounded by CSF, including supraclinoid segments of the internal carotid arteries, P1 segments of the posterior cerebral arteries, V4 segments of the vertebral artery, and the basilar arteries. Conclusion: Normal periarterial enhancement is common and usually symmetrical along major intracranial arteries but rarely seen around arterial segments bordered by CSF. Knowledge of these findings may be useful for a sensitive and specific interpretation of MR scans of patients with clinical concerns of vasculitis. [ABSTRACT FROM AUTHOR]

Arteriopathies are the leading cause of childhood stroke but mechanisms are poorly understood. Fibromuscular dysplasias are non-inflammatory arteriopathies classically described in adults with a cerebral-renal distribution and distinct ‘string-of-beads’ angiographic appearance. Diagnostic characteristics of paediatric fibromuscular dysplasia are uncharacterized. We aimed to compare pathologically proven versus clinically suspected paediatric fibromuscular dysplasia stroke cases to elucidate diagnostic features. Children in the Canadian Paediatric Ischaemic Stroke Registry, Calgary Paediatric Stroke Program, and published literature were screened for stroke associated with fibromuscular dysplasias or renal arteriopathy. Comparison variables included pathological classification, presentations, stroke types, imaging/angiography, treatments, and outcomes. We report 81 cases (15 new, 66 from the literature). For pathologically proven fibromuscular dysplasia (n = 27), intimal fibroplasia predominated (89%) and none had typical adult medial fibroplasia. Ischaemic strokes predominated (37% haemorrhagic) and were often multifocal (40%). Children often presented early (33% <12 months). Angiography demonstrated focal, stenotic arteriopathy (78%) rather than ‘string-of-beads’. Renal arteriopathy (63%) with hypertension (92%) was common, with systemic arteriopathy in 72%, and moyamoya in 35%. Anti-inflammatory (29%) and anti-thrombotic (27%) therapies were inconsistently applied. Outcomes (mean 43 months) were poor in 63%, with stroke recurrence in 36%. Clinically suspected fibromuscular dysplasias (n = 31) were usually older, normotensive with string-of-beads angiography and good outcome. We conclude that fibromuscular dysplasia causes childhood stroke with distinctive clinic-radiological features including hypertension and systemic arteriopathy. Intimal fibroplasia predominates while ‘string of beads’ angiography is rare. Accurate clinical diagnosis is currently challenging. [ABSTRACT FROM AUTHOR]

Abstract: Perinatal stroke is presented as the ideal human model of developmental neuroplasticity. The precise timing, mechanisms, and locations of specific perinatal stroke diseases provide common examples of well defined, focal, perinatal brain injuries. Motor disability (hemiparetic cerebral palsy) constitutes the primary adverse outcome and the focus of models explaining how motor systems develop in health and after early injury. Combining basic science animal work with human applied technology (functional magnetic resonance imaging, diffusion tensor imaging, and transcranial magnetic stimulation), a model of plastic motor development after perinatal stroke is presented. Potential central therapeutic targets are revealed. The means to measure and modulate these targets, including evidence-based rehabilitation therapies and noninvasive brain stimulation, are suggested. Implications for clinical trials and future directions are discussed. [Copyright &y& Elsevier]

Abstract: Arteriopathy is the leading cause of childhood arterial ischemic stroke, but its mechanisms are poorly understood. This review explores the possible role of inflammatory mechanisms and evidence for inflammatory pathophysiology in specific pediatric cerebral arteriopathies. Pathologically proven small-vessel central nervous system vasculitis provides a definitive inflammatory model where available treatments are likely improving outcomes. In contrast, a common large-vessel arteriopathy presents many features suggestive of inflammation, but definitive proof remains elusive. Recent advances and future research directions, including biomarker, neuroimaging, and pathologic approaches and how they might address these important clinical questions, are discussed. [Copyright &y& Elsevier]

Pediatric arterial ischemic stroke (AIS) is increasingly diagnosed and carries significant risks of recurrence, morbidity, and mortality. Anticoagulant therapy (ACT) is commonly prescribed in childhood AIS. Hemorrhagic complication rates in pediatric stroke are unknown, and adult safety data are of limited applicability. We analyzed a prospectively enrolled cohort of children (aged 1 month-18 years) with acute AIS selected using standardized criteria for protocol-based ACT over 14-year period. We assessed ACT-associated intracranial hemorrhage (ICH), including frequency, clinical and radiologic characteristics, predictors, and outcome. Among 215 children with AIS, 123 received ACT within 7 days after diagnosis. During anticoagulation, 14(11%) children developed new or increased ICH, all within 26 days from diagnosis. ICH was symptomatic in 5 (4%), asymptomatic in 9 (7%), and mild (European Cooperative Acute Stroke Study grades HIl or HI2) in all but 1 child (ECASS PH-2). Long-term neurologic outcomes after ACT-associated ICH in survivors were abnormal in 73% (8/11). Comparably, 12 of 75 (16%) children treated without anticoagulation developed new or increased ICH on follow-up imaging (P = .3507). We conclude that ACT is relatively safe in children with AIS, with a 4% risk of symptomatic ICH. Based on the safety of ACT in our study, clinical trials of ACT in childhood AIS are warranted. (Blood. 2012;119(4):949-956) [ABSTRACT FROM AUTHOR]

An improved understanding of perinatal stroke epidemiology, classification, neuroimaging, and outcomes has emerged in recent years. Despite this, little is known regarding the pathophysiological mechanisms responsible for most cases. A multitude of possible associations and putative risk factors have been reported, but most lack definitive empirical evidence supporting primary causation. These include obstetrical and maternal factors, perinatal conditions, infectious diseases, prothrombotic abnormalities, cardiac disorders, medications, and many others. The bulk of evidence is weak, dominated by case reports and retrospective case series. Findings from the small number of case-control and cohort studies that exist are limited by heterogeneous populations and methodologies. The single largest barrier to ultimately understanding and potentially improving outcomes from this common and disabling condition is the lack of comprehensive, fully powered risk factor studies required to definitively describe perinatal stroke pathogenesis. This review summarizes current evidence and suggests future directions for research. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Arterial ischemic stroke (AIS) causes disability in children but plastic developmental neurophysiology is unstudied. Imbalance of interhemispheric inhibition (IHI) in adult subcortical stroke is a therapeutic target. We hypothesized that IHI imbalance occurs in childhood AIS and is modifiable by rTMS. Methods: Eligible SickKids Children’s Stroke Program patients included children >7years with subcortical AIS (>2years previous) and functional hand impairment. TMS with electromyography over first dorsal interosseous measured baseline motor cortex (M1) rest and 1mV thresholds and stimulus–response curves (100–150%). Paired-pulse TMS studied bidirectional short (SIHI) and long (LIHI) interval IHI. Children were matched for age/weakness and randomized to contralesional inhibitory rTMS or sham (8days) with measures repeated. Results: Ten children (mean 13.9 years) had variable weakness (4 mild/2 moderate/4 severe). Stroke M1 motor thresholds were elevated (75±25% versus 55±14%, p =0.05) and decreased with age. Baseline measures suggested excessive LIHI from non-stroke to stroke side (−46±17% versus −28±23%, p =0.08). Following inhibitory rTMS, increases in stroke side maximal MEP amplitudes were suggested and LIHI from stroke to non-stroke side appeared to increase (−20% to −40%). Procedures were well tolerated. Conclusion: TMS measurement of developmental plastic organization and rTMS interventions are feasible in childhood stroke and IHI imbalance may occur. Significance: Improved understanding of developmental plasticity after childhood stroke will facilitate better rehabilitational therapy. [ABSTRACT FROM AUTHOR]

Increasingly distinct patterns of focal ischemic injury in the fetal and perinatal brain are recognized. Improved classification has afforded advances in risk factor identification, pathophysiology hypotheses, outcome prediction, and potential avenues for intervention. Cerebrovascular occlusion leading to perinatal stroke may be arterial or venous, symptomatic or subclinical, and it can occur across multiple time frames. Distinguishing causative factors from mere associations represents a major challenge with important implications for studies of pathogenesis. The adverse outcomes suffered by most children highlight the need for further research. Reviewed here are the current understandings, recent advancements, and future directions for research in perinatal ischemic stroke. [Copyright &y& Elsevier]

Summary: Background: Arterial ischaemic stroke (AIS) can cause disabling hemiparesis in children. We aimed to test whether contralesional, inhibitory repetitive transcranial magnetic stimulation (rTMS) could affect interhemispheric inhibition to improve hand function in chronic subcortical paediatric AIS. Methods: Patients were eligible for this parallel, randomised trial if they were in the SickKids Children''s Stroke Program and had subcortical AIS more than 2 years previously, had transcallosal sparing, were more than 7 years of age, had hand motor impairment, had no seizures or dyskinesia, and were taking no drugs that alter cortical excitability. Patients were paired for age and weakness and were randomised within each pair to sham treatment or inhibitory, low-frequency rTMS over contralesional motor cortex (20 min, 1200 stimuli) once per day for 8 days. An occupational therapist did standardised tests of hand function at days 1 (baseline), 5, 10, and 17 (1 week post-treatment), and the primary outcomes were changes in grip strength and the Melbourne assessment of upper extremity function (MAUEF) between baseline and day 10. Patients, parents, and occupational therapists were blinded to treatment allocation. Analysis was per protocol. Findings: Ten patients with paediatric stroke were enrolled (median age 13·25 [IQR 10·08–16·78] years, mean time post-stroke 6·33 [SD 3·56] years): four with mild weakness, two with moderate weakness, and four with severe weakness. A repeated-measures ANOVA showed a significant interaction between time and the effect of treatment on grip strength (p=0·03). At day 10, grip strength was 2·28 (SD 1·01) kg greater than baseline in the rTMS group and 2·92 (1·20) kg less than baseline in the sham group (p=0·009). Benefits in mean grip strength persisted at day 17 (2·63 [0·56] kg greater than baseline with rTMS and 1·00 [0·70] kg less than baseline with sham treatment; p=0·01). Day 10 MAUEF score improved by more in the rTMS group than in the sham group (7·25 [3·8] vs 0·79 [1·3] points greater than baseline; p=0·002), but this benefit did not persist to day 17. Function of the unaffected hand remained stable. rTMS was well tolerated with no serious adverse events. Interpretation: Contralesional inhibitory rTMS was safe and feasible for patients with paediatric subcortical AIS, and seemed to improve hand function in patients with hemiparesis. Further studies are required to confirm the potential role of rTMS in paediatric neurorehabilitation. Funding: Canadian Stroke Consortium; Canadian Institutes of Health Research; American Academy of Neurology Foundation; Alberta Heritage Foundation for Medical Research. [Copyright &y& Elsevier]

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 review provides an overview of pediatric ischemic stroke to serve as a foundation for the discussion of rehabilitation strategies following focal injury in the developing brain. Cerebrovascular disease is an important cause of acquired brain injury in neonates and children. Ischemic strokes are caused by a multitude of risk factors and advances in neuroimaging have improved diagnosis and understanding of pathophysiology. Pediatric stroke provides the ideal model for the study of injury and recovery in a plastic nervous system. Though their brains likely posses greater potential and unique reorganizational skills, most children suffer neurological morbidity after stroke. An improved understanding of these systems is helping us understand, validate, and improve traditional approaches to rehabilitation while opening the door to new opportunities to improve outcome. All aspects of a patient's function, from the physical to psychological, including issues unique to children and their families, must be addressed and are reviewed. New advances and future directions for research are highlighted. [ABSTRACT FROM AUTHOR]

Background After a year of unsuccessful treatment for hypertension, a young boy underwent a stenting procedure for aortic hypoplasia and awoke with hemiparesis and language deficits. Investigations Neuroimaging, echocardiography, craniocervical vascular imaging and prothrombotic testing. Diagnosis Procedure-related acute arterial ischemic stroke and malignant cerebral edema with herniation. Management Anticoagulation with heparin, seizure prophylaxis and neuroprotective care, including external cooling for hyperthermia. Medical management of increased intracranial pressure and hemicraniectomy at 48 h for malignant cerebral edema. Treatment of deep vein thrombosis with inferior vena cava filter was also required. Long term treatments included extensive rehabilitation, aspirin, antiepileptics, antidyskinetics, antidepressants, antihypertensives and cosmetic skull reconstruction. [ABSTRACT FROM AUTHOR]

The article discusses methods for facilitating recognition and improving understanding of perinatal stroke. It has been noted that the advances in neuroimaging have helped increased the diagnosis of focal ischemia. This is believed to be a key factor in the management of the condition. Furthermore, it was emphasized that the focal nature of perinatal stroke brings important implications for treatment interventions.

Acute necrotizing encephalopathy is a fulminant neurologic disease seen predominantly in Japan and Taiwan. We present two cases diagnosed at a Canadian center within the same year in Caucasian children. Both were previously well, developed an acute viral illness with fever and vomiting, and progressed to brain death within 2 to 4 days. Neuroimaging and postmortem examination demonstrated the unique features of bilateral and severe necrosis of deep gray-and subcortical white-matter structures. The first case was associated with extensive, but transient, hepatic involvement, recent varicella and rotavirus infections, and detailed metabolic studies, including mitochondrial functional analysis, were normal. The second case tested positive for influenza A infection, whereas evidence of liver damage was lacking. Both children demonstrated early lymphopenia and myocardial necrosis, two features not previously associated with acute necrotizing encephalopathy. These cases are unique in their occurrence in non-Japanese children and are among the first published reports in Canada. (J Child Neurol 2005;20:527-532). [ABSTRACT FROM AUTHOR]

The physical manifestations a seizure produces provide critical information. It is assumed that all generalized convulsions are ostensibly the same, regardless of whether they are primary or secondary generalized seizures. We undertook a pilot study to determine if the clinical phenomenology of secondary generalized seizures in children with epilepsy is different from classic descriptions of generalized tonic-clonic convulsions. A data capture sheet was created and applied to the video-electroencephalographic (EEG) records of 64 secondary generalized seizures from 13 children with intractable and/or refractory epilepsy. Many features of secondary generalized seizures were different from traditional descriptions of generalized convulsions. In 100% of cases, the mouth either remained open or repeatedly opened and closed rather than slamming shut. In 77% of cases, a variety of late motor activities were seen to occur after the seizure activity had ceased and the EEG record was quiet. The clinical features of a generalized convulsion in a child, especially mouth opening and late motor events, can be useful in establishing the origin as either focal or primary generalized. (J Child Neurol 2004:19:265-2701 [ABSTRACT FROM AUTHOR]

Pediatric stroke is an underrecognized, potentially treatable cause of childhood neurologic disease. Acute basilar artery thrombosis is a devastating disease rarely encountered in children. Acute interventions with both chemical and mechanical thrombolysis techniques can improve outcomes in adults with arterial thrombosis of the posterior cerebral circulation. We report a case of intervention with both intra-arterial alteplase (tissue plasminogen activator) and cerebral balloon angioplasty to treat a prolonged basilar artery occlusion secondary to idiopathic thrombosis in an adolescent. Despite the patient being clinically locked-in and intervention being delayed at least 20 hours from symptom onset, he obtained complete neurologic recovery. Issues of pediatric stroke, late therapeutic intervention, chemical thrombolysis, and cerebral angioplasty are discussed. This case highlights the underrecognition and subsequent delay in diagnosis of pediatric stroke and how acute intervention may cure otherwise catastrophic strokes in children. [ABSTRACT FROM AUTHOR]

To identify if a predetermined set of potential risk factors are associated with spastic diplegic cerebral palsy (SDCP) in term-born children. This is a case-control study with cases (n = 134) extracted from the Canadian Cerebral Palsy Registry (CCPR) and controls (n = 1950) from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Our primary variable was the SDCP phenotype in term-born children. Possible risk factors were selected a priori and include extreme maternal age (<19 or >35 years), pregnancy complications, maternal disease, substance use, perinatal infection, mode of delivery, perinatal adversity (i.e., neonatal encephalopathy presumably on the basis of intrapartum hypoxia-ischemia), sex, and birth weight. Multivariable analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Multivariable analysis revealed associations between term-born SDCP and pregnancy complications (OR = 4.73; 95% CI = 1.91 to 10.56), maternal disease (OR = 2.52; 95% CI = 1.57 to 3.93), substance use (OR = 3.11; 95% CI = 2.10 to 4.55), perinatal infection (OR = 2.72; 95% CI 1.32 to 5.10), Caesarean section (OR = 2.35; 95% CI = 1.62 to 3.40), and perinatal adversity (OR = 2.91; 95% CI = 1.94 to 4.50). Multiple regression analysis revealed associations between SDCP and pregnancy complications (OR = 3.28; 95% CI 1.20 to 8.15), maternal disease (OR = 2.52; 95% CI 1.50 to 4.12), substance use (OR = 3.59; 95% CI 2.37 to 5.40), perinatal infection (OR = 3.78, 95% CI 1.71 to 7.72), Caesarean section (OR = 2.72; 95% CI 1.82 to 4.03), and perinatal adversity (OR = 4.16; 95% CI 2.67 to 6.70). Antenatal (pregnancy complications, maternal disease, substance use) and perinatal (infections, Caesarean section, and perinatal adversity) risk factors are associated with an increased risk of SDCP in term-born children, suggesting variable interactions between risk factors to provide a clinicopathologic framework that is different from SDCP observed in preterm-born children. [ABSTRACT FROM AUTHOR]

Examines the role of maxi-potassium (K) channels in endothelin-induced vasoconstriction of mesenteric and submucosal arterioles. Description of endothelins; Findings of studies conducted; Methodology used in studies.

Investigates the role of maxi-potassium (K+) channels in endothelin-induced vasoconstriction of mesenteric and submucosal arterioles. Association of submucosal and mesenteric arteriole endothelin receptors to maxi-K+ channel activation and membrane potential stabilization; Role of Maxi-K+ in the stimulus-contraction coupling pathway for endothelin-1.

• Application of anodal tDCS concurrent to surgical training enhances unimanual skill acquisition compared to training alone. • Changes in delta EEG activity in the sensorimotor network are associated with surgical skill improvement. • EEG patterns of unimanual and bimanual surgical skill performance differ, primarily within the parietal cortex. • Anodal tDCS modulated alpha frequency band activity during bimanual surgical skill performance. Transcranial direct-current stimulation (tDCS), an increasingly applied form of non-invasive brain stimulation, can augment the acquisition of motor skills. Motor learning investigations of tDCS are limited to simple skills, where mechanisms are increasingly understood. Investigations of meaningful, complex motor skills possessed by humans, such as surgical skills, are limited. This replication and extension of our previous findings used electroencephalography (EEG) to determine how tDCS and complex surgical training alters electrical activity in the sensorimotor network to enhance complex surgical skill acquisition. In twenty-two participants, EEG was recorded during baseline performance of simulation-based laparoscopic surgical skills. Participants were randomized to receive 20 min of primary motor cortex targeting anodal tDCS or sham concurrent to 1 h of surgical skill training. EEG was reassessed following training, during a post-training repetition of the surgical tasks. Our results replicated our previous study suggesting that compared to sham, anodal tDCS enhanced the acquisition of unimanual surgical skill. Surgical training modulated delta frequency band activity in sensorimotor regions. Next, the performance of unimanual and bimanual skills evoked unique EEG profiles, primarily within the beta frequency-band in parietal regions. Finally, tDCS-paired surgical training independently modulated delta and alpha frequency-bands in sensorimotor regions. Application of tDCS during surgical skill training is feasible, safe and tolerable. In conclusion, we are the first to explore electrical brain activity during performance of surgical skills, how electrical activity may change during surgical training and how tDCS alters the brain to enhance skill acquisition. The results provide preliminary evidence of neural markers that can be targeted by neuromodulation to optimize complex surgical training. [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]

Background: Perinatal stroke is a leading cause of hemiparetic cerebral palsy and lifelong disability. Neurodevelopmental outcomes are difficult to predict and markers of long-term poor outcome continue to be investigated. Deceleration in growth of head circumference has been associated with worse developmental outcomes in neonatal brain injury. We hypothesized that perinatal stroke would result in decreased rates of head growth during childhood that would be associated with worse developmental outcomes. Methods: Patients with magnetic resonance imaging (MRI)–confirmed neonatal arterial ischemic stroke and arterial presumed perinatal ischemic stroke were identified from a population-based research cohort (Alberta Perinatal Stroke Project). Demographics and occipital-frontal circumference data were collected from medical records. Head growth was compared to typically developing control charts using a 2-tailed t test. The Fisher exact test was used to examine associations between Pediatric Stroke Outcome Measures (PSOM) scores and occipital-frontal head circumference. Results: Three hundred fifteen occipital-frontal head circumference measurements were collected from 102 patients (48 female, 54 male), over a median of 3.2 years (standard deviation = 5.18, range = 0-18.3). After 3 months for female patients and 1 year for male patients, occipital-frontal head circumference deviated and remained below normal growth trajectories (P <.05) with a large effect size (Cohen d >0.8). Poor outcome (PSOM ≥ 1) was associated with smaller occipital-frontal head circumference (P <.05). Conclusion: Head growth deceleration is observed in children with perinatal arterial ischemic stroke and is associated with poor outcome. Head circumference may be a tool to alert clinicians to the potential of abnormal neurologic outcome. [ABSTRACT FROM AUTHOR]

Background: Detailed kinematics of motor impairment of the contralesional ("affected") and ipsilesional ("unaffected") limbs in children with hemiparetic cerebral palsy are not well understood. We aimed to 1) quantify the kinematics of reaching in both arms of hemiparetic children with perinatal stroke using a robotic exoskeleton, and 2) assess the correlation of kinematic reaching parameters with clinical motor assessments.Methods: This prospective, case-control study involved the Alberta Perinatal Stroke Project, a population-based research cohort, and the Foothills Medical Center Stroke Robotics Laboratory in Calgary, Alberta over a four year period. Prospective cases were collected through the Calgary Stroke Program and included term-born children with magnetic resonance imaging confirmed perinatal ischemic stroke and upper extremity deficits. Control participants were recruited from the community. Participants completed a visually guided reaching task in the KINARM robot with each arm separately, with 10 parameters quantifying motor function. Kinematic measures were compared to clinical assessments and stroke type.Results: Fifty children with perinatal ischemic stroke (28 arterial, mean age: 12.5 ± 3.9 years; 22 venous, mean age: 11.5 ± 3.8 years) and upper extremity deficits were compared to healthy controls (n = 147, mean age: 12.7 ± 3.9 years). Perinatal stroke groups demonstrated contralesional motor impairments compared to controls when reaching out (arterial = 10/10, venous = 8/10), and back (arterial = 10/10, venous = 6/10) with largest errors in reaction time, initial direction error, movement length and time. Ipsilesional impairments were also found when reaching out (arterial = 7/10, venous = 1/10) and back (arterial = 6/10). The arterial group performed worse than venous on both contralesional and ipsilesional parameters. Contralesional reaching parameters showed modest correlations with clinical measures in the arterial group.Conclusions: Robotic assessment of reaching behavior can quantify complex, upper limb dysfunction in children with perinatal ischemic stroke. The ipsilesional, "unaffected" limb is often abnormal and may be a target for therapeutic interventions in stroke-induced hemiparetic cerebral palsy. [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]

Some conditions within specific populations are so rare rigorous evidence is unavailable. Childhood hyperkinesis is one example, yet presents an opportunity to examine sensation's contribution to motor function. The patient experienced functional difficulty from hyperkinesis as a result of childhood stroke. Home-based passive neuromuscular electrical stimulation (NMES) was implemented an hour/day, six days/week, over 6 weeks (36 hours). Clinical and robotic measures (Assisting Hand Assessment, Box and Block Test, Jebsen Taylor Test of Hand Function, Kinarm) were administered before and after the intervention and at 9 months. NMES was feasible and well tolerated. Clinically important gains of arm function were maintained at 9 months. Robotic measures showed improved hyperkinesis, namely reduced movement segmentation and improved target approximation, in addition to improved proprioceptive function after NMES. This case study illustrates the use of NMES within a previously unexplored population and highlights the potential importance of sensory systems to motor gains. [ABSTRACT FROM AUTHOR]

Background: Activities of daily living frequently require children to make rapid decisions and execute desired motor actions while inhibiting unwanted actions. Children with hemiparetic cerebral palsy due to perinatal stroke may have deficits in executive functioning in addition to motor impairments. The objective of this study was to use a robotic object hit and avoid task to assess the ability of children with hemiparetic cerebral palsy to make rapid motor decisions.Methods: Forty-five children with hemiparetic cerebral palsy due to perinatal stroke and 146 typically developing children (both groups ages 6-19 years) completed a robotic object hit and avoid task using the Kinarm Exoskeleton. Objects of different shapes fell from the top of the screen with increasing speed and frequency. Children were instructed to hit two specific target shapes with either hand, while avoiding six distractor shapes. The number of targets and distractors hit were compared between children with hemiparetic cerebral palsy and typically developing children, accounting for age effects. We also compared performance to a simpler object hit task where there were no distractors.Results: We found that children with hemiparetic cerebral palsy hit a greater proportion of total distractors compared to typically developing children, demonstrating impairments in inhibitory control. Performance for all children improved with age. Children with hemiparetic cerebral palsy hit a greater percentage of targets with each arm on the more complex object hit and avoid task compared to the simpler object hit task, which was not found in typically developing children.Conclusions: Children with hemiparetic cerebral palsy due to perinatal stroke demonstrated impairments in rapid motor decision making including inhibitory control, which can impede their ability to perform real-world tasks. Therapies that address both motor performance and executive functions are necessary to maximize function in children with hemiparetic cerebral palsy. [ABSTRACT FROM AUTHOR]

Background: While motor deficits are the hallmark of hemiparetic cerebral palsy, children may also experience impairments in visuospatial attention that interfere with participation in complex activities, including sports or driving. In this study, we used a robotic object hitting task to assess bilateral sensorimotor control and visuospatial skills in children with hemiparesis due to perinatal arterial ischemic stroke (AIS) or periventricular venous infarct (PVI). We hypothesized that performance would be impaired bilaterally and be related to motor behavior and clinical assessment of visuospatial attention.Methods: Forty-nine children with perinatal stroke and hemiparetic cerebral palsy and 155 typically developing (TD) children participated in the study. Participants performed a bilateral object hitting task using the KINARM Exoskeleton Robot, in which they used virtual paddles at their fingertips to hit balls that fell from the top of the screen with increasing speed and frequency over 2.3 min. We quantified performance across 13 parameters including number of balls hit with each hand, movement speed and area, biases between hands, and spatial biases. We determined normative ranges of performance accounting for age by fitting 95% prediction bands to the TD children. We compared parameters between TD, AIS, and PVI groups using ANCOVAs accounting for age effects. Lastly, we performed regression analysis between robotic and clinical measures.Results: The majority of children with perinatal stroke hit fewer balls with their affected arm compared to their typically developing peers. We also found deficits with the ipsilesional ("unaffected") arm. Children with AIS had greater impairments than PVI. Despite hitting fewer balls, we only identified 18% of children as impaired in hand speed or movement area. Performance on the Behavioral Inattention Test accounted for 21-32% of the variance in number of balls hit with the unaffected hand.Conclusions: Children with perinatal stroke-induced hemiparetic cerebral palsy may have complex bilateral deficits reflecting a combination of impairments in motor skill and visuospatial attention. Clinical assessments and interventions should address the interplay between motor and visuospatial skills. [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]

Pediatric applications of transcranial magnetic stimulation are rapidly expanding, but lack the safety data established for adults. Transcranial magnetic stimulation-induced neurocardiogenic syncope may represent an age-dependent adverse event that is essentially undescribed in the transcranial magnetic stimulation literature. We report on 2 adolescents (of 10 children studied) with transcranial magnetic stimulation-related neurocardiogenic syncope, identify modifiable risk factors, and suggest measures to improve the safety of future pediatric transcranial magnetic stimulation studies. [Copyright &y& Elsevier]

Presents the case of a 12-year-old girl with pharyngitis, meningitis and sinovenous thrombosis. Initial diagnosis; Treatment given; Analysis of the cerebrospinal fluid; Discussion on Lemierre syndrome.

Perinatal stroke causes most hemiparetic cerebral palsy and cognitive dysfunction may co-occur. Compensatory developmental changes in the intact contralesional hemisphere may mediate residual function and represent targets for neuromodulation. We used morphometry to explore cortical thickness, grey matter volume, gyrification, and sulcal depth of the contralesional hemisphere in children, adolescents, and young adults after perinatal stroke and explored associations with motor, attention, and executive function. Participants aged 6–20 years (N = 109, 63% male) with unilateral perinatal stroke underwent T1-weighted imaging. Participants had arterial ischemic stroke (AIS; n = 36), periventricular venous infarction (PVI; n = 37) or were controls (n = 36). Morphometry was performed using the Computational Anatomy Toolbox (CAT12). Group differences and associations with motor and executive function (in a smaller subsample) were assessed. Group comparisons revealed areas of lower cortical thickness in contralesional hemispheres in both AIS and PVI and greater gyrification in AIS compared to controls. Areas of greater grey matter volume and sulcal depth were also seen for AIS. The PVI group showed lower grey matter volume in cingulate cortex and less volume in precuneus relative to controls. No associations were found between morphometry metrics, motor, attention, and executive function. Cortical structure of the intact contralesional hemisphere is altered after perinatal stroke. Alterations in contralesional cortical morphometry shown in perinatal stroke may be associated with different mechanisms of damage or timing of early injury. Further investigations with larger samples are required to more thoroughly explore associations with motor and cognitive function. [ABSTRACT FROM AUTHOR]

Background: Risk factors for pediatric stroke are poorly understood and require study to improve prevention. Total cholesterol and triglyceride values peak to near-adult levels before puberty, a period of increased stroke incidence. The role of lipids in childhood arterial ischemic stroke has been minimally investigated.Methods: We performed a cross-sectional analysis of lipid and Lp(a) concentrations in children with arterial ischemic stroke in the International Pediatric Stroke Study to compare the prevalence of dyslipidemia and high- or low-ranking lipid values in our dataset with reported population values. We analyzed sex, body mass index, race, ethnicity, family history, and stroke risk factors for associations with dyslipidemia, high non-high-density lipoprotein cholesterol, and hypertriglyceridemia.Results: Compared with the National Health and Nutrition Examination Survey, a higher proportion of children ≥5 years with arterial ischemic stroke had dyslipidemia (38.4% versus 21%), high total cholesterol (10.6% versus 7.4%), high non-high-density lipoprotein cholesterol (23.1% versus 8.4%), and low high-density lipoprotein cholesterol (39.8% versus 13.4%). The lipid values that corresponded to one standard deviation above the mean (84th percentile) in multiple published national studies generally corresponded to a lower ranking percentile in children aged five years or older with arterial ischemic stroke. Dyslipidemia was more likely associated with an underweight, overweight, or obese body mass index compared with a healthy weight. Ethnic background and an acute systemic illness were also associated with abnormal lipids.Conclusions: Dyslipidemia and hypertriglyceridemia may be more prevalent in children with arterial ischemic stroke compared with stroke-free children. [ABSTRACT FROM AUTHOR]

This study aimed to describe children with moyamoya disease from an international multicenter stroke database, and explore risk factors for stroke recurrence. We reviewed data of children >28-days old with moyamoya disease enrolled in the International Pediatric Stroke Study from January 2003 to March 2013. A total of 174 children from 32 sites and 14 countries had moyamoya disease; median age 7.4 years, 49% male. Of these, 90% presented with ischemic stroke, 7.5% with transient ischemic attack, and 2.5% with hemorrhagic stroke. One-third of patients had moyamoya syndrome. Stroke recurrence was 20% over median follow-up of 13 months; 9% had multiple recurrences. Children treated with surgical revascularization were less likely to have stroke recurrence (P = .046). Moyamoya disease accounted for 8% of arterial strokes in this international pediatric stroke registry. One-third of pediatric patients with moyamoya disease have an underlying syndromic condition. Surgical revascularization is effective at reducing the incidence of stroke recurrence. [ABSTRACT FROM AUTHOR]