Making waves: The changing tide of cerebral palsy.

Cerebral palsy (CP) is a broad diagnosis unbound by aetiology and is based on a clinical examination demonstrating abnormalities of movement or posture. CP represents a static neurological condition, provided that neurodegenerative conditions, leukoencephalopathies and neuromuscular disorders are excluded. In paediatrics, the genetic conditions associated with CP are rapidly increasing, with primary and overlapping neurodevelopmental conditions perhaps better categorised by the predominant clinical feature such as CP, intellectual disability, autism spectrum disorder or epilepsy. Progress in molecular genetics may challenge what constitutes CP, but a genetic diagnosis does not negate the CP diagnosis. As clinicians working in the field, we discuss the changing tide of CP. Neuroimaging provides essential information through pattern recognition and demonstration of static brain changes. We present examples of children where a layered clinical diagnosis or dual aetiologies are appropriate. We also present examples of children with genetic causes of CP to highlight the challenges and limitations of neuroimaging to provide an aetiological diagnosis. In consultation with a geneticist, access to genomic testing (exome or genome sequencing) is now available in Australia under Medicare billing for children under the age of 10 with dysmorphic features, one or more major structural organ anomalies, (an evolving) intellectual disability or global developmental delay. We encourage the uptake of genomic testing in CP, because it can be difficult to tell whether a child has an environmental or genetic cause for CP. A specific genetic diagnosis may change patient management, reduce guilt and enable more distinctive research in the future to assist with understanding disease mechanisms.

Association of Pediatric ASPECTS and NIH Stroke Scale, Hemorrhagic Transformation, and 12-Month Outcome in Children With Acute Ischemic Stroke.

OBJECTIVE: We aimed to determine whether a modified pediatric Alberta Stroke Program Early CT Score (modASPECTS) is associated with clinical stroke severity, hemorrhagic transformation, and 12-month functional outcomes in children with acute AIS. METHODS: Children (29 days to <18 years) with acute AIS enrolled in two institutional prospective stroke registries at Children's Hospital of Philadelphia and Royal Children's Hospital Melbourne, Australia were retrospectively analyzed to determine whether modASPECTS, in which higher scores are worse, correlated with acute Pediatric NIH Stroke Scale (PedNIHSS) scores (children ≥2 years of age), was associated with hemorrhagic transformation on acute MRI, and correlated with 12-month functional outcome on the Pediatric Stroke Outcome Measure (PSOM). RESULTS: 131 children were included; 91 were ≥2 years of age. Median days from stroke to MRI was 1 (interquartile range [IQR] 0-1). Median modASPECTS was 4 (IQR 3-7). ModASPECTS correlated with PedNIHSS (rho=0.40, P=0.0001). ModASPECTS was associated with hemorrhagic transformation (OR 1.13 95% CI 1.02-1.25, P=0.018). Among children with follow-up (N=128, median 12.2 months, IQR 9.5-15.4 months), worse outcomes were associated with higher modASPECTS (common OR 1.14, 95%CI 1.04-1.24, P=0.005). The association between modASPECTS and outcome persisted when we adjusted for age at stroke ictus and the presence of tumor or meningitis as stroke risk factors (common OR 1.14, 95%CI 1.03-1.25, P=0.008). CONCLUSIONS: ModASPECTS correlates with PedNIHSS scores, hemorrhagic transformation, and 12-month functional outcome in children with acute AIS. Future pediatric studies should evaluate its usefulness in predicting symptomatic intracranial hemorrhage and outcome after acute revascularization therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the modified pediatric ASPECTS on MRI is associated with stroke severity (as measured by the baseline pediatric NIH Stroke Scale), hemorrhagic transformation, and 12-month outcome in children with acute supratentorial ischemic stroke.

Long-term outcomes of warfarin versus aspirin after Fontan surgery.

OBJECTIVES: Because of the nature of the Fontan physiology, patients are at an increased risk of thromboembolic complications. As such, warfarin or aspirin is generally prescribed lifelong for thromboprophylaxis. This study aimed to compare long-term rates of cerebrovascular injury, thrombosis, bleeding, bone mineral density, and quality of life in people living with Fontan circulation receiving warfarin compared with aspirin. METHODS: This was a multicenter study of a selected cohort from the Australia and New Zealand Fontan population. Participants underwent cerebral magnetic resonance imaging to detect the presence of cerebrovascular injury (n = 84) and dual-energy X-ray absorptiometry to assess bone mineral density (n = 120). Bleeding (n = 100) and quality of life (n = 90) were assessed using validated questionnaires: Warfarin and Aspirin Bleeding assessment tool and Pediatric Quality of Life Inventory, respectively. RESULTS: Stroke was detected in 33 participants (39%), with only 7 (6%) being clinically symptomatic. There was no association between stroke and Fontan type or thromboprophylaxis type. Microhemorrhage and white matter injury were detected in most participants (96% and 86%, respectively), regardless of thromboprophylaxis type. Bleeding rates were high in both groups; however, bleeding was more frequent in the warfarin group. Bone mineral density was reduced in our cohort compared with the general population; however, this was further attenuated in the warfarin group. Quality of life was similar between the warfarin and aspirin groups. Home international normalized ratio monitoring was associated with better quality of life scores in the warfarin group. CONCLUSIONS: Cerebrovascular injury is a frequent occurrence in the Australia and New Zealand Fontan population regardless of thromboprophylaxis type. No benefit of long-term warfarin prophylaxis could be demonstrated over aspirin; however, consideration must be given to important clinical features such as cardiac function and lung function. Furthermore, the association of reduced bone health in children receiving warfarin warrants further mechanistic studies.

The severe epilepsy syndromes of infancy: A population-based study.

OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.

Neurocognitive Dysfunction and Smaller Brain Volumes in Adolescents and Adults With a Fontan Circulation.

BACKGROUND: Neurocognitive outcomes beyond childhood in people with a Fontan circulation are not well defined. This study aimed to investigate neurocognitive functioning in adolescents and adults with a Fontan circulation and associations with structural brain injury, brain volumetry, and postnatal clinical factors. METHODS: In a binational study, participants with a Fontan circulation without a preexisting major neurological disability were prospectively recruited from the Australia and New Zealand Fontan Registry. Neurocognitive function was assessed by using Cogstate software in 107 participants with a Fontan circulation and compared with control groups with transposition of the great arteries (n=50) and a normal circulation (n=41). Brain MRI with volumetric analysis was performed in the participants with a Fontan circulation and compared with healthy control data from the ABIDE I and II (Autism Brain Imaging Data Exchange) and PING (Pediatric Imaging, Neurocognition, and Genetics) data repositories. Clinical data were retrospectively collected. RESULTS: Of the participants with a Fontan circulation who had a neurocognitive assessment, 55% were male and the mean age was 22.6 years (SD 7.8). Participants with a Fontan circulation performed worse in several areas of neurocognitive function compared with those with transposition of the great arteries and healthy controls (P<0.05). Clinical factors associated with worse neurocognitive outcomes included more inpatient days during childhood, younger age at Fontan surgery, and longer time since Fontan procedure (P<0.05). Adults with a Fontan circulation had more marked neurocognitive dysfunction than adolescents with a Fontan circulation in 2 domains (psychomotor function, P=0.01 and working memory, P=0.02). Structural brain injury was present in the entire Fontan cohort; the presence of white matter injury was associated with worse paired associate learning (P<0.001), but neither the presence nor severity of infarct, subcortical gray matter injury, and microhemorrhage was associated with neurocognitive outcomes. Compared with healthy controls, people with a Fontan circulation had smaller global brain volumes (P<0.001 in all regions) and smaller regional brain volumes in most cerebral cortical regions (P<0.05). Smaller global brain volumes were associated with worse neurocognitive functioning in several domains (P<0.05). A significant positive association was also identified between global brain volumes and resting oxygen saturations (P≤0.04). CONCLUSIONS: Neurocognitive impairment is common in adolescents and adults with a Fontan circulation and is associated with smaller gray and white matter brain volume. Understanding modifiable factors that contribute to brain injury to optimize neurocognitive function is paramount.

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke.

OBJECTIVE: To determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features. METHODS: We report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes. RESULTS: Of 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions. CONCLUSION: Specific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.

Arterial Ischemic Stroke Secondary to Cardiac Disease in Neonates and Children.

OBJECTIVE: We describe the risk factors for peri-procedural and spontaneous arterial ischemic stroke (AIS) in children with cardiac disease. METHODS: We identified children with cardiac causes of AIS enrolled in the International Pediatric Stroke Study registry from January 2003 to July 2014. Isolated patent foramen ovale was excluded. Peri-procedural AIS (those occurring during or within 72 hours of cardiac surgery, cardiac catheterization, or mechanical circulatory support) and spontaneous AIS that occurred outside of these time periods were compared. RESULTS: We identified 672 patients with congenital or acquired cardiac disease as the primary risk factor for AIS. Among these, 177 patients (26%) had peri-procedural AIS and 495 patients (74%) had spontaneous AIS. Among non-neonates, spontaneous AIS occurred at older ages (median 4.2 years, interquartile range 0.97 to 12.4) compared with peri-procedural AIS (median 2.4 years, interquartile range 0.35 to 6.1, P < 0.001). About a third of patients in both groups had a systemic illness at the time of AIS. Patients who had spontaneous AIS were more likely to have a preceding thrombotic event (16 % versus 9 %, P = 0.02) and to have a moderate or severe neurological deficit at discharge (67% versus 33%, P = 0.01) compared to those with peri-procedural AIS. CONCLUSIONS: Children with cardiac disease are at risk for AIS at the time of cardiac procedures but also outside of the immediate 72 hours after procedures. Many have acute systemic illness or thrombotic event preceding AIS, suggesting that inflammatory or prothrombotic conditions could act as a stroke trigger in this susceptible population.

Recent developments and new frontiers in childhood arterial ischemic stroke.

This review will discuss important developments in childhood arterial ischemic stroke over the past decade, focusing on improved understanding of the causes, consequences, and targets for intervention. Risk factors for childhood arterial ischemic stroke are different to adults. Infections, particularly herpes group viruses, are important precipitants for stroke. Non-atherosclerotic arteriopathies are the most common cause of childhood arterial ischemic stroke and an important predictor of recurrent events. Recent advances include the identification of serum biomarkers for inflammation and endothelial injury, and imaging biomarkers to monitor for vascular progression. Multicenter trials of immunotherapies in focal cerebral arteriopathies are currently in development. Recognition of clinical and radiological phenotypic patterns has facilitated the discovery of multisystem disorders associated with arterial ischemic stroke including ACTA2 arteriopathy and adenosine deaminase 2 deficiency. Identification of these Mendelian disorders provide insights into genetic mechanisms of disease and have implications for medical and surgical management. In contrast to adults, there are long diagnostic delays in childhood arterial ischemic stroke. Refinement of pediatric Code Stroke protocols and clinical decision support tools are essential to improve diagnostic certainty and improve access to reperfusion therapies. Children do not recover better than adults following arterial ischemic stroke, with more than half of survivors having long-term impairments. The physical, cognitive, and behavioral consequences of childhood arterial ischemic stroke are increasingly reported but further research is required to understand their impact on participation, quality of life, psychosocial, and family functioning. Longitudinal studies and the use of advanced imaging techniques, to understand neurobiological correlates of functional reorganization, are essential to developing targeted intervention strategies to facilitate recovery.

Infantile-Onset Myelin Protein Zero-Related Demyelinating Neuropathy Presenting as an Upper Extremity Monoplegia.

We describe an infant with an early-onset demyelinating neuropathy who presented with an upper extremity monoplegia and progressive asymmetric weakness. Neurophysiologic testing revealed a generalized severe neuropathy with marked slowing of nerve conduction. The disproportionate severity and asymmetry of upper extremity involvement at presentation was atypical of inherited neuropathies, and an initial diagnosis of chronic inflammatory demyelinating polyneuropathy was considered. Nerve biopsy showed severe depletion of large myelinated fibers without inflammatory cells, and focally folded myelin sheaths were seen on electron microscopy. Genetic testing revealed a de novo heterozygous mutation in the myelin protein zero gene.

Retrospective review of screening for Sturge-Weber syndrome with brain magnetic resonance imaging and electroencephalography in infants with high-risk port-wine stains.

BACKGROUND: There is a lack of consensus regarding how best to screen children with facial port-wine stains for Sturge-Weber syndrome. Many favor brain magnetic resonance imaging, and adjunctive electroencephalography is increasingly used. However, the sensitivity, specificity, and negative and positive predictive value of magnetic resonance imaging and electroencephalography and whether screening improves seizure recognition is unclear. METHODS: A retrospective review of children with high-risk port-wine stains presenting consecutively to the outpatient laser clinic of a tertiary pediatric hospital between December 2015 and November 2016 was undertaken. Primary outcome measures were yield, accuracy, age of and protocols for screening magnetic resonance imaging and electroencephalography, type of and age at presenting seizure, and percentage referred to neurology. RESULTS: Of 126 patients with facial port-wine stains, 25.4% (32/126) were at high risk of Sturge-Weber syndrome (hemifacial, median, and forehead PWS phenotypes); 43.7% of these (14/32) underwent screening magnetic resonance imaging. Sturge-Weber syndrome was detected in 7.1% (1/14). Magnetic resonance imaging had false-negative results in 23.1% (3/13) of those screened. Screening magnetic resonance imaging had sensitivity of 25%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9% for the detection of Sturge-Weber syndrome (hemifacial, median and forehead PWS phenotypes). Only one-third of those with false-negative magnetic resonance imaging were referred to neurology. Mean age of first seizure in those with false-negative screening magnetic resonance imaging was 28 months, vs 14 months in those not screened. Abnormal electroencephalographic signs were detected in the two infants who underwent presymptomatic electroencephalography. CONCLUSIONS: Findings from this small cohort of individuals with port-wine stains that put them at high risk of Sturge-Weber syndrome suggest that children with positive screening magnetic resonance imaging will almost certainly develop Sturge-Weber syndrome but that negative screening magnetic resonance imaging cannot exclude Sturge-Weber syndrome (in up to 23.1% of cases). False-negative magnetic resonance imaging may delay seizure recognition. Seizure education, monitoring, and consideration of adjunctive electroencephalography are important irrespective of magnetic resonance imaging findings.

Screening for Sturge-Weber syndrome: A state-of-the-art review.

Infants with a high-risk distribution of port-wine stains are commonly screened for Sturge-Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port-wine stain phenotypes to screen, optimal timing, screening sensitivity, or whether presymptomatic diagnosis improves neurodevelopmental outcomes. This state-of-the-art review examines the evidence in favor of screening for Sturge-Weber syndrome, based on its effect on neurodevelopmental outcomes, against the risks and limitations of screening magnetic resonance imaging and electroencephalography. A literature search of PubMed/MEDLINE was conducted between January 2005 and May 2017 using key search terms. Relevant articles published in English were reviewed; 34 articles meeting the search criteria were analyzed according to the following outcome measures: neurodevelopmental outcome benefit of screening, diagnostic yield, financial costs, procedural risks, and limitations of screening magnetic resonance imaging and electroencephalography. There is no evidence that a presymptomatic Sturge-Weber syndrome diagnosis with magnetic resonance imaging results in better neurodevelopmental outcomes. The utility of electroencephalographic screening is also unestablished. In Sturge-Weber syndrome, neurodevelopmental outcomes depend on prompt recognition of neurologic red flags and early seizure control. Small numbers and a lack of prospective randomized controlled trials limit these findings. For infants with port-wine stain involving skin derived from the frontonasal placode (forehead and hemifacial phenotypes), we recommend early referral to a pediatric neurologist for parental education, counselling, and monitoring for neurologic red flags and seizures and consideration of electroencephalography regardless of whether magnetic resonance imaging is performed or its findings.

Risk Factors for Peri-Procedural Arterial Ischaemic Stroke in Children with Cardiac Disease.

Improved survival of children with congenital heart disease has led to increasing focus on neurodevelopmental outcome, as close to half of the infants undergoing cardiac surgery are affected by neurodevelopmental disability. Stroke is particularly important as it frequently results in permanent neurologic sequelae. The aim of this study was to investigate risk factors for peri-procedural arterial ischaemic stroke (AIS) in children with cardiac disease. A retrospective case-control analysis of children aged <18 years with radiologically confirmed AIS following a cardiac procedure admitted to the Royal Children's Hospital Melbourne between 1993 and 2010. Each case was matched with two controls with similar cardiac diagnosis, procedure type, age and date of procedure. Demographics and peri-procedural data were collected from medical records and departmental database. Fifty-two cases were identified. Multivariable analysis identified post-procedural infection (OR 6.1, CI 1.3-27, p = 0.017) and length of ICU stay (OR 4.0, CI 1.4-11, p = 0.009) as risk factors for AIS. Although the study is limited to a single-centre cohort, length of ICU stay and post-procedural infection were identified as risk factors for AIS. These findings demonstrate these factors to be important areas to focus attention for stroke prevention in children with cardiac disease.

Profiles of Executive Function Across Children with Distinct Brain Disorders: Traumatic Brain Injury, Stroke, and Brain Tumor.

OBJECTIVES: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. METHODS: Participants were children with traumatic brain injury (N=82; 8-13 years of age), arterial ischemic stroke (N=36; 6-16 years of age), and brain tumor (N=74; 9-18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children's Version (TEA-Ch) subtests: Creature Counting, Walk-Don't-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. RESULTS: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. CONCLUSIONS: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529-538).

Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke: Correlates of Stroke Cause and Recurrence.

BACKGROUND AND PURPOSE: Among children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS. METHODS: In an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS. RESULTS: Median age at index stroke was 8.2 years (interquartile range, 3.6-14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3-10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of high-sensitivity C-reactive protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group, higher high-sensitivity C-reactive protein and serum amyloid A predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend toward higher high-sensitivity C-reactive protein and serum amyloid A, compared with children with stable or improved arteriopathies. CONCLUSIONS: Among children with AIS, specific inflammatory biomarkers correlate with cause and-in the arteriopathy group-risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

Neurologic Melioidosis: Case Report of a Rare Cause of Acute Flaccid Paralysis.

Acute flaccid paralysis is associated with inflammation, infection, or tumors in the spinal cord or peripheral nerves. Melioidosis (Burkholderia pseudomallei infection) can rarely cause this presentation. We describe a case of spinal melioidosis in a 4-year-old boy presenting with flaccid paralysis, and review the literature on this rare disease.

Arterial ischemic stroke in children with cardiac disease.

OBJECTIVE: To describe the spectrum of cardiac disorders, timing in relation to interventional procedures, and outcome in children with cardiac disease and arterial ischemic stroke (AIS). METHODS: Children younger than 18 years with cardiac disease and radiologically confirmed AIS admitted to the Royal Children's Hospital Melbourne between 1993 and 2010 were retrospectively identified using ICD-9 and ICD-10 searches. RESULTS: Seventy-six children with cardiac disease and radiologically confirmed AIS were identified with the median age at diagnosis of 5 months (interquartile range 0-58). Cardiac lesions included cyanotic congenital heart disease (CHD) in 42 (55%), acyanotic heart disease in 24 (29%), cardiomyopathies/myocarditis in 6 (8%), infective endocarditis in 3 (4%), and primary arrhythmias in 3 (4%). Stroke occurred following cardiac procedures in 52 patients (68%): 41 post cardiac surgery (4.6 strokes per 1,000 surgical procedures) and 11 post cardiac catheterization (1.7 strokes per 1,000 catheterizations). The median time from procedure to diagnosis of stroke was 3 days (interquartile range 2-7), with 68% (95% confidence interval 58%-79%) of strokes estimated to occur within the periprocedural period. Prevalence of periprocedural stroke varied by diagnostic category, but was most common in patients with cyanotic CHD undergoing palliative surgery (22/2,256, 1%) (p < 0.005). There were 3 AIS-related deaths, and 54 survivors (84%) had persisting neurologic deficits. CONCLUSIONS: Infants with cyanotic CHD were most frequently affected by AIS during the periprocedural period. Prospective cohort studies are required to determine effective primary and secondary prevention strategies.

Early-onset bilateral cerebral arteriopathies: Cohort study of phenotype and disease course.

OBJECTIVE: To describe characteristics of young children with arterial ischemic stroke (AIS) and bilateral cerebral arteriopathies. METHODS: Retrospective review of clinical features, course, and outcome. Neuroimaging was analyzed for infarct pattern, cerebrovascular diagnosis (anatomic/Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation [CASCADE] criteria), and disease progression. RESULTS: In the 31 children (median age, 18 months), presentations included acute hemiparesis (n=23) and focal seizures (n=12). Seven had systemic arterial disease; 13 had cardiac abnormalities. Twenty had recurrent AIS or transient ischemic attack (after median of 3 months); 16 had >1 recurrence. Median modified Rankin Scale score was 3, with motor impairments in 20, cognitive impairments in 11, and seizures in 7. At presentation, 17 had old and acute infarcts. Twenty-five had high signal in white matter. A total of 13/23 reimaged patients accrued further infarcts over a median of 39 months. Arteriopathy involved the carotid circulation bilaterally in all; 6 had posterior circulation and 11 had extracranial involvement. Arteriopathy distribution was symmetric in 24/31. CASCADE categories were 3A in 19, 3B in 5, 3C in 5, and 7 in 2. After a median of 35 months, 14 had had progression of arteriopathy. Patients categorized as CASCADE 3A (moyamoya) had significantly shorter time to recurrence than other groups. CONCLUSION: Young children with bilateral cerebral arteriopathies (particularly meeting criteria for CASCADE 3A) have a malignant course, with frequent recurrent events, progressive disease, and poor outcomes. Current classifications are limited in characterizing disease in many cases. Symmetric involvement suggests these arteriopathies may be developmentally determined, while systemic involvement suggests potential genetic etiology.

Emergency management of ischemic stroke in children.

OPINION STATEMENT: Children who present with acute neurological symptoms suggestive of a stroke need immediate clinical assessment and urgent neuroimaging to confirm diagnosis. Magnetic resonance imaging (MRI) is the investigation of first choice due to limited sensitivity of computed tomography (CT) for detection of ischaemia. Acute monitoring should include monitoring of blood pressure and body temperature, and neurological observations. Surveillance in a paediatric high dependency or intensive care unit and neurosurgical consultation are mandatory in children with large infarcts at risk of developing malignant oedema or haemorrhagic transformation. Thrombolysis and/or endovascular treatment, whilst not currently approved for use in children, may be considered when stroke diagnosis is confirmed within 4.5 to 6 h, provided there are no contraindications on standard adult criteria. Standard treatment consists of aspirin, but anticoagulation therapy is frequently prescribed in stroke due to cardiac disease and extracranial dissection. Steroids and immunosuppression have a definite place in children with proven vasculitis, but their role in focal arteriopathies is less clear. Decompressive craniotomy should be considered in children with deteriorating consciousness or signs of raised intracranial pressure.