Inter-Rater Reliability of the CASCADE Criteria: Challenges in Classifying Arteriopathies.

BACKGROUND AND PURPOSE: There are limited data about the reliability of subtype classification in childhood arterial ischemic stroke, an issue that prompted the IPSS (International Pediatric Stroke Study) to develop the CASCADE criteria (Childhood AIS Standardized Classification and Diagnostic Evaluation). Our purpose was to determine the CASCADE criteria's reliability in a population of children with stroke. METHODS: Eight raters from the IPSS reviewed neuroimaging and clinical records of 64 cases (16 cases each) randomly selected from a prospectively collected cohort of 113 children with arterial ischemic stroke and classified them using the CASCADE criteria. Clinical data abstracted included history of present illness, risk factors, and acute imaging. Agreement among raters was measured by unweighted κ statistic. RESULTS: The CASCADE criteria demonstrated a moderate inter-rater reliability, with an overall κ statistic of 0.53 (95% confidence interval [CI]=0.39-0.67). Cardioembolic and bilateral cerebral arteriopathy subtypes had much higher agreement (κ=0.84; 95% CI=0.70-0.99; and κ=0.90; 95% CI=0.71-1.00, respectively) than cases of aortic/cervical arteriopathy (κ=0.36; 95% CI=0.01-0.71), unilateral focal cerebral arteriopathy of childhood (FCA; κ=0.49; 95% CI=0.23-0.76), and small vessel arteriopathy of childhood (κ=-0.012; 95% CI=-0.04 to 0.01). CONCLUSIONS: The CASCADE criteria have moderate reliability when used by trained and experienced raters, which suggests that it can be used for classification in multicenter pediatric stroke studies. However, the moderate reliability of the arteriopathic subtypes suggests that further refinement is needed for defining subtypes. Such revisions may reduce the variability in the literature describing risk factors, recurrence, and outcomes associated with childhood arteriopathy.

Paradoxical centrally increased diffusivity in perinatal arterial ischemic stroke.

BACKGROUND: Restricted diffusion on acute MRI is the diagnostic standard for perinatal arterial ischemic stroke. In a subset of children with perinatal arterial ischemic stroke, primarily those with large infarct volumes, we noted a core of centrally increased diffusivity with a periphery of restricted diffusion. OBJECTIVE: Given the paradoxical diffusion-weighted imaging (DWI) appearance observed in some children with perinatal arterial ischemic stroke, we sought to determine its significance and hypothesized that: (1) centrally increased diffusivity is associated with larger infarcts in perinatal arterial ischemic stroke and (2) this tissue is irreversibly injured (infarcted). MATERIALS AND METHODS: We reviewed all perinatal arterial ischemic stroke cases in a prospective cohort study from Aug. 1, 2000, to Jan. 1, 2012. Infarct volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. The Mann-Whitney U test was used to compare means between groups. RESULTS: Of 25 eligible cases, centrally increased diffusivity was seen in 4 (16%). Cases with centrally increased diffusivity had larger average infarct volumes (mean 117,182 mm(3) vs. 36,995 mm(3); P = 0.008), higher average apparent diffusion coefficient (ADC) values in the infarct core (1,679 × 10(-6) mm(2)/s vs. 611 × 10(-6) mm(2)/s, P < 0.0001), and higher ADC ratio (1.2 vs. 0.5, P < 0.0001). At last clinical follow-up, children with perinatal arterial ischemic stroke and centrally increased diffusivity were more often treated for ongoing seizures (75% vs. 0%; P < 0.001) than those without. CONCLUSION: Centrally increased diffusivity was associated with larger stroke volume and the involved tissue was confirmed to be infarcted on follow-up imaging. Radiologists should be aware of this unusual appearance of perinatal arterial ischemic stroke in order to avoid underestimating infarct volume or making an incorrect early diagnosis.

Inflammatory predictors of neurologic disability after preterm premature rupture of membranes.

OBJECTIVE: The maternal-fetal inflammatory response contributes to both preterm premature rupture of membranes (PPROM) and adverse neurological outcomes. Additionally, cytokines associated with fetal placental inflammation can be detrimental to brain development regardless of inciting infection. We investigated whether differential patterns of cytokine markers in maternal and fetal plasma samples reflect subtypes of placental inflammation and neurological outcomes at 6 months in infants born to mothers with PPROM. STUDY DESIGN: Within a prospective cohort study of 25 women with PPROM, plasma cytokines (interleukin [IL]-1ß, IL-6, IL-8, and tumor necrosis factor-α) were measured by enzyme-linked immunosorbent assay from maternal blood samples at rupture and delivery, and from fetal umbilical cord blood samples. Patterns of cytokine expression were correlated with specific placenta pathologies. Infants underwent cranial ultrasound after birth and standardized neurological examinations at 6 months' corrected gestational age. Predictors of inflammation and adverse neurological outcome were assessed by logistic regression, adjusting for gestational age at birth. RESULTS: Inflammation of the fetal side of the placenta was associated with elevated maternal IL-6 and IL-8 at delivery and fetal IL-1ß, IL-6, IL-8, and tumor necrosis factor-α. Worse neurological outcome at 6 months was associated with inflammation of the fetal side of the placenta and shorter duration from rupture of membrane to delivery, independent of gestational age at birth or cranial ultrasound results. CONCLUSION: Our findings support the connection between fetal inflammation with adverse neurological outcome with PPROM, regardless of cranial ultrasound results. Further longitudinal studies are needed to adequately examine these patterns, and will aid in risk assessment and intervention strategies.

Diagnosis and acute management of perinatal arterial ischemic stroke.

Perinatal arterial ischemic stroke (PAIS) can be an unrecognized cause of short- and long-term neurologic disability. Focal clonic seizure in the newborn period is the most common clinical presentation of PAIS. MRI is optimal in diagnosing PAIS; negative cranial ultrasound or CT does not rule out PAIS. Given the low rate of recurrence in combination with risk factors thought to be isolated to the maternal-fetal unit, anticoagulation or antiplatelet treatment is usually not recommended. The majority of newborns with PAIS do not go on to develop epilepsy, although further research is warranted in this area. Long-term morbidity, including motor, cognitive, and behavioral disabilities, can follow PAIS, necessitating early recognition, diagnosis, and therapy initiation.

The methylenetetrahydrofolate reductase polymorphism (MTHFR c.677C>T) and elevated plasma homocysteine levels in a U.S. pediatric population with incident thromboembolism.

OBJECTIVE: Elevated plasma homocysteine (tHcy) and the MTHFR c.677C>T variant have been postulated to increase the risk of venous thromboembolism (VTE), although mechanisms and implications to pediatrics remain incompletely understood. The objectives of this study were to determine the prevalences of elevated tHcy and MTHFR variant in a pediatric population with VTE or arterial ischemic stroke (AIS), and to determine associations with thrombus outcomes. STUDY DESIGN: Subjects were enrolled in an institution-based prospective cohort of children with VTE or AIS. Inclusion criteria consisted of objectively confirmed thrombus, ≤21years at diagnosis, tHcy measured and MTHFR c.677C>T mutation analysis. Clinical and laboratory data were collected. Frequencies for elevated tHcy and MTHFR variant were compared with NHANES values for healthy US children and also between study groups (VTE vs AIS, provoked vs idiopathic) and by age. RESULTS: The prevalences of hyperhomocysteinemia or MTHFR variant were not increased in comparison to NHANES. tHcy did not differ between those with wild-type MTHFR versus either c.677C>T heterozygotes or homozygotes. There was no association between tHcy or MTHFR variant and thrombus outcomes. CONCLUSION: In this cohort of US children with VTE or AIS, neither the prevalence of hyperhomocysteinemia nor that of MTHFR variant was increased relative to reference values, and adverse thrombus outcomes were not definitively associated with either. While it is important to consider that milder forms of pyridoxine-responsive classical homocystinuria will be detected only by tHcy, we suggest that routine testing of MTHFR c.677C>T genotype as part of a thrombophilia evaluation in children with incident thromboembolism is not warranted until larger studies have been performed in order to establish or refute a link between MTHFR and adverse outcomes.

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children.

Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days - <21 years at onset; n=43) and healthy controls (n=127) were recruited for plasma sampling and laboratory determinations. Cases were followed for recurrence in a prospective cohort study. The median lipoprotein (a) concentration did not differ between groups [cases: median 18.0 nmol/L (7.5 mg/dL) and observed range 0.9-259 nmol/L (0.38-108.0 mg/dL), controls: 20.4 nmol/L (8.5 mg/dL) and 0.2-282 nmol/L (0.08-117.5 mg/dL); P=0.62]. While odds of incident stroke were not significantly increased, risks of recurrent arterial ischemic stroke were each more than ten-times increased for lipoprotein(a) >90(th) percentile of race-specific reference values and apolipoprotein (a) <10(th) percentiles [odds ratio=14.0 (95% confidence interval: 1.0-184), P=0.05 and odds ratio=12.8 (1.61-101), P=0.02]. Statistically significant but weak correlations were observed between euglobulin lysis time and both lipoprotein (a) level (r=0.18, P=0.03) and apolipoprotein (a) size (r= -0.26, P=0.002). In conclusion, elevated lipoprotein (a) and small apolipoprotein (a) potently increase the risk of recurrent arterial ischemic stroke in children, with a mechanism only partially attributable to impaired fibrinolysis. Collaborative studies are warranted to investigate these findings further and, more broadly, to establish key risk factors for incident and recurrent arterial ischemic stroke in children.

The institution-based prospective inception cohort study: design, implementation, and quality assurance in pediatric thrombosis and stroke research.

The development of well-designed cohort studies in rare diseases can lead to the discovery of new risk factors and prognostic markers, enhance understanding of natural history and outcomes, and provide preliminary data for randomized controlled trials of treatment strategies. Designing a robust cohort requires substantial upfront design and planning. Ideally, a cohort study of diseased individuals follows patients prospectively from the time of diagnosis (i.e., from the disease's inception). The objective of this article is to discuss the design and implementation of an institution-based prospective inception cohort study, with applied examples in pediatric stroke and thrombosis. Furthermore, we will discuss the ongoing management and quality assurance mechanisms necessary to optimize such a study. Although the resources necessary to implement a prospective inception cohort study are large, this approach can provide critical observational evidence on natural history and prognostic factors. Following multicenter validation, its findings can inform the design and execution of much-needed randomized controlled clinical trials.

Arteriopathy, D-dimer, and risk of poor neurologic outcome in childhood-onset arterial ischemic stroke.

OBJECTIVE: To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS). STUDY DESIGN: Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Children's Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. RESULTS: Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02). CONCLUSION: Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.

Late cytotoxic edema in 2 children with hemiplegia: hemiplegic migraine or stroke?

Hemiplegic migraine (HM) is a rare variant of migraine with aura, characterized by migrainous headache and fully reversible motor deficit within 24 hours. Both sporadic and familial forms of HMs are genetically heterogenous with little information on neuroimaging during and after acute attacks. We report 2 cases of children with presumed HM and late cytotoxic edema.

Towards a consensus-based classification of childhood arterial ischemic stroke.

BACKGROUND AND PURPOSE: The implementation of uniform nomenclature and classification in adult arterial ischemic stroke (AIS) has been critical for defining outcomes and recurrence risks according to etiology and in developing risk-stratified treatments. In contrast, current classification and nomenclature in childhood AIS are often overlapping or contradictory. Our purpose was to develop a comprehensive consensus-based classification system for childhood AIS. METHODS: Using a modified-Delphi method, members of the International Pediatric Stroke Study (IPSS) developed the Childhood AIS Standardized Classification And Diagnostic Evaluation (CASCADE) criteria. Two groups of pediatric stroke specialists from the IPSS classified 7 test cases using 2 methods each: (1) classification typical of the individual clinician's current clinical practice; and (2) classification based on the CASCADE criteria. Group 1 underwent in-person training in the utilization of the CASCADE criteria. Group 2 classified the same cases via an online survey, including definitions but without training. Inter-rater reliability (IRR) was assessed via multi-rater unweighted κ-statistic. RESULTS: In Group 1 (with training), IRR was improved using CASCADE criteria (κ=0.78, 95% CI=[0.49, 0.94]), compared with typical clinical practice (κ=0.40, 95% CI=[0.11, 0.60]). In Group 2 (without training), IRR was lower than among trained raters (κ=0.61, 95% CI=[0.29, 0.77]), but higher than current practice (κ=0.23, 95% CI=[0.03, 0.36]). CONCLUSIONS: A new, consensus-based classification system for childhood AIS, the CASCADE criteria, can be used to classify cases with good IRR. These preliminary findings suggest that the CASCADE criteria may be particularity useful in the setting of prospective multicenter studies in childhood-onset AIS, where standardized training of investigators is feasible.

Symptomatic neonatal arterial ischemic stroke: the International Pediatric Stroke Study.

BACKGROUND: Neonatal arterial ischemic stroke (AIS) has emerged as a leading cause of perinatal brain injury, cerebral palsy, and lifelong disability. The pathogenesis is poorly understood, which limits the development of treatment and prevention strategies. Multicenter studies must define epidemiology, risk factors, treatment practices, and outcomes to advance clinical trials and improve the adverse outcomes suffered by most survivors. METHODS: The International Pediatric Stroke Study is a global research initiative of 149 coinvestigators (30 centers in 10 countries). Patients with clinical and neuroimaging confirmation of symptomatic neonatal AIS were enrolled (2003-2007). Standardized, Web-based data entry collected clinical presentations, risk factors, investigations, treatments, and early outcomes. We examined predictors of infarct characteristics and discharge outcome by using multivariate logistic regression. RESULTS: Two hundred forty-eight neonates were studied (57% male, 10% premature). Most of them presented with seizure (72%) and nonfocal neurologic signs (63%). MRI was completed for 92% of the infants, although <50% had vascular imaging. Infarcts preferentially involved the anterior circulation and left hemisphere and were multifocal in 30%. Maternal health and pregnancies were usually normal. Neonates often required resuscitation (30%) and had systemic illnesses (23%). Cardiac and prothrombotic abnormalities were identified in <20% of the infants. Antithrombotic treatment was uncommon (21%) and varied internationally. Half (49%) of the infants had deficits at discharge, and data on their long-term outcomes are pending. CONCLUSIONS: Newborns with AIS are often systemically sick, whereas their mothers are usually healthy. Definitive causes for most neonatal AISs have not been established, and large-scale case-control studies are required to understand pathogenesis if outcomes are to be improved.

Craniocervical arterial dissection in children: diagnosis and treatment.

OPINION STATEMENT: Diagnosis of craniocervical arterial dissection (CCAD) in children begins with a careful history and physical in a child with a transient ischemic attack (TIA) or arterial ischemic stroke (AIS). The extent of radiologic evaluation for suspected CCAD is based upon careful consideration of the risks associated with the best imaging techniques, weighed against the benefits of enhanced vascular imaging with better diagnostic sensitivity. Although conventional angiography (CA) and CT angiography (CTA) have a higher sensitivity than magnetic resonance angiography (MRA), they are accompanied by risks: for CA, femoral hematoma, femoral arterial pseudoaneurysm, recurrent AIS, and radiation exposure; for CTA, radiation. For children (non-neonates) with suspected CCAD, MRI with MRA is recommended as the first-line imaging study. MRI usually includes diffusion-weighted, FLAIR, and T1 images of the brain, and T1 or T2 fat-saturation axial imaging through the neck. MRA should include 3D time-of-flight MRA of the head and neck (from the aortic arch through the circle of Willis). Contrast-enhanced MRA should be highly considered in neck imaging. If MRI/MRA is equivocal, CCAD is strongly suspected but not detected on MRI/MRA (especially in the posterior circulation), or the child has recurrent events, additional imaging of the craniocervical vasculature is likely warranted. Individual clinical circumstances warrant careful, case-by-case consideration. Treatment of CCAD in children is challenging and differs for intracranial and extracranial dissections. In extracranial CCAD, we most commonly use anticoagulation for 6 weeks to 6 months in patients with TIA or AIS. Typically, unfractionated heparin is used in the acutely ill patient at heightened risk for bleeding (because of its short half-life), whereas low-molecular-weight heparin (LMWH) or warfarin are reserved for the stable patient. If the history is suspicious for dissection (head and neck trauma, recent cervical chiropractic manipulation, recent car accident, or neck pain), we consider treatment for dissection even with normal MRI/MRA. For patients with CCAD with a stroke size greater than one third to one half of the middle cerebral artery territory (or other bleeding risk factors) and extracranial CCAD, in whom there is concern about heightened risk for hemorrhagic conversion, we commonly use aspirin therapy during the acute phase. Regardless of their treatment in the initial weeks to months, we subsequently treat all patients with aspirin for 1 year after their event, and sometimes longer if they have other risk factors. Interventional techniques, such as extracranial cerebral arterial stent placement or selective occlusion, are understudied in children. Interventional techniques are typically reserved for patients who fail aggressive medical management and have recurrent TIA or AIS. The diagnosis and treatment of intracranial dissection is extraordinarily challenging in children, in whom inflammatory intracranial arteriopathies are common. When intracranial arteriopathy is clearly associated with dissection, the clinician should look for the presence of subarachnoid hemorrhage and/or dissecting aneurysm. Treatment decisions should be made by a multidisciplinary pediatric stroke team, given the lack of data in this area. Intracranial cerebral artery stent placement carries high risk and is not recommended for intracranial CCAD in children. Most importantly, we educate all children with CCAD and their parents about the paucity of evidence in the treatment of this disease, the risks of enhanced imaging techniques such as CTA or CA, and the challenges involved in weighing the risks of aggressive therapies and interventions against the costs of unclear diagnosis and potentially ineffective treatments. We also educate our patients with CCAD about the signs and symptoms of recurrence and the importance of emergent evaluation.

Institution-based prospective inception cohort studies in neonatal rare disease research.

In rare diseases, wherein the conduct of randomized controlled clinical trials (RCTs) is challenging, cohort studies can offer important, and, in certain instances, high quality (e.g. the prospective inception cohort study) evidence on relationships among risk factors, treatments, and outcomes. The objective of this perspective article is to provide an overview of salient issues in the design and application of institution-based prospective inception cohort studies in neonatal rare disease research, with emphasis on quality assurance measures. Rigorous implementation of the prospective inception cohort study is challenging, and application to neonates renders it even more difficult. However, when performed collaboratively among institutions employing uniform methods and quality assurance mechanisms, institution-based prospective inception cohort studies can provide optimal observational evidence to inform the design and execution of RCTs in this special pediatric population.

Neurocognitive outcomes following neonatal encephalopathy.

Neonatal encephalopathy (NE) from perinatal asphyxia (PA) has long been recognized as an important cause of lasting motor impairment in term newborns. NE has also, more recently, been implicated as an important risk factor for cognitive and behavioral difficulties as these children age. Newborns with mild NE appear to have normal neurocognitive outcomes, while those survivors with severe NE tend to have profound impediments. Yet, newborns with moderate NE seem to exhibit a wide range of cognitive outcomes - regardless of motor function - making prognostication in these children difficult in the newborn period. Since deficits are often subtle and remote from the initial injury, cognitive impairment is likely underdiagnosed in survivors of moderate perinatal NE. Therefore, it is important for ongoing formal neuropsychological evaluation, as well as parental and teacher education, to help aid in the cognitive and behavioral rehabilitation resulting from NE and perinatal hypoxic-ischemic brain injury.

Biomarkers of hypercoagulability and inflammation in childhood-onset arterial ischemic stroke.

OBJECTIVE: To test the hypothesis that acute elevations of biomarkers of hypercoagulability and inflammation are common in children with arterial ischemic stroke (AIS), particularly among etiologic subtypes that carry an increased risk of recurrent stroke. STUDY DESIGN: In this prospective/retrospective institutional-based cohort study of acute childhood-onset AIS (n = 50) conducted between 2005 and 2009, D-dimer, factor VIII (FVIII) activity, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were serially evaluated at the time of clinical blood sampling. Patients were classified by stroke subtype as cardioembolic, moyamoya, non-moyamoya arteriopathy, or other. RESULTS: Both D-dimer and CRP were frequently elevated in acute childhood-onset AIS and exhibited a decreasing trend with time. Acute D-dimer levels were significantly higher in cardioembolic AIS compared with noncardioembolic AIS (median, 2.04 microg/mL [range 0.54-4.54 microg/mL] vs 0.32 microg/mL [0.22-3.18 microg/mL]; P = .002). At an optimal threshold of > or = 0.50 microg/mL, the sensitivity and specificity of D-dimer for cardioembolic subtype were 78% and 79%, respectively. CONCLUSIONS: Our findings identify D-dimer and CRP as candidate biomarkers for etiology and prognosis in childhood-onset AIS. Further studies should investigate the role of these and other biomarkers of hypercoagulability and inflammation in childhood-onset AIS.

Multiple intracranial aneurysms and moyamoya disease associated with microcephalic osteodysplastic primordial dwarfism type II: surgical considerations.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by extremely small stature and microcephaly, and is associated in 25% of patients with intracranial aneurysms and moyamoya disease. Although aneurysmal subarachnoid hemorrhage and stroke are leading causes of morbidity and death in these patients, MOPD II is rarely examined in the neurosurgical literature. The authors report their experience with 3 patients who presented with MOPD II, which includes a patient with 8 aneurysms (the most aneurysms reported in the literature), and the first report of a patient with both moyamoya disease and multiple aneurysms. The poor natural history of these lesions indicates aggressive microsurgical and/or endovascular therapy. Microsurgery, whether for aneurysm clip placement or extracranial-intracranial bypass, is challenging due to tight surgical corridors and diminutive arteries in these patients, but is technically feasible and strongly indicated when multiple aneurysms must be treated or cerebral revascularization is needed.

Prevalence and predictors of perinatal hemorrhagic stroke: results from the kaiser pediatric stroke study.

OBJECTIVES: Predictors for perinatal arterial ischemic stroke include both maternal and intrapartum factors, but predictors of perinatal hemorrhagic stroke have not been studied. We sought to determine both the prevalence and predictors of perinatal hemorrhagic stroke within a large, multiethnic population. PATIENTS AND METHODS: We performed a case-control study nested within the cohort of all infants born from 1993 to 2003 in the Northern California Kaiser Permanente Medical Care Program, a health maintenance organization providing care for >3 million members. Cases of symptomatic perinatal hemorrhagic stroke and perinatal arterial ischemic stroke in neonates (28 weeks' gestational age through 28 days of life) were identified through electronic searches of diagnosis and radiology databases and confirmed by medical chart review. Three controls per case were randomly selected and matched on birth year and facility. This analysis included cases of perinatal hemorrhagic stroke (intracerebral hemorrhage or subarachnoid hemorrhage, excluding pure intraventricular hemorrhage) and all controls. Predictors of perinatal hemorrhagic stroke were assessed by using logistic regression, adjusting for the matching criteria. RESULTS: Among 323 532 live births, we identified 20 cases of perinatal hemorrhagic stroke (19 intracerebral hemorrhage and 1 subarachnoid hemorrhage), which yielded a population prevalence for perinatal hemorrhagic stroke of 6.2 in 100 000 live births. Cases presented with encephalopathy (100%) and seizures (65%). Perinatal hemorrhagic stroke was typically unifocal (74%) and unilateral (83%). Etiologies included thrombocytopenia (n = 4) and cavernous malformation (n = 1); 15 (75%) were idiopathic. Univariate predictors of perinatal hemorrhagic stroke included male gender, fetal distress, emergent cesarean delivery, prematurity, and postmaturity but not birth weight. When entered into a multivariate model, fetal distress and postmaturity continued to be independent predictors. CONCLUSIONS: Fetal distress is an independent predictor of perinatal hemorrhagic stroke, perhaps suggesting a prenatal event. Postmaturity also predicts perinatal hemorrhagic stroke, an association not explained by large birth weight in our study.

Treatment of childhood arterial ischemic stroke.

Traditional risk factors associated with adult arterial ischemic stroke (AIS; ie, hypertension, hyperlipidemia, diabetes, smoking, and atherosclerosis) are relatively rare in children. Childhood AIS is instead associated with a variety of conditions including cerebral arteriopathies, congenital heart disease, infection, head and neck trauma, sickle cell anemia, and prothrombotic abnormalities. Although the pathophysiology and outcomes of adult AIS differ significantly from those in childhood AIS, therapeutic management remains similar, largely because of the paucity of evidence from devoted pediatric observational studies and clinical trials. The purpose of this article is to review the current guidelines and evidence in the treatment of childhood AIS, within the context of that which exists in adult AIS. Medical management of hypoxia, hyperglycemia, fever, blood pressure, and increased intracranial pressure has been insufficiently investigated in childhood stroke, resulting in a lack of guidance in these areas. Although acute antithrombotic management in childhood AIS has received relatively greater attention in published recommendations, it is based almost exclusively on consensus and expert opinion, and differs considerably among existing pediatric guidelines. Rehabilitation therapy in childhood AIS has great potential for meaningful improvements in long-term outcomes, especially given the plasticity of the young brain; however, little guidance for rehabilitative measures is provided by published recommendations. Ongoing and future multicenter cohort study efforts, and ultimately devoted pediatric clinical trials, will be essential to establish comprehensive evidence-based guidelines for the treatment of childhood AIS.

Pain during Mogen or PlastiBell circumcision.

UNLABELLED: Routine neonatal circumcision can be a painful procedure. Although analgesia for circumcision has been studied extensively, there are few studies comparing which surgical technique may be associated with the least pain and discomfort when carried out by pediatric trainees. OBJECTIVE: We studied two commonly used techniques for circumcision to determine which was associated with less pain and discomfort. STUDY DESIGN: In a randomized, prospective, but not blinded study, newborns were circumcised either by Mogen clamp or by PlastiBell. All received dorsal nerve blocks with lidocaine. Fifty-nine well, term, newborn infants at San Francisco General Hospital were studied from 1997 to 1998. Circumcisions were carried out mostly by interns and residents in family practice and pediatrics. Pain was assessed by measuring duration of the procedure and by a simple behavioral score done sequentially. RESULTS: Dorsal nerve blocks were judged to be fully effective in over 70% of cases. Neither Mogen nor PlastiBell was associated with greater pain per 3-minute time period, but the PlastiBell technique on average took nearly twice as long as the Mogen procedure (20 vs 12 minutes). We judged that 60% of the infants had pain or discomfort associated with the procedure that was excessive. Residents and interns universally preferred the Mogen technique over the PlastiBell because of the former's simplicity. CONCLUSION: During the procedure, Mogen circumcision is associated with less pain and discomfort, takes less time, and is preferred by trainees when compared with the PlastiBell.