Stroke transcranial Doppler in children with human immunodeficiency virus.

AIMS: To describe stroke syndromes and transcranial Doppler (TCD) findings in children with human immunodeficiency virus (HIV) and examine the associations between TCD and clinical and laboratory data. METHOD: We enrolled 42 children (24 males, 18 females) with HIV (median age=7y 6mo; 2y 7mo-15y 6mo), with and without stroke who underwent a TCD examination of the anterior and posterior circulations to derive time-averaged maximum mean velocity (TAMMV) measurements for comparison with previous studies. Clinical and laboratory variables were extracted from the medical records. RESULTS: Of the 42 children with HIV, five had right-sided hemiparesis, three had chronic lung disease, two occurred post-varicella infection, one after herpetic oral ulceration, and one had a poorly functioning left ventricle. Neuroimaging showed middle cerebral artery (MCA) TAMMV greater than 200cm/s, moyamoya-like arteriopathy, left basal ganglia infarction with ipsilateral stenosis, hygroma consistent with venous thrombosis, and a hyperdense left MCA. Eight neurologically asymptomatic children had atypical TCD. The CD4 cell count was non-significantly lower in 6 out of 30 children with atypical TCD (median=21.5; interquartile range=16.1-26.5) compared with the remainder (median=29; interquartile range=21.3-35.0; p=0.09). INTERPRETATION: A variety of stroke syndromes occur in children with HIV. TCD suggests atypical intracranial vessels and/or haemodynamics in some children with HIV infection, consistent with vasculopathy, possibly related directly to immunodeficiency and/or infection. WHAT THIS PAPER ADDS: A range of stroke syndromes are found in children with human immunodeficiency virus (HIV). Transcranial Doppler (TCD) velocities in HIV are commonly outside the range for typically developing children. TCD and neuroimaging data in children with HIV suggest intracranial vasculopathy as one mechanism for stroke. CD4 cell count is non-significantly lower in children with HIV and atypical TCD.

Safety of anticoagulants in children with arterial ischemic stroke.

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 HI1 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.

Basilar artery strokes in children: good outcomes with conservative medical treatment.

AIM: To describe outcomes and outcome predictors in childhood basilar artery stroke (BAS). METHOD: We prospectively enrolled children with BAS with or without basilar artery occlusion (BAO) in the Toronto Children's Stroke Registry from 1992 to 2009. We assessed presenting features and outcomes including Pediatric Stroke Outcome Measure scores. RESULTS: Among 578 children with acute arterial ischemic stroke, 27 had BAS (4.6% including neonates, 6% excluding neonates). Twenty-four (14 males, 10 females) children met study criteria (mean age at stroke was 8 y 10 mo; range 0-17 y). Eleven children had BAO. Aspirin or anticoagulation was given to 15 children. None received tissue plasminogen activator or endovascular treatments. At mean follow-up (3 y 2 mo, range 1 mo-11 y 8 mo), 12 had a 'good outcome' (seven normal, five insignificant deficit) and 12 had 'poor outcome' (10 moderate or severe deficit, two acute deaths). Larger infarct size (≥50% of axial brainstem diameter) independently predicted poor outcome (p=0.02; odds ratio 21.2, 95% confidence interval 1.6-274.9) but not BAO, altered level of consciousness, or age. INTERPRETATION: Compared with adults, in childhood BAS death is rare and survivors frequently have good outcomes. Aggressive endovascular interventions may not be justifiable in this population.

Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study.

OBJECTIVE: Clinical trials are lacking in pediatric cerebral sinovenous thrombosis (CSVT). Neonates and children increasingly receive anticoagulant therapy (ACT) based on adult studies. Safety data for ACT in pediatric CSVT are scant and urgently needed. The objective was to assess the safety and outcome of ACT in pediatric CSVT. METHODS: In a single-center prospective study, neonates and children with CSVT received ACT (standard/low molecular weight heparin, warfarin) by standardized protocol. A study neuroradiologist (M.S.) assessed all initial and follow-up neuroimaging for intracranial hemorrhage (ICH), thrombus propagation, and recanalization. Clinical outcome was assessed with the Pediatric Stroke Outcome Measure. RESULTS: Among 162 pediatric patients, 85 received ACT at diagnosis, including 29/83 (35%) neonates and 56/79 (71%) children. Major hemorrhage occurred in 6% (6/99) of treated patients, including 14% (3/21 neonates, 2/15 children) with and 2% (0/17 neonates, 1/46 children) without pretreatment ICH. ACT-associated bleeds were all nonfatal, and clinical outcome was favorable in 50%, similar to the remaining patients (53%). Early follow-up imaging demonstrated thrombus propagation in 11/57 neonates (10/35 [28%] without and 1/22 [4%] with ACT [p = 0.037]) and 10/63 children (7/19 [37%] without and 3/44 [7%] with ACT [p = 0.006]). Propagation was associated with new venous infarcts in 10% neonates and 40% children and worse clinical outcome in children (p = 0.053). Recanalization occurred earlier and more completely in neonates (p = 0.002). Clinical outcome was unfavorable in 47%. INTERPRETATION: In pediatric CSVT, ACT appears safe. Nontreatment with ACT is associated with thrombus propagation, observed in (1/4) of untreated neonates and over (1/3) of children. Anticoagulants merit strong consideration in pediatric CSVT.

Delay to diagnosis in acute pediatric arterial ischemic stroke.

BACKGROUND AND PURPOSE: For the clinician, the diagnosis of arterial ischemic stroke (AIS) in children is a challenge. Prompt diagnosis of pediatric AIS within 6 hours enables stroke-specific thrombolytic and neuroprotective strategies. METHODS: We conducted a retrospective study of prospectively enrolled consecutive cohort of children with AIS, admitted to The Hospital for Sick Children, Toronto, from January 1992 to December 2004. The data on clinical presentation, symptom onset, emergency department arrival, neuroimaging and stroke diagnosis were recorded. The putative predictors of delayed diagnosis were selected a priori for analysis. RESULTS: A total of 209 children with AIS were studied. The median interval from symptom onset to AIS diagnosis was 22.7 hours (interquartile range: 7.1 to 57.7 hours), prehospital delay (symptom onset to hospital arrival) was 1.7 hours (interquartile range: 49 minutes to 8.1 hours), and the in-hospital delay (presentation to diagnosis) was 12.7 hours (interquartile range: 4.5 to 33.5 hours). The initial assessment was completed in 16 minutes and initial neuroimaging in 8.8 hours. The diagnosis of AIS was suspected on initial assessment in 79 (38%) children and the initial neuroimaging diagnosed AIS in 47%. The parent's help seeking action, nonabrupt onset of symptoms, altered consciousness, milder stroke severity, posterior circulation infarction and lack of initial neuroimaging at a tertiary hospital were predictive delayed AIS diagnosis. CONCLUSIONS: In the diagnosis of AIS, significant prehospital and in-hospital delays exist in children. Several predictors of the delayed AIS diagnosis were identified in the present study. Efforts to target these predictors can reduce diagnostic delays and optimize the management of AIS in children.

Presumed perinatal ischemic stroke: vascular classification predicts outcomes.

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.

Association Between Prolonged Seizures and Malignant Middle Cerebral Artery Infarction in Children With Acute Ischemic Stroke.

BACKGROUND: Malignant middle cerebral artery infarct syndrome is a potentially fatal complication of stroke that is poorly understood in children. We studied the frequency, associated characteristics, and outcomes of this condition in children. METHODS: Children, aged two months to 18 years with acute middle cerebral artery infarct diagnosed at our center between January 2005 and December 2012 were studied. Associations with malignant middle cerebral artery infarct syndrome were sought, including age, seizures, neurological deficit severity (Pediatric National Institute of Health Stroke Severity Score), stroke etiology, fever, blood pressure, blood glucose, infarct location, infarct volume (modified pediatric Alberta Stroke Program Early Computed Tomography Score), and arterial occlusion. Death and neurological outcomes were determined. RESULTS: Among 66 children with middle cerebral artery stroke, 12 (18%) developed malignant middle cerebral artery infarct syndrome, fatal in three. Prolonged seizures during the first 24 hours (odds ratio, 25.51; 95% confidence interval, 3.10 to 334.81; P = 0.005) and a higher Pediatric National Institute of Health Stroke Severity Score (odds ratio, 1.22; 95% confidence interval, 1.08 to 1.45; P = 0.006) were independently associated with malignant middle cerebral artery infarct syndrome. All children aged greater than two years with a Pediatric National Institute of Health Stroke Severity Score ≥8 and initial seizures ≥5 minutes duration developed malignant middle cerebral artery infarct syndrome (100%). CONCLUSIONS: Malignant middle cerebral artery infarct syndrome affects nearly one in five children with acute middle cerebral artery stroke. Children with higher Pediatric National Institute of Health Stroke Severity Scores and prolonged initial seizures are at greatly increased risk for malignant middle cerebral artery infarct syndrome. Children with middle cerebral artery infarcts warrant intensive neuroprotective management and close monitoring to enable early referral for hemicraniectomy surgery.

Long-term outcomes of pediatric ischemic stroke in adulthood.

This population-based study assesses the long-term impact of childhood stroke on function and independence in young adults. We undertook a cross-sectional outcome study of patients with arterial ischemic stroke and cerebral sinovenous thrombosis, beyond 18 years of age. We studied 26 patients; 21 arterial stroke, 5 cerebral sinovenous thrombosis, with 16 females. Mean age at assessment was 21.5 years, and mean follow-up time was 10.8 years. According to the modified Rankin Scale, final outcomes were 37% normal, 42% mild, 8% moderate, and 15% severe deficits. Risk factors for abnormal functional outcome included arterial ischemic stroke, presence of arteriopathy, and 1-year poststroke Pediatric Stroke Outcome Measure score ≥ 2 (P < .05). Most (77-84%) were independent in driving, relationships, and employment. Functional status at 1 year poststroke strongly predicts long-term outcome. Mental illness in one-quarter of young adults surviving childhood stroke represents an important direction for research.

A prospective outcome study of neonatal cerebral sinovenous thrombosis.

Neonatal cerebral sinovenous thrombosis is a frequent contributor to neonatal mortality and morbidity. Treatment is controversial, and reported clinical outcomes vary widely. Newborns with radiologically confirmed neonatal cerebral sinovenous thrombosis from 1992 to 2009 were prospectively followed in our Children's Stroke Clinic for standardized outcomes, including the Pediatric Stroke Outcome Measure. Outcomes were available in 90 of 104 (87%) neonates. Early outcomes included cerebral sinovenous thrombosis-associated death (5) and thrombus propagation (15 [6 associated with new venous infarcts]). Lack of anticoagulation predicted propagation (RR = 13; P = .0007). Complete thrombus recanalization occurred in 90% by 3 months. Late outcomes (median, 2.5 years) were epilepsy (15) and neurological disability (50), which included moderate-severe language (43), sensorimotor (38), and cognitive/behavioral (24) deficits. Overall, 61% had poor outcome (death/any deficit). Concurrent neurological comorbidity at diagnosis (odds ratio = 2.8; P = .029) predicted poor outcome. Clinical trials are urgently needed to establish more effective treatment strategies.

Risk factors and presentations of periventricular venous infarction vs arterial presumed perinatal ischemic stroke.

OBJECTIVE: To determine whether clinical presentations and risk factor profiles differ between periventricular venous infarction (PVI) and arterial presumed perinatal ischemic stroke (APPIS). DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 59 children with presumed perinatal ischemic stroke (PPIS) from the SickKids Children's Stroke Program who were carried to term (63% boys). SETTING: Single tertiary care center subspecialty program. INTERVENTIONS: Participants had validated magnetic resonance imaging classification to define PVI and APPIS subgroups. MAIN OUTCOME MEASURES: Clinical presentations, times to parental and physician concern, age at diagnosis, and standardized risk factor evaluations including maternal, fetal, obstetrical, neonatal, and prothrombotic variables. Patients with PVI and APPIS were compared using chi(2) or Fisher exact tests and Wilcoxon rank sum or Mann-Whitney U tests. RESULTS: A total of 12 children (20%) had PVI and 47 (80%) had APPIS. Median parental concern was 5 months, with delays to physician concern (7 months) and diagnosis (12 months). Delays were longer in PVI cases compared with APPIS (P = .002). Most presented with asymmetrical motor development but children with APPIS were more likely to present with seizures or nonmotor delays (P = .01). Children with APPIS were more likely to have acute perinatal risk factors (66% vs 17%; P = .002) including fetal distress, emergency caesarian section, or neonatal resuscitation. Cardiac evaluations were unremarkable. Prothrombotic abnormalities were common (44%) including protein S deficiency, lupus anticoagulant, and elevated factor IX but were comparable between APPIS and PVI subgroups. CONCLUSIONS: Diagnosis of PPIS is often delayed. The association of acute perinatal risk factors with APPIS compared with PVI supports distinct timing of these diseases. Prospective, case-control risk factor studies of PPIS subtypes are required to develop prevention strategies.