Ischemic Stroke In Children Research Articles

P13.1 Risk factors and clinical courses of childhood ischemic stroke

P13.1 Risk factors and clinical courses of childhood ischemic stroke

Seizures as a Presenting Symptom of Acute Arterial Ischemic Stroke in Childhood

To define the incidence of seizures as a presenting symptom of acute arterial ischemic stroke (AIS) in children and to determine whether younger age, infarct location, or AIS etiology were risk factors for seizure at AIS presentation. Children aged 2 months to 18 years presenting with AIS between January 2005 and December 2008 were identified from a single center prospective pediatric stroke registry. Clinical data were abstracted, and a neuroradiologist reviewed imaging studies. Among the 60 children who met our inclusion criteria, 13 experienced seizure at stroke presentation (22%). Median age was significantly younger in children who presented with seizures than in those who did not (1.1 years vs 10 years; P = .0009). Seizures were accompanied by hemiparesis in all patients. Three of 4 children with clinically overt seizures at presentation also had nonconvulsive seizures on continuous electroencephalography monitoring. Twenty-two percent of children with acute AIS present with seizures. Seizures were always accompanied by focal neurologic deficits. Younger age was a risk factor for seizures at presentation. Seizure at presentation was not associated with infarct location or etiology. Nonconvulsive seizures may occur during the acute period.

Stroke in a Child Safely Treated with Intravenous Tissue Plasminogen Activator and Edaravone, a Free Radical Scavenger

An 11-year-old female felt discomfort in her head, and left hemispheric syndrome occurred shortly thereafter. At presentation, her National Institutes of Health stroke scale (NIHSS) score was 13, and a magnetic resonance imaging scan revealed acute brain infarction in the left thalamus. She was immediately treated with the intravenous administration of tissue plasminogen activator (IV t-PA) followed by edaravone, a free radical scavenger. Two hours after IV t-PA, her symptoms dramatically resolved and her NIHSS score decreased to 5. No adverse events were observed. She was the youngest patient treated with IV t-PA in Japan, and would be the youngest treated in most developed countries. An optimal treatment for stroke in children has not been established, and this case highlights the urgent need to examine the safety and efficacy of IV t-PA and edaravone therapy for ischemic stroke in children.

APOE Gene ɛ Polymorphism and Ischemic Stroke in Children

Balcerzyk et al. evaluated the association between apolipoprotein E (APOE) gene ɛ polymorphism and ischemic stroke in children and found that APOE gene ɛ polymorphism did not determine predisposition to ischemic stroke in children [ [1] Balcerzyk A. Zak I. Niemiec P. Kopyta I. Emich-Widera E. Iwanicki T. APOE gene ɛ polymorphism does not determine predisposition to ischemic stroke in children. Pediatr Neurol. 2010; 43: 25-28 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ]. The study was well designed and conducted, but their findings contradicted previous ones in adults. Although the data were analyzed by statistical methods, the data should be interpreted with caution. APOE Gene ε Polymorphism Does Not Determine Predisposition to Ischemic Stroke in ChildrenPediatric NeurologyVol. 43Issue 1PreviewIschemic stroke in children is relatively rare, but it remains an important medical problem. Previous studies on Polish children have implicated dyslipidemias as significant risk factors in stroke. To search for genetic factors associated with the disease, the possible association between apolipoprotein E gene ε polymorphism and childhood stroke was evaluated. The study population consisted of 243 individuals: 72 children with ischemic stroke and 100 of their biological parents and 71 children without any symptoms of stroke. Full-Text PDF ResponsePediatric NeurologyVol. 44Issue 1PreviewThe examined number of children with ischemic stroke is comparably large if the frequency of the problem in the children’s population is taken into consideration. Our aim was to create a group that would be as large as possible but also ethnically homogenous so as to permit genetic evaluation. If we compare the number of our patients with the number of pediatric stroke patients from other publications, we find it satisfactory. Some larger studies also exist, but in these studies, stroke patients often come not only from different cities of one country, but also from different countries and continents [1]. Full-Text PDF

Basal ganglia stroke due to mild head trauma in pediatric age - clinical and therapeutic management: a case report and 10 year literature review

Ischemia of the basal ganglia as an immediate consequence of minor head injury in children is rare (< 2% of all ischemic stroke in childhood) and is due to vasospasm of the lenticulostriate arteries. The clinical history of these lesions is particularly favourable because they are usually small, and also because the facial-brachial-crural hemiparesis typical of this pathology usually regresses after a period ranging from several weeks to several months, despite the persistence of an ischemic area on MRI. This is due to the well known neuronal plasticity of the CNS, in particular, of the primary motor cortex. The most effective therapeutic approach appears to be the conservative one, although the best treatment regimen is still not well defined.Young patients should be closely monitored and treated conservatively with osmotic diuretics to reduce perilesional edema. At the same time, however, it is very important to exclude, by means of instrumental and laboratory studies, conditions that could favour the onset of ischemia, including emboligen heart disease, thrombophilia and acute traumatic arterial dissections. Generally speaking, the prognosis in these cases is good. The authors describe their experience treating a 10-month old baby girl, with a left lenticular nucleus ischemia and report a literature review.

Arterial Ischaemic Stroke in Children with Heart Disease: Experience in a Single Centre Over 17 Years

therapies have not been trialled in children and there is little information about long-term survival in treated children. Methods: A multicentre, web-based Australian and New Zealand registry for children with PAH was established to better understand the profile of children with IPAH, aiming to describe demographics, presenting features, clinical course and outcomes of children aged three months to 18years at timeofPAHdiagnosis, from1/1/2002. A group of historic controlswith IPAHdiagnosed between 1970 and 1990 were used for comparison. Results:Of the 24 patients enrolled with IPAH, 54% are female and 75% Caucasian. The mean (SD) age at diagnosis was 9.3 (4.90) years and 50% were WHO functional class III at presentation. Baseline cardiac catheterisation data for both groups is shown. During follow-up, 20 (83%) subjects were treated with an endothelin receptor antagonist (exclusively Bosentan monohydrate), 17 (71%) with a phosphodiesterase 5 inhibitor (sildenafil) and 10 (42%) with either epoprostenol or iloprost; 19 (79%) are anticoagulated with warfarin. Themean duration of follow-up was 3.45 years, with an annualisedmortality of 6%. Study endpoints of death/transplant occurred in 6/24, compared to 10/12 controls (p= .001). Severity of PAH from cardiac catheterisationwas similar between patients and controls. Conclusions: Multiple medical therapies have resulted in improved survival for children with IPAH diagn c d r

Association between APOE Gene ɛ Polymorphism and Ischemic Stroke in Children

Balcerzyk et al. observed that there were no significant differences in APOE genotype and allele distribution between patients and control subjects [ [1] Balcerzyk A. Żak I. Niemiec P. Kopyta I. Emich-Widera E. Iwanicki T. APOE gene ɛ polymorphism does not determine predisposition to ischemic stroke in children. Pediatr Neurol. 2010; 43 (25-8) Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ]. Although there is a discrepancy between clinical correlation and applying pathological principles, this study has important potential limitations. APOE Gene ε Polymorphism Does Not Determine Predisposition to Ischemic Stroke in ChildrenPediatric NeurologyVol. 43Issue 1PreviewIschemic stroke in children is relatively rare, but it remains an important medical problem. Previous studies on Polish children have implicated dyslipidemias as significant risk factors in stroke. To search for genetic factors associated with the disease, the possible association between apolipoprotein E gene ε polymorphism and childhood stroke was evaluated. The study population consisted of 243 individuals: 72 children with ischemic stroke and 100 of their biological parents and 71 children without any symptoms of stroke. Full-Text PDF ResponsePediatric NeurologyVol. 44Issue 1PreviewOur study was carried out in various centers of neuropediatrics in Poland to recruit sufficient number of patients because pediatric ischemic stroke is rare. Thus we find the multicenter character of our study to be a strength, not a weakness. The diagnostic standards concerning children with stroke are homogenous in Poland, and the ethnicity of the patients is homogenous too. All the patients were enrolled onto the study while they were in the so-called acute phase of the disease—that is, the first 3 weeks from onset of stroke. Full-Text PDF

Cerebral Angiopathies as a Cause of Ischemic Stroke in Children

Ischemic stroke in children can present with an epileptic seizure or be initially asymptomatic. The median time to diagnosis is 24 hours. This review is based on a selective literature search, with additional consideration of published guidelines and the authors' personal experience. In Europe and the USA, the combined incidence of ischemic and hemorrhagic stroke in childhood is 2.5 to 10 per 100 000 children per year. 40% of ischemic strokes in childhood occur after an infectious illness or in association with a congenital heart defect, sickle-cell anemia, or a coagulopathy. Arterial dissection and chronic, progressive cerebral arteriopathies, particularly moyamoya disease, each account for up to 10% of childhood strokes. Magnetic resonance imaging can be used to demonstrate infarcts and to display the perfusion of ischemic areas and the surrounding brain tissue; arterial and venous occlusions can be defined more precisely. Children with arterial dissection, vasculitis, and para-infectious cerebral ischemia should be treated empirically, with medications and supportive care, according to the treatment plans developed for adults. For patients with moyamoya disease, surgical revascularization with extra-intracranial bypass techniques is recommended. The current data provide an inadequate evidence base for the treatment of stroke in children. Potential revascularization or thrombolysis must be discussed individually in each case. For the treatment of temporary, para-infectious cerebral ischemia, hemodynamic optimization is an available option. Better evidence is needed regarding the surgical treatment of moyamoya disease.

Fatal Ischemic Stroke Due to Dissecting Aneurysm of the Intracranial Arteries Presenting as Sudden Unexpected Death in Childhood

Sudden unexpected death is any nontraumatic death in healthy individuals with normal activities for age until acute demise. Whereas not uncommon in adults and infants, it is considered a rarity in children, with most cases due to infection or occult cardiovascular abnormalities. Pathologic intracranial findings are rarely found in sudden unexpected death in childhood, with most cases due to occult intracranial neoplasms. Cerebral arterial dissection is an uncommon cause of arterial ischemic stroke in childhood. Outcome is poor, with more than 20% of patients dying. We report 4 cases of sudden unexpected death due to arterial ischemic stroke after cerebral arterial dissection in childhood and present a review of the literature.

High reticulocyte count is an independent risk factor for cerebrovascular disease in children with sickle cell anemia

Transcranial Doppler ultrasonography (TCD) is an important way of detecting risk of ischemic stroke in children with sickle cell anemia. A random sample of 262 FS-hemoglobin children from a newborn screening inception cohort in Brazil (1998-2005) was followed up to May 2009. Pulsed TCD followed STOP protocol. Children with mean blood flow velocity < 170 cm/sec in cerebral arteries were classified as low risk; between 170 and 184, low conditional risk; between 185 and 199, high conditional risk; and ≥ 200, high risk. Median age, 6.2 years (2-11.2 years); 147 female; 13 children (5%) had ischemic stroke prior to TCD; 186/249 (74.7%) were classified as low risk; 19 (7.6%) as low conditional; 7 (2.8%) as high conditional; and 8 (3.2%) as high risk; inadequate tests, 11.6%. The probability of ischemic stroke at 10 years was 8.3% (SEM 2.3%); of stroke or high-risk TCD 15.6% (3.5%). Children with stroke or altered TCD (conditional and high risk) were compared to children with normal examinations. They were younger (P = 0.03), with lower hemoglobin (P = 0.003), higher leukocytosis (P = 0.015), and higher reticulocytosis (P < 0.001). Episodes per year of acute chest syndrome were also higher in that group, but not significantly (P = 0.09). Reticulocytosis remained the only significant variable upon multivariate analysis (P = 0.004). Basilar and middle cerebral artery velocities were significantly correlated (R = 0.55; P < 0.001). Probability of stroke was similar to international reports; of belonging to high-risk group, lower. High-reticulocyte count was the most important factor associated with cerebrovascular disease. Basilar artery velocity > 130 cm/sec seems to be an indirect sign of an underlying cerebrovascular disease.

Association analysis of the E‐selectin 98G &gt; T polymorphism and the risk of childhood ischemic stroke

Genes related to platelet and arterial endothelial function have been recently considered as independent risk factors for stroke. We aimed to analyze a relationship between the E-selectin 98G > T polymorphism and stroke in children and to observe the transmission of E-selectin alleles from heterozygous parents to their affected children. We studied 59 children after stroke, 112 parents, and 87 healthy children. The E-selectin 98G > T polymorphism was analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of the 98T allele in patients was almost twofold lower than in controls (5.1% vs. 9.8%, p = 0.145, odds ratios (OR) = 0.49) as well as carriers of the 98T allele (19.5% in controls vs. 8.5% in cases, p = 0.067, OR = 0.38). The G allele of the E-selectin 98G > T polymorphism was more frequently transmitted to the children after stroke compared to the T allele (68% vs. 32%). In conclusion, we did not confirm the relationship between the 98G > T polymorphism of the E-selectin gene and childhood ischemic stroke. There is still a need for further studies.

Pediatric stroke: the importance of cerebral arteriopathy and vascular malformations

Population-based estimates of the annual incidence of childhood stroke range from 2 to 13 per 100,000 person-years. More than half of children who have had a stroke have long-term neurological sequelae. The goal of this article is to review recent literature on both hemorrhagic and ischemic stroke in children with a focus on cerebral arteriopathy and vascular malformations as stroke risk factors. Additionally, we review diagnostic studies for childhood stroke, outcome data, and regional and geographic practice differences. PubMed was searched using the terms child, childhood, pediatric, stroke, ischemic, intracerebral hemorrhage, vasculopathy, and vascular malformation. Reference lists of these articles were reviewed for additional key publications. Preference was given to articles published since the year 2000; however, seminal articles in the field were also reviewed. Pediatric stroke is a heterogeneous disorder and a major cause of morbidity in the pediatric population. Five-year recurrence risk is estimated to be 5-19%. Children with cerebrovascular abnormalities are at the highest risk of recurrence (66% at 5 years for ischemic stroke in one study). Furthermore, cerebral arteriopathy including arterial dissection may account for up to 80% of childhood stroke in otherwise healthy children. In many cases, evaluation and treatment of pediatric stroke is not evidence-based, and regional and geographic variations in practice patterns exist. Ultimately multicenter cohort studies and dedicated pediatric clinical trials are essential to establish comprehensive evidence-based guidelines for pediatric stroke care.

Meta-Analysis of Factor V Leiden and Ischemic Stroke in Young Adults

The factor V Leiden mutation is associated with ischemic stroke in children but not in adults. Whether it is associated with ischemic stroke in young adults, however, is uncertain. To address this issue, we performed a meta-analysis of 18 case-control studies of ischemic stroke in adults 50 years of age and younger published before June 2009. Across all studies, factor V Leiden was detected in 154 of 2045 cases (7.5%) and 217 of 5307 controls (4.1%), yielding a fixed-effect odds ratio of 2.00 (95% CI, 1.59-2.51). However, further analyses revealed substantial heterogeneity among these studies (P=0.005 for Q-test of heterogeneity). Hypothesizing that this heterogeneity could be related to differences among studies in case selection criteria, we stratified the meta-analysis into studies for which case samples were enriched or not enriched to include cases having an increased likelihood of prothrombotic genetic involvement ("selected" ischemic stroke studies, n=9) and those that recruited cases from consecutive neurology referrals or hospitalizations ("unselected" ischemic stroke studies, n=8). Among the 9 "selected" ischemic stroke studies, factor V Leiden was more strongly associated with stroke (OR, 2.73; 95% CI, 1.98-3.75), whereas among the 8 "unselected" ischemic stroke studies, the association between factor V Leiden and stroke was substantially weaker (OR, 1.40; 95% CI, 0.998-1.95). This difference was found to be statistically significant (P=0.003 for Woolf test for heterogeneity). We conclude that factor V Leiden is associated with ischemic stroke in young adults, particularly in patient populations in which there is an increased clinical suspicion of prothrombotic state.

APOE Gene ε Polymorphism Does Not Determine Predisposition to Ischemic Stroke in Children

Ischemic stroke in children is relatively rare, but it remains an important medical problem. Previous studies on Polish children have implicated dyslipidemias as significant risk factors in stroke. To search for genetic factors associated with the disease, the possible association between apolipoprotein E gene epsilon polymorphism and childhood stroke was evaluated. The study population consisted of 243 individuals: 72 children with ischemic stroke and 100 of their biological parents and 71 children without any symptoms of stroke. The apolipoprotein E gene epsilon polymorphism was genotyped using restriction fragment length polymorphism methodology. To analyze the possible association between this polymorphism and stroke, the transmission disequilibrium test and the case-control model were used. No preferential distribution of any allele from parents to the affected children was observed. There were also no significant differences in genotype and allele distribution between patients and control subjects. Study findings did not confirm that epsilon polymorphism of the apolipoprotein E gene is a risk factor of ischemic stroke in children.

Risk factors and treatment outcomes for children with arterial ischemic stroke

To investigate the risk factors and treatment outcomes for ischemic stroke in children, we reviewed the charts of 93 children with ischemic stroke seen at our hospital between 1997 and 2006. Age at stroke, sex, medical history, family history, clinical findings upon admission, history of seizure, and radiological findings were recorded. Mean age at onset of the initial stroke was 56.6+/-46.9 months, ranging from 1 month to 14 years. The male:female ratio was 1.6:1. Cardiac and infectious disease were the most common risk factors (37.7%). There were five children (5.4%) who had recurrent stroke and three (3.2%) who had multiple risk factors. Cardiac and infectious causes appeared to be the most important risk factors for ischemic stroke in children in the Adana region of Turkey.

Cognitive outcome following unilateral arterial ischaemic stroke in childhood: effects of age at stroke and lesion location

Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long-term neuropsychological impairment. Our aim was to investigate the relationship among age at injury, lesion location and intellectual outcome. Using age-appropriate Wechsler scales of intellectual ability, we explored this issue by evaluating a large group (n=145) of children (89 males, 56 females) who experienced unilateral arterial ischaemic stroke during the perinatal period (diagnosed mean 73d, SD 29d), between the ages of 1 month and 5 years (mean 2y 10mo, SD 1y 9mo), or between the ages of 6 and 16 years (mean 11y 1mo SD 3y 6mo). The mean age at assessment was 8 years (SD 3y 10mo) in the perinatal group, 7 years 5 months (SD 2y 9mo) in the 1 month to 5 years group, and 12 years 5 months (SD 3y 9mo) in the 6 to 16 years group. The mean time interval between stroke and assessment was 8 years (SD 18d) for perinatal, 4 years 6 months (SD 1y 5mo) for 1 month to 5 years, and 1 year 4 months (SD 2y 9mo) for 6 to 16 years. The relationship between age at stroke and lesion location (subcortical, cortical, or combined) as it pertains to cognitive outcome was also examined. Measures of overall intelligence, verbal ability, working memory, and processing speed were significantly lower in children who had had a stroke than in the normative sample (all z>2.5, all p<0.01). The perinatal group performed more poorly than the other two groups on most cognitive measures, regardless of lesion location. The combined lesion location group performed more poorly than those with damage to either cortical or subcortical areas alone. Further investigation revealed different periods of peak vulnerability for subcortical lesions (perinatal) and cortical lesions (1mo-5y). Lesion location modulates the relationship between age at stroke and cognitive outcome.

Craniocervical Arterial Dissection: A Cause of Childhood Arterial Ischemic Stroke in Taiwan

To describe the clinical characteristics and imaging findings of craniocervical dissection in childhood ischemic stroke, in a tertiary medical center. In this retrospective study, we investigated children (aged 1 month to 18 years) with symptoms and radiographic confirmation of ischemic stroke from January 1996 to January 2007. Stroke work-up included neuroimaging (magnetic resonance imaging, computed tomography, conventional angiography, and magnetic resonance angiography), cardiac assessment, prothrombotic assays, immunoassays, infection screening, and metabolic screening. Among 95 children with arterial ischemic stroke, arterial dissection was identified as the underlying risk factor in nine patients (7 boys and 2 girls; age range, 1.9 17.2 years). All the patients had focal neurological signs and two had warning symptoms. A history of trauma was noted in two patients and another two had stroke during physical exertion. The other five patients had spontaneous dissection. Six patients had anterior circulation arterial dissection. Three patients had posterior circulation arterial dissection, and the most common location was in the vertebral artery. Antiplatelet treatment was given to five patients and anticoagulants to one. Endovascular treatment was given to one patient with dissecting aneurysm. One patient died at the acute stage and another seven had neurological deficits after 9 months to 8 years follow-up. The ninth patient had no residual neurological impairment. No patients had recurrent stroke. Arterial dissection should be considered in childhood ischemic stroke. Spontaneous arterial dissection is an important factor in this group. Early investigation and treatment can improve the outcome.

Antithrombotic Therapy for Ischemic Stroke in Childhood

Antithrombotic Therapy for Ischemic Stroke in Childhood

Trombosis venosas cerebrales en la edad pediátrica: presentación clínica, factores de riesgo, diagnóstico y tratamiento

Since its first description at the beginning of the 19th century, greater awareness of this disorder has been achieved, becoming nowadays a recognized but sometimes underdiagnosed cause of ischemic stroke in childhood. AIM. To describe a population of children with cerebral venous thrombosis, analyzing clinical presentation, risk factors, treatment and evolution. A descriptive, retrospective and longitudinal review of children from 0 to 17 years of age diagnosed with sinovenous thrombosis was conducted, during the period of time between 2004 and 2009. Thirty one cases with cerebral sinus thrombosis were identified, 18 of them were boys. Clinical presentation included 18 patients with seizures and 13 with high intracranial pressure. We found infections as a risk factor in 23 patients, 3 newborns with obstetric trauma, 5 patients with prothrombotic states, 4 with chronic systemic diseases, 5 with more than one risk factor and 1 with none. Diagnosis was done by magnetic resonance imaging in 18 patients, computed tomography in 11 and magnetic resonance angiography in the other 2. Regarding location, 16 patients showed compromise of the transverse sinus, 4 of the superior longitudinal sinus, another 4 an affectation of the sigmoid sinus, 2 of the cavernous sinus and 5 with a combination of them. Anticoagulation therapy was done in 21 patients and treatment abstention in 10. None of the patients suffered complications or death due to anticoagulation therapy or sinovenous thrombosis. No recurrent symptomatic thrombosis in long term follow up was found. Sinovenous cerebral thromboses are an important but underestimated cause of stroke in childhood. Clinical suspicion should be high, in patients with risk factors and intracranial hypertension or seizures.

Disecciones arteriales craneocervicales en la edad pediátrica: ¿una patología emergente o infradiagnosticada?

Cranio-cervical arterial dissections are a recognized cause of ischemic stroke in childhood, with an approximate incidence of 0.4 to 20%. AIM. To describe a population of children with cranio-cervical arterial dissections, analyzing clinical presentation, risk factors, angiographic findings, evolution and treatment. A descriptive, retrospective, longitudinal collaborative review (Sant Joan de Deu and Pereira Rossell Children's Hospital), of children one month to 17 years old of age was conducted, during the period of time between 2000 to 2009. Ten cases with arterial dissection were identified, 7 of them were boys and 3 girls. Nine had a traumatism preceding neurological symptoms. Clinical presentation included 5 patients with hemiparesis, 3 with hemicerebelus syndrome, 1 with VI cranial nerve palsy and 1 with intracranial soplus as the only symptom at physical examination. Three of them had seizures, while headache preceding the onset of cerebral ischemic symptoms was founded in 6 of them. Dissection involved anterior circulation in 5 patients and posterior circulation in the other 5. In reference to the localization of arterial compromise 4 patients had intracranial dissections and 6 had extracranial dissections. Anticoagulation therapy was done in 5, antiagregation in 3, and treatment abstention in two. None of them suffered neither complications due to anticoagulation therapy nor dead or recurrent dissections in long term follow up (2 months to 8 years). Cranio-cervical dissections are a frequent cause of stroke in childhood. Clinical suspicious related to cranio-cervical traumatisms and subsequent neurological symptoms should be high.