Vijeya Ganesan

Investigation of risk factors in children with arterial ischemic stroke

We present data on the known risk factors encountered in children presenting with a first arterial ischemic stroke to a single tertiary center over 22 years. Two hundred twelve patients (54% male; median age, 5 years) were identified. One hundred fifteen (54%) were previously healthy. Cerebral arterial imaging was undertaken in 185 patients (87%) and was abnormal in 79%. Of 104 previously healthy patients investigated with echocardiography, only 8 had abnormal studies. Genetic or acquired conditions causing thrombophilia were rare. Forty percent of patients were anemic, and 21% either had elevated total plasma homocysteine or were homozygous for the t‐MTHFR mutation. Trauma and previous varicella zoster infection were significantly more common in the previously healthy group. There was a significant association between cerebral arterial abnormalities and systolic blood pressure greater than 90th percentile and a trend for an association with varicella within the previous year. Clinical history and examination usually identify underlying risk factors and precipitating triggers for arterial ischemic stroke in childhood. Cerebral arterial imaging is usually abnormal, but echocardiography and prothrombotic screening are commonly negative. Ann Neurol 2003

Outcome after ischaemic stroke in childhood.

A parental questionnaire was used to investigate the outcome for children who had had ischaemic stroke, who were seen at Great Ormond Street Hospital, London between 1990 and 1996. The results of functional assessments carried out by a physiotherapist and an occupational therapist, and of quantitative evaluations carried out by a neuropsychologist were used for validation where possible. The relationship between clinical and radiological factors and outcome were examined. The children were aged between 3 months and 15 years at the time of stroke (median age 5 years) and the period of follow‐up ranged from 3 months to 13 years (median duration 3 years). Of the 90 children for whom data were obtained, 13 (14%) had no residual impairments. Outcome was good in 37 children (40%) and poor in 53 (60%) (defined according to whether impairments interfered with daily life). Agreement, as measured by Cohens kappa, was good or very good between the parents’responses and the qualitative measures provided by the medical professionals and the therapists, but only fair to moderate for the quantitative measures provided by the neuropsychologists. This may reflect different parental perceptions of the physical and cognitive aspects of outcome. Younger age at time of the stroke was the only significant predictor of adverse outcome.

Arterial ischemic stroke risk factors: The international pediatric stroke study

To describe presumptive risk factors (RFs) for childhood arterial ischemic stroke (AIS) and explore their relationship with presentation, age, geography, and infarct characteristics.

Revascularisation surgery for paediatric moyamoya: a review of the literature

Introduction and aimsThe role of and optimal surgical revascularisation technique for paediatric moyamoya syndrome (MMS) are controversial. In this literature review our primary aim was to evaluate the evidence base for the efficacy of surgical revascularisation for the treatment of paediatric MMS. Secondary aims were to estimate the rate of peri-operative complications and to ascertain whether direct or indirect revascularisation techniques resulted in differences in clinical or radiological outcomes.MethodsPapers describing surgical revascularisation and its outcome in the treatment of children with MMS were identified from the OVID Medline database (1966–2004). Only papers in English were reviewed. Data were abstracted using a standardised form.ResultsFifty-seven studies, including data on 1,448 patients, were reviewed. Most were Japanese; 10% were from Western institutions. Indications for revascularisation were described in <15% of studies and varied between centres. Indirect procedures were most commonly performed (alone in 73% of cases, combined with direct procedures in 23%). The rates of peri-operative stroke and reversible ischaemic events were 4.4 and 6.1% respectively. Out of 1,156 (87%) patients, 1,003 derived symptomatic benefit from surgical revascularisation (complete disappearance or reduction in symptomatic cerebral ischaemia), with no significant difference between the indirect and direct/combined groups. Data on developmental and functional outcomes were limited and of uncertain significance as they were not related to pre-operative status. Good collateral formation was significantly more frequent in the direct/combined group than in the indirect group (χ2, p<0.001).ConclusionsData from the medical literature suggest that surgical revascularisation is a safe intervention for paediatric MMS and most treated patients derive some symptomatic benefit. However, paucity of data on selection criteria and more global outcome measures means that the impact of surgical revascularisation on natural history remains uncertain. Direct and/or combined procedures provide better revascularisation, but this is not associated with differences in symptomatic outcome. International standardisation of the clinical approach to the treatment of paediatric MMS is urgently needed to critically evaluate the optimal indications for and timing of surgical revascularisation.

Clinical and Radiological Recurrence After Childhood Arterial Ischemic Stroke

Background— Data on rates and risk factors for clinical and radiological recurrence of childhood arterial ischemic stroke (AIS) might inform secondary prevention strategies. Methods and Results— Consecutive Great Ormond Street Hospital patients with first AIS were identified retrospectively (1978–1990) and prospectively (1990–2000). Patients underwent repeat neuroimaging at the time of clinical recurrence or, if asymptomatic, at least 1 year after AIS. Cox and logistic regression analyses were used to explore the relationships between risk factors and clinical and radiological recurrence, respectively. A total of 212 patients were identified, of whom 97 had another prior diagnosis. Seventy-nine children had a clinical recurrence (29 strokes, 46 transient ischemic attacks [TIAs], 4 deaths with reinfarction 1 day to 11.5 years (median 267 days) later); after 5 years, 59% (95% confidence interval, 51% to 67%) were recurrence free. Moyamoya on angiography and low birth weight were independently associated with clinical recurrence in the whole group. Genetic thrombophilia was associated with clinical recurrence in previously healthy patients, independent of the presence of moyamoya. Sixty of 179 patients who had repeat neuroimaging had radiological reinfarction, which was clinically silent in 20. Previous TIA, bilateral infarction, prior diagnosis (specifically immunodeficiency), and leukocytosis were independently associated with reinfarction. Previous TIA and leukocytosis were also independently associated with clinically silent reinfarction. Conclusions— Clinical and radiological recurrence are common after childhood AIS. The risk of clinical recurrence is increased in children with moyamoya and, in previously healthy patients, in those with genetic thrombophilia. Preexisting pathology, including immunodeficiency, and persistent leukocytosis are risk factors for radiological recurrence, which suggests a potential role for chronic infection.

Magnetic Resonance Image Correlates of Hemiparesis After Neonatal and Childhood Middle Cerebral Artery Stroke

Objective. Motor impairment after neonatal and childhood-onset ischemic stroke (IS) is common, although the prevalence and type of hemiparesis differs between the 2 age groups. Lesion topography is an important predictor of hemiparesis after neonatal IS, but it is not known if the same topographic predictors of adverse motor outcome apply to childhood-onset IS. We used a consistent approach to define lesion topography and evaluate motor outcome in both age groups to (1) investigate whether early topographic predictors of hemiparesis after unilateral middle cerebral artery–territory stroke are the same in neonates and older children and (2) compare the prevalence of dystonia and loss of independent finger movements between the 2 age groups. Design. Twenty-eight patients with neonatal-onset IS (Hammersmith Hospital, London, United Kingdom) were studied together with 43 patients with childhood-onset IS (Great Ormond Street Hospital, London, United Kingdom). All patients had exclusive unilateral middle cerebral artery–territory IS. Lesion topography was studied by using the first magnetic resonance image acquired after the onset of symptoms and was coded for involvement of cerebral cortex (CC), posterior limb of the internal capsule (PLIC), basal ganglia (BG), and white matter. The primary outcome was hemiparesis, and secondary outcomes were dystonia and loss of age-appropriate independent finger movements. Results. Hemiparesis was more common after childhood-onset IS (56%) than neonatal-onset IS (24%). In neonatal-onset IS, concomitant involvement of BG, CC, and PLIC predicts the development of hemiparesis (odds ratio: 99; 95% confidence interval: 5.2-1883.8), and no child with 1 or 2 of these structures involved developed hemiparesis. In contrast, in childhood-onset IS, concomitant BG, CC, and PLIC lesions tended to be associated with hemiparesis (9 of 11), but this adverse outcome was seen also among patients with 1- or 2-site involvement. However, hemiparesis was less likely if the infarction involved BG only (odds ratio: 0.162; 95% confidence interval: 0.036-0.729). Dystonia was present in 15 of 24 in the childhood-onset group with hemiparesis but was not seen after neonatal-onset IS. In both age groups upper-limb impairment was more severe than lower-limb impairment, with frequent loss of independent hand function among hemiparetic patients. Conclusions. In neonatal and childhood-onset IS, early magnetic resonance imaging provides useful prognostic information about subsequent motor outcome. There are differences in the functional response of the neuromotor system to injury between the 2 age groups that cannot be attributed to methodological differences alone.

Risk Factors for Arterial Ischemic Stroke in Children

Since early recurrence occurs in at least 10% of patients presenting with their first stroke in childhood in the reported series, the search for modifiable risk factors should be a priority. Risk factors for stroke in adults include hypertension, diabetes, and smoking, as well as cardiac disease and sickle cell anemia; asymptomatic cerebrovascular disease and transient ischemic events may predict stroke in this age group. The investigation of a child with a stroke has traditionally focused on finding a single cause rather than looking for risk factors to which the patient may be exposed life long. Approximately half of children presenting with stroke have a known predisposing condition, but some have unexpected pathologies such as primary cerebrovascular disease associated with congenital heart anomalies, or may have modifiable risk factors such as hypertension associated with sickle cell disease. The literature on children presenting with initially unexplained (cryptogenic) stroke suggests that there is a daunting list of possible causes, but since the series have mainly been small, it has been difficult to evaluate the relative importance of the reported associations. This paper reviews the literature on congenital, genetic, and acquired risk factors for stroke in childhood, and includes data from the large series of patients seen at Great Ormond Street Hospital over the past 10 years. The majority have arteriographic abnormalities and there is little evidence for asymptomatic cardiac disease. Genetic predisposition, trauma, infection, and nutritional deficiencies appear to be important, although case-control studies will be required to prove causation. Appropriate screening for modifiable risk factors may lead to prevention of recurrence in some patients. In the long term, an understanding of the multiple etiologies of childhood cerebrovascular disease and ischemic stroke may lead to primary prevention in this age group, and perhaps in adults. (J Child Neurol 2000;15:299-307).

Functional Outcome Following Stroke in Children

The aim of this study was to describe the functional consequences of childhood stroke in terms of activity limitation and to explore the relationship between extent of brain damage, impairment, and functional sequelae. A further aim was to describe the health of the parents of these children. Seventeen children and adolescents with cerebral infarction in the territory of the middle cerebral artery were enrolled in the study. A new activity limitation measure with a 4-point Likert scale (the Paediatric Stroke Activity Limitation Measure) was designed to examine the degree of difficulty experienced by the children in daily activities. The relationship between activity limitation scores, standardized health-related quality of life assessment (Child Health Questionnaire), extent of brain damage, and results of a comprehensive neurologic examination (Pediatric Stroke Outcome Measure) were investigated. Parent health was assessed using the Short-Form 36 General Health Survey. Activity limitation was evident in the domains of education, self-care, and motor skills. There was very good interobserver agreement using the new activity limitation scale between the occupational therapist and pediatric neurologist (Cohens kappa = 0.88). In comparison with population norms, the subjects scored below average in both physical and psychologic health. There was a clear relationship between radiologically apparent extent of brain damage, degree of impairment, and functional outcome. Parental health also rated generally lower than expected. This exploratory study suggests that both children who have had a stroke and their parents have significant and wide-ranging health needs. (J Child Neurol 2002;17:429-434).

Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study

BACKGROUND Arterial ischaemic stroke is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood arterial ischaemic stroke have been undertaken. We aimed to investigate the epidemiology and clinical features of childhood arterial ischaemic stroke in a population-based cohort. METHODS Children aged 29 days to less than 16 years with radiologically confirmed arterial ischaemic stroke occurring over a 1-year period (July 1, 2008, to June 30, 2009) residing in southern England (population denominator 5·99 million children) were eligible for inclusion. Cases were identified using several sources (paediatric neurologists and trainees, the British Paediatric Neurology Surveillance Unit, paediatricians, radiologists, physiotherapists, neurosurgeons, parents, and the Paediatric Intensive Care Audit Network). Cases were confirmed by personal examination of cases and case notes. Details of presenting features, risk factors, and investigations for risk factors were recorded by analysis of case notes. Capture-recapture analysis was used to estimate completeness of ascertainment. FINDINGS We identified 96 cases of arterial ischaemic stroke. The crude incidence of childhood arterial ischaemic stroke was 1·60 per 100 000 per year (95% CI 1·30-1·96). Capture-recapture analysis suggested that case ascertainment was 89% (95% CI 77-97) complete. The incidence of arterial ischaemic stroke was highest in children aged under 1 year (4·14 per 100 000 per year, 95% CI 2·36-6·72). There was no difference in the risk of arterial ischaemic stroke between sexes (crude incidence 1·60 per 100 000 per year [95% CI 1·18-2·12] for boys and 1·61 per 100 000 per year [1·18-2·14] for girls). Asian (relative risk 2·14, 95% CI 1·11-3·85; p=0·017) and black (2·28, 1·00-4·60; p=0·034) children were at higher risk of arterial ischaemic stroke than were white children. 82 (85%) children had focal features (most commonly hemiparesis) at presentation. Seizures were more common in younger children (≤1 year) and headache was more common in older children (>5 years; p<0·0001). At least one risk factor for childhood arterial ischaemic stroke was identified in 80 (83%) cases. INTERPRETATION Age and racial group, but not sex, affected the risk of arterial ischaemic stroke in children. Investigation of such differences might provide causative insights. FUNDING The Stroke Association, UK.

Guanidinoacetate methyltransferase deficiency: New clinical features

Guanidinoacetate methyltransferase deficiency is a recently described inborn error of creatine biosynthesis that responds to treatment with oral creatine supplementation. The previously reported clinical features consist of developmental arrest and an extrapyramidal movement disorder. We describe a patient who presented with epilepsy, global developmental delay, and a persistently low plasma creatinine level. The diagnosis was established by measuring urinary guanidinoacetate and by demonstrating absence of the creatine/phosphocreatine peak in the patients basal ganglia in 1H magnetic resonance spectroscopy. The clinical and biochemical abnormalities responded to creatine replacement.