Daune MacGregor

Neurologic Outcome in Survivors of Childhood Arterial Ischemic Stroke and Sinovenous Thrombosis

Ischemic stroke during infancy and childhood has the potential for life-long morbidity. Information on the neurologic outcome of children who survive ischemic stroke is lacking. Children surviving ischemic stroke between January 1, 1995 and July 1, 1999 were prospectively followed. Neurologic deficit severity was based on the Pediatric Stroke Outcome Measure (PSOM) developed in this study and parental response to two recovery questions. Predictor variables for poor outcome were tested. One-hundred twenty-three children with arterial ischemic stroke and 38 with sinovenous thrombosis were followed for a mean of 2.1 years (range, 0.8 to 6.6 years). The primary outcome based on PSOM assessment was: normal, 37%; mild deficit, 20%; moderate deficit, 26%; and severe deficit, 16%. The secondary outcome was full recovery in 45% of patients, based on parental response. The primary and secondary outcome measures were moderately correlated (P < .001; K = 0.5). In bivariate analysis, arterial stroke type, male gender, age of at least 28 days, presence of associated neurologic disorders, and need for rehabilitation therapy after stroke were predictors of poor outcome (P < .05). Multivariate analysis showed that only arterial ischemic stroke, associated neurologic disorders, and presence of rehabilitation therapy were independent predictors of poor outcome (P < .02). Poor outcome in children after ischemic stroke is therefore frequent and more likely in the presence of arterial stroke, rehabilitation therapy, and associated neurologic disorders, which justifies clinical trials of treatment strategies in childhood ischemic stroke. (J Child Neurol 2000;15:316-324).

Chickenpox and Stroke in Childhood A Study of Frequency and Causation

Background and Purpose— The purpose of this study was to determine whether infection with varicella is causal for arterial ischemic stroke (AIS) in children. Methods— First, a prospective cohort study was conducted in young children (aged 6 months to 10 years) with AIS at 2 institutions (cohort study). The presence of varicella infection <12 months before AIS was determined and compared with the published frequency of varicella infection in the healthy pediatric population. The clinical and radiographic features of AIS were compared between the varicella and nonvaricella study cohorts. Second, a literature search of varicella-associated AIS was conducted, and the clinical and radiographic features were compared with the study nonvaricella cohort. Results— In the cohort study, 22 (31%) of 70 consecutive children with AIS had a varicella infection in the preceding year compared with 9% in the healthy population. Children in the varicella cohort were more likely to have basal ganglia infarcts (P <0.001), abnormal cerebral vascular imaging (P <0.05), and recurrent AIS or transient ischemic attacks (P <0.05) than those in the nonvaricella cohort. The pooled literature analysis of 51 cases of varicella-associated AIS showed similar findings to the varicella cohort. Conclusion— In young children with AIS, there is a 3-fold increase in preceding varicella infection compared with published population rates, and varicella-associated AIS accounts for nearly one third of childhood AIS. Varicella-associated AIS has characteristic features, including a 2-fold increase in recurrent AIS and transient ischemic attacks. Varicella is an important risk factor for childhood AIS.

Presumed pre- or perinatal arterial ischemic stroke : Risk factors and outcomes

A subgroup of children with arterial ischemic stroke in the pre‐ or perinatal period present with delayed diagnosis. We identified 22 children who met the following criteria: (1) normal neonatal neurological history, (2) hemiparesis and/or seizures first recognized after 2 months of age, and (3) computed tomography or magnetic resonance imaging showing remote cerebral infarct. Laboratory evaluations included protein C, protein S, antithrombin, activated protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin antibody (ACLA), and lupus anticoagulant. Not all children received all tests. Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve were boys. Fourteen had left hemisphere infarcts. Median age at presentation was 6 months. Eighteen had gestational complications. Fourteen children had at least transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with FVL + MTHFR = 1); 6 of these children had family histories suggestive of thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes included persistent hemiparesis in 22; speech, behavior, or learning problems in 12; and persistent seizures in 5, with no evidence of further stroke in any patient. The persistence and importance of coagulation abnormalities in this group need further study.

Etiology of Acute Childhood Encephalitis at The Hospital for Sick Children, Toronto, 1994–1995

Of 145 patients admitted to our hospital because of encephalitis-like illness, 50 patients hospitalized for > or =72 hours underwent standardized microbiological investigations. A confirmed or probable etiologic agent was identified in 20 cases (40%), including Mycoplasma pneumoniae (9 cases). M. pneumoniae and enterovirus (2), herpes simplex virus (4), Epstein-Barr virus (1), human herpes-virus 6 (HHV-6) (1), HHV-6 and influenza virus type A (1), influenza virus type A (1), and Powassan virus (1). In 13 cases (26%), a possible pathogen was identified, including M. pneumoniae in nine cases. Presenting features included fever (80% of patients), seizures (78%), focal neurological findings (78%), and decreased consciousness (47%). The frequency of findings at the time of admission vs. later in hospitalization was as follows: pleocytosis, 59% vs. 63%; electroencephalogram abnormalities, 87% vs. 96%; and neuroimaging abnormalities, 37% vs. 69%, respectively. The outcomes at the time of discharge were as follows: normal results of physical examination, 32% (16) of the patients; death, 2% (1); motor difficulties, 26% (13); global neurological deficits, 16% (severe, 6; mild, 2); mental status changes, 14% (7); visual defects, 8% (4); and hearing impairment, 2% (1).

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. Conclusion— 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

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.

Acute Childhood Encephalitis and Mycoplasma pneumoniae

In a prospective 5-year study of children with acute encephalitis, evidence of Mycoplasma pneumoniae infection was demonstrated in 50 (31%) of 159 children. In 11 (6.9%) of these patients, M. pneumoniae was determined to be the probable cause of encephalitis on the basis of its detection in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) or by positive results of serologic tests for M. pneumoniae and detection of the organism in the throat by PCR. CSF PCR positivity correlated with a shorter prodromal illness (P=.015) and lack of respiratory symptoms (P=.06). Long-term neurologic sequelae occurred in 64% of probable cases. Thirty children (18.9%) who were seropositive for M. pneumoniae but did not have the organism detected by culture or PCR had convincing evidence implicating other organisms as the cause of encephalitis, suggesting that current serologic assays for M. pneumoniae are not sufficiently specific to establish a diagnosis of M. pneumoniae encephalitis.

Late Emergence of Cognitive Deficits After Unilateral Neonatal Stroke

Background and Purpose— Neonatal arterial ischemic stroke (AIS) affects a surprisingly large number of children each year, yet little is known about the long-term neuropsychological implications. Methods— Using age-appropriate Wechsler scales of intellectual ability, this longitudinal study examined 26 children with a history of acutely diagnosed unilateral neonatal AIS as preschoolers (3 years 6 months to 5 years 11 months) and again as grade-school students (6 years 1 month to 12 years 5 months), and contrasted performance with the normative sample of the test. Results— As preschoolers, patients’ performance did not differ from the normative sample for Full Scale IQ, Verbal IQ, or Performance IQ, and there were no significant differences associated with infarct laterality. As school-age children, performance was significantly lower than the normative sample for Full Scale IQ Working Memory and Processing Speed, but not for Verbal IQ or Performance IQ. Contrasts between Time 1 and Time 2 revealed a significant decline in Full Scale IQ, which reflected emerging deficits in nonverbal reasoning, working memory, and processing speed. Individual subject analyses revealed that 69% of the children showed significant declines in 1 or more IQ index measures. We found no significant differences in cognitive performance associated with lesion laterality, though males performed more poorly than females on several cognitive measures at Time 2. Conclusions— These findings suggest that children with unilateral neonatal stroke, particularly males, are at increased risk for emerging deficits in higher-level cognitive skills during the school years. Continued follow-up of these children is needed, even those with no apparent deficits as toddlers or preschoolers.

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

Aim  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.

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

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.