Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study.
BACKGROUND
The safety and efficacy of thrombolysis after acute stroke in children have not been established. Our aim was to describe current practices and results of the use of alteplase for acute arterial ischaemic stroke in children enrolled in an international pediatric stroke registry and to compare current practices with those published in case reports and with guidelines for the use of alteplase for adult stroke.


METHODS
In this multicentre observational cohort study, we analysed the clinical features, the dosing and timing of treatment, and the short-term outcome in children treated with alteplase for acute arterial ischaemic stroke who were enrolled in the International Pediatric Stroke Study (IPSS) between January, 2003, and July, 2007. The findings from the IPSS were compared with published case reports for clinical features, adherence to adult guidelines for alteplase, and outcomes.


RESULTS
Of 687 children with acute arterial ischaemic stroke enrolled in the IPSS, 15 (2%) received alteplase: nine received intravenous alteplase and six received intra-arterial alteplase. The median time to treatment from stroke onset was 3.3 h (range 2.0-52.0 h) for intravenous alteplase and 4.5 h (3.8-24.0 h) for intra-arterial alteplase. Two patients died (one owing to massive infarction and brain herniation, and one owing to brainstem infarction). At discharge from hospital, one patient was healthy and 12 patients had neurological deficits. Intracranial haemorrhage after alteplase occurred in four of 15 patients, although none of the bleeding events was judged to be acutely symptomatic. When compared with ten patients reported in published articles who were given intravenous alteplase, the nine patients in the IPSS cohort were mostly younger, waited longer for treatment, and had worse outcomes, which suggests there is a publication bias towards short treatment intervals from symptom onset and favourable outcomes.


CONCLUSIONS
Children with acute stroke received alteplase infrequently and at time intervals that often deviated from adult guidelines. Although no alteplase-related deaths or symptomatic intracranial haemorrhage was reported, poor neurological outcome was common. Clinical trials to evaluate the dose and the safety and efficacy of alteplase are needed in childhood stroke.
Department of Neurology, Division of Pediatric Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
Catherine
C
Amlie-Lefond
Gabrielle
G
deVeber
Anthony K
AK
Chan
Susan
S
Benedict
Timothy
T
Bernard
Jessica
J
Carpenter
Michael M
MM
Dowling
Heather
H
Fullerton
Collin
C
Hovinga
Adam
A
Kirton
Warren
W
Lo
Khaled
K
Zamel
Rebecca
R
Ichord
D000293:Adolescent; D002545:Brain Ischemia / Q000150:complications; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007391:International Cooperation; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D008297:Male; D019370:Observation / Q000379:methods; D010372:Pediatrics; D012189:Retrospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator