Within our pediatric population, only 1 of 29 subjects (3%) with ischemic stroke would have been eligible for recombinant tissue plasminogen activator, according to adult criteria, over the 3 separate study periods. If time and relative contraindications were not used as exclusions, 20 (77%) of the 29 children would have been eligible for intravenous recombinant tissue plasminogen activator over the 3 study periods.
By the most liberal estimates (excluding time and relative contraindications), 178 children would meet eligibility to receive intravenous recombinant tissue plasminogen activator in the United States annually. This calculation is based on (1) an ischemic stroke incidence for children younger than 18 years of 2.4 per 100 000 per year (95% confidence interval, 1.7-3.6) in the United States after adjustment for age, sex, and race, and (2) a population estimate of 74 431 511 children younger than 18 years, including neonates, in the United States in 2010 from the Centers for Disease Control and Prevention Web site.39
Population-based eligibility rates could be even lower than what our analysis suggests despite our liberal assumptions. We used adult eligibility criteria for this analysis, as pediatric eligibility criteria have not been determined. Pediatric criteria are likely to be more restrictive. For example, blood pressure thresholds for children will likely be lower than the adult threshold of less than 185/110 mm Hg. In addition, it may be appropriate to exclude neonates. We also had a lack of data regarding some of the relative contraindications that could lead to further exclusions for intravenous recombinant tissue plasminogen activator therapy in this group.
Although our estimate of eligibility for intravenous recombinant tissue plasminogen activator in the United States did not exclude patients with relative exclusions, further discussion of the specific relative contraindication of seizures is warranted. Seizures in the setting of stroke are much more common in pediatric stroke patients (59%) compared with adult stroke patients (3.1%), based on a study of seizures among pediatric strokes from the same Greater Cincinnati/Northern Kentucky cohort.33
Precise timing of the seizures was not available, but it was assumed these occurred prior to determining eligibility for intravenous recombinant tissue plasminogen activator and they were treated as relative contraindications to intravenous recombinant tissue plasminogen activator treatment in this analysis. However, if stroke had been confirmed by emergent imaging in these cases, these patients may have been eligible for intravenous recombinant tissue plasminogen activator despite this relative contraindication.
This analysis is limited by a very small sample size, which is likely to reflect the low incidence of the condition. Although the population-based design may have missed some cases given the retrospective chart review, due to either misclassified in-patient ICH-9
codes, incomplete documentation in the medical record, underdiagnosis by clinicians, or presentations to outpatient settings, these limitations are unlikely to change our estimates in a meaningfully way.40
The population-based design allowed for more comprehensive ascertainment of true rates in a population, including adult hospitals, and with less bias than that of a referral center cohort.
Our analysis suggests that up to 170 cases might be eligible for a clinical trial of intravenous recombinant tissue plasminogen activator in the acute pediatric stroke population study in the US population annually. Whether recombinant tissue plasminogen activator is safe and efficacious in this pediatric population needs further study, but recruitment will likely be very challenging because of limited availability of cases.