DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY COMMENTARY

Thrombolytics for acute stroke in children: eligibility, practicevariability, and pediatric stroke centers

LORI C JORDANDivision of Pediatric Neurology, Department of Pediatrics, Vanderbilt UniversityMedical Center, Nashville, TN, USA.

doi: 10.1111/dmcn.12604

This commentary is on the original article by Marecos et al. To viewthis paper visit http:/dx.doi.org/10.1111/dmcn.12588.

Thrombolysis improves outcome in adults with stroke;healthcare providers are hopeful that children may also ben-efit, though there are no completed studies that show safetyand efficacy for patients less than 18 years of age. Marecoset al. audited charts of children with acute and non-acutearterial ischemic stroke (AIS) seen at their quaternary pedi-atric medical center (no emergency department or adultstroke unit, but serves as a national referral center for pedi-atric cerebrovascular disease) to assess which children wouldhave been eligible for thrombolytic therapy.1 The authorsalso defined their local criteria for stroke thrombolysis inchildren and looked for barriers to thrombolytic use. Of107 children with acute AIS, they found that none wouldhave qualified for thrombolytic therapy based on their crite-ria, though three (2.8%) would have qualified if diagnosisand transfer had been timely. The authors determined thatthey would give tissue plasminogen activator (tPA) to chil-dren less 8 years old arriving within 6 hours of stroke onset.They also state that they would require a pediatric NationalInstitutes of Health Stroke Scale (PedNIHSS)2 of 10 orgreater. A PedNIHSS was not scored prospectively or retro-spectively for these children.

Controversial issues in this report include the agegroup, time-window, and stroke severity as measured bythe PedNIHSS. The Thrombolysis in Pediatric Stroke(TIPS) trial, a safety and dose-finding study for tPA,included children aged 2 to 17 years old but was closedfor low enrollment.3 If we reassess age in the currentstudy, there were 14 children with stroke, an occludedartery, and no thrombolysis contraindications. Of these14, three were infants, three had delayed presentation dueto lack of stroke recognition by their family, and two haddelayed diagnosis due to stroke recognition by medicalproviders. The additional six children were all delayed by

transport to the quaternary center but otherwise appear tohave met criteria for thrombolysis as per the TIPS trial.The lack of an emergency department certainly delayedarrival of children with stroke to this center. Therefore,perhaps eight out of 107 (7.4%) would have been eligiblewithout delays in diagnosis or transport. Of note, tPA isutilized in approximately 5% of adults with acute stroke.4

Typical time windows are 4.5 hours from stroke onset forintravenous tPA and up to 6 hours for off-label intra-arte-rial thrombolysis for adult stroke. TIPS utilized a 4.5hour standard for intravenous tPA. In terms of strokeseverity, the adult standard is to give tPA for an NIHSSof 4. The initial TIPS trial required a PedNIHSS of atleast 6 and then dropped this to 4 to aid recruitment andparallel adult studies. The current study utilized a Ped-NIHSS of 10 as the authors’ threshold for an unproventherapy (tPA). For reference, flaccid paralysis of one limbis recorded as a PedNIHSS of 4.2

The study is important is shows that there will be prac-tice variability for off-label use of stroke thrombolysis inchildren unless convincing studies can be done. Further-more, this study highlights the importance of ‘pediatricstroke centers’. The TIPS investigators noted that at thebeginning of the trial that less than 25% of TIPS sites hadcontinuous 24-hour availability of acute stroke teams, 24/7sedated magnetic resonance imaging capability, or strokeorder sets, despite significant pediatric stroke expertise.5

After TIPS preparation, more than 80% of sites had thesesystems in place.

The actual number of children who qualify for tPA maybe small due to delays in presentation for medical care,delays in diagnosis of stroke, and comorbid medical condi-tions that make them ineligible. However, in clinical trialsin adult stroke, two acute stroke treatments clearly save livesand improve neurological outcome: the use of tPA and dedi-cated stroke units to provide supportive, acute post-strokecare to prevent complications. Therefore, when acute strokeis considered in the differential diagnosis for a child, rapidtransfer to a pediatric medical center with pediatric strokeexpertise and readiness for rapid evaluation and treatment iscritically important. Regional pediatric stroke centersshould be developed to provide the best care.

REFERENCES

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3. Amlie-Lefond C. Thrombolysis in Pediatric Stroke Trial

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in Pediatric Stroke (TIPS) Trial. Stroke 2014; 7: 2018–23.

© 2014 Mac Keith Press 1