Thrombolysis for Acute Stroke in Pediatrics

Thrombolysis with tissue plasminogen activator (tPA) for patients with acute stroke began in the eighties. After several small series and some pilot trials, the National Institute of Neurological Disorders and Stroke (NINDS) study was the first randomized, controlled, double-blind trial that demonstrated with evidences the efficacy and safety of intravenous tPA in acute stroke. However, in all these studies the 3 usual groups of patients: pregnant women, old men and children were excluded on ethical grounds. Therefore, they were also excluded from clinical practice since tPA was approved.

Stroke is an infrequent condition in pediatrics and the etiological subtype distribution is different in children to adult patients. For example, prothrombotic factors account for 68% of strokes in newborns, and for 56% in infants and children. Other etiologies more frequent in children than in adults are: congenital heart malformations, vascular abnormalities, infectious diseases or some rare metabolic problems. In most of these conditions (cardioembolism, hypercoagulable states), the formed thrombus is fresh and rich in fibrin, the better for the recanalization with tPA.

Despite the fact that “less than 18 years of age” is an exclusion criterion for thrombolysis, in recent years some pediatric cases have been published. Most of them are intra-arterial thrombolysis with tPA or urokinase and sometimes plus intracranial Angioplasty . Moreover, several patients are already young adults (15 to 18 years of age). Although the cases are diverse, the neurological recovery was complete in all of them and neither death nor symptomatic intracranial hemorrhage was reported.

The excellent article by Janjua et al provides us with the first national register of thrombolysis in children. It is a retrospective study that analyzes 20% of all community hospital admissions in the United States. Over a 4-year period, 2904 pediatric patients with stroke were included in the study, with <2% of them receiving intravenous or intra-arterial thrombolysis. After reading the article, we can establish 3 ideas about thrombolysis in children: firstly, no symptomatic intracranial hemorrhage was reported in the tPA group; secondly, mortality and dependency were more frequent in the tPA group at discharge, but the difference was not significant, and thirdly, patients of the tPA group needed mechanical ventilation more frequently and their stay was longer.

However, mortality, dependency, hospital stay and mechanical ventilation are related to the severity of the stroke, and this variable is not controlled in this study. In addition, no data about the National Institutes of Health Stroke Scale (NIHSS; before and after thrombolysis), the modified Rankin Scale and the Barthel Index scores are provided, because this register is retrospective. Finally, neither the therapeutic window, tPA doses, nor information about the vessel occluded are explained. Without these data no conclusion about efficacy of thrombolysis can be drawn.

This original and provocative study of Janjua et al is the first approach to thrombolysis in children with acute stroke, and it proves the need for a randomized, controlled, double-blind trial to check tPA efficacy and safety in this group of patients. However, thrombolysis is a neurological therapy and pediatricians are not familiarized with this treatment. For this reason, neurologists are responsible for informing pediatricians of our experience in thrombolysis in adults. At present, thrombolysis in pediatric stroke is following the same path that thrombolysis in adults followed at the end of the past century.

References

# The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med.  1995; 333: 1581–1587.
# Günter G, Junker R, Sträter R, Schobess R, Kurnik K, Kosch A, Nowak-Göttl U. Symptomatic ischemic stroke in full-term neonates: role of acquired and genetic prothrombotic risk factors. Stroke.  2000; 31: 2437–2441.
# Nowak-Göttl U, Gunther G, Kurnik K, Strater R, Kirkham F. Arterial ischemic stroke in neonates, infants, and children: an overview of underlying conditions, imaging methods, and treatment modalities. Semin Thromb Hemost. 2003; 29: 405–414.

Full Text

Robert Belvi’s, PhD

From the Stroke Unit, Department of Neurology, USP-Dexeus University Institute, Autonomous University of Barcelona, Barcelona, Spain.

Correspondence to Robert Belvi’s, Stroke Unit, Department of Neurology, USP-Dexeus University Institute, Autonomous University of Barcelona, Paseo de la Bonanova n 67, E-08017 Barcelona, Spain. E-mail

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