Case study
Safe use of alteplase in a 10 months old infant with cardio-embolic stroke

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Abstract

The knowledge about safety and efficacy of thrombolysis in paediatric stroke is limited, especially for very young children. We present an infant with cardioembolic stroke treated with alteplase. He had hypoplastic left heart syndrome since birth. He underwent Norwood operation, followed by bidirectional cavopulmonary anastomosis at 3 months. On aspirin therapy he was well until heart failure developed at the age of 9 months with 2 thrombi in the right ventricle. During the course of enoxaparin therapy sudden acute left-sided haemiplegia occurred. The emergency brain CT scan was normal. Informed consent was obtained from parents after explaining the alteplase treatment protocol and possible complications. Alteplase was administered i.v. according to standard adult stroke regimen. A control CT scan obtained 24 h later was negative for intracranial haemorrhage but the hypodense area in insula, internal capsule and subcortical area of the right parietal region were indicative of ischaemic stroke. Anticoagulation therapy was continued. He recovered hand functions after 5 days and full repertoire of movements on his left side 3 weeks later. A neurological examination performed 2 months after indicated mild residual haemiparesis and a modified Rankin scale score of 1. Three months later, the patient died of progressive heart failure. An international multicentre prospective trial is ongoing to investigate the safety and appropriate dose of alteplase for paediatric ages 2–17 years. The aim of this paper is to report safe use of alteplase even in a very young child.

Introduction

Although rare, arterial ischaemic stroke (AIS) in childhood represents an important cause of morbidity. At least 50% of patients are left with a life-long disability.1, 2, 3 The aetiology of AIS in children differs largely from that in adults. The common causes of paediatric AIS are cardiac disorders, arteriopathies, arterial dissection, haematological disorders, metabolic disorders, and infections.1, 4, 5 Multiple risk factors may be involved in the pathogenesis of AIS in children. A risk factor can be identified in 90% of the cases, whereas 52% of children with AIS have more than 1 risk factor.3, 4, 5

Such variability in pathogenesis in addition to the maturation of the coagulation system is the main reason why thrombolysis with alteplase (rtPA), which is well accepted for adult AIS, is not implemented in paediatric stroke patients. According to the 2008 guidelines for the management of childhood stroke, because of the lack of data on the safety and efficacy, thrombolysis is recommended only for clinical trials.6, 7

Successful use of rtPA in paediatric AIS has been reported several times since 2000.8 The IPSS group has reported 15 paediatric AIS patients out of 687 children (2%) who received alteplase between 2003 and 2007.9 In the same year, a Swiss group published 2 additional cases and reviewed 15 cases from previously published literature.10 Intracranial haemorrhage after alteplase treatment occurred in 4 patients from the IPSS cohort and in 2 of the 17 patients in the Swiss group, all of whom were asymptomatic.9, 10

The age of the paediatric patients who were treated with alteplase ranged from 2 to 17 years. Only 1 patient in the IPSS group was younger than 1 year and had a stroke during cardiac surgery.9 We report a case of rtPA use in a 10-month-old male infant with cardio-embolic stroke.

Section snippets

Case study

The 10-month-old patient was found to have hypoplastic left heart syndrome during the early neonatal period. A Norwood procedure with a Sano shunt was performed 13 days after birth, followed by bidirectional cavopulmonary anastomosis at the age of 3 months. He had been receiving aspirin at a dose 5 mg/kg of body weight. His clinical course was uneventful until the age of 9 months, when he became pale, tachypnoeic, and refused to eat within a week. Echocardiography revealed a severely dilated,

Discussion

Until recently, randomised clinical trials to investigate safety and efficacy of rtPA treatment had excluded children and adolescents mainly because of diverse aetiologies of AIS. Because arterial vasculitis or vasculopathy was the reported cause in nearly two-thirds of paediatric AIS cases,4, 5, 6, 7 a higher risk of bleeding complications might be expected. In addition to different stroke aetiology, age-related differences in the coagulation and fibrinolytic systems might affect the

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