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Three Part Question

In children with stroke [patient], does thrombolysis [intervention] improve mortality and morbidity [outcome]?

Clinical Scenario

A 4-year-old boy presents in A&E with sudden onset facial paralysis and hemiplegia. CT scan followed by MR angiogram diagnose stroke as a result of thrombosis to Middle Cerebral Artery (MCA). The GP trainee who has worked in Medicine has seen thrombolysis being used in adult patients with stroke. He wonders whether thrombolysis should be carried out for this child.

Search Strategy

Primary Sources

A search of EMBASE, MEDLINE and PsycINFO healthcare databases (limits: human, English language and Age groups Infant, Preschool Child, Child, School Child and Adolescent) with no publication year limit identified 70 articles.


The following title and abstract/medical subject headings [MeSH] were used: [stroke OR cerebrovascular accident AND thrombolysis OR thrombolysis therapy OR child mortality OR infant mortality OR newborn mortality OR morbidity]

Secondary Sources

No systemic reviews were identified from a search of the Cochrane Library or the NHS Centre for Reviews and Dissemination. Four clinically appraised topics were identified from Up-to-Date and Turning Research into Practice (TRIP) identified 2 guideline statements from the United States and 1 guideline from the UK.

Search Outcome

7 case reports were found.4 children showed marked improvement after commencement of thrombolysis. 2 children had neurological sequelae and 1 child showed no improvement at all with complete MCA infarction.There was no specific recommendation of using thrombolysis in children with stroke from the guidelines published by RCP ( Royal College of Physicians), ACCP ( American College of Chest Physicians) and AHA ( American Heart Asoociation)

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Cremer S, Berliner Y, Warren D , Jones AE November 2008 Canada	15 yr old with acute right hemi paresis.	Interventional IV rt-PA given	Normal power on right in 24-48hrs.No dysarthria in 10 days.	Dramatic improvement following thrombolysis within 2.5 hours of onset of symptoms.	No paediatric protocol was available so adult protocol was followed.
Arnold M, Steinlin M,Baumann A,Nedeltchev K, Remonda L, Moser SJ, Manom L, Schroth G, Mattle H P et March 2009 USA	Case1:12 yr old with acute right hemi-paresis Case2: 9 yr old with sudden onset of severe tetra- paresis	Intervention with intra-arterial urokinase	Case1:Clinical deterioration in 10hrs.Complete MCA infarction. Case2: Normal consciousness returned in 24hrs.Follow-up MRI showed multiple infarcts	Case1: No improvement but there was no ICH in CT. Case2: Child was able to walk on day 10. Mild dysphasia, right hemi paresis and left hemi ataxia at 3 months.	2 similar age group of children with same intervention but varying result
Sungerian A, Duncan III JA January 2003 USA	2 cases of vertebrobasilar thrombosis	Intra-arterial urokinase used within 4hrs	Complete resolution of neurological symptoms.	Complete recanalisation of BA in both	Both children were treated with very high dose of urokinase. Small study.
Bourdial H,Sassolas F,Ville D, Di Fillipo S October 2008 France	3 yr old with AIS	Intravenous rt-PA was used 2 hr after stroke	No improvement seen	In spite of early use of thrombolysis there was neurological deterioration	The paper was published in French, only summary can be accessed
Bhatt A, Naravetla B, Majid A , Kassab M, Gupta R 2008 USA	3 year old with basilar artery occlusion	Intra-arterial rt-PA	Some clinical improvement at day3.At 6 months he was able to walk short distances	Thrombolysis was effective in this child	There was delay in starting thrombolysis(18 hrs after onset) but effective with 2 doses

Comment(s)

Thrombolysis is routinely used in adult stroke patients who present early.Currently there is no clear guideline available for the management of acute stroke and secondary prevention in paediatrics. To evaluate the use of thrombolysis in children with stroke; Amlie-Lefond, C et al have proposed an international multicentre study called TIPS (Thrombolysis in Pediatric Stroke).The study will recruit 48 patients from 30 centres.Perhaps this study will enable to highlight the need for developing a consensus guideline for using thrombolysis in children with stroke.

Clinical Bottom Line

Stroke in children can result in significant morbidity and mortality.Various case reports suggest that thrombolysis is effective in children with stroke.The results from proposed large multicentre trial is going to help the clinicians in deciding the best approach in treating these children.

References

1. Cremer S, Berliner Y, Warren D, Jones AE Successful treatment of Pediatric stroke with recombinant tissue plasminogen activator (rt-PA): a case report and review of the literature CJEM 2008; 10:575-8.
2. Arnold M, Steinlin M,Baumann A,Nedeltchev K, Remonda L, Moser SJ, Manom L, Schroth G, Mattle H P, Baumgartner RW Thrombolysis in childhood stroke: report of 2 cases and review of the literature. Stroke 2009; 40:801-7
3. Sungerian A, Duncan III JA Vertebrobasilar thrombosis in children: report of two cases and recommendations for treatment Pediatr Neurosurg 2003; 38:16-20.
4. Bourdial H,Sassolas F,Ville D, Di Fillipo S Intravenous thrombolysis in Pediatric arterial Ischemic stroke: case report and review of literature [in French]. Arch Pediatr 2008; 15:1541-6
5. Bhatt A, Naravetla B, Majid A , Kassab M, Gupta R Treatment of a basilar artery occlusion with intra-arterial thrombolysis in a 3-year-old girl Neurocrit Care 2008; 9:357-60