Top

Published in:

01-07-2013 | Review

Therapy in pediatric stroke

Authors: B. Simma, I. Höliner, J. Luetschg

Published in: European Journal of Pediatrics | Issue 7/2013

Abstract

The aim of this review is to summarize the existing literature on therapy and management of cerebrovascular insults in children and adolescents. As data sources, studies were identified by MEDLINE, PubMed, Cochrane Library, and relevant bibliographies for the topic “pediatric stroke.” We also reviewed guidelines for “stroke in adults.” As a result, pediatric stroke is underestimated. The annual incidence for all stroke entities (cerebral venous thrombosis and hemorrhagic and arterial ischemic stroke) is as high as for pediatric brain tumors, 3–15/100.000 children per year. A distinct etiology can be determined only in a minority of them. Underlying risk factors are multiple, mainly vasculopathies, congential heart diseases, coagulopathies, lipometabolic disorders, and sickle cell anemia. Current recommendations for therapy are based on adult studies, are preliminary, and discussed controversially. Antithrombotic therapy is uniformly recommended for the acute stage of pediatric stroke; no consensus exists on antiplatelet therapy with acetylsalicylic acid (ASA, aspirin) (5 mg/d), with ultra-fractionated or low-molecular-weight heparin. Thrombolysis using recombinant tissue plasminogen activator is not advised, despite the fact that current practice takes a different approach. None of the guidelines specify the duration of ASA for secondary prevention. Additional supportive therapy measures are osmotherapy and decompressive craniectomy. Oxygen in the absence of hypoxemia, intensive insulin therapy, antiepileptic drugs in the absence of clinical or electrographic seizures, corticosteroids, and GP-IIb/IIIa-receptor antagonists should not be used outside clinical trials. In conclusions, current therapeutic guidelines for pediatric stoke are still based on consensus and expert and society opinions and differ between countries. Consensus prevails on the need for acute anticoagulation using either antiplatelets or heparin. Long-term treatment with acetylsalicylic acid in all or only high-risk patients and for how long remains the subject of debate. Lifelong secondary prevention has never been investigated in children or adults. All guidelines agree that there is no indication for thrombolysis in children outside clinical trials, although clinical practice in large centers differs.

Abend NS, Beslow LA, Smith SE et al (2011) Seizures as a presenting symptom of acute arterial ischemic stroke in childhood. J Pediatr 159:479–483PubMedCrossRef

Adams HP Jr, del Zoppo G, Alberts MJ et al (2007) Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation 115:e478–e534PubMedCrossRef

Agrawal N, Johnston SC, Wu YW et al (2009) Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke 40:3415–3421PubMedCrossRef

Amlie-Lefond C, Bernard TJ, Sébire G et al (2009) Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study. Circulation 119:1417–1423PubMedCrossRef

Amlie-Lefond C, de Veber G, Chan A, International Pediatric Stroke Study et al (2009) Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 8:530–536PubMedCrossRef

Askalan R, Laughlin S, Mayank S et al (2001) Chickenpox and stroke in childhood: a study of frequency and causation. Stroke 32:1257–1262PubMedCrossRef

Benedik MP, Zaletel M, Meglic NP, Podnar T (2011) Patent foramen ovale and unexplained ischemic cerebrovascular events in children. Arch Dis Child 96:461–467PubMedCrossRef

Beslow LA, Licht DJ, Smith SE et al (2010) Predictors of outcome in childhood intracerebral hemorrhage: a prospective consecutive cohort study. Stroke 41:313–318PubMedCrossRef

Bigi S, Fischer U, Wehrli E et al (2011) Acute ischemic stroke in children versus young adults. Ann Neurol 70:245–254PubMedCrossRef

10.

Bousser MG, Ferro JM (2007) Cerebral venous thrombosis: an update. Lancet Neurol 6:162–170PubMedCrossRef

11.

Broderick JP, Adams HP Jr, Barsan W et al (1999) Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 30:905–915PubMedCrossRef

12.

Burak CR, Bowen MD, Barron TF (2003) The use of enoxaparin in children with acute, nonhemorrhagic stroke. Pediatr Neurol 29:295–298PubMedCrossRef

13.

Cellucci T, Benseler SM (2010) Diagnosing central nervous system vasculitis in children. Curr Opin Pediatr 22:731–738PubMedCrossRef

14.

Chun DS, Schamberger MS, Flaspohler T et al (2004) Incidence, outcome, and risk factors for stroke after Fontan procedure. Am J Cardiol 93:117–119PubMedCrossRef

15.

Condie J, Shaibani A, Wainwright MS (2012) Successful treatment of recurrent basilar artery occlusion with intra-arterial thrombolysis and vertebral artery coiling in a child. Neurocrit Care 16:158–162PubMedCrossRef

16.

Cooper DJ, Rosenfeld JV, Murray L, DECRA Trial Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group et al (2011) Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med 364:1493–1502PubMedCrossRef

17.

Coutinho J, de Bruijn SF, Deveber G et al (2011) Anticoagulation for cerebral sinus thrombosis. Cochrane Database Syst Rev CD002005

18.

Den Hertog HM, van der Worp HB, Tseng MC et al (2009) Cooling therapy for acute stroke. Cochrane Database Syst Rev (1):CD001247

19.

de Veber G (2005) In pursuit of evidence-based treatments for paediatric stroke: the UK and Chest guidelines. Lancet Neurol 4:432–436CrossRef

20.

de Veber G, Kirkham F (2008) Guidelines for treatment and prevention of stroke in children. Lancet Neurol 7:983–985CrossRef

21.

Dowling MM, Ikemba CM (2011) Intracardiac shunting and stroke in children: a systematic review. J Child Neurol 26:72–82PubMedCrossRef

22.

Engelmann KA, Jordan LC (2012) Outcome measures used in pediatric stroke studies. Arch Neurol 69:23–27PubMedCrossRef

23.

European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee (2008) Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 25:457–507CrossRef

24.

Forsyth RJ, Wolny S, Rodrigues B (2010) Routine intracranial pressure monitoring in acute coma. Cochrane Database Syst Rev (2):CD002043

25.

Fullerton HJ, Wu YW, Sidney S et al (2007) Recurrent hemorrhagic stroke in children: a population-based cohort study. Stroke 38:2658–2662PubMedCrossRef

26.

Fullerton HJ, Wu YW, Sidney S et al (2007) Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging. Pediatrics 119:495–501PubMedCrossRef

27.

Ganesan V, Prengler M, Wade A et al (2006) Clinical and radiological recurrence after childhood arterial ischemic stroke. Circulation 114:2170–2177PubMedCrossRef

28.

Gemeinsame Leitlinie der Deutschen Gesellschaft für Neurologie und Deutsche Schlaganfallgesellschaft (2012) Primär- und Sekundärprävention der zerebralen Ischämie. Available online at: http://www.dsg-info.de/images/stories/DSG/PDF/Leitlinien/ll08kap_024.pdf

29.

Giroud M, Lemesle M, Gouyon KB et al (1995) Cerebrovascular disease in children under 16 years of age in the city of Dijon, France: a study of incidence and clinical features from 1985 to 1993. J Clin Epidemiol 48:1343–1348PubMedCrossRef

30.

Goldenberg NA, Bernard TJ, Fullerton HJ, International Pediatric Stroke Study Group et al (2009) Antithrombotic treatments, outcomes, and prognostic factors in acute childhood-onset arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 8:1120–1127PubMedCrossRef

31.

Gupta R, Connolly ES, Mayer S et al (2004) Hemicraniectomy for massive middle cerebral artery territory infarction: a systematic review. Stroke 35:539–543PubMedCrossRef

32.

Hacke W, Kaste M, Bluhmki E et al (2008) Thrombolysis with alteplase 3 to 4.5 hours after ischemic stroke. N Engl J Med 359:1317–1329PubMedCrossRef

33.

Hacke W, Furlan AJ, Al-Rawi Y et al (2009) Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol 8:141–150PubMedCrossRef

34.

Hajat C, Hajat S, Sharma P (2000) Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke 31:410–414PubMedCrossRef

35.

Hajj-Ali RA, Singhal AB, Benseler S, Molloy E, Calabrese LH (2011) Primary angitis of the CNS. Lancet Neurol 10:561–572PubMedCrossRef

36.

Janjua N, Nasar A, Lynch JK et al (2007) Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample. Stroke 38:1850–1854PubMedCrossRef

37.

Katsetos C, Smith ER, Scott RM (2009) In: Legido A, Piatt JH (eds) Cerebrovascular disorders in children. Clinical pediatric neurosciences, 1st edn. American Academy of Pediatrics, Elk Grove Village, pp 171–215

38.

Kenet G, Kirkham F, Niederstadt T, European Thromboses Study Group et al (2007) Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study. Lancet Neurol 6:595–603PubMedCrossRef

39.

Kenet G, Lütkhoff LK, Albisetti M et al (2010) Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation 121:1838–1847PubMedCrossRef

40.

Kenet G, Sadetzki S, Murad H et al (2000) Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children. Stroke 31:1283–1288PubMedCrossRef

41.

Kennedy C, Pediatric neurology (2011) Understanding risk and improving therapeutic choices. Lancet Neurol 10:15–16PubMedCrossRef

42.

Lanthier S, Armstrong D, Domi T et al (2005) Postvaricella arteriopathy of childhood: natural history of vascular stenosis. Neurology 64:660–663PubMedCrossRef

43.

Lynch JK, Han CJ, Nee LE et al (2005) Prothrombotic factors in children with stroke or porencephaly. Pediatrics 116:447–453PubMedCrossRef

44.

Mackay MT, Wiznitzer M, Benedict SL et al (2011) International Pediatric Stroke Study Group. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol 69:130–140PubMedCrossRef

45.

Maguire JL, deVeber G, Parkin PC (2007) Association between iron-deficiency anemia and stroke in young children. Pediatrics 120:1053–1057PubMedCrossRef

46.

Mahle WT, Tavani F, Zimmermann RA et al (2002) An MRI study of neurological injury before and after congenital heart surgery. Circulation 106(12Suppl):I109–I1114PubMed

47.

Mayer SA, Brun NC, Begtrup K, FAST Trial Investigators et al (2008) Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 358:2127–2137PubMedCrossRef

48.

McClure CD, Johnston JK, Fitts JA et al (2006) Postmortem intracranial neuropathology in children following cardiac transplantation. Pediatr Neurol 2006(35):107–113CrossRef

49.

McQuillen PS, Barkovich AJ, Hnarick SE et al (2007) Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke 38(Suppl):736–741PubMedCrossRef

50.

McQuillen PS, Hamrick SE, Perez MJ et al (2006) Balloon atrial septostomy is associated with preoperative stroke in neonates with transposition of the great arteries. Circulation 113:280–285PubMedCrossRef

51.

Michelson AD, Bovill E, Andrew M et al (1995) Antithrombotic therapy in children. Chest 108(Suppl):506–522CrossRef

52.

Moharir MD, Shroff M, Stephens D et al (2010) Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study. Ann Neurol 67:590–599PubMed

53.

Monagle P, Chalmers E, Chan A et al (2008) Antithrombotic therapy in neonates and children: American College of Chest Physicians evidenced-based clinical practice guidelines (8th ed). Chest 133(Suppl):887–968CrossRef

54.

Normann S, de Veber G, Fobker M et al (2009) Role of endogenous testosterone concentration in pediatric stroke. Ann Neurol 66:754–758PubMedCrossRef

55.

Poca MA, Benejam B, Sahuquillo J et al (2010) Monitoring intracranial pressure in patients with malignant middle cerebral artery infarction: is it useful? J Neurosurg 112:648–657PubMedCrossRef

56.

Roach ES, Golomb MR, Adams R et al (2008) Management of stroke in infants and children. A scientific statement from a special writing group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 39:2644–2691PubMedCrossRef

57.

Sébire G, Tabarki B, Saunders DE et al (2005) Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. Brain 128:477–489PubMedCrossRef

58.

Shann F (2010) Drug doses, 15th edn. Royal Children’s Hospital, Melbourne

59.

Simma B, Tscharre A, Hejazi N et al (2002) Neurologic outcome after decompressive craniectomy in children. Intensive Care Med 28:1000PubMedCrossRef

60.

Simma B, Martin G, Mueller T et al (2007) Risk factors for pediatric stroke: consequences for therapy and quality of life. Pediatr Neurol 37:121–126PubMedCrossRef

61.

Smith S, Kirkham F, de Veber G et al (2011) Outcome following decompressive craniectomy for malignant middle cerebral infarction in children. Dev Med Child Neurol 53:29–33PubMedCrossRef

62.

Schechter T, Kirton A, Laughlin S et al (2012) Safety of anticoagulants in children with arterial ischemic stroke. Blood 119:949–956PubMedCrossRef

63.

Stein DG (2011) Is progesterone a worthy candidate as a novel therapy for traumatic brain injury? Dialogues Clin Neurosci 13:352–359PubMed

64.

Steinlin M, Pfister I, Pavlovic J et al (2005) The first three years of the Swiss Neuropaediatric Stroke Registry (SNPSR): a population-based study of incidence, symptoms and risk factors. Neuropediatrics 36:90–97PubMedCrossRef

65.

Sträter R, Kurnik K, Heller C et al (2001) Aspirin versus low-dose low-molecular-weight heparin: antithrombotic therapy in pediatric ischemic stroke patients: a prospective follow-up study. Stroke 32:2554–2558PubMedCrossRef

66.

Sträter R, Becker S, von Eckard A et al (2002) Prospective assessment of risk factors for recurrent stroke during childhood—a 5-year follow-up study. Lancet 360:1540–1545PubMedCrossRef

67.

Tasker RC (2011) Paediatric neurointensive care and decompressive craniectomy for malignant middle cerebral artery infarction. Dev Med Child Neurol 53:5–6PubMedCrossRef

68.

Tatum J, Farid H, Cooke D, Fullerton H, Smith W, Higashida R, Halbach VV, Dowd C (2012) Mechanical embolectomy for treatment of large vessel acute ischemic stroke in children. J Neurointerv Surg 2 [Epub ahead of print]

69.

Trenor CC, Michelson AD (2010) Thrombophilia and paediatric stroke. Circulation 121:1795–1797PubMedCrossRef

70.

Vahedi K, Hofmeijer J, Juettler E et al (2007) Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol 6:215–222PubMedCrossRef

71.

van Beynum IM, Smeitink JA, den Heijer M et al (1999) Hyperhomocysteinemia: a risk factor for ischemic stroke in children. Circulation 99:2070–2072PubMedCrossRef

72.

Vannucci SJ, Hurn PD (2009) Gender differences in pediatric stroke: is elevated testosterone a risk factor for boys? Ann Neurol 66:713–714PubMedCrossRef

73.

Wasay M, Bakshi R, Kojan S et al (2001) Nonrandomized comparison of local urokinase thrombolysis versus systemic heparin anticoagulation for superior sagittal sinus thrombosis. Stroke 32:2310–2317PubMedCrossRef

74.

www.who.int/topics/cerebrovascualr_accident/en. Accessed 30 Jan 2012

Title: Therapy in pediatric stroke
Authors: B. Simma
I. Höliner
J. Luetschg
Publication date: 01-07-2013
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 7/2013
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-012-1863-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Therapy in pediatric stroke

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2013

The use of ethanol in paediatric formulations in New Zealand

Caroli disease, bilateral diffuse cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas: a ciliopathy caused by a homozygous NPHP3 mutation

Epidemiological changes in rotavirus gastroenteritis in children under 5 years of age after the introduction of rotavirus vaccines in Korea

Management of ADHD in children across Europe: patient demographics, physician characteristics and treatment patterns

Development of a mnemonic screening tool for identifying subjects with Hunter syndrome

Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature