Skip to main content
PMC home page
NeuroRx logoLink to NeuroRx
. 2012 Sep 5;3(2):133–142. doi: 10.1016/j.nurx.2006.01.003

Therapeutic approaches and advances in pediatric stroke

Adam Kirton 1, Gabrielle deVeber 1,✉
PMCID: PMC3593435  PMID: 16554252

Summary

Evidence-based therapeutic interventions for pediatric ischemic cerebrovascular disease are beginning to emerge. The primary therapeutic target is usually the pathological prothrombotic disturbance that underlies the majority of pediatric stroke. A battle between anticoagulation and anti-platelet therapies continues to provide controversy and is the inspiration for upcoming randomized trials. Supportive care and neuroprotective strategies are an important consideration in children with stroke. Attempts to determine the safety of acute thrombolytic interventions are also underway. Finally, unique medical and surgical treatments for specific diseases leading to stroke in children continue to evolve. After briefly summarizing the epidemiology, pathophysiology, diagnosis, and outcomes of ischemic strokes in children, treatment approaches and alternatives will be reviewed in detail with emphasis placed on current areas of controversy and future directions for clinical research.

Key Words: Cerebrovascular disease, pediatric stroke, child, anticoagulation

References

  • 1.Murphy SL. Deaths: final data for 1998. Natl Vital Stat Rep. 2000;48:1–105. [PubMed] [Google Scholar]
  • 2.Fullerton HJ, Chetkovich DM, Wu YW, Smith WS, Johnston SC. Deaths from stroke in US children, 1979 to 1998. Neurology. 2002;59:34–39. doi: 10.1212/WNL.59.1.34. [DOI] [PubMed] [Google Scholar]
  • 3.deVeber G. Canadian Paediatric Ischemic Stroke Study Group. Canadian Paediatric Ischemic Stroke Registry: Analysis of children with arterial ischemic stroke. Ann Neurol. 2000;48:514–514. [Google Scholar]
  • 4.Lynch JK, Hirtz DG, deVeber G, Nelson KB. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics. 2002;109:116–123. doi: 10.1542/peds.109.1.116. [DOI] [PubMed] [Google Scholar]
  • 5.deVeber G. Stroke and the child’s brain: an overview of epidemiology, syndromes and risk factors. Curr Opin Neurol. 2002;15:133–138. doi: 10.1097/00019052-200204000-00002. [DOI] [PubMed] [Google Scholar]
  • 6.Nelson KB, Lynch JK. Stroke in newborn infants. Lancet Neurol. 2004;3:150–158. doi: 10.1016/S1474-4422(04)00679-9. [DOI] [PubMed] [Google Scholar]
  • 7.Lynch JK. Cerebrovascular disorders in children. Curr Neurol Neurosci Rep. 2004;4:129–138. doi: 10.1007/s11910-004-0027-3. [DOI] [PubMed] [Google Scholar]
  • 8.Golomb MR, MacGregor DL, Domi T, Armstrong DC, Mc-Crindle BW, Mayank S, et al. Resumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. Ann Neurol. 2001;50:163–168. doi: 10.1002/ana.1078. [DOI] [PubMed] [Google Scholar]
  • 9.Chabrier S, Husson B, Lasjaunias P, Landrieu P, Tardieu M. Stroke in childhood: outcome and recurrence risk by mechanism in 59 patients. J Child Neurol. 2000;15:290–294. doi: 10.1177/088307380001500504. [DOI] [PubMed] [Google Scholar]
  • 10.Lanthier S, Carmant L, David M, Larbrisseau A, de Veber G. Stroke in children: the coexistence of multiple risk factors predicts poor outcome. Neurology. 2000;54:371–378. doi: 10.1212/WNL.54.2.371. [DOI] [PubMed] [Google Scholar]
  • 11.Ganesan V, Prengler M, McShane MA, Wade AM, Kirkham FJ. Investigation of risk factors in children with arterial ischemic stroke. Ann Neurol. 2003;53:167–173. doi: 10.1002/ana.10423. [DOI] [PubMed] [Google Scholar]
  • 12.Sebire G, Fullerton H, Riou E, deVeber G. Toward the definition of cerebral arteriopathies of childhood. Curr Opin Pediatr. 2004;16:617–622. doi: 10.1097/01.mop.0000144441.29899.20. [DOI] [PubMed] [Google Scholar]
  • 13.Fullerton HJ, Johnston SC, Smith WS. Arterial dissection and stroke in children. Neurology. 2001;57:1155–1160. doi: 10.1212/WNL.57.7.1155. [DOI] [PubMed] [Google Scholar]
  • 14.Chabrier S, Lasjaunias P, Husson B, Landrieu P, Tardieu M. Ischaemic stroke from dissection of the craniocervical arteries in childhood: report of 12 patients. Eur J Paediatr Neurol. 2003;7:39–42. doi: 10.1016/S1090-3798(02)00138-1. [DOI] [PubMed] [Google Scholar]
  • 15.Ishii K, Isono M, Kobayashi H, Kamida T. Temporal profile of angiographical stages of moyamoya disease: when does moyamoya disease progress? Neurol Res. 2003;25:405–410. doi: 10.1179/016164103101201571. [DOI] [PubMed] [Google Scholar]
  • 16.Steen RG, Xiong X, Langsten JW, Helton KJ. Brain injury in children with sickle cell disease: prevalence and etiology. Ann Neurol. 2003;54:564–572. doi: 10.1002/ana.10727. [DOI] [PubMed] [Google Scholar]
  • 17.Pegelow CH, Macklin EA, Moser FG, Wang WC, Bello JA, Miller ST, et al. Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease. Blood. 2002;99:3014–3018. doi: 10.1182/blood.V99.8.3014. [DOI] [PubMed] [Google Scholar]
  • 18.Shirane R, Sato S, Yoshimoto T. Angiographic findings of ischemic stroke in children. Childs Nervous System. 1992;8:432–436. doi: 10.1007/BF00274403. [DOI] [PubMed] [Google Scholar]
  • 19.Chabrier S, Rodesch G, Lasjaunias P, Tardieu M, Landrieu P, Sebire G. Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke. J Child Neurol. 1998;13:27–32. doi: 10.1177/088307389801300105. [DOI] [PubMed] [Google Scholar]
  • 20.Sebire G, Meyer L, Chabrier S. Varicella as a risk factor for cerebral infarction in childhood: a case-control study. Ann Neurol. 1999;45:679–680. doi: 10.1002/1531-8249(199905)45:5<679::AID-ANA22>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  • 21.Askalan R, Laughlin S, Mayank S, Chan A, MacGregor D, Andrew M, et al. Chickenpox and stroke in childhood: a study of frequency and causation. Stroke. 2001;32:1257–1262. doi: 10.1161/01.STR.32.6.1257. [DOI] [PubMed] [Google Scholar]
  • 22.Lanthier S, Lortie A, Michaud J, Laxer R, Jay V, deVeber G. Isolated angiitis of the CNS in children. Neurology. 2001;56:837–842. doi: 10.1212/WNL.56.7.837. [DOI] [PubMed] [Google Scholar]
  • 23.Gallagher KT, Shaham B, Reiff A, Tournay A, Villablanca JP, Curran J, et al. Primary angiitis of the central nervous system in children: 5 cases. J Rheumatol. 2001;28:616–623. [PubMed] [Google Scholar]
  • 24.Benseler S, Schneider R. Central nervous system vasculitis in children. Curr Opin Rheumatol. 2004;16:43–50. doi: 10.1097/00002281-200401000-00009. [DOI] [PubMed] [Google Scholar]
  • 25.Graf WK, Milstein JM, Sherry DD. Stroke and mixed connective tissue disease. J Child Neurol. 1993;8:256–259. doi: 10.1177/088307389300800309. [DOI] [PubMed] [Google Scholar]
  • 26.Takeoka M, Takahashi T. Infectious and inflammatory disorders of the circulatory system and stroke in childhood. Curr Opin Neurol. 2002;15:159–164. doi: 10.1097/00019052-200204000-00006. [DOI] [PubMed] [Google Scholar]
  • 27.Patsalides AD, Wood LV, Atac GK, Sandifer E, Butman JA, Patronas NJ. Cerebrovascular disease in HIV-infected pediatric patients: neuroimaging findings. AJR Am J Roentgenol. 2002;179:999–1003. doi: 10.2214/ajr.179.4.1790999. [DOI] [PubMed] [Google Scholar]
  • 28.Camacho A, Villarejo A, Moreno T, Simon R, Munoz A, Mateos F. Vertebral artery fibromuscular dysplasia: an unusual cause of stroke in a 3-year-old child. Dev Med Child Neurol. 2003;45:709–711. doi: 10.1111/j.1469-8749.2003.tb00875.x. [DOI] [PubMed] [Google Scholar]
  • 29.Omura M, Aida N, Sekido K, Kakehi M, Matsubara S. Large intracranial vessel occlusive vasculopathy after radiation therapy in children: clinical features and usefulness of magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 1997;38:241–249. doi: 10.1016/S0360-3016(97)82497-2. [DOI] [PubMed] [Google Scholar]
  • 30.Nezu A, Kimura S, Ohtsuki N, Tanaka M, Takebayashi S. Acute confusional migraine and migrainous infarction in childhood. Brain Dev. 1997;19:148–151. doi: 10.1016/S0387-7604(96)00551-7. [DOI] [PubMed] [Google Scholar]
  • 31.Santiago R, Dominguez M, Campos CJ. [Cerebral infarct in childhood as a complication of migraine with aura. A case report] Rev Neurol. 2001;33:1143–1148. [PubMed] [Google Scholar]
  • 32.Menache CC, du Plessis AJ, Wessel DL, Jonas RA, Newburger JW. Current incidence of acute neurologic complications after open-heart operations in children. Ann Thorac Surg. 2002;73:1752–1758. doi: 10.1016/S0003-4975(02)03534-8. [DOI] [PubMed] [Google Scholar]
  • 33.Domi T, Edgell D, McCrindle B.W, William G.W, MacGregor D, Kaplan D, et al. Frequency and predictors of vasoocclusive strokes associated with congenital heart disease. Ann Neurol. 2002;52:S129–133. doi: 10.1002/ana.5039. [DOI] [Google Scholar]
  • 34.Monagle P, Karl TR. Thromboembolic problems after the Fontan operation. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2002;5:36–47. doi: 10.1053/pcsu.2002.29716. [DOI] [PubMed] [Google Scholar]
  • 35.Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med. 2001;345:1740–1746. doi: 10.1056/NEJMoa011503. [DOI] [PubMed] [Google Scholar]
  • 36.Barnes C, deVeber G. Prothrombotic abnormalities in childhood ischaemic stroke.Submitted to Thrombosis Research 2004. [DOI] [PubMed]
  • 37.Nowak-Goettl U, von Eckardstein A, Junder R, Schuierer G, Strater R. Lipoprotein (a) and genetic polymorphisms of MTHFR TT677, factor V G1691A, and prothrombin G20210A are risk factors of spontaneous ischaemic stroke in childhood.Thromb Haemostas suppl: 1999. [PubMed]
  • 38.Hartfield DS, Lowry NJ, Keene DL, Yager JY. Iron deficiency: a cause of stroke in infants and children. Pediatr Neurol. 1997;16:50–53. doi: 10.1016/S0887-8994(96)00290-1. [DOI] [PubMed] [Google Scholar]
  • 39.Gunther G, Junker R, Strater R, Schobess R, Kumik K, Kosch A, et al. Symptomatic ischemic stroke in full-term neonates:role of acquired and genetic prothrombotic risk factors. Stroke. 2000;31:2437–2441. doi: 10.1161/01.STR.31.10.2437. [DOI] [PubMed] [Google Scholar]
  • 40.Lee J, Croen LA, Lindan C, Nash KB, Yoshida CK, Ferriero DM, et al. Predictors of outcome in perinatal arterial stroke: A population-based study. Ann Neurol. 2005;58:303–308. doi: 10.1002/ana.20557. [DOI] [PubMed] [Google Scholar]
  • 41.Iizuka T, Sakai F, Suzuki N, Hata T, Tsukahara S, Fukuda M, et al. Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome. Neurology. 2002;59:816–824. doi: 10.1212/WNL.59.6.816. [DOI] [PubMed] [Google Scholar]
  • 42.Desnick RJ, Brady RO. Fabry disease in childhood. J Pediatr. 2004;144:S20–S26. doi: 10.1016/j.jpeds.2004.01.051. [DOI] [PubMed] [Google Scholar]
  • 43.Guillamo JS, Creange A, Kalifa C, Grill J, Rodriguez D, Doz F, et al. Prognostic factors of CNS tumours in Neurofibromatosis 1 (NF1): a retrospective study of 104 patients. Brain. 2003;126:152–160. doi: 10.1093/brain/awg016. [DOI] [PubMed] [Google Scholar]
  • 44.Bhattacharya JJ, Luo CB, Alvarez H, Rodesch G, Pongpech S, Lasjaunias PL. PHACES syndrome: a review of eight previously unreported cases with late arterial occlusions. Neuroradiology. 2004;46:227–233. doi: 10.1007/s00234-002-0902-z. [DOI] [PubMed] [Google Scholar]
  • 45.Ho J, Pacaud D, Hill MD, Ross C, Hamiwka L, Mah JK. Diabetic ketoacidosis and pediatric stroke. CMAJ. 2005;172:327–328. doi: 10.1503/cmaj.1032013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Igarashi M, Roy S, Stapleton FB. Cerebrovascular complications in children with nephrotic syndrome. Pediatr Neurol. 1988;4:362–365. doi: 10.1016/0887-8994(88)90084-7. [DOI] [PubMed] [Google Scholar]
  • 47.deVeber G, Andrew M. Canadian Pediatric Ischemic Stroke Study Group. Cerebral sinovenous thrombosis in children. N Engl J Med. 2001;345:417–423. doi: 10.1056/NEJM200108093450604. [DOI] [PubMed] [Google Scholar]
  • 48.Heller C, Heinecke A, Junker R, Knofler R, Kosch A, Kurnik K, et al. Cerebral venous thrombosis in children: a multifactorial origin. Circulation. 2003;108:1362–1367. doi: 10.1161/01.CIR.0000087598.05977.45. [DOI] [PubMed] [Google Scholar]
  • 49.Sebire G, Tabarki B, Saunders DE, Leroy I, Liesner R, Saint-Martin C, et al. Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. Brain. 2005;128:477–489. doi: 10.1093/brain/awh412. [DOI] [PubMed] [Google Scholar]
  • 50.Demierre B, Rondot P. Dystonia caused by putamino-capsulocaudate vascular lesions. J Neurol Neurosurg Psychiatry. 1983;46:404–409. doi: 10.1136/jnnp.46.5.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Ganesan V, Chong WK, Cox TC, Chawda SJ, Prengler M, Kirkham FJ. Posterior circulation stroke in childhood: risk factors and recurrence. Neurology. 2002;59:1552–1556. doi: 10.1212/01.WNL.0000033092.87560.1A. [DOI] [PubMed] [Google Scholar]
  • 52.Trescher WH. Ischemic stroke syndromes in childhood. Pediatr Ann. 1992;21:374–383. doi: 10.3928/0090-4481-19920601-10. [DOI] [PubMed] [Google Scholar]
  • 53.Delsing BJ, Catsman-Berrevoets CE, Appel IM. Early prognostic indicators of outcome in ischemic childhood stroke. Pediatr Neurol. 2001;24:283–289. doi: 10.1016/S0887-8994(01)00245-4. [DOI] [PubMed] [Google Scholar]
  • 54.Carvalho KS, Bodensteiner JB, Connolly PJ, Garg BP. Cerebral venous thrombosis in children. J Child Neurol. 2001;16:574–580. doi: 10.1177/088307380101600807. [DOI] [PubMed] [Google Scholar]
  • 55.Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics. 2002;110:924–928. doi: 10.1542/peds.110.5.924. [DOI] [PubMed] [Google Scholar]
  • 56.Strater R, Becker S, von Eckardstein A, Heinecke A, Gutsche S, Junker R, et al. Prospective assessment of risk factors for recurrent stroke during childhood-a 5-year follow-up study. Lancet. 2002;360:1540–1545. doi: 10.1016/S0140-6736(02)11520-0. [DOI] [PubMed] [Google Scholar]
  • 57.Hunter JV. New radiographic techniques to evaluate cerebrovascular disorders in children. Semin Pediatr Neurol. 2000;7:261–277. doi: 10.1053/spen.2000.20226. [DOI] [PubMed] [Google Scholar]
  • 58.Ganesan V, Savvy L, Chong WK, Kirkham FJ. Conventional cerebral angiography in children with ischemic stroke. Pediatr Neurol. 1999;20:38–42. doi: 10.1016/S0887-8994(98)00112-X. [DOI] [PubMed] [Google Scholar]
  • 59.Husson B, Lasjaunias P. Radiological approach to disorders of arterial brain vessels associated with childhood arterial stroke-a comparison between MRA and contrast angiography. Pediatr Radiol. 2004;34:10–15. doi: 10.1007/s00247-003-1109-0. [DOI] [PubMed] [Google Scholar]
  • 60.Golomb MR, Dick PT, MacGregor DL, Armstrong DC, deVeber GA. Cranial ultrasonography has a low sensitivity for detecting arterial ischemic stroke in term neonates. J Child Neurol. 2003;18:98–103. doi: 10.1177/08830738030180021401. [DOI] [PubMed] [Google Scholar]
  • 61.Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998;339:5–11. doi: 10.1056/NEJM199807023390102. [DOI] [PubMed] [Google Scholar]
  • 62.Shroff M, deVeber G. Sinovenous thrombosis in children. Neuroimaging Clin N Am. 2003;13:115–138. doi: 10.1016/S1052-5149(02)00064-3. [DOI] [PubMed] [Google Scholar]
  • 63.Farb RI, Scott JN, Willinsky RA, Montanera WJ, Wright GA, terBrugge KG. Intracranial venous system: gadolinium-enhanced three-dimensional MR venography with auto-triggered elliptic centric-ordered sequence-initial experience. Radiology. 2003;226:203–209. doi: 10.1148/radiol.2261020670. [DOI] [PubMed] [Google Scholar]
  • 64.Ferriero DM. Neonatal brain injury. N Engl J Med. 2004;351:1985–1995. doi: 10.1056/NEJMra041996. [DOI] [PubMed] [Google Scholar]
  • 65.Lynch J, Hirtz D, deVeber G, Nelson K. Report of the national institute of neurological disorders and stroke workshop on perinatal and childhood stroke.Pediatr (submitted) 2001. [DOI] [PubMed]
  • 66.deVeber G, MacGregor D, Curtis R, Friefeld S, Anderson P, Chan A, et al. Neurological Outcome in Survivors of Neonatal Arterial Ischemic Stroke. Pediatr Res. 2003;53:537A–537A. doi: 10.1203/01.PDR.0000063362.91000.AB. [DOI] [Google Scholar]
  • 67.deVeber G, MacGregor D, Curtis R, Mayank S. Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis. J Child Neurol. 2000;15:316–324. doi: 10.1177/088307380001500508. [DOI] [PubMed] [Google Scholar]
  • 68.Ganesan V, Hogan A, Shack N, Gordon A, Isaacs E, Kirkham FJ. Outcome after ischaemic stroke in childhood. Dev Med Child Neurol. 2000;42:455–461. doi: 10.1017/S0012162200000852. [DOI] [PubMed] [Google Scholar]
  • 69.Hurvitz EA, Beale L, Ried S, Nelson VS. Functional outcome of paediatric stroke survivors. Pediatr Rehabil. 1999;3:43–51. doi: 10.1080/136384999289577. [DOI] [PubMed] [Google Scholar]
  • 70.Max JE, Mathews K, Lansing AE, Robertson BA, Fox PT, Lancaster JL, et al. Psychiatric disorders after childhood stroke. J Am Acad Child Adolesc Psychiatry. 2002;41:555–562. doi: 10.1097/00004583-200205000-00013. [DOI] [PubMed] [Google Scholar]
  • 71.Lansing AE, Max JE, Delis DC, Fox PT, Lancaster J, Manes FF, et al. Verbal learning and memory after childhood stroke. J Int Neuropsychol Soc. 2004;10:742–752. doi: 10.1017/S1355617704105122. [DOI] [PubMed] [Google Scholar]
  • 72.Yang JS, Yong DP, Hartlage P. Seizures associated with stroke in childhood. Pediatr Neurol. 1995;12:136–138. doi: 10.1016/0887-8994(94)00152-R. [DOI] [PubMed] [Google Scholar]
  • 73.Kwak CH, Jankovic J. Tourettism and dystonia after subcortical stroke. Mov Disord. 2002;17:821–825. doi: 10.1002/mds.10207. [DOI] [PubMed] [Google Scholar]
  • 74.Boardman JP, Ganesan V, Rutherford MA, Saunders DE, Mercuri E, Cowan F. Magnetic resonance image correlates of hemiparesis after neonatal and childhood middle cerebral artery stroke. Pediatrics. 2005;115:321–326. doi: 10.1542/peds.2004-0427. [DOI] [PubMed] [Google Scholar]
  • 75.De Schryver EL, Blom I, Braun KP, Kappelle LJ, Rinkel GJ, Peters AC, et al. Long-term prognosis of cerebral venous sinus thrombosis in childhood. Dev Med Child Neurol. 2004;46:514–519. doi: 10.1111/j.1469-8749.2004.tb01008.x. [DOI] [PubMed] [Google Scholar]
  • 76.Gordon AL, Ganesan V, Towell A, Kirkham FJ. Functional outcome following stroke in children. J Child Neurol. 2002;17:429–434. doi: 10.1177/088307380201700606. [DOI] [PubMed] [Google Scholar]
  • 77.Friefeld S, Yeboah O, Jones JE, deVeber G. Health-related quality of life and its relationship to neurological outcome in child survivors of stroke. CNS Spectr. 2004;9:465–475. doi: 10.1017/s1092852900009500. [DOI] [PubMed] [Google Scholar]
  • 78.Monagle P, Chan A, Massicotte P, Chalmers E, Michelson AD. Antithrombotic Therapy in Children: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:645S–687S. doi: 10.1378/chest.126.3_suppl.645S. [DOI] [PubMed] [Google Scholar]
  • 79.Paediatric Sfroke Working Group. Sfroke in Childhood: Clinical Guidelines for Diagnosis, Management and Rehabilitation. Available at: http://www.rcplondon.ac.uk/pubs/books/childstroke/, accessed July 12, 2005.
  • 80.deVeber G. In pursuit of evidence-based treatments for paediatric stroke: the UK and Chest guidelines. Lancet Neurol. 2005;4:432–436. doi: 10.1016/S1474-4422(05)70120-4. [DOI] [PubMed] [Google Scholar]
  • 81.Gruber A, Nasel C, Lang W, Kitzmuller E, Bavinzski G, Czech T. Intra-arterial thrombolysis for the treatment of perioperative childhood cardioembolic sfroke. Neurology. 2000;54:1684–1686. doi: 10.1212/WNL.54.8.1684. [DOI] [PubMed] [Google Scholar]
  • 82.Carlson MD, Leber S, Deveikis J, Silverstein FS. Successful use of rt-PA in pediatric stroke. Neurology. 2001;57:157–158. doi: 10.1212/WNL.57.1.157. [DOI] [PubMed] [Google Scholar]
  • 83.Noser EA, Felberg RA, Alexandrov AV. Thrombolytic therapy in an adolescent ischemic sfroke. J Child Neurol. 2001;16:286–288. doi: 10.1177/088307380101600410. [DOI] [PubMed] [Google Scholar]
  • 84.Kirton A, Wong JH, Mah J, Ross BC, Kennedy J, Bell K, et al. Successful endovascular therapy for acute basilar thrombosis in an adolescent. Pediatrics. 2003;112:e248–e251. doi: 10.1542/peds.112.3.e248. [DOI] [PubMed] [Google Scholar]
  • 85.Golomb MR, Rafay M, Armstrong D, Massicotte P, Curtis R, Hune S, et al. Infra-arterial tissue plasminogen activator for thrombosis complicating cerebral angiography in a 17-year-old girl. J Child Neurol. 2003;18:420–423. doi: 10.1177/08830738030180060301. [DOI] [PubMed] [Google Scholar]
  • 86.NINDS TPA, The National Institute of Neurological Disorders and Sfroke rt-PA Stroke Study Group Tissue plasminogen activator for acute ischemic sfroke. N Engl J Med. 1995;333:1580–1587. [Google Scholar]
  • 87.Meschia JF, Miller DA, Brott TG. Thrombolytic treatment of acute ischemic sfroke. Mayo Clin Proc. 2002;77:542–551. doi: 10.4065/77.6.542. [DOI] [PubMed] [Google Scholar]
  • 88.Hill MD, Buchan AM. Thrombolysis for acute ischemic sfroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ. 2005;172:1307–1312. doi: 10.1503/cmaj.1041561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Monagle P, Michelson AD, Bovill E, Andrew M. Antithrombotic therapy in children. Chest. 2001;119:344S–370S. doi: 10.1378/chest.119.1_suppl.344S. [DOI] [PubMed] [Google Scholar]
  • 90.Cognard C, Weill A, Lindgren S, Piotin M, Castaings L, Moret J. Basilar artery occlusion in a child: “clot angioplasty” followed by thrombolysis. Childs Nerv Syst. 2000;16:496–500. doi: 10.1007/s003819900197. [DOI] [PubMed] [Google Scholar]
  • 91.Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood. 1992;80:1998–2005. [PubMed] [Google Scholar]
  • 92.Burak CR, Bowen MD, Barron TF. The use of enoxaparin in children with acute, nonhemorrhagic ischemic stroke. Pediatr Neurol. 2003;29:295–298. doi: 10.1016/S0887-8994(03)00270-4. [DOI] [PubMed] [Google Scholar]
  • 93.Dix D, Andrew M, Marzinotto V, Charpentier K, Bridge S, Monagle P, et al. The use of low molecular weight heparin in pediatric patients: a prospective cohort study. J Pediatr. 2000;136:439–445. doi: 10.1016/S0022-3476(00)90005-2. [DOI] [PubMed] [Google Scholar]
  • 94.Strater R, Kumik K, Heller C, Schobess R, Luigs P, Nowak-Goettl U. Aspirin versus low-dose low-molecular-weight heparin: antithrombotic therapy in pediatric ischemic stroke patients: a prospective follow-up study. Stroke. 2001;32:2554–2558. doi: 10.1161/hs1101.097379. [DOI] [PubMed] [Google Scholar]
  • 95.Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen JE. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest. 1998;114:489S–510S. doi: 10.1378/chest.114.5_Supplement.489S. [DOI] [PubMed] [Google Scholar]
  • 96.Andrew M, Marzinotto V, Massicotte P, Blanchette V, Ginsberg J, Brill-Edwards P, et al. Heparin therapy in pediatric patients: a prospective cohort study. Pediatr Res. 1994;35:78–83. doi: 10.1203/00006450-199401000-00016. [DOI] [PubMed] [Google Scholar]
  • 97.Newall F, Barnes C, Ignjatovic V, Monagle P. Heparin-induced thrombocytopenia in children. J Paediatr Child Health. 2003;39:289–292. doi: 10.1046/j.1440-1754.2003.00139.x. [DOI] [PubMed] [Google Scholar]
  • 98.Massicotte P, Adams M, Marzinotto V, Brooker LA, Andrew M. Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study. J Pediatr. 1996;128:313–318. doi: 10.1016/S0022-3476(96)70273-1. [DOI] [PubMed] [Google Scholar]
  • 99.Maiti B, Chakrabarti I. Study in cerebral venous thrombosis with specific reference to efficacy of heparin. J Neurol Sci. 1997;150:S147–S147. doi: 10.1016/S0022-510X(97)85563-3. [DOI] [Google Scholar]
  • 100.Stam J, de Bruijn S, deVeber G. Anticoagulation for cerebral sinus thrombosis. Stroke. 2003;34:1054–1055. doi: 10.1161/01.STR.0000062344.87396.72. [DOI] [PubMed] [Google Scholar]
  • 101.Reter M, Tzourio C, Amen A, Bousser MG. Long term prognosis in cerebral venous thrombosis: Followup of 77 patients. Stroke. 1996;27:243–246. doi: 10.1161/01.STR.27.2.243. [DOI] [PubMed] [Google Scholar]
  • 102.deVeber G, Chan A, Monagle P, Marzinotto V, Armstrong D, Massicotte P, et al. Anticoagulation therapy in pediatric patients with sinovenous thrombosis: a cohort study. Arch Neurol. 1998;55:1533–1537. doi: 10.1001/archneur.55.12.1533. [DOI] [PubMed] [Google Scholar]
  • 103.Ciccone A, Canhao P, Falcao F, Ferro JM, Sterzi R. Thrombolysis for cerebral vein and durai sinus thrombosis.Cochrane Database Syst RevCD003693-2004. [DOI] [PMC free article] [PubMed]
  • 104.Griesemer DA, Theodorou AA, Berg RA, Spera TD. Local fibrinolysis in cerebral venous thrombosis. Pediatr Neurol. 1994;10:78–80. doi: 10.1016/0887-8994(94)90075-2. [DOI] [PubMed] [Google Scholar]
  • 105.Wong VK, LeMesurier J, Franceschini R, Heikali M, Hanson R. Cerebral venous thrombosis as a cause of neonatal seizures. Pediatr Neurol. 1987;3:235–237. doi: 10.1016/0887-8994(87)90026-9. [DOI] [PubMed] [Google Scholar]
  • 106.Hutchison JS, Ichord R, Guerguerian AM, deVeber G. Cerebro-vascular disorders. Semin Pediatr Neurol. 2004;11:139–146. doi: 10.1016/j.spen.2004.04.004. [DOI] [PubMed] [Google Scholar]
  • 107.Becker K. Intensive care unit management of the sfroke patient. Neurol Clin. 2000;18:439–454. doi: 10.1016/S0733-8619(05)70201-2. [DOI] [PubMed] [Google Scholar]
  • 108.Yager JY, Thomhill JA. The effect of age on susceptibility to hypoxic-ischemic brain damage. Neurosci Biobehav Rev. 1997;21:167–174. doi: 10.1016/S0149-7634(96)00006-1. [DOI] [PubMed] [Google Scholar]
  • 109.Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, et al. Persistent postsfroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003;34:2208–2214. doi: 10.1161/01.STR.0000085087.41330.FF. [DOI] [PubMed] [Google Scholar]
  • 110.Volpe JJ. Perinatal brain injury: from pathogenesis to neuroprotection. Ment Retard Dev Disabil Res Rev. 2001;7:56–64. doi: 10.1002/1098-2779(200102)7:1<56::AID-MRDD1008>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  • 111.Wirrell EC, Armstrong EA, Osman LD, Yager JY. Prolonged seizures exacerbate perinatal hypoxic-ischemic brain damage. Pediatr Res. 2001;50:445–454. doi: 10.1203/00006450-200110000-00005. [DOI] [PubMed] [Google Scholar]
  • 112.Sugawara T, Fujimura M, Noshita N, Kim GW, Saito A, Hayashi T, et al. Neuronal death/survival signaling pathways in cerebral ischemia. NeuroRx. 2004;1:17–25. doi: 10.1602/neurorx.1.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 113.Cho DY, Chen TC, Lee HC. Ultra-early decompressive craniectomy for malignant middle cerebral artery infarction. Surg Neurol. 2003;60:227–232. doi: 10.1016/S0090-3019(03)00266-0. [DOI] [PubMed] [Google Scholar]
  • 114.Gupta R, Connolly ES, Mayer S, Elkind MS. Hemicraniectomy for massive middle cerebral artery territory infarction: a systematic review. Stroke. 2004;35:539–543. doi: 10.1161/01.STR.0000109772.64650.18. [DOI] [PubMed] [Google Scholar]
  • 115.Kirkham F, deVeber G, Chan A, Strater R, Ganesan V, Prengler M, Nowak-Gottl U. Recurrent arterial ischemic sfroke: The role of prothrombotic disorders. Ann Neurol. 2003;54(Supp 7):S110–S110. [Google Scholar]
  • 116.deVeber G, Monagle P, Chan A, MacGregor D, Curtis R, Lee S, et al. Prothrombotic disorders in infants and children with cerebral thromboembolism. Arch Neurol. 1998;55:1539–1543. doi: 10.1001/archneur.55.12.1539. [DOI] [PubMed] [Google Scholar]
  • 117.Lanthier S, Kirkham FJ, Mitchell LG, Laxer RM, Atenafu E, Male C, et al. Increased anticardiolipin antibody IgG titers do not predict recurrent stroke or TIA in children. Neurology. 2004;62:194–200. doi: 10.1212/WNL.62.2.194. [DOI] [PubMed] [Google Scholar]
  • 118.Kumik K, Kosch A, Sfrater R, Schobess R, Heller C, Nowak-Gottl U. Recurrent thromboembolism in infants and children suffering from symptomatic neonatal arterial sfroke: a prospective follow-up study. Stroke. 2003;34:2887–2892. doi: 10.1161/01.STR.0000103745.03393.39. [DOI] [PubMed] [Google Scholar]
  • 119.Sandercock PA, van den Belt AG, Lindley RI, Slattery J. Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials [see comments] J Neurol Neurosurg Psychiatry. 1993;56:17–25. doi: 10.1136/jnnp.56.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 120.Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic sfroke. Chest. 2001;119:300S–320S. doi: 10.1378/chest.119.1_suppl.300S. [DOI] [PubMed] [Google Scholar]
  • 121.Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345:1444–1451. doi: 10.1056/NEJMoa011258. [DOI] [PubMed] [Google Scholar]
  • 122.Nowak-Goettl U, Straeter R, Sebire G, Kirkham F. Antithrombotic drug treatment of pediatric patients with ischemic sfroke. Paediatr Drugs. 2003;5:167–175. doi: 10.2165/00128072-200305030-00003. [DOI] [PubMed] [Google Scholar]
  • 123.Domi T, Thomas S, Rand M, Chan AK, Lanthier S, Clarke D, deVeber G. A study of platelet response to aspirin in children with arterial ischemic sfroke utilizing the PFA 100 analyzer. Stroke. 2005;35(1):P284–P284. [Google Scholar]
  • 124.Hune S, Rafay MF, Domi T, Allen A, Chan C, deVeber G. Plavix (Clopidogrel) in Pediatric Sfroke: Monitoring of side effects and patient education strategies. Stroke. 2004;35:284–284. [Google Scholar]
  • 125.Golomb MR, Hune S, MacGregor DL, deVeber GA. Alternative therapy use by Chinese-Canadian children with stroke and cerebrovascular disease. J Child Neurol. 2003;18:714–717. doi: 10.1177/08830738030180100201. [DOI] [PubMed] [Google Scholar]
  • 126.Wolters HJ, ten Cate H, Thomas LL, Brandjes DP, van der EA, van der HY, et al. Low-intensity oral anticoagulation in sickle-cell disease reverses the prethrombotic state: promises for treatment? Br J Haematol. 1995;90:715–717. doi: 10.1111/j.1365-2141.1995.tb05607.x. [DOI] [PubMed] [Google Scholar]
  • 127.Sumoza A, de Bisotti R, Sumoza D, Fairbanks V. Hydroxyurea (HU) for prevention of recurrent stroke in sickle cell anemia (SCA) Am J Hematol. 2002;71:161–165. doi: 10.1002/ajh.10205. [DOI] [PubMed] [Google Scholar]
  • 128.Kirkham FJ, Hewes DK, Prengler M, Wade A, Lane R, Evans JP. Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease. Lancet. 2001;357:1656–1659. doi: 10.1016/S0140-6736(00)04821-2. [DOI] [PubMed] [Google Scholar]
  • 129.Mikulis DJ, Krolczyk G, Desal H, Logan W, deVeber G, Dirks P, et al. Preoperative and postoperative mapping of cerebrovascular reactivity in moyamoya disease by using blood oxygen level-dependent magnetic resonance imaging. J Neurosurg. 2005;103:347–355. doi: 10.3171/jns.2005.103.2.0347. [DOI] [PubMed] [Google Scholar]
  • 130.Fung LW, Thompson D, Ganesan V. Revascularisation surgery for paediatric moyamoya: a review of the literature. Childs Nerv Syst. 2005;21:358–364. doi: 10.1007/s00381-004-1118-9. [DOI] [PubMed] [Google Scholar]
  • 131.Kim SK, Seol HJ, Cho BK, Hwang YS, Lee DS, Wang KC. Moyamoya disease among young patients: its aggressive clinical course and the role of active surgical treatment. Neurosurgery. 2004;54:840–844. doi: 10.1227/01.NEU.0000114140.41509.14. [DOI] [PubMed] [Google Scholar]
  • 132.Taub E, Ramey SL, DeLuca S, Echols K. Efficacy of constraint-induced movement therapy for children with cerebral palsy with asymmetric motor impairment. Pediatrics. 2004;113:305–312. doi: 10.1542/peds.113.2.305. [DOI] [PubMed] [Google Scholar]

Articles from NeuroRx are provided here courtesy of Am. Soc. for Experimental NeuroTherapeutics

RESOURCES