A Clinical Approach to Arterial Ischemic Childhood Stroke: Increasing Knowledge over the Last Decade

Abstract

Childhood stroke is increasingly being recognized as an important burden not only for affected children and families, but also for socioeconomic reasons. A primary problem is delayed diagnosis, due to the many mimics of childhood stroke, and the variety of manifesting symptoms. The most important is hemiparesis (with/without dysphasia or facial palsy), but ataxia, seizures, and many more are also possible. Suspicion of stroke has to be ascertained by neuroimaging, gold standard being (diffusion weighted) magnetic resonance. Risk factors are multiple, but their presence might help to increase the suspicion of stroke. The most important factors are infectious/parainfectious etiologies, frequently possibly manifesting by transient focal cerebral arteriopathy (FCA). Cardiological underlying problems are the second most important. Arteriopathies can be detected in about half of the children, besides FCA and dissection and MoyaMoya disease are the most important. Hereditary coagulopathies increase the risk of stroke. There is still a controversy on best treatment in children: platelet antiaggregation and heparinization are used about equally. Thrombolysis is being discussed increasingly. Severity of symptoms at manifestation and on follow-up are not less significant in children than in young adults. About two-third of the children have significant residual neurological problems and a majority cognitive and behavior problems.

Keywords

childhood stroke - risk factors - etiology - treatment - manifestation - outcome

• References

• 1 Amlie-Lefond C, Sébire G, Fullerton HJ. Recent developments in childhood arterial ischaemic stroke. Lancet Neurol 2008; 7 (5) 425-435
• 2 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 (1) 116-123
• 3 Mallick AA, Ganesan V, O'Callaghan FJ. Mortality from childhood stroke in England and Wales, 1921-2000. Arch Dis Child 2010; 95 (1) 12-19
• 4 Gardner MA, Hills NK, Sidney S, Johnston SC, Fullerton HJ. The 5-year direct medical cost of neonatal and childhood stroke in a population-based cohort. Neurology 2010; 74 (5) 372-378
• 5 Steinlin M, Pfister I, Pavlovic J , et al; Swiss Societies of Paediatric Neurology and Neonatology. The first three years of the Swiss Neuropaediatric Stroke Registry (SNPSR): a population-based study of incidence, symptoms and risk factors. Neuropediatrics 2005; 36 (2) 90-97
• 6 Agrawal N, Johnston SC, Wu YW, Sidney S, Fullerton HJ. Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke 2009; 40 (11) 3415-3421
• 7 Golomb MR, Fullerton HJ, Nowak-Gottl U, Deveber G ; International Pediatric Stroke Study Group. Male predominance in childhood ischemic stroke: findings from the international pediatric stroke study. Stroke 2009; 40 (1) 52-57
• 8 Tan MA, DeVeber G, Kirton A, Vidarsson L, MacGregor D, Shroff M. Low detection rate of craniocervical arterial dissection in children using time-of-flight magnetic resonance angiography: causes and strategies to improve diagnosis. J Child Neurol 2009; 24 (10) 1250-1257
• 9 Bernard TJ, Goldenberg NA. Pediatric arterial ischemic stroke. Hematol Oncol North Am 2010; 24: 167-80
• 10 Bernard TJ, Goldenberg NA. Pediatric arterial ischemic stroke. Pediatr Clin North Am 2008; 55 (2) 323-338 , viii
• 11 Fox CK, Fullerton HJ. Recent advances in childhood arterial ischemic stroke. Curr Atheroscler Rep 2010; 12 (4) 217-224
• 12 Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan V ; International Pediatric Stroke Study Group. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol 2011; 69 (1) 130-140
• 13 Monagle P, Chan A, Massicotte P , et al. Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 645-687S
• 14 Roach ES, Golomb MR, Adams R , et al; American Heart Association Stroke Council ; Council on Cardiovascular Disease in the Young. 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 2008; 39 (9) 2644-2691
• 15 Royal College of Physicians, Pediatric Stroke Working Group. Stroke in childhood: clinical guidelines for diagnosis, management and rehabilitation. 2004
• 16 Martin C, von Elm E, El Koussy M, Boltshauser E, Steinlin M. Delayed diagnosis of acute ischemic stroke in children: a registry based study in Switzerland. Swiss Med Wkly 2011; 19 141w 13281
• 17 McGlennan C, Ganesan V. Delays in investigation and management of acute arterial ischaemic stroke in children. Dev Med Child Neurol 2008; 50 (7) 537-540
• 18 Rafay MF, Pontigon AM, Chiang J , et al. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke 2009; 40 (1) 58-64
• 19 Srinivasan J, Miller SP, Phan TG, Mackay MT. Delayed recognition of initial stroke in children: need for increased awareness. Pediatrics 2009; 124 (2) e227 –e234
• 20 Shellhaas RA, Smith SE, O'Tool E, Licht DJ, Ichord RN. Mimics of childhood stroke: characteristics of a prospective cohort. Pediatrics 2006; 118 (2) 704-709
• 21 Braun KP, Kappelle LJ, Kirkham FJ, Deveber G. Diagnostic pitfalls in paediatric ischaemic stroke. Dev Med Child Neurol 2006; 48 (12) 985-990
• 22 Everts R, Lidzba K, Wilke M , et al. Strengthening of laterality of verbal and visuospatial functions during childhood and adolescence. Hum Brain Mapp 2009; 30 (2) 473-483
• 23 Adams RJ, McKie VC, Hsu L , 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 (1) 5-11
• 24 Thompson JK. Diagnosis of head pain: an idiographic approach to assessment and classification. Headache 1982; 22 (5) 221-232
• 25 Fullerton HJ, Johnston SC, Smith WS. Arterial dissection and stroke in children. Neurology 2001; 57 (7) 1155-1160
• 26 Rafay MF, Armstrong D, Deveber G, Domi T, Chan A, MacGregor DL. Craniocervical arterial dissection in children: clinical and radiographic presentation and outcome. J Child Neurol 2006; 21 (1) 8-16
• 27 Krasravi N, Leung A, Silver I, Burneo JG. Dissection of the internal carotid artery causing Horner syndrome and palsy of nerve XII. CMAJ 2010; 15: 182
• 28 Abend NS, Beslow LA, Smith SE , et al. Seizures as a presenting symptom of acute arterial ischemic stroke in childhood. J Pediatr 2011; 159 (3) 479-483
• 29 Shing RK, Zecavati N, Shing J , et al. Seizures in childhood stroke. J Pediatr 2011;
• 30 Yock-Corrales A, Mackay MT, Mosley I, Maixner W, Babl FE. Acute childhood arterial ischemic and hemorrhagic stroke in the emergency department. Ann Emerg Med 2011; 58 (2) 156-163
• 31 Zimmer JA, Garg BP, Williams LS, Golomb MR. Age-related variation in presenting signs of childhood arterial ischemic stroke. Pediatr Neurol 2007; 37 (3) 171-175
• 32 Buerki S, Roellin K, Remonda L , et al. Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies. Dev Med Child Neurol 2010; 52 (11) 1033-1037
• 33 Jones BP, Ganesan V, Saunders DE, Chong WK. Imaging in childhood arterial ischaemic stroke. Neuroradiology 2010; 52 (6) 577-589
• 34 Bash S, Villablanca JP, Jahan R , et al. Intracranial vascular stenosis and occlusive disease: evaluation with CT angiography, MR angiography, and digital subtraction angiography. AJNR Am J Neuroradiol 2005; 26 (5) 1012-1021
• 35 Shah GV, Quint DJ, Trobe JD. Magnetic resonance imaging of suspected cervicocranial arterial dissections. J Neuroophthalmol 2004; 24 (4) 315-318
• 36 Provenzale JM, Sarikaya B. Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature. AJR Am J Roentgenol 2009; 193 (4) 1167-1174
• 37 Nebelsieck J, Sengelhoff C, Nassenstein I , et al. Sensitivity of neurovascular ultrasound for the detection of spontaneous cervical artery dissection. J Clin Neurosci 2009; 16 (1) 79-82
• 38 Amlie-Lefond C, Bernard TJ, Sébire G , et al; International Pediatric Stroke Study Group. Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study. Circulation 2009; 119 (10) 1417-1423
• 39 Fullerton HJ, Wu YW, Sidney S, Johnston SC. Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging. Pediatrics 2007; 119 (3) 495-501
• 40 Mallick AA, O'Callaghan FJ. Risk factors and treatment outcomes of childhood stroke. Expert Rev Neurother 2010; 10 (8) 1331-1346
• 41 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 (1) 39-42
• 42 Guillon B, Bousser MG. [Epidemiology and pathophysiology of spontaneous cervical artery dissection]. J Neuroradiol 2002; 29 (4) 241-249
• 43 Lotze TE, Paolicchi J. Vertebral artery dissection and migraine headaches in children. J Child Neurol 2000; 15 (10) 694-696
• 44 Smith ER, Scott RM. Moyamoya: epidemiology, presentation, and diagnosis. Neurosurg Clin N Am 2010; 21 (3) 543-551
• 45 Hajj-Ali RA, Singhal AB, Benseler S, Molloy E, Calabrese LH. Primary angiitis of the CNS. Lancet Neurol 2011; 10 (6) 561-572
• 46 Amlie-Lefond C, Fullerton HJ. Rashes, sniffles, and stroke: a role for infection in ischemic stroke of childhood. Infect Disord Drug Targets 2010; 10 (2) 67-75
• 47 Bernard TJ, Fenton LZ, Apkon SD , et al. Biomarkers of hypercoagulability and inflammation in childhood-onset arterial ischemic stroke. J Pediatr 2010; 156 (4) 651-656
• 48 Amlie-Lefond C, Jubelt B. Neurologic manifestations of varicella zoster virus infections. Curr Neurol Neurosci Rep 2009; 9 (6) 430-434
• 49 Askalan R, Laughlin S, Mayank S , et al. Chickenpox and stroke in childhood: a study of frequency and causation. Stroke 2001; 32 (6) 1257-1262
• 50 Berger TM, Caduff JH, Gebbers JO. Fatal varicella-zoster virus antigen-positive giant cell arteritis of the central nervous system. Pediatr Infect Dis J 2000; 19 (7) 653-656
• 51 Riou EM, Amlie-Lefond C, Echenne B, Farmer M, Sébire G. Cerebrospinal fluid analysis in the diagnosis and treatment of arterial ischemic stroke. Pediatr Neurol 2008; 38 (1) 1-9
• 52 Wang JJ, Jiang LQ, He B, Shi KL, Li JW, Zou LP. The association of CTLA-4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population. Int J Immunogenet 2009; 36 (2) 113-118
• 53 Enenstein J, Milbauer L, Domingo E , et al. Proinflammatory phenotype with imbalance of KLF2 and RelA: risk of childhood stroke with sickle cell anemia. Am J Hematol 2010; 85 (1) 18-23
• 54 McQuillen PS, Barkovich AJ, Hamrick SE , et al. Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke 2007; 38 (2, Suppl) 736-741
• 55 Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 1: Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Arch Neurol 2010; 67 (1) 19-24
• 56 Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders. Arch Neurol 2010; 67 (2) 148-153
• 57 Bernard TJ, Manco-Johnson MJ, Goldenberg NA , et al. The roles of anatomic factors, thrombophilia, and antithrombotic therapies in childhood onset arterial ischemic stroke. Thromb Res 2010;
• 58 Kenet G, Lütkhoff LK, Albisetti M , et al. 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 2010; 121: 1795-1797
• 59 Lippi G, Franchini M, Montagnana M, Salvagno GL, Targher G, Guidi GC. Inherited and acquired risk factors for arterial ischemic stroke in childhood. J Thromb Thrombolysis 2009; 27 (2) 239-248
• 60 Nowak-Göttl U, Langer C, Bergs S, Thedieck S, Sträter R, Stoll M. Genetics of hemostasis: differential effects of heritability and household components influencing lipid concentrations and clotting factor levels in 282 pediatric stroke families. Environ Health Perspect 2008; 116 (6) 839-843
• 61 Munot P, De Vile C, Hemingway C, Gunny R, Ganesan V. Severe iron deficiency anaemia and ischaemic stroke in children. Arch Dis Child 2011; 96 (3) 276-279
• 62 Hubail Z, Lemler M, Ramaciotti C, Moore J, Ikemba C. Diagnosing a patent foramen ovale in children: is transesophageal echocardiography necessary?. Stroke 2011; 42 (1) 98-101
• 63 Ramaswamy V, Mehta V, Bauman M, Richer L, Massicotte P, Yager JY. Decompressive hemicraniectomy in children with severe ischemic stroke and life-threatening cerebral edema. J Child Neurol 2008; 23 (8) 889-894
• 64 Smith SE, Kirkham FJ, Deveber G , et al. Outcome following decompressive craniectomy for malignant middle cerebral artery infarction in children. Dev Med Child Neurol 2011; 53 (1) 29-33
• 65 Amlie-Lefond C, Chan AK, Kirton A , et al; Thrombolysis in Pediatric Stroke (TIPS) Investigators. Thrombolysis in acute childhood stroke: design and challenges of the thrombolysis in pediatric stroke clinical trial. Neuroepidemiology 2009; 32 (4) 279-286
• 66 Arnold M, Steinlin M, Baumann A , et al. Thrombolysis in childhood stroke: report of 2 cases and review of the literature. Stroke 2009; 40 (3) 801-807
• 67 Grunwald IQ, Walter S, Shamdeen MG , et al. New mechanical recanalization devices - the future in pediatric stroke treatment?. J Invasive Cardiol 2010; 22 (2) 63-66
• 68 Bernard TJ, Goldenberg NA, Tripputi M , et al. Anticoagulation in childhood-onset arterial ischemic stroke with non-moyamoya arteriopathy: Findings from the Colorado and German (COAG) collaboration. Stroke 2009;
• 69 Goldenberg NA, Bernard TJ, Fullerton HJ, Gordon A, deVeber G ; International Pediatric Stroke Study Group. Antithrombotic treatments, outcomes, and prognostic factors in acute childhood-onset arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 2009; 8 (12) 1120-1127
• 70 Bigi S, Fischer U, Wehrli E , et al. Acute ischemic stroke in children versus young adults. Ann Neurol 2011; 70 (2) 245-254
• 71 Christerson S, Strömberg B. Stroke in Swedish children II: long-term outcome. Acta Paediatr 2010; 99 (11) 1650-1656
• 72 Daseking M, Petermann F, Simonis A. [Behavioral disorders and psycho-social outcome after stroke in children]. Fortschr Neurol Psychiatr 2008; 76 (11) 662-671
• 73 Eikelmann A, Petermann F, Daseking M. [Attention deficit disorders after stroke in childhood]. Z Kinder Jugendpsychiatr Psychother 2008; 36 (6) 419-426
• 74 Everts R, Pavlovic J, Kaufmann F , et al. Cognitive functioning, behavior, and quality of life after stroke in childhood. Child Neuropsychol 2008; 14 (4) 323-338
• 75 Westmacott R, Askalan R, MacGregor D, Anderson P, Deveber G. Cognitive outcome following unilateral arterial ischaemic stroke in childhood: effects of age at stroke and lesion location. Dev Med Child Neurol 2010; 52 (4) 386-393
• 76 Domi T, deVeber G, Shroff M, Kouzmitcheva E, MacGregor DL, Kirton A. Corticospinal tract pre-wallerian degeneration: a novel outcome predictor for pediatric stroke on acute MRI. Stroke 2009; 40 (3) 780-787
• 77 Ganesan V, Prengler M, Wade A, Kirkham FJ. Clinical and radiological recurrence after childhood arterial ischemic stroke. Circulation 2006; 114 (20) 2170-2177
• 78 Eleftheriou D, Ganesan V. Controversies in childhood arterial ischemic stroke and cerebral venous sinus thrombosis. Expert Rev Cardiovasc Ther 2009; 7 (7) 853-861
• 79 Härtel C, Schilling S, Sperner J, Thyen U. The clinical outcomes of neonatal and childhood stroke: review of the literature and implications for future research. Eur J Neurol 2004; 11 (7) 431-438
• 80 Pavlovic J, Kaufmann F, Boltshauser E , et al. Neuropsychological problems after paediatric stroke: two year follow-up of Swiss children. Neuropediatrics 2006; 37 (1) 13-19