Childhood Arterial Ischemic Stroke: A Review of Etiologies, Antithrombotic Treatments, Prognostic Factors, and Priorities for Future Research

Courtney A. Lyle; Timothy J. Bernard; Neil A. Goldenberg

doi:10.1055/s-0031-1297169

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2011; 37(7): 786-793
DOI: 10.1055/s-0031-1297169

Childhood Arterial Ischemic Stroke: A Review of Etiologies, Antithrombotic Treatments, Prognostic Factors, and Priorities for Future Research

Courtney A. Lyle¹ ^, ² , Timothy J. Bernard³ ^, ⁴ ^, ⁵ , Neil A. Goldenberg³ ^, ⁵ ^, ⁶

¹Division of Hematology/Oncology, Department of Pediatrics, University of California
²Rady Children's Hospital, San Diego, California, University of Colorado, Aurora, Colorado
³Department of Pediatrics, University of Colorado, Aurora, Colorado
⁴Sections of Child Neurology, University of Colorado, Aurora, Colorado
⁵Department of Hematology/Oncology/Bone Marrow Transplantation and the Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado, Aurora, Colorado
⁶Department of Medicine, University of Colorado, Aurora, Colorado, University of Colorado, Aurora, Colorado

Abstract

ABSTRACT

Childhood arterial ischemic stroke (AIS) is a rare, but serious, medical condition, which is fatal in approximately 3% and associated with both acute and long-term neurologic impairment in over 70% of cases. Common etiologies include sickle cell disease, congenital heart disease, arterial dissection, prothrombotic conditions, and preceding viral infections; however, one in four cases is considered idiopathic. To date, no randomized controlled clinical trials (RCTs) have been conducted to establish evidence for current therapeutic strategies outside of sickle cell disease, thus, treatment strategies are largely shaped by consensus-based guidelines, in which, beyond the acute period, aspirin is the mainstay of therapy and anticoagulation is reserved for select circumstances. In recent years, evidence on prognostic factors has accumulated, helping to inform the future design of prognostically stratified RCTs. In this narrative review, we discuss the current understanding of etiologies, consensus-based treatment recommendations, contemporary treatment data, and prognostic factors in childhood AIS. We also identify priorities for future research.

KEYWORDS

Childhood arterial ischemic stroke - pediatric stroke

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Referenzen

REFERENCES

1 Fullerton H J, Wu Y W, Zhao S, Johnston S C. Risk of stroke in children: ethnic and gender disparities. Neurology. 2003; 61 (2) 189-194
2 Agrawal N, Johnston S C, Wu Y W, Sidney S, Fullerton H J. Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke. 2009; 40 (11) 3415-3421
3 Giroud M, Lemesle M, Gouyon J B, Nivelon J L, Milan C, Dumas R. 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. 1995; 48 (11) 1343-1348
4 Bernard T J, Goldenberg N A. Pediatric arterial ischemic stroke. Hematol Oncol Clin North Am. 2010; 24 (1) 167-180
5 Bernard T J, Goldenberg N A, Armstrong-Wells J, Amlie-Lefond C, Fullerton H J. Treatment of childhood arterial ischemic stroke. Ann Neurol. 2008; 63 (6) 679-696
6 Goldenberg N A, Bernard T J, Fullerton H J, 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
7 Sträter R, Becker S, von Eckardstein A et al.. Prospective assessment of risk factors for recurrent stroke during childhood—a 5-year follow-up study. Lancet. 2002; 360 (9345) 1540-1545
8 Ganesan V, Prengler M, Wade A, Kirkham F J. Clinical and radiological recurrence after childhood arterial ischemic stroke. Circulation. 2006; 114 (20) 2170-2177
9 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 (2) 371-378
10 Fullerton H J, Wu Y W, Sidney S, Johnston S C. Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging. Pediatrics. 2007; 119 (3) 495-501
11 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 (5) 290-294
12 deVeber G A, MacGregor D, Curtis R, Mayank S. Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis. J Child Neurol. 2000; 15 (5) 316-324
13 Ganesan V, Hogan A, Shack N, Gordon A, Isaacs E, Kirkham F J. Outcome after ischaemic stroke in childhood. Dev Med Child Neurol. 2000; 42 (7) 455-461
14 Steinlin M, Roellin K, Schroth G. Long-term follow-up after stroke in childhood. Eur J Pediatr. 2004; 163 (4-5) 245-250
15 Lee J C, Lin K L, Wang H S et al.. Seizures in childhood ischemic stroke in Taiwan. Brain Dev. 2009; 31 (4) 294-299
16 Monagle P, Chalmers E, Chan A American College of Chest Physicians et al. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133 (6, Suppl) 887S-968S
17 Pediatric Stroke Working Group .Stroke in childhood: Clinical guidelines for diagnosis, management, and rehabilitation. Royal College of Physicians; 2004. Available at: http://bookshop.rcplondon.ac.uk/contents/f98c6540-a541-4bed-837d-ef293ac458bf.pdf Accessed November 15, 2010
18 Roach E S, Golomb M R, Adams R American Heart Association Stroke Council et al. 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
19 Biller J. Stroke in Children and Young Adults. 2nd ed. Philadelphia, PA: Saunders/Elsevier; 2009
20 Lo W, Stephens J, Fernandez S. Pediatric stroke in the United States and the impact of risk factors. J Child Neurol. 2009; 24 (2) 194-203
21 Ricci S. Embolism from the heart in the young patient: a short review. Neurol Sci. 2003; 24 (Suppl 1) S13-S14
22 deVeber G. Arterial ischemic strokes in infants and children: an overview of current approaches. Semin Thromb Hemost. 2003; 29 (6) 567-573
23 DeVeber G. Risk factors for childhood stroke: little folks have different strokes!. Ann Neurol. 2003; 53 (2) 149-150
24 Ganesan V, Prengler M, McShane M A, Wade A M, Kirkham F J. Investigation of risk factors in children with arterial ischemic stroke. Ann Neurol. 2003; 53 (2) 167-173
25 Benedik M P, Zaletel M, Meglic N P, Podnar T. Patent foramen ovale and unexplained ischemic cerebrovascular events in children. Catheter Cardiovasc Interv. 2007; 70 (7) 999-1007
26 Wu L A, Malouf J F, Dearani J A et al.. Patent foramen ovale in cryptogenic stroke: current understanding and management options. Arch Intern Med. 2004; 164 (9) 950-956
27 Earley C J, Kittner S J, Feeser B R et al.. Stroke in children and sickle-cell disease: Baltimore-Washington Cooperative Young Stroke Study. Neurology. 1998; 51 (1) 169-176
28 Rothman S M, Fulling K H, Nelson J S. Sickle cell anemia and central nervous system infarction: a neuropathological study. Ann Neurol. 1986; 20 (6) 684-690
29 Tuohy A M, McKie V, Manci E A, Adams R J. Internal carotid artery occlusion in a child with sickle cell disease: case report and immunohistochemical study. J Pediatr Hematol Oncol. 1997; 19 (5) 455-458
30 Merkel K H, Ginsberg P L, Parker Jr J C, Post M J. Cerebrovascular disease in sickle cell anemia: a clinical, pathological and radiological correlation. Stroke. 1978; 9 (1) 45-52
31 Dowling M M, Lee N, Quinn C T et al.. Prevalence of intracardiac shunting in children with sickle cell disease and stroke. J Pediatr. 2010; 156 (4) 645-650
32 Danchaivijitr N, Cox T C, Saunders D E, Ganesan V. Evolution of cerebral arteriopathies in childhood arterial ischemic stroke. Ann Neurol. 2006; 59 (4) 620-626
33 Amlie-Lefond C, Bernard T J, Sébire G International Pediatric Stroke Study Group et al. Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study. Circulation. 2009; 119 (10) 1417-1423
34 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
35 Sepelyak K, Gailloud P, Jordan L C. Athletics, minor trauma, and pediatric arterial ischemic stroke. Eur J Pediatr. 2010; 169 (5) 557-562
36 Shaffer L, Rich P M, Pohl K R, Ganesan V. Can mild head injury cause ischaemic stroke?. Arch Dis Child. 2003; 88 (3) 267-269
37 Kieslich M, Fiedler A, Heller C, Kreuz W, Jacobi G. Minor head injury as cause and co-factor in the aetiology of stroke in childhood: a report of eight cases. J Neurol Neurosurg Psychiatry. 2002; 73 (1) 13-16
38 Fullerton H J, Johnston S C, Smith W S. Arterial dissection and stroke in children. Neurology. 2001; 57 (7) 1155-1160
39 Rafay M F, Armstrong D, Deveber G, Domi T, Chan A, MacGregor D L. Craniocervical arterial dissection in children: clinical and radiographic presentation and outcome. J Child Neurol. 2006; 21 (1) 8-16
40 Patel H, Smith R R, Garg B P. Spontaneous extracranial carotid artery dissection in children. Pediatr Neurol. 1995; 13 (1) 55-60
41 Brandt T, Grond-Ginsbach C. Spontaneous cervical artery dissection: from risk factors toward pathogenesis. Stroke. 2002; 33 (3) 657-658
42 Sébire G, Fullerton H, Riou E, deVeber G. Toward the definition of cerebral arteriopathies of childhood. Curr Opin Pediatr. 2004; 16 (6) 617-622
43 Manceau E, Giroud M, Dumas R. Moyamoya disease in children. A review of the clinical and radiological features and current treatment. Childs Nerv Syst. 1997; 13 (11-12) 595-600
44 Rosser T L, Vezina G, Packer R J. Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1. Neurology. 2005; 64 (3) 553-555
45 Kirkham F J, DeBaun M R. Stroke in children with sickle cell disease. Curr Treat Options Neurol. 2004; 6 (5) 357-375
46 Jea A, Smith E R, Robertson R, Scott R M. Moyamoya syndrome associated with Down syndrome: outcome after surgical revascularization. Pediatrics. 2005; 116 (5) e694-e701
47 Morris B, Partap S, Yeom K, Gibbs I C, Fisher P G, King A A. Cerebrovascular disease in childhood cancer survivors: A Children's Oncology Group Report. Neurology. 2009; 73 (22) 1906-1913
48 Roder C, Nayak N R, Khan N, Tatagiba M, Inoue I, Krischek B. Genetics of Moyamoya disease. J Hum Genet. 2010; 55 (11) 711-716
49 Bernard T J, Fenton L Z, Apkon S D et al.. Biomarkers of hypercoagulability and inflammation in childhood-onset arterial ischemic stroke. J Pediatr. 2010; 156 (4) 651-656
50 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
51 Kutlesa M, Tesović G, Knezović I, Mise B, Visković K, Barisić N. Ischemic stroke associated with adenoviral infection in a 4-year-old boy. Wien Klin Wochenschr. 2009; 121 (23-24) 776-779
52 Lanthier S, Armstrong D, Domi T, deVeber G. Post-varicella arteriopathy of childhood: natural history of vascular stenosis. Neurology. 2005; 64 (4) 660-663
53 Dlamini N, Mackay M, Fullerton H, Freeman J, deVeber G. Intracranial Dissection Mimicking Transient Cerebral Arteriopathy in Childhood Arterial Ischemic Stroke. International Stroke Conference Abstract 2010
54 Braun K P, Bulder M M, Chabrier S et al.. The course and outcome of unilateral intracranial arteriopathy in 79 children with ischaemic stroke. Brain. 2009; 132 (Pt 2) 544-557
55 Kenet G, Sadetzki S, Murad H et al.. Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children. Stroke. 2000; 31 (6) 1283-1288
56 deVeber G, Monagle P, Chan A et al.. Prothrombotic disorders in infants and children with cerebral thromboembolism. Arch Neurol. 1998; 55 (12) 1539-1543
57 Sträter R, Vielhaber H, Kassenböhmer R, von Kries R, Göbel U, Nowak-Göttl U. Genetic risk factors of thrombophilia in ischaemic childhood stroke of cardiac origin. A prospective ESPED survey. Eur J Pediatr. 1999; 158 (Suppl 3) S122-S125
58 Kenet G, Lütkhoff L K, 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 (16) 1838-1847
59 Haywood S, Liesner R, Pindora S, Ganesan V. Thrombophilia and first arterial ischaemic stroke: a systematic review. Arch Dis Child. 2005; 90 (4) 402-405
60 Nowak-Göttl U, Sträter R, Heinecke A et al.. Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. Blood. 1999; 94 (11) 3678-3682
61 Maguire J L, deVeber G, Parkin P C. Association between iron-deficiency anemia and stroke in young children. Pediatrics. 2007; 120 (5) 1053-1057
62 Alvarez-Larrán A, Cervantes F, Bellosillo B et al.. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia. 2007; 21 (6) 1218-1223
63 Rolfs A, Böttcher T, Zschiesche M et al.. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005; 366 (9499) 1794-1796
64 Granild-Jensen J, Jensen U B, Schwartz M, Hansen U S. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy resulting in stroke in an 11-year-old male. Dev Med Child Neurol. 2009; 51 (9) 754-757
65 Hsich G E, Robertson R L, Irons M, Soul J S, du Plessis A J. Cerebral infarction in Menkes' disease. Pediatr Neurol. 2000; 23 (5) 425-428
66 Alehan F, Saygi S, Gedik S, Kayahan Ulu E M. Stroke in early childhood due to homocystinuria. Pediatr Neurol. 2010; 43 (4) 294-296
67 Kaku D A, Lowenstein D H. Emergence of recreational drug abuse as a major risk factor for stroke in young adults. Ann Intern Med. 1990; 113 (11) 821-827
68 Westover A N, McBride S, Haley R W. Stroke in young adults who abuse amphetamines or cocaine: a population-based study of hospitalized patients. Arch Gen Psychiatry. 2007; 64 (4) 495-502
69 Sträter R, Kurnik K, Heller C, Schobess R, Luigs P, Nowak-Göttl U. Aspirin versus low-dose low-molecular-weight heparin: antithrombotic therapy in pediatric ischemic stroke patients: a prospective follow-up study. Stroke. 2001; 32 (11) 2554-2558
70 Burak C R, Bowen M D, Barron T F. The use of enoxaparin in children with acute, nonhemorrhagic ischemic stroke. Pediatr Neurol. 2003; 29 (4) 295-298
71 Bernard T J, Goldenberg N A, Tripputi M, Manco-Johnson M J, Niederstadt T, Nowak-Göttl U. Anticoagulation in childhood-onset arterial ischemic stroke with non-moyamoya arteriopathy: findings from the Colorado and German (COAG) collaboration. Stroke. 2009; 40 (8) 2869-2871
72 Georgiadis D, Arnold M, von Buedingen H C et al.. Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients. Neurology. 2009; 72 (21) 1810-1815
73 Amlie-Lefond C, deVeber G, Chan A K International Pediatric Stroke Study et al. Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol. 2009; 8 (6) 530-536
74 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
75 Carlson M D, Leber S, Deveikis J, Silverstein F S. Successful use of rt-PA in pediatric stroke. Neurology. 2001; 57 (1) 157-158
76 Gruber A, Nasel C, Lang W, Kitzmüller E, Bavinzski G, Czech T. Intra-arterial thrombolysis for the treatment of perioperative childhood cardioembolic stroke. Neurology. 2000; 54 (8) 1684-1686
77 Noser E A, Felberg R A, Alexandrov A V. Thrombolytic therapy in an adolescent ischemic stroke. J Child Neurol. 2001; 16 (4) 286-288
78 Thirumalai S S, Shubin R A. Successful treatment for stroke in a child using recombinant tissue plasminogen activator. J Child Neurol. 2000; 15 (8) 558
79 Amlie-Lefond C, Chan A K, Kirton A Thrombolysis in Pediatric Stroke (TIPS) Investigators et al. Thrombolysis in acute childhood stroke: design and challenges of the thrombolysis in pediatric stroke clinical trial. Neuroepidemiology. 2009; 32 (4) 279-286
80 Rafay M F, Pontigon A M, Chiang J et al.. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke. 2009; 40 (1) 58-64
81 Srinivasan J, Miller S P, Phan T G, Mackay M T. Delayed recognition of initial stroke in children: need for increased awareness. Pediatrics. 2009; 124 (2) e227-e234
82 Gabis L V, Yangala R, Lenn N J. Time lag to diagnosis of stroke in children. Pediatrics. 2002; 110 (5) 924-928
83 Domi T, deVeber G, Shroff M, Kouzmitcheva E, MacGregor D L, Kirton A. Corticospinal tract pre-wallerian degeneration: a novel outcome predictor for pediatric stroke on acute MRI. Stroke. 2009; 40 (3) 780-787
84 Ganesan V, Ng V, Chong W K, Kirkham F J, Connelly A. Lesion volume, lesion location, and outcome after middle cerebral artery territory stroke. Arch Dis Child. 1999; 81 (4) 295-300
85 Cnossen M H, Aarsen F K, Akker SLj et al.. Paediatric arterial ischaemic stroke: functional outcome and risk factors. Dev Med Child Neurol. 2010; 52 (4) 394-399

Courtney A. LyleM.D.

Rady Children's Hospital, 3020 Children's Way MC 5035

San Diego, CA 92123

eMail: calyle@rchsd.org