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DOI: 10.1055/s-0031-1297169
Childhood Arterial Ischemic Stroke: A Review of Etiologies, Antithrombotic Treatments, Prognostic Factors, and Priorities for Future Research
Publication History
Publication Date:
20 December 2011 (online)

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
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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 4
Bernard T J, Goldenberg N A.
Pediatric arterial ischemic stroke.
Hematol Oncol Clin North Am.
2010;
24
(1)
167-180
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 14
Steinlin M, Roellin K, Schroth G.
Long-term follow-up after stroke in childhood.
Eur J Pediatr.
2004;
163
(4-5)
245-250
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 19 Biller J. Stroke in Children and Young Adults. 2nd ed. Philadelphia, PA: Saunders/Elsevier; 2009
MissingFormLabel
- 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
MissingFormLabel
- 21
Ricci S.
Embolism from the heart in the young patient: a short review.
Neurol Sci.
2003;
24
(Suppl 1)
S13-S14
MissingFormLabel
- 22
deVeber G.
Arterial ischemic strokes in infants and children: an overview of current approaches.
Semin Thromb Hemost.
2003;
29
(6)
567-573
MissingFormLabel
- 23
DeVeber G.
Risk factors for childhood stroke: little folks have different strokes!.
Ann Neurol.
2003;
53
(2)
149-150
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 35
Sepelyak K, Gailloud P, Jordan L C.
Athletics, minor trauma, and pediatric arterial ischemic stroke.
Eur J Pediatr.
2010;
169
(5)
557-562
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 38
Fullerton H J, Johnston S C, Smith W S.
Arterial dissection and stroke in children.
Neurology.
2001;
57
(7)
1155-1160
MissingFormLabel
- 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
MissingFormLabel
- 40
Patel H, Smith R R, Garg B P.
Spontaneous extracranial carotid artery dissection in children.
Pediatr Neurol.
1995;
13
(1)
55-60
MissingFormLabel
- 41
Brandt T, Grond-Ginsbach C.
Spontaneous cervical artery dissection: from risk factors toward pathogenesis.
Stroke.
2002;
33
(3)
657-658
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 45
Kirkham F J, DeBaun M R.
Stroke in children with sickle cell disease.
Curr Treat Options Neurol.
2004;
6
(5)
357-375
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 82
Gabis L V, Yangala R, Lenn N J.
Time lag to diagnosis of stroke in children.
Pediatrics.
2002;
110
(5)
924-928
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
Courtney A. LyleM.D.
Rady Children's Hospital, 3020 Children's Way MC 5035
San Diego, CA 92123
Email: calyle@rchsd.org