Ischemic stroke in children and young adults: Etiology and clinical features
- Sabrina E Smith, MD, PhD
Sabrina E Smith, MD, PhD
- Pediatric Neurologist
- Kaiser Permanente Oakland Medical Center
- Christine Fox, MD, MAS
Christine Fox, MD, MAS
- Assistant Professor of Neurology
- University of California, San Francisco
- Section Editors
- Scott E Kasner, MD
Scott E Kasner, MD
- Section Editor — Stroke
- Professor of Neurology
- University of Pennsylvania School of Medicine
- Douglas R Nordli, Jr, MD
Douglas R Nordli, Jr, MD
- Section Editor — Pediatric Neurology
- Chief of Neurology
- Children’s Hospital Los Angeles
- Vice Chair of Neurology
- USC Keck School of Medicine
Although more common in older adults, stroke also occurs in neonates, infants, children, and young adults, resulting in significant morbidity and mortality.
An overview of the epidemiology, risk factors, etiology, clinical presentation, and differential diagnosis of arterial ischemic stroke (AIS) in children one month of age or older and adults younger than 50 years of age is provided here. Other aspects of ischemic stroke in children and young adults are reviewed elsewhere. (See "Ischemic stroke in children: Evaluation, initial management, and prognosis" and "Ischemic stroke in children: Secondary prevention" and "Stroke in the newborn: Classification, manifestations, and diagnosis" and "Etiology, clinical features, and diagnosis of cerebral venous thrombosis".)
Annual incidence rates of arterial ischemic stroke (AIS) in infants and children range from 0.6 to 7.9/100,000 children per year [1-4]. In adults younger than 45 years old, incidence ranges from 3.4 to 11.3/100,000 people per year in primarily white populations [5,6], while the incidence in young black adults is as high as 22.8/100,000 people per year .
Several studies have found that pediatric ischemic stroke is more common in boys than in girls [8-10]. As an example, among 1187 children in a multinational pediatric registry of arterial ischemic stroke and cerebral sinovenous thrombosis cases, boys made up 710 of 1187 cases (60 percent) . Male predominance was present regardless of age, stroke subtype, or a history of trauma. The explanation for the apparent male predominance is unknown.
The etiologies and risk factors for arterial ischemic stroke (AIS) in children and young adults differ from those typical in older adults:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Giroud M, Lemesle M, Gouyon JB, et al. 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; 48:1343.
- Earley CJ, Kittner SJ, Feeser BR, et al. Stroke in children and sickle-cell disease: Baltimore-Washington Cooperative Young Stroke Study. Neurology 1998; 51:169.
- Tuckuviene R, Christensen AL, Helgestad J, et al. Paediatric arterial ischaemic stroke and cerebral sinovenous thrombosis in Denmark 1994-2006: a nationwide population-based study. Acta Paediatr 2011; 100:543.
- deVeber GA, Kirton A, Booth FA, et al. Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: The Canadian Pediatric Ischemic Stroke Registry. Pediatr Neurol 2017; 69:58.
- Nencini P, Inzitari D, Baruffi MC, et al. Incidence of stroke in young adults in Florence, Italy. Stroke 1988; 19:977.
- Kristensen B, Malm J, Carlberg B, et al. Epidemiology and etiology of ischemic stroke in young adults aged 18 to 44 years in northern Sweden. Stroke 1997; 28:1702.
- Kittner SJ, McCarter RJ, Sherwin RW, et al. Black-white differences in stroke risk among young adults. Stroke 1993; 24:I13.
- 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; 360:1540.
- Fullerton HJ, Wu YW, Zhao S, Johnston SC. Risk of stroke in children: ethnic and gender disparities. Neurology 2003; 61:189.
- Golomb MR, Fullerton HJ, Nowak-Gottl U, et al. Male predominance in childhood ischemic stroke: findings from the international pediatric stroke study. Stroke 2009; 40:52.
- Leys D, Bandu L, Hénon H, et al. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 2002; 59:26.
- Naess H, Waje-Andreassen U, Thomassen L, et al. Do all young ischemic stroke patients need long-term secondary preventive medication? Neurology 2005; 65:609.
- Ji R, Schwamm LH, Pervez MA, Singhal AB. Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis. JAMA Neurol 2013; 70:51.
- Ganesan V, Prengler M, McShane MA, et al. Investigation of risk factors in children with arterial ischemic stroke. Ann Neurol 2003; 53:167.
- Amlie-Lefond C, Bernard TJ, Sébire G, et al. Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study. Circulation 2009; 119:1417.
- Mackay MT, Wiznitzer M, Benedict SL, et al. Arterial ischemic stroke risk factors: the International Pediatric Stroke Study. Ann Neurol 2011; 69:130.
- Hills NK, Johnston SC, Sidney S, et al. Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke. Ann Neurol 2012; 72:850.
- Fullerton HJ, Hills NK, Elkind MS, et al. Infection, vaccination, and childhood arterial ischemic stroke: Results of the VIPS study. Neurology 2015; 85:1459.
- Elkind MS, Hills NK, Glaser CA, et al. Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study. Circulation 2016; 133:732.
- Kittner SJ, Stern BJ, Feeser BR, et al. Pregnancy and the risk of stroke. N Engl J Med 1996; 335:768.
- de los Ríos F, Kleindorfer DO, Khoury J, et al. Trends in substance abuse preceding stroke among young adults: a population-based study. Stroke 2012; 43:3179.
- von Sarnowski B, Schminke U, Tatlisumak T, et al. Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients. Neurology 2013; 80:1287.
- Putaala J, Metso AJ, Metso TM, et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry. Stroke 2009; 40:1195.
- Rasura M, Spalloni A, Ferrari M, et al. A case series of young stroke in Rome. Eur J Neurol 2006; 13:146.
- Bhat VM, Cole JW, Sorkin JD, et al. Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women. Stroke 2008; 39:2439.
- Cerrato P, Grasso M, Imperiale D, et al. Stroke in young patients: etiopathogenesis and risk factors in different age classes. Cerebrovasc Dis 2004; 18:154.
- Rodan L, McCrindle BW, Manlhiot C, et al. Stroke recurrence in children with congenital heart disease. Ann Neurol 2012; 72:103.
- Sinclair AJ, Fox CK, Ichord RN, et al. Stroke in children with cardiac disease: report from the International Pediatric Stroke Study Group Symposium. Pediatr Neurol 2015; 52:5.
- Lanz J, Brophy JM, Therrien J, et al. Stroke in Adults With Congenital Heart Disease: Incidence, Cumulative Risk, and Predictors. Circulation 2015; 132:2385.
- Mandalenakis Z, Rosengren A, Lappas G, et al. Ischemic Stroke in Children and Young Adults With Congenital Heart Disease. J Am Heart Assoc 2016; 5.
- Asakai H, Cardamone M, Hutchinson D, et al. Arterial ischemic stroke in children with cardiac disease. Neurology 2015; 85:2053.
- Attar H, Sachdeva A, Sundararajan S. Cardioembolic Stroke in Adults With a History of Congenital Heart Disease. Stroke 2016; 47:e79.
- Cheng HH, Rajagopal S, McDavitt E, et al. Stroke in Acquired and Congenital Heart Disease Patients and Its Relationship to Hospital Mortality and Lasting Neurologic Deficits. Pediatr Crit Care Med 2016; 17:976.
- Ricci S. Embolism from the heart in the young patient: a short review. Neurol Sci 2003; 24 Suppl 1:S13.
- deVeber G, Monagle P, Chan A, et al. Prothrombotic disorders in infants and children with cerebral thromboembolism. Arch Neurol 1998; 55:1539.
- 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; 94:3678.
- 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; 31:1283.
- Maguire JL, deVeber G, Parkin PC. Association between iron-deficiency anemia and stroke in young children. Pediatrics 2007; 120:1053.
- Sarecka-Hujar B, Kopyta I, Skrzypek M, Sordyl J. Association Between the 20210G>A Prothrombin Gene Polymorphism and Arterial Ischemic Stroke in Children and Young Adults-Two Meta-analyses of 3586 Cases and 6440 Control Subjects in Total. Pediatr Neurol 2017; 69:93.
- 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; 121:1838.
- Trenor CC 3rd, Michelson AD. Thrombophilia and pediatric stroke. Circulation 2010; 121:1795.
- Waddy SP. Disorders of coagulation in stroke. Semin Neurol 2006; 26:57.
- Sciascia S, Sanna G, Khamashta MA, et al. The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann Rheum Dis 2015; 74:2028.
- Hamedani AG, Cole JW, Mitchell BD, Kittner SJ. Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment. Stroke 2010; 41:1599.
- Sébire G, Fullerton H, Riou E, deVeber G. Toward the definition of cerebral arteriopathies of childhood. Curr Opin Pediatr 2004; 16:617.
- Mineyko A, Kirton A. Mechanisms of pediatric cerebral arteriopathy: an inflammatory debate. Pediatr Neurol 2013; 48:14.
- Chabrier S, Rodesch G, Lasjaunias P, et al. Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke. J Child Neurol 1998; 13:27.
- Braun KP, Bulder MM, Chabrier S, et al. The course and outcome of unilateral intracranial arteriopathy in 79 children with ischaemic stroke. Brain 2009; 132:544.
- Askalan R, Laughlin S, Mayank S, et al. Chickenpox and stroke in childhood: a study of frequency and causation. Stroke 2001; 32:1257.
- Danchaivijitr N, Cox TC, Saunders DE, Ganesan V. Evolution of cerebral arteriopathies in childhood arterial ischemic stroke. Ann Neurol 2006; 59:620.
- Sébire G. Transient cerebral arteriopathy in childhood. Lancet 2006; 368:8.
- Mineyko A, Narendran A, Fritzler ML, et al. Inflammatory biomarkers of pediatric focal cerebral arteriopathy. Neurology 2012; 79:1406.
- Lanthier S, Armstrong D, Domi T, deVeber G. Post-varicella arteriopathy of childhood: natural history of vascular stenosis. Neurology 2005; 64:660.
- Miravet E, Danchaivijitr N, Basu H, et al. Clinical and radiological features of childhood cerebral infarction following varicella zoster virus infection. Dev Med Child Neurol 2007; 49:417.
- Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998; 91:288.
- Nedeltchev K, der Maur TA, Georgiadis D, et al. Ischaemic stroke in young adults: predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry 2005; 76:191.
- Ortiz G, Koch S, Romano JG, et al. Mechanisms of ischemic stroke in HIV-infected patients. Neurology 2007; 68:1257.
- Tipping B, de Villiers L, Wainwright H, et al. Stroke in patients with human immunodeficiency virus infection. J Neurol Neurosurg Psychiatry 2007; 78:1320.
- Coucke PJ, Wessels MW, Van Acker P, et al. Homozygosity mapping of a gene for arterial tortuosity syndrome to chromosome 20q13. J Med Genet 2003; 40:747.
- Cartwright MS, Hickling WH, Roach ES. Ischemic stroke in an adolescent with arterial tortuosity syndrome. Neurology 2006; 67:360.
- Kirton A, Crone M, Benseler S, et al. Fibromuscular dysplasia and childhood stroke. Brain 2013; 136:1846.
- Campen CJ, Kranick SM, Kasner SE, et al. Cranial irradiation increases risk of stroke in pediatric brain tumor survivors. Stroke 2012; 43:3035.
- Mueller S, Sear K, Hills NK, et al. Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy. Int J Radiat Oncol Biol Phys 2013; 86:643.
- Siegel DH, Tefft KA, Kelly T, et al. Stroke in children with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome: a systematic review of the literature. Stroke 2012; 43:1672.
- Kelly PJ, Furie KL, Kistler JP, et al. Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency. Neurology 2003; 60:275.
- Alehan F, Saygi S, Gedik S, Kayahan Ulu EM. Stroke in early childhood due to homocystinuria. Pediatr Neurol 2010; 43:294.
- Ruhoy IS, Merritt JL 2nd, Amlie-Lefond C. Cystathionine beta-synthase deficiency heralded by cerebral sinus venous thrombosis and stroke. Pediatr Neurol 2014; 50:108.
- Hsich GE, Robertson RL, Irons M, et al. Cerebral infarction in Menkes' disease. Pediatr Neurol 2000; 23:425.
- Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014; 370:911.
- Pavlakis SG, Phillips PC, DiMauro S, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 1984; 16:481.
- Sproule DM, Kaufmann P. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci 2008; 1142:133.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-1998. A 13-year-old girl with a relapsing-remitting neurologic disorder. N Engl J Med 1998; 339:1914.
- Hirano M, Ricci E, Koenigsberger MR, et al. Melas: an original case and clinical criteria for diagnosis. Neuromuscul Disord 1992; 2:125.
- Dimauro S, Tay S, Mancuso M. Mitochondrial encephalomyopathies: diagnostic approach. Ann N Y Acad Sci 2004; 1011:217.
- Dickerson BC, Holtzman D, Grant PE, Tian D. Case records of the Massachusetts General Hospital. Case 36-2005. A 61-year-old woman with seizure, disturbed gait, and altered mental status. N Engl J Med 2005; 353:2271.
- Clarke JTR. A clinical guide to inherited metabolic diseases, 2nd, Cambridge University Press, Cambridge 2003. p.49.
- De Silva DA, Wong MC, Lee MP, et al. Amphetamine-associated ischemic stroke: clinical presentation and proposed pathogenesis. J Stroke Cerebrovasc Dis 2007; 16:185.
- Yeung M, Bhalla A, Birns J. Recreational drug misuse and stroke. Curr Drug Abuse Rev 2011; 4:286.
- Wolff V, Armspach JP, Lauer V, et al. Cannabis-related stroke: myth or reality? Stroke 2013; 44:558.
- Esse K, Fossati-Bellani M, Traylor A, Martin-Schild S. Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard. Brain Behav 2011; 1:44.
- Freeman MJ, Rose DZ, Myers MA, et al. Ischemic stroke after use of the synthetic marijuana "spice". Neurology 2013; 81:2090.
- Zimmer JA, Garg BP, Williams LS, Golomb MR. Age-related variation in presenting signs of childhood arterial ischemic stroke. Pediatr Neurol 2007; 37:171.
- deVeber G. Arterial ischemic strokes in infants and children: an overview of current approaches. Semin Thromb Hemost 2003; 29:567.
- Chadehumbe MA, Khatri P, Khoury JC, et al. Seizures are common in the acute setting of childhood stroke: a population-based study. J Child Neurol 2009; 24:9.
- Abend NS, Beslow LA, Smith SE, et al. Seizures as a presenting symptom of acute arterial ischemic stroke in childhood. J Pediatr 2011; 159:479.
- Yock-Corrales A, Mackay MT, Mosley I, et al. Acute childhood arterial ischemic and hemorrhagic stroke in the emergency department. Ann Emerg Med 2011; 58:156.
- Andrade A, Bigi S, Laughlin S, et al. Association Between Prolonged Seizures and Malignant Middle Cerebral Artery Infarction in Children With Acute Ischemic Stroke. Pediatr Neurol 2016; 64:44.
- Beslow LA, Smith SE, Vossough A, et al. Hemorrhagic transformation of childhood arterial ischemic stroke. Stroke 2011; 42:941.
- Rafay MF, Pontigon AM, Chiang J, et al. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke 2009; 40:58.
- Shellhaas RA, Smith SE, O'Tool E, et al. Mimics of childhood stroke: characteristics of a prospective cohort. Pediatrics 2006; 118:704.
- Harbison J, Hossain O, Jenkinson D, et al. Diagnostic accuracy of stroke referrals from primary care, emergency room physicians, and ambulance staff using the face arm speech test. Stroke 2003; 34:71.
- Etiologies and risk factors in children
- Etiologies and risk factors in young adults
- - Focal cerebral arteriopathy
- - Moyamoya
- - Dissection
- - Vasculitis
- - Others
- Metabolic disorders
- - MELAS and disorders causing metabolic stroke
- Substance abuse
- CLINICAL PRESENTATION
- DIFFERENTIAL DIAGNOSIS