Arterial ischemic stroke in infants, children, and adolescents: results of a Germany-wide surveillance study 2015–2017

  • Lucia GerstlEmail author
  • Raphael Weinberger
  • Florian Heinen
  • Michaela V. Bonfert
  • Ingo Borggraefe
  • A. Sebastian Schroeder
  • Moritz Tacke
  • Mirjam N. Landgraf
  • Katharina Vill
  • Karin Kurnik
  • Anna-Lisa Sorg
  • Martin Olivieri
Original Communication



Childhood arterial ischaemic stroke (AIS) is rare, but causes significant morbidity and mortality. We aimed to investigate incidence, age-dependent clinical presentation, and risk factors and to discuss the medical care situation in Germany.


This prospective epidemiological study was conducted via ESPED (Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland), a hospital-based German nation-wide surveillance unit for rare pediatric diseases. Children aged 28 days–18 years with first AIS between January 2015 and December 2017 were included.


In the 3-year period, 164 children were reported. Incidence showed peaks in infants, children < 2 years of age, and adolescents (12–18 years), with a significant male predominance observed in adolescents only. Independent of age, most children (91%) presented with focal symptoms, particularly with acute hemiparesis. The occurrence of seizures in infants (57%) and more nonspecific symptoms in school-children and adolescents (54%) is considered noteworthy. Prothrombotic states (34%), cardiac disorders (29%), and arteriopathies (19%) were the most frequently identified risk factors. The majority of children (72/131, thus 55%) were discharged home after acute care phase. At time of discharge, most common neurological symptoms were hemiparesis (42%), facial palsy (15%), and speech disturbance (12%).


This study provides population-based data of childhood AIS which may be useful for further research. The improvement of acute stroke management is needed for children, but also the standardization of post-stroke care in the outpatient setting has to be structured. Considering the higher stroke incidence in (male) adolescents, it is advisable to combine research activities in adolescents and young adults.


Childhood stroke Pediatric stroke Symptoms Risk factors 



The authors thank all pediatricians reporting to ESPED.


Building up the database was financially supported by Friedrich-Baur-Stiftung, München.

Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards statement

The study was approved by the ethics committee of the Medical Faculty of the Ludwig-Maximilians-University Munich, Number 42-15 (05-04-2015) and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Supplementary material

415_2019_9508_MOESM1_ESM.pdf (241 kb)
Supplementary file1 (PDF 240 kb)
415_2019_9508_MOESM2_ESM.pdf (1.5 mb)
Supplementary file2 (PDF 1541 kb)


  1. 1.
    Bhogal P, Andersson T, Maus V, Mpotsaris A, Yeo L (2018) Mechanical thrombectomy-a brief review of a revolutionary new treatment for thromboembolic stroke. Clin Neuroradiol. Google Scholar
  2. 2.
    Bigi S, Dulcey A, Gralla J, Bernasconi C, Melliger A, Datta AN, Arnold M, Kaesmacher J, Fluss J, Hackenberg A, Maier O, Weber J, Poloni C, Fischer U, Steinlin M (2018) Feasibility, safety, and outcome of recanalization treatment in childhood stroke. Ann Neurol 83(6):1125–1132. Google Scholar
  3. 3.
    Bonfert MV, Badura K, Gerstl J, Borggraefe I, Heinen F, Schroeder S, Olivieri M, Weinberger R, Landgraf MN, Vill K, Tacke M, Berweck S, Reiter K, Hoffmann F, Nicolai T, Gerstl L (2018) Childhood stroke: awareness, interest, and knowledge among the pediatric community. Front Pediatr 6:182. Google Scholar
  4. 4.
    Fullerton HJ, Wu YW, Zhao S, Johnston SC (2003) Risk of stroke in children: ethnic and gender disparities. Neurology 61(2):189–194Google Scholar
  5. 5.
    Gerstl L, Bonfert MV, Nicolai T, Dieterich M, Adamczyk C, Heinen F, Olivieri M, Steinlin M (2017) Childhood stroke: what are the special features of childhood stroke? Nervenarzt 88(12):1367–1376. Google Scholar
  6. 6.
    Mackay MT, Yock-Corrales A, Churilov L, Monagle P, Donnan GA, Babl FE (2016) Differentiating childhood stroke from mimics in the Emergency Department. Stroke 47(10):2476–2481. Google Scholar
  7. 7.
    Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, Parker AP, Wassmer E, Wraige E, Amin S, Edwards HB, O'Callaghan FJ (2015) Diagnostic delays in paediatric stroke. J Neurol Neurosurg Psychiatry 86(8):917–921. Google Scholar
  8. 8.
    Statistisches Bundesamt Deutschland (2019) GENESIS-Online: Bevölkerung: Deutschland, Stichtag, Altersjahre, Nationalität/Geschlecht/Familienstand; Ergebnis—12411-0006. Accessed 4 February 2019
  9. 9.
    Mackay MT, Wiznitzer M, Benedict SL, Lee KJ, Deveber GA, Ganesan V, International Pediatric Stroke Study G (2011) Arterial ischemic stroke risk factors: the international pediatric stroke study. Ann Neurol 69(1):130–140. Google Scholar
  10. 10.
    Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, Parker AP, Wassmer E, Wraige E, Amin S, Edwards HB, Tilling K, O'Callaghan FJ (2014) Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol 13(1):35–43. Google Scholar
  11. 11.
    Steinlin M, Pfister I, Pavlovic J, Everts R, Boltshauser E, Capone Mori A, Gubser Mercati D, Hanggeli CA, Keller E, Luetschg J, Marcoz J, Ramelli GP, Roulet Perez E, Schmitt-Mechelke T, Weissert M, Societies Swiss, of Paediatric N, Neonatology, (2005) The first three years of the Swiss Neuropaediatric Stroke Registry (SNPSR): a population-based study of incidence, symptoms and risk factors. Neuropediatrics 36(2):90–97. Google Scholar
  12. 12.
    Lehman LL, Beslow LA, Steinlin M, Kossorotoff M, Mackay MT (2019) What will improve pediatric acute stroke care? Stroke 50(2):249–256. Google Scholar
  13. 13.
    Martin C, von Elm E, El-Koussy M, Boltshauser E, Steinlin M, Swiss Neuropediatric Stroke Registry study g (2011) Delayed diagnosis of acute ischemic stroke in children—a registry-based study in Switzerland. Swiss Med Wkly 141:w13281. Google Scholar
  14. 14.
    Aroor S, Singh R, Goldstein LB (2017) BE-FAST (Balance, Eyes, Face, Arm, Speech, Time): reducing the proportion of strokes missed using the FAST Mnemonic. Stroke 48(2):479–481. Google Scholar
  15. 15.
    Mackay MT, Chua ZK, Lee M, Yock-Corrales A, Churilov L, Monagle P, Donnan GA, Babl FE (2014) Stroke and nonstroke brain attacks in children. Neurology 82(16):1434–1440. Google Scholar
  16. 16.
    Mackay MT, Churilov L, Donnan GA, Babl FE, Monagle P (2016) Performance of bedside stroke recognition tools in discriminating childhood stroke from mimics. Neurology 86(23):2154–2161. Google Scholar
  17. 17.
    Mackay MT, Lee M, Yock-Corrales A, Churilov L, Donnan GA, Monagle P, Babl FE (2018) Differentiating arterial ischaemic stroke from migraine in the paediatric emergency department. Dev Med Child Neurol 60(11):1117–1122. Google Scholar
  18. 18.
    Mackay MT, Monagle P, Babl FE (2016) Brain attacks and stroke in children. J Paediatr Child Health 52(2):158–163. Google Scholar
  19. 19.
    Neville K, Lo W (2016) Sensitivity and specificity of an adult stroke screening tool in childhood ischemic stroke. Pediatr Neurol 58:53–56. Google Scholar
  20. 20.
    Yock-Corrales A, Babl FE, Mosley IT, Mackay MT (2011) Can the FAST and ROSIER adult stroke recognition tools be applied to confirmed childhood arterial ischemic stroke? BMC Pediatr 11:93. Google Scholar
  21. 21.
    Yock-Corrales A, Varela-Bulgarelli F, Barboza C, Gutierrez-Mata A, Mackay MT, Babl F (2016) Presentation of acute childhood stroke in a Tertiary Pediatric Emergency Department. Pediatr Emerg Care. Google Scholar
  22. 22.
    Bulder MM, Hellmann PM, van Nieuwenhuizen O, Kappelle LJ, Klijn CJ, Braun KP (2011) Measuring outcome after arterial ischemic stroke in childhood with two different instruments. Cerebrovasc Dis 32(5):463–470. Google Scholar
  23. 23.
    Cooper AN, Anderson V, Hearps S, Greenham M, Hunt RW, Mackay MT, Monagle P, Gordon AL (2018) The Pediatric stroke outcome measure: a predictor of outcome following arterial ischemic stroke. Neurology 90(5):e365–e372. Google Scholar
  24. 24.
    Ichord RN, Bastian R, Abraham L, Askalan R, Benedict S, Bernard TJ, Beslow L, Deveber G, Dowling M, Friedman N, Fullerton H, Jordan L, Kan L, Kirton A, Amlie-Lefond C, Licht D, Lo W, McClure C, Pavlakis S, Smith SE, Tan M, Kasner S, Jawad AF (2011) Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 42(3):613–617. Google Scholar
  25. 25.
    Chan AK, deVeber G (2000) Prothrombotic disorders and ischemic stroke in children. Semin Pediatr Neurol 7(4):301–308Google Scholar
  26. 26.
    Deng Y, Wang Y, Yang W, Yu Y, Xu J, Wang Y, Gao B (2015) Risk factors and imaging characteristics of childhood stroke in china. J Child Neurol 30(3):339–343. Google Scholar
  27. 27.
    Zadro R, Herak DC (2012) Inherited prothrombotic risk factors in children with first ischemic stroke. Biochem Med 22(3):298–310Google Scholar
  28. 28.
    Amlie-Lefond C, Bernard TJ, Sebire G, Friedman NR, Heyer GL, Lerner NB, DeVeber G, Fullerton HJ, International Pediatric Stroke Study G (2009) Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the international pediatric stroke study. Circulation 119(10):1417–1423. Google Scholar
  29. 29.
    Braun KP, Bulder MM, Chabrier S, Kirkham FJ, Uiterwaal CS, Tardieu M, Sebire G (2009) The course and outcome of unilateral intracranial arteriopathy in 79 children with ischaemic stroke. Brain 132(Pt 2):544–557. Google Scholar
  30. 30.
    Kirton A, deVeber G (2015) Paediatric stroke: pressing issues and promising directions. Lancet Neurol 14(1):92–102. Google Scholar
  31. 31.
    Wintermark M, Hills NK, deVeber GA, Barkovich AJ, Elkind MS, Sear K, Zhu G, Leiva-Salinas C, Hou Q, Dowling MM, Bernard TJ, Friedman NR, Ichord RN, Fullerton HJ, Investigators V (2014) Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study. Stroke 45(12):3597–3605. Google Scholar
  32. 32.
    Steinlin M, Bigi S, Stojanovski B, Gajera J, Regenyi M, El-Koussy M, Mackay MT (2017) Focal cerebral arteriopathy: do steroids improve outcome? Stroke. Google Scholar
  33. 33.
    Yeon JY, Shin HJ, Seol HJ, Kim JS, Hong SC (2014) Unilateral intracranial arteriopathy in pediatric stroke: course, outcome, and prediction of reversible arteriopathy. Stroke 45(4):1173–1176. Google Scholar
  34. 34.
    Kottoor SJ, Arora RR (2018) Cryptogenic stroke: to close a patent Foramen Ovale or not to close? J Cent Nerv Syst Dis 10:1179573518819476. Google Scholar
  35. 35.
    Khan R, Chan AK, Mondal TK, Paes BA, Thrombosis Hemostasis in Newborns G (2016) Patent foramen ovale and stroke in childhood: a systematic review of the literature. Eur J Paediatr Neurol 20(4):500–511. Google Scholar
  36. 36.
    Sultan S, Dowling M, Kirton A, DeVeber G, Linds A, Elkind MSV, Investigators I (2018) Dyslipidemia in children with arterial ischemic stroke: prevalence and risk factors. Pediatr Neurol 78:46–54. Google Scholar
  37. 37.
    Sultan SM, Schupf N, Dowling MM, Deveber GA, Kirton A, Elkind MS (2014) Review of lipid and lipoprotein(a) abnormalities in childhood arterial ischemic stroke. Int J Stroke 9(1):79–87. Google Scholar
  38. 38.
    Willeit P, Kiechl S, Kronenberg F, Witztum JL, Santer P, Mayr M, Xu Q, Mayr A, Willeit J, Tsimikas S (2014) Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. J Am Coll Cardiol 64(9):851–860. Google Scholar
  39. 39.
    deVeber G, Kirkham F, Shannon K, Brandao L, Strater R, Kenet G, Clausnizer H, Moharir M, Kausch M, Askalan R, MacGregor D, Stoll M, Torge A, Dlamini N, Ganesan V, Prengler M, Singh J, Nowak-Gottl U (2019) Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population. Haematologica. Google Scholar
  40. 40.
    Goldenberg NA, Bernard TJ, Hillhouse J, Armstrong-Wells J, Galinkin J, Knapp-Clevenger R, Jacobson L, Marcovina SM, Manco-Johnson MJ (2013) Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children. Haematologica 98(5):802–807. Google Scholar
  41. 41.
    Nowak-Gottl U, Strater R, Heinecke A, Junker R, Koch HG, Schuierer G, von Eckardstein A (1999) Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. Blood 94(11):3678–3682Google Scholar
  42. 42.
    Strater R, Becker S, von Eckardstein A, Heinecke A, Gutsche S, Junker R, Kurnik K, Schobess R, Nowak-Gottl U (2002) Prospective assessment of risk factors for recurrent stroke during childhood–a 5-year follow-up study. Lancet 360(9345):1540–1545. Google Scholar
  43. 43.
    Androulakis XM, Kodumuri N, Giamberardino LD, Rosamond WD, Gottesman RF, Yim E, Sen S (2016) Ischemic stroke subtypes and migraine with visual aura in the ARIC study. Neurology 87(24):2527–2532. Google Scholar
  44. 44.
    Gelfand AA, Fullerton HJ, Jacobson A, Sidney S, Goadsby PJ, Kurth T, Pressman A (2015) Is migraine a risk factor for pediatric stroke? Cephalalgia 35(14):1252–1260. Google Scholar
  45. 45.
    Schurks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T (2009) Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 339:b3914. Google Scholar
  46. 46.
    Sen S, Androulakis XM, Duda V, Alonso A, Chen LY, Soliman EZ, Magnani J, Trivedi T, Merchant AT, Gottesman RF, Rosamond WD (2018) Migraine with visual aura is a risk factor for incident atrial fibrillation: a cohort study. Neurology 91(24):e2202–e2210. Google Scholar
  47. 47.
    Elkind MS, Hills NK, Glaser CA, Lo WD, Amlie-Lefond C, Dlamini N, Kneen R, Hod EA, Wintermark M, deVeber GA, Fullerton HJ, Investigators* V, (2016) herpesvirus infections and childhood arterial ischemic stroke: results of the VIPS study. Circulation 133(8):732–741. Google Scholar
  48. 48.
    Fullerton HJ, Hills NK, Elkind MS, Dowling MM, Wintermark M, Glaser CA, Tan M, Rivkin MJ, Titomanlio L, Barkovich AJ, deVeber GA, Investigators V (2015) Infection, vaccination, and childhood arterial ischemic stroke: results of the VIPS study. Neurology 85(17):1459–1466. Google Scholar
  49. 49.
    Fullerton HJ, Luna JM, Wintermark M, Hills NK, Tokarz R, Li Y, Glaser C, DeVeber GA, Lipkin WI, Elkind MSV, Investigators* V, (2017) Parvovirus B19 infection in children with arterial ischemic stroke. Stroke 48(10):2875–2877. Google Scholar
  50. 50.
    Czlonkowska A, Ciesielska A, Gromadzka G, Kurkowska-Jastrzebska I (2006) Gender differences in neurological disease: role of estrogens and cytokines. Endocrine 29(2):243–256. Google Scholar
  51. 51.
    Golomb MR, Fullerton HJ, Nowak-Gottl U, Deveber G, International Pediatric Stroke Study G (2009) Male predominance in childhood ischemic stroke: findings from the international pediatric stroke study. Stroke 40(1):52–57. Google Scholar
  52. 52.
    Normann S, de Veber G, Fobker M, Langer C, Kenet G, Bernard TJ, Fiedler B, Strater R, Goldenberg NA, Nowak-Gottl U (2009) Role of endogenous testosterone concentration in pediatric stroke. Ann Neurol 66(6):754–758. Google Scholar
  53. 53.
    Stack CA, Cole JW (2018) Ischemic stroke in young adults. Curr Opin Cardiol 33(6):594–604. Google Scholar
  54. 54.
    Kivioja R, Pietila A, Martinez-Majander N, Gordin D, Havulinna AS, Salomaa V, Aarnio K, Curtze S, Leiviska J, Rodriguez-Pardo J, Surakka I, Kaste M, Tatlisumak T, Putaala J (2018) Risk factors for early-onset ischemic stroke: a case-control study. J Am Heart Assoc 7(21):e009774. Google Scholar
  55. 55.
    Aigner A, Grittner U, Rolfs A, Norrving B, Siegerink B, Busch MA (2017) Contribution of established stroke risk factors to the burden of stroke in young adults. Stroke 48(7):1744–1751. Google Scholar
  56. 56.
    Bhatt N, Malik AM, Chaturvedi S (2018) Stroke in young adults: five new things. Neurol Clin Pract 8(6):501–506. Google Scholar
  57. 57.
    van Alebeek ME, Arntz RM, Ekker MS, Synhaeve NE, Maaijwee NA, Schoonderwaldt H, van der Vlugt MJ, van Dijk EJ, Rutten-Jacobs LC, de Leeuw FE (2018) Risk factors and mechanisms of stroke in young adults: the FUTURE study. J Cereb Blood Flow Metab 38(9):1631–1641. Google Scholar
  58. 58.
    Ferriero DM, Fullerton HJ, Bernard TJ, Billinghurst L, Daniels SR, DeBaun MR, deVeber G, Ichord RN, Jordan LC, Massicotte P, Meldau J, Roach ES, Smith ER, American Heart Association Stroke C, Council on C, Stroke N (2019) Management of Stroke in Neonates and Children: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke.
  59. 59.
    Medley TL, Miteff C, Andrews I, Ware T, Cheung M, Monagle P, Mandelstam S, Wray A, Pridmore C, Troedson C, Dale RC, Fahey M, Sinclair A, Walsh P, Stojanovski B, Mackay MT (2018) Australian Clinical Consensus Guideline: The diagnosis and acute management of childhood stroke. Int J Stroke.
  60. 60.
    Barlinn J, Barlinn K, Helbig U, Siepmann T, Pallesen LP, Urban H, Putz V, Schmitt J, Reichmann H, Bodechtel U (2016) Organized post-stroke care through case management on the basis of a standardized treatment pathway : results of a single-centre pilot study. Nervenarzt 87(8):860–869. Google Scholar
  61. 61.
    Bodechtel U, Barlinn K, Helbig U, Arnold K, Siepmann T, Pallesen LP, Puetz V, Reichmann H, Schmitt J, Kepplinger J (2016) The stroke east Saxony pilot project for organized post-stroke care: a case-control study. Brain Behav 6(5):e00455. Google Scholar
  62. 62.
    Lynch JK, Hirtz DG, DeVeber G, Nelson KB (2002) Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics 109(1):116–123Google Scholar
  63. 63.
    Bundesamt für gesundheitliche Aufklärung (2019) Welches Krankenhaus ist das Richtige? Accessed 18 Mar 2019

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lucia Gerstl
    • 1
    Email author
  • Raphael Weinberger
    • 2
  • Florian Heinen
    • 1
  • Michaela V. Bonfert
    • 1
  • Ingo Borggraefe
    • 1
  • A. Sebastian Schroeder
    • 1
  • Moritz Tacke
    • 1
  • Mirjam N. Landgraf
    • 1
  • Katharina Vill
    • 1
  • Karin Kurnik
    • 3
  • Anna-Lisa Sorg
    • 2
  • Martin Olivieri
    • 3
  1. 1.Department of Pediatric Neurology and Developmental MedicineLMU Munich, University Hospital, Dr. von Hauner Children`s HospitalMunichGermany
  2. 2.Division of Epidemiology, Institute of Social Pediatrics and Adolescent MedicineLMU MunichMunichGermany
  3. 3.Department of Pediatric Hemostasis and ThrombosisLMU Munich, University Hospital, Dr. von Hauner Children`s HospitalMunichGermany

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