Arteriopathy diagnosis in childhood arterial ischemic stroke

Results of the vascular effects of infection in pediatric stroke study

Max Wintermark, Nancy K. Hills, Gabrielle A. DeVeber, A. James Barkovich, Mitchell S V Elkind, Katherine Sear, Guangming Zhu, Carlos Leiva-Salinas, Qinghua Hou, Michael M. Dowling, Timothy J. Bernard, Neil R. Friedman, Rebecca N. Ichord, Heather J. Fullerton, S. L. Benedict, C. K. Fox, W. D. Lo, M. A. Tan, M. T. Mackay, A. Kirton & 26 others M. I. Hernandez Chavez, P. Humphreys, L. C. Jordan, S. M. Sultan, M. J. Rivkin, M. F. Rafay, L. Titomanlio, G. S. Kovacevic, J. Y. Yager, C. Amlie-Lefond, N. Dlamini, J. Condie, A. Yeh, R. Kneen, B. H. Bjornson, P. Pergami, L. P. Zou, J. Elbers, A. Abdalla, A. K. Chan, O. Farooq, M. J. Lim, J. L. Carpenter, S. Pavlakis, V. C. Wong, R. Forsyth

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background and Purpose - Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.

Methods - Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.

Results - Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (=0.77, 0.81, and 0.78).

Conclusions - Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Original languageEnglish (US)
Pages (from-to)3597-3605
Number of pages9
JournalStroke
Volume45
Issue number12
DOIs
StatePublished - Dec 11 2014

Fingerprint

Blood Vessels
Stroke
Pediatrics
Infection
Neuroimaging
Uncertainty
Neck
Prospective Studies
Sensitivity and Specificity

Keywords

  • Cerebral arterial diseases
  • Pediatrics
  • Stroke
  • Transient ischemic attack

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Wintermark, M., Hills, N. K., DeVeber, G. A., Barkovich, A. J., Elkind, M. S. V., Sear, K., ... Forsyth, R. (2014). Arteriopathy diagnosis in childhood arterial ischemic stroke: Results of the vascular effects of infection in pediatric stroke study. Stroke, 45(12), 3597-3605. https://doi.org/10.1161/STROKEAHA.114.007404

Arteriopathy diagnosis in childhood arterial ischemic stroke : Results of the vascular effects of infection in pediatric stroke study. / Wintermark, Max; Hills, Nancy K.; DeVeber, Gabrielle A.; Barkovich, A. James; Elkind, Mitchell S V; Sear, Katherine; Zhu, Guangming; Leiva-Salinas, Carlos; Hou, Qinghua; Dowling, Michael M.; Bernard, Timothy J.; Friedman, Neil R.; Ichord, Rebecca N.; Fullerton, Heather J.; Benedict, S. L.; Fox, C. K.; Lo, W. D.; Tan, M. A.; Mackay, M. T.; Kirton, A.; Hernandez Chavez, M. I.; Humphreys, P.; Jordan, L. C.; Sultan, S. M.; Rivkin, M. J.; Rafay, M. F.; Titomanlio, L.; Kovacevic, G. S.; Yager, J. Y.; Amlie-Lefond, C.; Dlamini, N.; Condie, J.; Yeh, A.; Kneen, R.; Bjornson, B. H.; Pergami, P.; Zou, L. P.; Elbers, J.; Abdalla, A.; Chan, A. K.; Farooq, O.; Lim, M. J.; Carpenter, J. L.; Pavlakis, S.; Wong, V. C.; Forsyth, R.

In: Stroke, Vol. 45, No. 12, 11.12.2014, p. 3597-3605.

Research output: Contribution to journalArticle

Wintermark, M, Hills, NK, DeVeber, GA, Barkovich, AJ, Elkind, MSV, Sear, K, Zhu, G, Leiva-Salinas, C, Hou, Q, Dowling, MM, Bernard, TJ, Friedman, NR, Ichord, RN, Fullerton, HJ, Benedict, SL, Fox, CK, Lo, WD, Tan, MA, Mackay, MT, Kirton, A, Hernandez Chavez, MI, Humphreys, P, Jordan, LC, Sultan, SM, Rivkin, MJ, Rafay, MF, Titomanlio, L, Kovacevic, GS, Yager, JY, Amlie-Lefond, C, Dlamini, N, Condie, J, Yeh, A, Kneen, R, Bjornson, BH, Pergami, P, Zou, LP, Elbers, J, Abdalla, A, Chan, AK, Farooq, O, Lim, MJ, Carpenter, JL, Pavlakis, S, Wong, VC & Forsyth, R 2014, 'Arteriopathy diagnosis in childhood arterial ischemic stroke: Results of the vascular effects of infection in pediatric stroke study', Stroke, vol. 45, no. 12, pp. 3597-3605. https://doi.org/10.1161/STROKEAHA.114.007404
Wintermark, Max ; Hills, Nancy K. ; DeVeber, Gabrielle A. ; Barkovich, A. James ; Elkind, Mitchell S V ; Sear, Katherine ; Zhu, Guangming ; Leiva-Salinas, Carlos ; Hou, Qinghua ; Dowling, Michael M. ; Bernard, Timothy J. ; Friedman, Neil R. ; Ichord, Rebecca N. ; Fullerton, Heather J. ; Benedict, S. L. ; Fox, C. K. ; Lo, W. D. ; Tan, M. A. ; Mackay, M. T. ; Kirton, A. ; Hernandez Chavez, M. I. ; Humphreys, P. ; Jordan, L. C. ; Sultan, S. M. ; Rivkin, M. J. ; Rafay, M. F. ; Titomanlio, L. ; Kovacevic, G. S. ; Yager, J. Y. ; Amlie-Lefond, C. ; Dlamini, N. ; Condie, J. ; Yeh, A. ; Kneen, R. ; Bjornson, B. H. ; Pergami, P. ; Zou, L. P. ; Elbers, J. ; Abdalla, A. ; Chan, A. K. ; Farooq, O. ; Lim, M. J. ; Carpenter, J. L. ; Pavlakis, S. ; Wong, V. C. ; Forsyth, R. / Arteriopathy diagnosis in childhood arterial ischemic stroke : Results of the vascular effects of infection in pediatric stroke study. In: Stroke. 2014 ; Vol. 45, No. 12. pp. 3597-3605.
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abstract = "Background and Purpose - Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.Methods - Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.Results - Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56{\%} boys. The majority (52{\%}) was previously healthy; 41{\%} had follow-up vascular imaging. Only 56 (16{\%}) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36{\%}), possible in 34 (9.6{\%}), and absent in 194 (55{\%}). Sensitivity was 79{\%} at step 1, 90{\%} at step 2, and 94{\%} at step 3; specificity was high throughout (99{\%}, 100{\%}, and 100{\%}), as was agreement between reviewers (=0.77, 0.81, and 0.78).Conclusions - Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.",
keywords = "Cerebral arterial diseases, Pediatrics, Stroke, Transient ischemic attack",
author = "Max Wintermark and Hills, {Nancy K.} and DeVeber, {Gabrielle A.} and Barkovich, {A. James} and Elkind, {Mitchell S V} and Katherine Sear and Guangming Zhu and Carlos Leiva-Salinas and Qinghua Hou and Dowling, {Michael M.} and Bernard, {Timothy J.} and Friedman, {Neil R.} and Ichord, {Rebecca N.} and Fullerton, {Heather J.} and Benedict, {S. L.} and Fox, {C. K.} and Lo, {W. D.} and Tan, {M. A.} and Mackay, {M. T.} and A. Kirton and {Hernandez Chavez}, {M. I.} and P. Humphreys and Jordan, {L. C.} and Sultan, {S. M.} and Rivkin, {M. J.} and Rafay, {M. F.} and L. Titomanlio and Kovacevic, {G. S.} and Yager, {J. Y.} and C. Amlie-Lefond and N. Dlamini and J. Condie and A. Yeh and R. Kneen and Bjornson, {B. H.} and P. Pergami and Zou, {L. P.} and J. Elbers and A. Abdalla and Chan, {A. K.} and O. Farooq and Lim, {M. J.} and Carpenter, {J. L.} and S. Pavlakis and Wong, {V. C.} and R. Forsyth",
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TY - JOUR

T1 - Arteriopathy diagnosis in childhood arterial ischemic stroke

T2 - Results of the vascular effects of infection in pediatric stroke study

AU - Wintermark, Max

AU - Hills, Nancy K.

AU - DeVeber, Gabrielle A.

AU - Barkovich, A. James

AU - Elkind, Mitchell S V

AU - Sear, Katherine

AU - Zhu, Guangming

AU - Leiva-Salinas, Carlos

AU - Hou, Qinghua

AU - Dowling, Michael M.

AU - Bernard, Timothy J.

AU - Friedman, Neil R.

AU - Ichord, Rebecca N.

AU - Fullerton, Heather J.

AU - Benedict, S. L.

AU - Fox, C. K.

AU - Lo, W. D.

AU - Tan, M. A.

AU - Mackay, M. T.

AU - Kirton, A.

AU - Hernandez Chavez, M. I.

AU - Humphreys, P.

AU - Jordan, L. C.

AU - Sultan, S. M.

AU - Rivkin, M. J.

AU - Rafay, M. F.

AU - Titomanlio, L.

AU - Kovacevic, G. S.

AU - Yager, J. Y.

AU - Amlie-Lefond, C.

AU - Dlamini, N.

AU - Condie, J.

AU - Yeh, A.

AU - Kneen, R.

AU - Bjornson, B. H.

AU - Pergami, P.

AU - Zou, L. P.

AU - Elbers, J.

AU - Abdalla, A.

AU - Chan, A. K.

AU - Farooq, O.

AU - Lim, M. J.

AU - Carpenter, J. L.

AU - Pavlakis, S.

AU - Wong, V. C.

AU - Forsyth, R.

PY - 2014/12/11

Y1 - 2014/12/11

N2 - Background and Purpose - Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.Methods - Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.Results - Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (=0.77, 0.81, and 0.78).Conclusions - Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

AB - Background and Purpose - Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke.Methods - Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step.Results - Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (=0.77, 0.81, and 0.78).Conclusions - Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

KW - Cerebral arterial diseases

KW - Pediatrics

KW - Stroke

KW - Transient ischemic attack

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