Observational Study

. 2020 Jun 9;94(23):e2479-e2490.

doi: 10.1212/WNL.0000000000009557. Epub 2020 May 26.

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke

Collaborators, Affiliations

Collaborators

International Pediatric Stroke Study (IPSS) Group:
Steve Ashwal, Donna Ferriero, Rebecca Ichord, Fenella Kirkham, John K Lynch, Finbar O'Callaghan, Steve Pavlakis, Guillaume Sebire, Andrew Willan, Mahendranath Moharir, Michael Dowling, Janna Journeycake, Patricia Plumb, Belinda Stojanovski, Marta Hernandez, Jennifer Armstrong, Ulrike Nowak-Gottl, Susan Benedict, Jerome Yager, Patricia Massicotte, Warren Lo, Melissa Parakh, Lori Billinghurst, Maja Steinlin, Max Wiznitzer, Laura Lehman, Andrew Mallick, Li Kan, Dimitirios Zafeiriou, Christine Fox, Bruce Bjornson, Lori Jordan, Juliann Paolicchi, Chalmer McClure, Marcela Torres, Anneli Kolk, Monica Troncoso, Harry Whelan, Anthony Chan, Ilona Kopyta, Abdalla Abdalla, Terrence Gerard, Meredith Golomb, Peter Humphreys, Michael Noetzel, Kristin Guilliams, Geoffrey Heyer, Robert Fryer, Ann Yeh, Paola Pergami, Francesco Cardona, Gordana Kovacevic, Vijeya Ganesan, Jorina Elbers, Neil Friedman, Virginia Wong, Nana Tatishvili, Sally Sultan, Mitchell Elkind, Lisa Abraham, Veronica Gonzalez, Luigi Titomanlio, Montri Saengpattrachai, Norma B Lerner, Shalu Narang, Jill M Cholette, Carolina Oliviera, Hal Crosswell, Lucila Andrade Alveal, Ryan Felling, Maayke Hunfeld, Diana Altuna, Nassim Zecavati, David Buckley, Marcel Deray, Sahar Hassanein, Vesna Brankovic-Sreckovic, Anaita Hegde, Deepti Raybagkar, Christina Miteff, John Condie, Chaouki Khoury, Shannon Carpenter, Amanda Blair, Susanne Holzhauer, Patricia Garcia Soler, Lisa Nassif El-Hakam, Luis Conto, Jose Francisco Vilavedra, Barry Kosofsky, Dana Leifer, Yang Guang, Li-Ping Zou, J Michael Taylor, Neil Goldenberg, Adrian Toma, Lauren A Beslow, Mark Wainwright, John Condie, Frederico Xavier, Eric Grabowski, Ruth Nass, Jenny Wilson, Jason Coryell, Carter Wray

Affiliations

¹ From the Section of Pediatric Neurology (M.F.R.), Department of Pediatrics and Child Health, University of Manitoba, Children's Hospital Research Institute of Manitoba, Winnipeg, Canada; Department of Neurology and Pediatrics (K.A.S., H.J.F.), University of California, San Francisco; University of Toronto (A.-M.S.); Division of Neurology (G.A.d.V., N.D., A.L.), The Hospital for Sick Children, University of Toronto, Ontario; Department of Pediatrics and Clinical Neurosciences (A.K.), Cumming School of Medicine, University of Calgary, Alberta, Canada; Department of Neurology (C.A.-L.), University of Washington, Seattle; Department of Neuropediatrics (B.W.), Charité University Medicine Berlin, Germany; Department of Neurology (J.L.C.), George Washington University, Washington, DC; Department of Neurology (M.T.M.), Royal Children's Hospital Melbourne, Murdoch Children's Research Institute and University of Melbourne, Australia; Boston Children's Hospital (M.R.), Harvard Medical School, Boston, MA; and Division of Child Neurology (T.J.B.), Department of Pediatrics and the Hemophilia and Thrombosis Center, University of Colorado, Denver. mubeen.rafay@utoronto.ca.
² From the Section of Pediatric Neurology (M.F.R.), Department of Pediatrics and Child Health, University of Manitoba, Children's Hospital Research Institute of Manitoba, Winnipeg, Canada; Department of Neurology and Pediatrics (K.A.S., H.J.F.), University of California, San Francisco; University of Toronto (A.-M.S.); Division of Neurology (G.A.d.V., N.D., A.L.), The Hospital for Sick Children, University of Toronto, Ontario; Department of Pediatrics and Clinical Neurosciences (A.K.), Cumming School of Medicine, University of Calgary, Alberta, Canada; Department of Neurology (C.A.-L.), University of Washington, Seattle; Department of Neuropediatrics (B.W.), Charité University Medicine Berlin, Germany; Department of Neurology (J.L.C.), George Washington University, Washington, DC; Department of Neurology (M.T.M.), Royal Children's Hospital Melbourne, Murdoch Children's Research Institute and University of Melbourne, Australia; Boston Children's Hospital (M.R.), Harvard Medical School, Boston, MA; and Division of Child Neurology (T.J.B.), Department of Pediatrics and the Hemophilia and Thrombosis Center, University of Colorado, Denver.

PMID: 32457211
PMCID: PMC7455362
DOI: 10.1212/WNL.0000000000009557

Observational Study

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke

Mubeen F Rafay et al. Neurology. 2020.

. 2020 Jun 9;94(23):e2479-e2490.

doi: 10.1212/WNL.0000000000009557. Epub 2020 May 26.

Authors

Collaborators

International Pediatric Stroke Study (IPSS) Group:
Steve Ashwal, Donna Ferriero, Rebecca Ichord, Fenella Kirkham, John K Lynch, Finbar O'Callaghan, Steve Pavlakis, Guillaume Sebire, Andrew Willan, Mahendranath Moharir, Michael Dowling, Janna Journeycake, Patricia Plumb, Belinda Stojanovski, Marta Hernandez, Jennifer Armstrong, Ulrike Nowak-Gottl, Susan Benedict, Jerome Yager, Patricia Massicotte, Warren Lo, Melissa Parakh, Lori Billinghurst, Maja Steinlin, Max Wiznitzer, Laura Lehman, Andrew Mallick, Li Kan, Dimitirios Zafeiriou, Christine Fox, Bruce Bjornson, Lori Jordan, Juliann Paolicchi, Chalmer McClure, Marcela Torres, Anneli Kolk, Monica Troncoso, Harry Whelan, Anthony Chan, Ilona Kopyta, Abdalla Abdalla, Terrence Gerard, Meredith Golomb, Peter Humphreys, Michael Noetzel, Kristin Guilliams, Geoffrey Heyer, Robert Fryer, Ann Yeh, Paola Pergami, Francesco Cardona, Gordana Kovacevic, Vijeya Ganesan, Jorina Elbers, Neil Friedman, Virginia Wong, Nana Tatishvili, Sally Sultan, Mitchell Elkind, Lisa Abraham, Veronica Gonzalez, Luigi Titomanlio, Montri Saengpattrachai, Norma B Lerner, Shalu Narang, Jill M Cholette, Carolina Oliviera, Hal Crosswell, Lucila Andrade Alveal, Ryan Felling, Maayke Hunfeld, Diana Altuna, Nassim Zecavati, David Buckley, Marcel Deray, Sahar Hassanein, Vesna Brankovic-Sreckovic, Anaita Hegde, Deepti Raybagkar, Christina Miteff, John Condie, Chaouki Khoury, Shannon Carpenter, Amanda Blair, Susanne Holzhauer, Patricia Garcia Soler, Lisa Nassif El-Hakam, Luis Conto, Jose Francisco Vilavedra, Barry Kosofsky, Dana Leifer, Yang Guang, Li-Ping Zou, J Michael Taylor, Neil Goldenberg, Adrian Toma, Lauren A Beslow, Mark Wainwright, John Condie, Frederico Xavier, Eric Grabowski, Ruth Nass, Jenny Wilson, Jason Coryell, Carter Wray

Affiliations

¹ From the Section of Pediatric Neurology (M.F.R.), Department of Pediatrics and Child Health, University of Manitoba, Children's Hospital Research Institute of Manitoba, Winnipeg, Canada; Department of Neurology and Pediatrics (K.A.S., H.J.F.), University of California, San Francisco; University of Toronto (A.-M.S.); Division of Neurology (G.A.d.V., N.D., A.L.), The Hospital for Sick Children, University of Toronto, Ontario; Department of Pediatrics and Clinical Neurosciences (A.K.), Cumming School of Medicine, University of Calgary, Alberta, Canada; Department of Neurology (C.A.-L.), University of Washington, Seattle; Department of Neuropediatrics (B.W.), Charité University Medicine Berlin, Germany; Department of Neurology (J.L.C.), George Washington University, Washington, DC; Department of Neurology (M.T.M.), Royal Children's Hospital Melbourne, Murdoch Children's Research Institute and University of Melbourne, Australia; Boston Children's Hospital (M.R.), Harvard Medical School, Boston, MA; and Division of Child Neurology (T.J.B.), Department of Pediatrics and the Hemophilia and Thrombosis Center, University of Colorado, Denver. mubeen.rafay@utoronto.ca.
² From the Section of Pediatric Neurology (M.F.R.), Department of Pediatrics and Child Health, University of Manitoba, Children's Hospital Research Institute of Manitoba, Winnipeg, Canada; Department of Neurology and Pediatrics (K.A.S., H.J.F.), University of California, San Francisco; University of Toronto (A.-M.S.); Division of Neurology (G.A.d.V., N.D., A.L.), The Hospital for Sick Children, University of Toronto, Ontario; Department of Pediatrics and Clinical Neurosciences (A.K.), Cumming School of Medicine, University of Calgary, Alberta, Canada; Department of Neurology (C.A.-L.), University of Washington, Seattle; Department of Neuropediatrics (B.W.), Charité University Medicine Berlin, Germany; Department of Neurology (J.L.C.), George Washington University, Washington, DC; Department of Neurology (M.T.M.), Royal Children's Hospital Melbourne, Murdoch Children's Research Institute and University of Melbourne, Australia; Boston Children's Hospital (M.R.), Harvard Medical School, Boston, MA; and Division of Child Neurology (T.J.B.), Department of Pediatrics and the Hemophilia and Thrombosis Center, University of Colorado, Denver.

PMID: 32457211
PMCID: PMC7455362
DOI: 10.1212/WNL.0000000000009557

Abstract

Objective: To determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features.

Methods: We report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes.

Results: Of 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions.

Conclusion: Specific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.

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Figures

**Figure 1. Study population**
(A) International Pediatric Stroke Study (IPSS) cohort of children with arterial ischemic stroke (AIS) and cerebral arteriopathies. (B) IPSS cohort of children with AIS associated with arteriopathy. FCA-i = focal cerebral arteriopathy–inflammatory subtype.

**Figure 2. Association of age**
(A) Association of age and arteriopathy in children with arterial ischemic stroke (AIS). (B) Age distribution in children with AIS by arteriopathy type. FCA-i = focal cerebral arteriopathy–inflammatory subtype.

**Figure 3. Distribution of arteriopathy and first reported treatment of arteriopathy by geographic region**

See this image and copyright information in PMC

References

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1. Wintermark M, Hills NK, deVeber GA, et al. . Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the Vascular Effects of Infection in Pediatric Stroke Study. Stroke 2014;45:3597–3605. - PMC - PubMed
1. Chabrier S, Rodesch G, Lasjaunias P, Tardieu M, Landrieu P, Sebire G. Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke. J Child Neurol 1998;13:27–32. - PubMed
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Spectrum of cerebral arteriopathies in children with arterial ischemic stroke

Collaborators

Affiliations

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke

Authors

Collaborators

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources