Arteriopathy diagnosis in childhood arterial ischemic stroke: results of the vascular effects of infection in pediatric stroke study.
OBJECTIVE
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 (κ=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.
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Max
M
Wintermark
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Nancy K
NK
Hills
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Gabrielle A
GA
deVeber
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
A James
AJ
Barkovich
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Mitchell S V
MS
Elkind
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Katherine
K
Sear
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Guangming
G
Zhu
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Carlos
C
Leiva-Salinas
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Qinghua
Q
Hou
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Michael M
MM
Dowling
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Timothy J
TJ
Bernard
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Neil R
NR
Friedman
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.).
Rebecca N
RN
Ichord
From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.). fullertonh@neuropeds.ucsf.edu.
Heather J
HJ
Fullerton
D000293:Adolescent; D001158:Arteries / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D020521:Stroke / Q000209:etiology*; D014652:Vascular Diseases / Q000150:complications* / Q000175:diagnosis*
cerebral arterial diseases; pediatrics; stroke; transient ischemic attack