title: Arterial Tortuosity: An Imaging Biomarker of Childhood Stroke Pathogenesis?
abstract: Arteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.
  
  
  
  Children (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test).
  
  
  
  One hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15; P=0.998), meningitis (1.348±0.052; n=11; P=0.989), and cardioembolic (1.379±0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70).
  
  
  
  In children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.
authors.affiliation: From the Calgary Pediatric Stroke Program, Section of Neurology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada (F.W., J.H., A.K.); Mebio, Inc, Cambridge, MA (K.T.D.); Departments of Neurology and Pediatrics, University of California, San Francisco (H.J.F.); Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada (G.d.V.); and Division of Neuroradiology, Department of Radiology, University of Virginia, Charlottesville (W.M).
authors.forename: Felix
authors.initials: F
authors.lastname: Wei
authors.affiliation: From the Calgary Pediatric Stroke Program, Section of Neurology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada (F.W., J.H., A.K.); Mebio, Inc, Cambridge, MA (K.T.D.); Departments of Neurology and Pediatrics, University of California, San Francisco (H.J.F.); Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada (G.d.V.); and Division of Neuroradiology, Department of Radiology, University of Virginia, Charlottesville (W.M).
authors.forename: Karl T
authors.initials: KT
authors.lastname: Diedrich
authors.affiliation: From the Calgary Pediatric Stroke Program, Section of Neurology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada (F.W., J.H., A.K.); Mebio, Inc, Cambridge, MA (K.T.D.); Departments of Neurology and Pediatrics, University of California, San Francisco (H.J.F.); Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada (G.d.V.); and Division of Neuroradiology, Department of Radiology, University of Virginia, Charlottesville (W.M).
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Fullerton
authors.affiliation: From the Calgary Pediatric Stroke Program, Section of Neurology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada (F.W., J.H., A.K.); Mebio, Inc, Cambridge, MA (K.T.D.); Departments of Neurology and Pediatrics, University of California, San Francisco (H.J.F.); Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada (G.d.V.); and Division of Neuroradiology, Department of Radiology, University of Virginia, Charlottesville (W.M).
authors.forename: Gabrielle
authors.initials: G
authors.lastname: deVeber
authors.affiliation: From the Calgary Pediatric Stroke Program, Section of Neurology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada (F.W., J.H., A.K.); Mebio, Inc, Cambridge, MA (K.T.D.); Departments of Neurology and Pediatrics, University of California, San Francisco (H.J.F.); Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada (G.d.V.); and Division of Neuroradiology, Department of Radiology, University of Virginia, Charlottesville (W.M).
authors.forename: Max
authors.initials: M
authors.lastname: Wintermark
authors.affiliation: From the Calgary Pediatric Stroke Program, Section of Neurology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada (F.W., J.H., A.K.); Mebio, Inc, Cambridge, MA (K.T.D.); Departments of Neurology and Pediatrics, University of California, San Francisco (H.J.F.); Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada (G.d.V.); and Division of Neuroradiology, Department of Radiology, University of Virginia, Charlottesville (W.M).
authors.forename: Jacquie
authors.initials: J
authors.lastname: Hodge
authors.affiliation: From the Calgary Pediatric Stroke Program, Section of Neurology, Department of Pediatrics, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada (F.W., J.H., A.K.); Mebio, Inc, Cambridge, MA (K.T.D.); Departments of Neurology and Pediatrics, University of California, San Francisco (H.J.F.); Department of Neurology, Hospital for Sick Children, Toronto, ON, Canada (G.d.V.); and Division of Neuroradiology, Department of Radiology, University of Virginia, Charlottesville (W.M). adam.kirton@albertahealthservices.ca.
authors.forename: Adam
authors.initials: A
authors.lastname: Kirton
mesh_terms: D000293:Adolescent; D001158:Arteries / Q000002:abnormalities* / Q000000981:diagnostic imaging; D015415:Biomarkers; D002545:Brain Ischemia / Q000453:epidemiology*; D002539:Cerebral Arterial Diseases / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006801:Humans; D007223:Infant; D007593:Joint Instability / Q000000981:diagnostic imaging*; D008297:Male; D008581:Meningitis / Q000453:epidemiology; D009072:Moyamoya Disease / Q000453:epidemiology; D009203:Myocardial Infarction / Q000453:epidemiology; D011446:Prospective Studies; D012873:Skin Diseases, Genetic / Q000000981:diagnostic imaging*; D020521:Stroke / Q000453:epidemiology*; D054079:Vascular Malformations / Q000000981:diagnostic imaging*
chemical_list: D015415:Biomarkers
keywords: arterial tortuosity; child; dissection; magnetic resonance angiography; pediatric stroke; stroke