1. EP-121 Arterial Tortuosity as a Biomarker for Pediatric Stroke Risk Gabriel De Vela 1, Todd Abruzzo MD 2, Timothy Yates MD 1, Nicholas McDonald MD 1, James Leach MD 2, J. Michael Taylor MD 2, Sudhakar Vadivelu MD 2 1 University of Cincinnati College of Medicine, Cincinnati, OH 2 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH

2. Disclosures The authors have no financial disclosures or conflicts of interest to disclose

3. Background Pediatric stroke incidence: 1.2 to 13 cases per 100,000 children Causes significant morbidity and mortality Risk factors in adults: –HTN, diabetes, atherosclerosis Risk factors in pediatric population: –Infection, cardiac disease, syndromic disorders Syndromic disorders associated with arteriopathy –Multisystem disease markers (allow for phenotype recognition) Arteriopathy in absence of syndromic disorder –Non-neurovascular phenotypic traits typically absent Kliegman, Robert et al. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: W.B. Saunders, 2011. 2080-086. Tsze, Daniel S., and Jonathan H. Valente. "Pediatric Stroke: A Review.“ Emergency Med International 2011 (2011): 1- 10.

4. Background Arterial tortuosity index (ATI): –(Distance 1)/(Distance 2) ↑ ATI expressed in wide spectrum of arteriopathies characterized by: –Vulnerability for spontaneous dissection Marfan, Loeys Dietz, Ehlers Danlos –Dysplastic steno-occlusive arterial lesions Tuberous sclerosis, neurofibromatosis, Alagille syndrome, PHACES, Williams syndrome Morris, SA et al. "Increased Vertebral Artery Tortuosity Index Is Associated With Adverse Outcomes in Children and Young Adults With Connective Tissue Disorders." Circulation 124.4 (2011): 388-96

5. Purpose Evaluate feasibility of using cervical and intracranial arterial tortuosity as a biomarker for occult large vessel arteriopathy in pediatric arterial ischemic stroke (AIS)

6. Hypothesis Arterial tortuosity index is abnormally increased in pediatric stroke patients without cardioembolic, traumatic, or infection-related stroke and without known arteriopathy

7. Materials and Methods Assessment of the arterial tortuosity index (ATI) was performed for discrete segments of cervical and intracranial internal carotid artery (ICA) and vertebral artery (VA) in 31 consecutive pediatric patients with nonperinatal AIS, unrelated to cardioembolism, major trauma, or active infection. The ATI was measured using noncontrast MRA postprocessed with VitreaAdvanced® 3D volume rendering software. The ATI of each segment was calculated as the length of the luminal center-line between start and end points, divided by the length of the shortest distance between those points.

8. Materials and Methods The mean ATI of each segment was calculated and analyzed for subgroups differentiated according to etiology: –Cryptogenic stroke (N=15) –Dissection (N=7) –Bow-hunter's syndrome (BHS) (N=3) –Moyamoya arteriopathy (MMA) (N=3) –Transient cerebral arteriopathy of childhood (TCA) (N=3)

9. Materials and Methods Vessel segment analysis was performed on the following artery segments: –Proximal cervical vertebral artery (V1-V2) –Distal cervical vertebral artery (V3) –Intracranial vertebral artery (V4) –Basilar artery –Cervical internal carotid artery –Petrous internal carotid artery –Intracranial internal carotid artery

10. Materials and Methods Proximal cervical vertebral artery (V1-V2) Distal cervical vertebral artery (V3)

11. Materials and Methods Intracranial vertebral artery (V4) Basilar Artery

12. Materials and Methods Intracranial internal carotid artery Petrous internal carotid artery

13. Materials and Methods Cervical internal carotid artery

14. Results Mean age – 11 yo (5 months to 19 yo) 18 males, 13 females

15. Results Marked cervicocerebral arterial tortuosity (>2 standard deviations (SD) above mean) found in: –6/15 (40%) patients with cryptogenic stroke In 3/6 patients with elevated arterial tortuosity, two different vessel segments were >2 SD above mean –2/7 (28%) patients with arterial dissection –0/3 (0%) patients with transient cerebral arteriopathy of childhood –0/3 (0%) patients with bow-hunter’s syndrome –0/3 (0%) patients with moyamoya arteriopathy

16. Results 9 yo male with history of cryptogenic stroke and tortuous vessels 17 yo female with history of TCA and nontortuous vessels

17. Results 9 yo male with history of cryptogenic stroke and tortuous vessels 17 yo female with history of TCA and nontortuous vessels

18. Conclusions The neurovascular ATI is increased abnormally in a significant minority of pediatric patients with AIS that is cryptogenic or due to arterial dissection, but not in pediatric patients with AIS due to bow-hunter's syndrome, moyamoya arteriopathy, or transient cerebral arteriopathy of childhood. Further study of arterial tortuosity as a biomarker of occult large vessel arteriopathy in pediatric AIS is warranted.