原著論文 頭蓋内椎骨動脈および腹腔内動脈解離の同時破裂例の病理形態学的検討 : 頭蓋内動脈解離に おける Segmental arterial mediolysis の関与について 呂彩子 *,**, 景山則正 *,**, 向井敏二 *. ( *, 聖マリアンナ医科大学法医学教室, ** 東京都監察

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1 原著論文 頭蓋内椎骨動脈および腹腔内動脈解離の同時破裂例の病理形態学的検討 : 頭蓋内動脈解離に おける Segmental arterial mediolysis の関与について 呂彩子 *,**, 景山則正 *,**, 向井敏二 *. ( *, 聖マリアンナ医科大学法医学教室, ** 東京都監察医務院 ) 神奈川県川崎市宮前区菅生 Tel ( 内線 3556) chaeja@marianna-u.ac.jp keyword: Segmental arterial mediolysis, subarachnoid hemorrhage, vertebral artery dissection, autopsy 本論文を, 日本脳神経血管内治療学会機関誌 JNET Journal of Neuroendovascular Therapy に投稿するにあたり, 筆頭著者, 共著者によって, 国内外の他雑誌に掲載ないし投稿されていな いことを誓約致します.

2 [ ] Segmental arterial mediolysis (SAM) [ ] (Intracranial vertebral artery:iva) 4 IVA (Intra peritoneal artery:ipa) α SMA S100A4 [ ] IVA 2.4mm mm IVA IPA SAM IVA 3

3 IPA [ ] SAM SAM Intracranial vertebral artery;iva 50 IVA Segmental arterial mediolysis (SAM) 1) SAM 1976 Slavin 2) SAM SAM

4 SAM ) SAM 9 3) IVA 4 IVA 4 Case Case1 2

5 Case2 Case1-3 Case4 IVA IVA 0.2mm EVG 2mm α SMA DAKO S100A4 Abcam 3mm 30 HE EVG

6 α SMA S100A4 Case1,2 SAM Case4 IVA 1. 4 Fig1-4 IVA Case1 1100ml Case2,3,4 Fig2d,4g 2. IVA

7 (Fig1a,3b) EVG 2.4mm mm Table1 Case4 Fig1a,2b Case1 IVA Fig1c IVA Case2,3 Case3,4 (Fig3b,4b) Case3 (Fig3b). IVA α SMA EVG (Fig 3c) (Fig1a-d,4b)

8 S100A4 Case1,2,4 Fig1b,2c,4c Case3,4 Fig4d. α SMA EVG S100A4 僅 Fig1g,4h 4. Table2 Case 4 Fig4e Fig4f

9 Case1 Fig1e Fig1f Case2 SAM SAM 18% 3) 3) SAM 3-10) SAM 11) SAM IVA 12) SAM 1 8) IVA Yonas 13)

10 SAM SAM SAM IVA SAM SAM

11 IVA SAM 9) 4 3 SAM IVA 2.5mm 0.5-1cm

12 1 S100A4 3 Case1 Case3 IVA

13 SAM S100A4 SAM 9, SAM

14 IVA 58 43% 68 IVA 14) IVA 3 IVA SAM SAM IVA SAM Kalva Shinoda IVA 8 8 IVA

15 SAM SAM SAM SAM 15) D1 Fenoldopam 16 SAM IVA 1 IVA SAM

16 [ ] SAM SAM SAM 1. Ro A, Kageyama N.Pathomorphometry of ruptured intracranial vertebral arterial dissection: adventitial rupture, dilated lesion, intimal tear, and medial defect. J Neurosurg 2013;119:221-7.

17 2. Slavin RE, Gonzalez-Vitale JC. Segmental mediolytic arteritis: a clinical pathologic study. Lab Invest 1976;35: Shenouda M, Riga C, Naji Y, et al. Segmental arterial mediolysis: a systematic review of 85 cases. Ann Vasc Surg 2014 ;28: Obara H, Matsumoto K, Narimatsu Y, et al. Reconstructive surgery for segmental arterial mediolysis involving both the internal carotid artery and visceral arteries. J Vasc Surg 2006;43: Cooke DL, Meisel KM, Kim WT, et al. Serial angiographic appearance of segmental arterial mediolysis manifesting as vertebral, internal mammary and intra-abdominal visceral artery aneurysms in a patient presenting with subarachnoid hemorrhage and review of the literature. J Neurointerv Surg 2013;5: Alturkustani M, Ang LC. Intracranial segmental arterial mediolysis: report of 2 cases and review of the literature. Am J Forensic Med Pathol 2013;34: Sakata N, Takebayashi S, Shimizu K, et al. A case of

18 segmental mediolytic arteriopathy involving both intracranial and intraabdominal arteries. Pathol Res Pract 2002;198: Sinoda N, Hirai O, Mikami K, et al. Segmental Arterial Mediolysis Involving Both Vertebral and Middle Colic Arteries Leading to Subarachnoid and Intraperitoneal Hemorrhage. World Neurosurg 2016;88:694.e Slavin RE. Segmental arterial mediolysis: course, sequelae, prognosis, and pathologic-radiologic correlation. Cardiovasc Pathol 2009 ;18: Kalva SP, Somarouthu B, Jaff MR, et al. Segmental arterial mediolysis: clinical and imaging features at presentation and during follow-up. J Vasc Interv Radiol 2011;22: Ro A, Kageyama N, Hayashi K, et al. Non-traumatic rupture of the intracranial vertebral artery of a man found dead in a severe car accident - histopathological differentiation by step-serial sections. Leg Med (Tokyo) 2008;10: Ro A, Kageyama N, Takatsu A, et al. Segmental arterial mediolysis of varying phases affecting both the intraabdominal and

19 intracranial vertebral arteries: an autopsy case report. Cardiovasc Pathol 2010;19: Yonas H, Agamanolis D, Takaoka Y, et al. Dissecting intracranial aneurysms. Surg Neurol 1977;8: Ro A, Kageyama N, Abe N, et al. Intracranial vertebral arterial dissection resulting in fatal subarachnoid hemorrhage: Clinical and histopathological investigations from a medicolegal perspective. J Neurosurg 2009;110: Slavin RE, Yaeger MJ. Segmental arterial mediolysis--an iatrogenic vascular disorder induced by ractopamine. Cardiovasc Pathol 2012;21: Brott DA, Richardson RJ, Louden CS. Evidence for the nitric oxide pathway as a potential mode of action in fenoldopam-induced vascular injury. Toxicol Pathol. 2012;40: Figure1 Case1

20 a IVA EVG b a S100A4 c IVA EVG 3 d c α SMA e f EVG g S100A4

21 Figure2 Case2 a IVA IVA b IVA EVG c b S100A4 d e α SMA Figure3 Case3 a IVA IVA IVA ( ) b IVA EVG IVA *

22 IVA c IVA EVG d EVG Figure4 Case4 a IVA b IVA EVG IVA IVA c IVA S100A4 d IVA S100A4

23 * e EVG f EVG g 2 h S100A4 Table1 Table2

24

25

26 Table1 Ruptured IVA Around adventitial rupture Apart from the adventitial rupture Adventitia IEL disruption IEL rupture IEL disruption Length of Without With Without With Without With rupture (mm) organization* organization* organization* organization* organization* organization* Case (11.0) 1(1.2) 5 (14.0) 3 (4.4) 0 0 Case (8.6) (2.8) 0 Case (5.4) (0.8) 1(9.6) Case (5.4) (2.4) IVA : intracranial vertebral artery. IEL : internal elastic lamina *described as number (maximum length(mm)) Contralateral IVA

27 Table2 Contralateral IVA New dissection Other intracranial artery Intraabdomin al artery Contralatera l IVA Previous dissection Other Intraabdominal intracranial artery artery Case1 - N.E +* - N.E +** Case2 + N.E - - N.E - Case3 + N.E N.E + N.E N.E Case4 - - N.E + +*** N.E +* Right and left gastric artery, right and left gastro-epiploic artery, Inferior pancreaticoduodenal artery. Right renal artery +** Middle colic artery +*** Anterior cerebral artery, Internal carotid artery IVA Intracranial vertebral artery N.E Not examined

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