Accepted Manuscript Re-recurrence of intracranial aneurysm with proximal vascular stenosis after primary clipping and secondary endovascular embolization: A case report and literature review Donghuan Zhang, Honglei Wang, Tianyi Liu, Yingli Feng, Yuan Qi, Ning Xu PII: S1878-8750(18)32134-X DOI: 10.1016/j.wneu.2018.09.088 Reference: WNEU 10293 To appear in: World Neurosurgery Received Date: 3 August 2018 Revised Date: 10 September 2018 Accepted Date: 12 September 2018 Please cite this article as: Zhang D, Wang H, Liu T, Feng Y, Qi Y, Xu N, Re-recurrence of intracranial aneurysm with proximal vascular stenosis after primary clipping and secondary endovascular embolization: A case report and literature review, World Neurosurgery (2018), doi: https:// doi.org/10.1016/j.wneu.2018.09.088. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Re-recurrence of intracranial aneurysm with proximal vascular stenosis after primary clipping and secondary endovascular embolization: A case report and literature review RI PT Donghuan Zhang#, Honglei Wang#, Tianyi Liu, Yingli Feng, Yuan Qi, Ning Xu* Department of neurosurgery, the First Hospital of Jilin University, Jilin, 130021, These two authors contribute equally to this work. * Corresponding author: M AN U # SC China Ning Xu, Department of neurosurgery, the First Hospital of Jilin University, No. 71 Xinmin Street, TE D Changchun, 130021, China; Tel: +8613331766969; E-mail: x7s5lh@163.com AC C EP Running title: Re-recurrence of intracranial aneurysm ACCEPTED MANUSCRIPT Re-recurrence of intracranial aneurysm with proximal vascular stenosis after primary AC C EP TE D M AN U SC Running title: Re-recurrence of intracranial aneurysm RI PT clipping and secondary endovascular embolization: A case report and literature review ACCEPTED MANUSCRIPT Abstract Background: It was known that a small number of patients could have intracranial aneurysm recurrences after either surgical clipping or endovascular embolization treatment. However, early RI PT recurrence within one month after the treatment and re-recurrence was rarely reported before. Case presentation: We reported a 46-year-old male patient with a medical history of smoking and hypertension who was non-compliant with the treatments. He presented to the hospital due to right extremity paralysis and aphasia, and was found to have a ruptured middle cerebral artery SC aneurysm. Aneurysm was successfully treated by surgical clipping. Within one month after the treatment, the patient had a recurrent aneurysm at the same location and intracranial hemorrhage. M AN U The recurrent aneurysm was treated by endovascular embolization. However, during the followup visit 8 months after the treatment, angiography showed the aneurysm recurrence with proximal vascular stenosis. Conclusion: Re-recurrence of intracranial aneurysm could happen after initial successful treatment with surgical clipping and endovascular embolization. In addition to patient's medical TE D history and characteristics of the aneurysm, local vascular stenosis might also contribute to its recurrence. Close post-operative follow-up is required for these patients. AC C EP Keywords: Intracranial aneurysm; Clipping; Endovascular embolization; Recurrence ACCEPTED MANUSCRIPT Introduction Intracranial aneurysm is a serious condition, which can lead to intracranial hemorrhage with high mortality and morbidity [1, 2]. The onset of aneurysm is commonly insidious until rupture and hemorrhage occur. The main treatment options for a rupture intracranial aneurysm include either RI PT surgical clipping or endovascular coiling [3]. However, recurrent aneurysm and rupture could happen after initial successful treatments [4, 5]. Currently, there is no consensus on the screening for intracranial aneurysm and its recurrence [6, 7]. SC Here, we report a case with two-time recurrence of intracranial aneurysm after initial successful treatments with surgical clipping and endovascular embolization. We discussed the importance avoid its devastating outcomes. Case presentation M AN U of the clinic follow-up after successful treatment procedures for intracranial aneurysm in order to On February 27, 2017, a 46-year-old male patient presented to the local hospital with sudden onset of left extremity paralysis and aphasia, as well as worsening altered mental status. Brain TE D computed tomography (CT) revealed right intraparenchymal hematoma and subarachnoid hemorrhage (Figure 1). He had a medical history of long-term hypertension and cigarette smoking, with noncompliance in the treatments and blood pressure frequently above 180/120 mmHg. He immediately received emergent intracranial hematoma evacuation and decompressive EP craniectomy. An aneurysm, with approximate size of 3 x 5 mm, was identified at the bifurcation of the right middle cerebral artery during the operation. Surgical clipping was applied. AC C Postoperative computed tomography angiography (CTA) showed a clip at the bifurcation of the right middle cerebral artery with no obvious residual aneurysm sac at the clipping site (Figure 2). On March 17, 2017, the patient presented to the hospital with recurrent headache and altered mental status. Repeat head CT showed intracranial hemorrhages at the right basal ganglia area, with blood in the lateral ventricles (Figure 3). Brain CT angiography and digital subtraction angiography (DSA) was performed and revealed the recurrence of an aneurysm at the bifurcation of the right middle cerebral artery (Figure 4). Considering the difficulty in repeat craniotomy due to disrupted anatomy and adhesion from previous surgical craniectomy, endovascular ACCEPTED MANUSCRIPT embolization was performed on April 7, 2017 after informed consent obtained from the family members. Five minutes after embolization (d/b/a ev3 Neurovascular Irving, Micro Therapeutics Inc., CA, USA), complete obliteration of the aneurysm was shown by angiography (Raymond classification I, Figure 5). During the follow-up visit on December 4, 2017, CTA showed severe RI PT stenosis at the distal M1 segment of the right middle cerebral artery which was proximal to a recurrent aneurysm (Figure 6). The patient had no clinical symptoms and it was recommended to closely follow up patients in the clinic. SC Discussion The prevalence of intracranial aneurysm is relatively low, but once a rupture occurs, it can lead M AN U to catastrophic outcomes [1, 8]. Most patients with intracranial aneurysm have no clinical symptoms, which makes its diagnosis and treatment difficult. The treatment choice for a ruptured intracranial aneurysm include surgical clipping and endovascular embolization [3]. Unfortunately, recurrence of aneurysm had been reported after either of these two treatments. In 2002, study from the international subarachnoid aneurysm trial reported a recurrence rate of 0 one year after surgical craniotomy [4], whereas another study a recurrence rate of 3.8% during an TE D average postoperative follow-up period of 5.7 months after either surgical clipping or endovascular embolization treatment [9]. A latest study suggested that aneurysm at the middle cerebral artery had a higher risk for recurrence. Factors, such as smoking history, ruptured aneurysm, wide-necked aneurysm, aneurysm with a diameter > 10 mm, embolization with no EP stent placement, and volume embolization ratio < 20%, were the risk factors for aneurysm recurrence [10]. Our current case had several risk factors for aneurysm recurrence, including AC C cigarette smoking, middle cerebral artery and its lower trunk involvement, ruptured aneurysm, embolization without stent placement. However, the reported average time interval for aneurysm recurrence ranged from months to years after the initial treatment [11]. Our patient had aneurysm recurrence at the same location within one month after initial surgical clipping, which was never reported before. The underlying mechanism for this early recurrence is unknown. In 1986, Asari et al. reported a case with rapid regrowth and rupture of clipped middle cerebral artery aneurysm [12]. It was suggested that factors for rapid recurrence could be vascular wall injury from the clip, residual aneurysm, and clipping failure. In 2003, Sakamoto et al. reported ACCEPTED MANUSCRIPT another case with aneurysm recurrence 5 months after the initial clipping and wrapping treatment of a dissected distal middle cerebral artery [13]. In 2018, Oya et al. reported a case with subarachnoid hemorrhage from a dissected branch of the middle cerebral artery in a 2-yer-old boy. The aneurysm recurred 2 years after the treatment [14]. All of these reported cases had RI PT aneurysm recurred proximal to the previous aneurysm. The residual injured vascular epithelial cells in the aneurysm neck might affect the re-endothelialization and intimal formation, which increases the risk for aneurysm recurrence [15]. Considering previous reports and the medical history of our patient, we consider that the possible causes for early recurrence of the cerebral SC aneurysm in our patient include, 1), aneurysm might be a dissecting aneurysm and affect the epithelial cells in the aneurysm neck; 2), residual aneurysm at the aneurysm neck with M AN U inadequate clipping. Our patient received the surgical clipping during the initial treatment. After the first recurrence, endovascular embolization was performed due to consideration of difficult craniotomy from disrupted anatomy and adhesion from previous surgical craniectomy [16-18]. This treatment strategy was reported before during the treatment for recurrence aneurysm [19, 20]. The TE D aneurysm was successful treated by postoperative angiography study. However, 8 months after the second treatment, the aneurysm happened again. This recurrence of previous treated recurrent cerebral aneurysm has never been reported before. EP Angiography study showed a vascular stenosis proximal to the recurrent aneurysm in our patient. There were several studies reported arterial aneurysm with proximal vascular stenosis. AC C Intraluminal stenosis can change the vascular morphology and alter the hemodynamics. The disturbed blood flow may promote the formation of the aneurysm [21]. Kono et al. studied the hemodynamic parameters in the stenosis vessels and suggested that an unphysiologically high wall shear stress and its gradient changes could induce the initiation of aneurysm [22, 23]. Another recent study also showed that the degree of the proximal vascular stenosis and its distance from the aneurysmal neck had statistically significant associations with the formation and progression of the aneurysm [24]. Severe vascular stenosis and its close proximity to the aneurysmal neck could cause complex hemodynamic changes, which results in a high blood flow ACCEPTED MANUSCRIPT rate and increased intra-aneurysm pressure. Our patient had a vascular stenosis proximal to the aneurysm, which might be the cause for second-recurrence of the aneurysm. In our patient, we used a spring ring coil coved with the nylon to embolize the aneurysm. Dense RI PT embolization of the aneurysm might be related to the thrombotic tendency of nylon materials. The aneurysm was treated successfully via this technique, which was evidenced by the postoperative angiography study. However, it was reported that thrombosis in the aneurysm cavity could affect local hemodynamics. The inflammatory responses induced by the thrombus SC might also cause thrombolysis and injury to the vascular wall, which participated in the initiation and development of aneurysm [15]. Thus, the second recurrence of aneurysm after the M AN U endovascular embolization might be due to, 1), complex hemodynamics and remodeling of the vascular wall; 2), inflammation, and subsequent thrombolysis and reconstruction of vascular wall; 3), compressed and deformed spring ring with the evolution of disease. Causes for vascular stenosis could include vascular atherosclerosis and intramural dissection. Atherosclerosis can lead to thickening of the arterial intima and result in stenosis of the lumen TE D [25, 26]. Our patient had multiple risk factors for atherosclerosis, including hypertension, noncompliance with the treatment, and history of smoking. However, the stenosis was only observed in the vessel proximal to the aneurysm and close to the neck of the aneurysm. There were no other obvious stenotic changes in other vessels in the remaining brain in the EP angiography study. This suggested that atherosclerosis might not be the main cause for the observed stenosis in our patient. We suspected that our patient had vascular atherosclerotic AC C changes. The mechanic injury from the spring ring placement during the endovascular embolization might further cause the vascular intimal injury and vascular wall thickening, which finally lead to stenosis. Previous studies did show that atherosclerosis could increase vascular susceptibility for mechanic injury [26]. Conclusion Re-recurrence of intracranial aneurysm could happen after initial successful treatment with surgical clipping and endovascular embolization. In addition to patient's medical history and ACCEPTED MANUSCRIPT characteristics of the aneurysm, local vascular stenosis might also contribute to its recurrence. RI PT Close post-operative follow-up is required for these patients. Conflict of interest: None SC Ethical consideration: Informed consents were obtained from the patient to publish the imaging AC C EP TE D M AN U pictures. ACCEPTED MANUSCRIPT References 1. Bederson JB, Connolly ES, Jr., Batjer HH, Dacey RG, Dion JE, Diringer MN, Duldner JE, Jr., Harbaugh RE, Patel AB, Rosenwasser RH et al: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals RI PT from a special writing group of the Stroke Council, American Heart Association. Stroke 2009, 40(3):994-1025. 2. Pokorski RJ: Morbidity and mortality associated with intracranial aneurysms. J Insur Med 1997, 29(1):11-18. Zhao J, Lin H, Summers R, Yang M, Cousins BG, Tsui J: Current Treatment SC 3. Strategies for Intracranial Aneurysms: An Overview. Angiology 2018, 69(1):17-30. Molyneux A, Kerr R, Stratton I, Sandercock P, Clarke M, Shrimpton J, Holman R, International Subarachnoid Subarachnoid Aneurysm M AN U 4. Aneurysm Trial Trial (ISAT) of Collaborative G: International neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002, 360(9342):1267-1274. 5. Molyneux AJ, Kerr RS, Birks J, Ramzi N, Yarnold J, Sneade M, Rischmiller J, TE D Collaborators I: Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up. Lancet Neurol 2009, 8(5):427-433. Wermer MJ, Koffijberg H, van der Schaaf IC, Group AS: Effectiveness and costs of EP 6. screening for aneurysms every 5 years after subarachnoid hemorrhage. Neurology 7. AC C 2008, 70(22):2053-2062. Wermer MJ, van der Schaaf IC, Velthuis BK, Algra A, Buskens E, Rinkel GJ, Group AS: Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms. Brain 2005, 128(Pt 10):2421-2429. 8. Vlak MH, Algra A, Brandenburg R, Rinkel GJ: Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol 2011, 10(7):626-636. ACCEPTED MANUSCRIPT 9. Campi A, Ramzi N, Molyneux AJ, Summers PE, Kerr RS, Sneade M, Yarnold JA, Rischmiller J, Byrne JV: Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT). Stroke 2007, 38(5):1538-1544. Huang DZ, Jiang B, He W, Wang YH, Wang ZG: Risk factors for the recurrence of an RI PT 10. intracranial saccular aneurysm following endovascular treatment. Oncotarget 2017, 8(20):33676-33682. 11. Okada T, Ishikawa T, Moroi J, Suzuki A: Timing of retreatment for patients with SC previously coiled or clipped intracranial aneurysms: Analysis of 156 patients with multiple treatments. Surg Neurol Int 2016, 7(Suppl 2):S40-48. Asari S, Kunishio K, Sunami N, Yamamoto Y, Sakurai M, Suzuki K: [Rapid growth M AN U 12. and rupture of a newly originated aneurysm near the clipped middle cerebral artery aneurysm]. No Shinkei Geka 1986, 14(4):587-591. 13. Sakamoto S, Ikawa F, Kawamoto H, Ohbayashi N, Inagawa T: Subsequent rupture after clip on wrap method for ruptured dissecting aneurysm of the distal middle cerebral artery: a case report and review of the literature. Hiroshima J Med Sci 2003, 14. TE D 52(1):15-19. Oya S, Kiko I, Suyama K, Suzuki T, Yamamoto K, Mochida H, Watanabe S, Karasawa H: [A Ruptured Middle Cerebral Artery Dissecting Aneurysm Operation in a 2Year-Old Boy]. No Shinkei Geka 2018, 46(1):27-34. Marbacher S, Niemela M, Hernesniemi J, Frosen J: Recurrence of endovascularly and EP 15. microsurgically treated intracranial aneurysms-review of the putative role of 16. AC C aneurysm wall biology. Neurosurg Rev 2017. Drake CG, Friedman AH, Peerless SJ: Failed aneurysm surgery. Reoperation in 115 cases. J Neurosurg 1984, 61(5):848-856. 17. Lin T, Fox AJ, Drake CG: Regrowth of aneurysm sacs from residual neck following aneurysm clipping. J Neurosurg 1989, 70(4):556-560. 18. Chung J, Park IS, Park H, Hwang SH, Jung JM, Han JW: Endovascular coil embolization after clipping: endovascular treatment of incompletely clipped or recurred cerebral aneurysms. J Cerebrovasc Endovasc Neurosurg 2014, 16(3):262-267. ACCEPTED MANUSCRIPT 19. Cekirge HS, Islak C, Firat MM, Kocer N, Saatci I: Endovascular coil embolization of residual or recurrent aneurysms after surgical clipping. Acta Radiol 2000, 41(2):111115. 20. Forsting M, Albert FK, Jansen O, von Kummer R, Aschoff A, Kunze S, Sartor K: Coil RI PT placement after clipping: endovascular treatment of incompletely clipped cerebral aneurysms. Report of two cases. J Neurosurg 1996, 85(5):966-969. 21. Samano A, Ishikawa T, Moroi J, Yamashita S, Suzuki A, Yasui N: Ruptured de novo posterior communicating artery aneurysm associated with arteriosclerotic stenosis 22. SC of the internal carotid artery at the supraclinoid portion. Surg Neurol Int 2011, 2:35. Kono K, Masuo O, Nakao N, Meng H: De novo cerebral aneurysm formation 23. M AN U associated with proximal stenosis. Neurosurgery 2013, 73(6):E1080-1090. Kono K, Fujimoto T, Terada T: Proximal stenosis may induce initiation of cerebral aneurysms by increasing wall shear stress and wall shear stress gradient. Int J Numer Method Biomed Eng 2014, 30(10):942-950. 24. Antonov A, Kono K, Greim-Kuczewski K, Hippelheuser JE, Lauric A, Malek AM: Proximal Stenosis Is Associated with Rupture Status in Middle Cerebral Artery 25. TE D Aneurysms. World Neurosurg 2018, 109:e835-e844. Sakata N, Takebayashi S, Kojima M, Masawa N, Suzuki K, Takatama M, Kusumi Y, Mitsumata M: Different roles of arteriosclerosis in the rupture of intracranial dissecting aneurysms. Histopathology 2001, 38(4):325-337. EP Ishikawa M, Akishita M, Kozaki K, Toba K, Namiki A, Yamaguchi T, Orimo H, Ouchi Y: Expression of parathyroid hormone-related protein in human and experimental atherosclerotic lesions: functional role in arterial intimal thickening. Atherosclerosis AC C 26. 2000, 152(1):97-105. ACCEPTED MANUSCRIPT Figure legends Figure 1. Right intraparenchymal hematoma (A) and subarachnoid hemorrhage (B) shown in the RI PT brain computed tomography during the first hospital visit. Figure 2. A clip (red arrow) shown at the bifurcation of the right middle cerebral artery, with no aneurysm observed, in the brain computed tomography angiography after the surgical clipping. SC Figure 3. Intracranial hemorrhage at the right basal ganglia area (A) with bleeding into the lateral M AN U ventricles (B) shown in the brain computed tomography during the second hospital visit. Figure 4. Recurrent aneurysm (red arrow) at the bifurcation of the right middle cerebral artery shown in the brain computed tomography angiography (A) and digital subtraction angiography (B). Figure 5. Complete obliteration of the aneurysm (red arrow) after endovascular embolization in TE D the brain computed tomography angiography. Figure 6. Arterial stenosis (red arrow) proximal to the recurrent aneurysm shown in the brain AC C EP computed tomography angiography (A) and digital subtraction angiography (B). ACCEPTED MANUSCRIPT Table Table 1. Characteristics and disease course for the patient Clinical symptoms and signs Left extremity paralysis, aphasia, altered mental status Brain imaging study and surgical finding March 17, 2017 Basal ganglia hemorrhage with blood in lateral ventricles. Aneurysm recurrence Treatment RI PT Vital signs Blood Heart rate pressure February 27, 180/105 95 /min 2017 mmHg SC Right intraparenchymal hematoma and subarachnoid hemorrhage. Right middle cerebral artery aneurysm Surgical clipping 89/min Left extremity paralysis, aphasia, headacheļ¼Œ altered mental status December 4, 140/85 2017 mmHg 70/min Left extremity Aneurysm recurrence with Clinical paralysis proximal vascular stenosis follow-up AC C EP TE D M AN U 180/100 mmHg Endovascular embolization AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT Highlights 1. Re-recurrence of intracranial aneurysm could happen after initial successful treatment with surgical clipping and endovascular embolization. 2. In addition to patient's medical history and characteristics of the aneurysm, local vascular stenosis might also contribute to its recurrence. 3. Close post-operative follow-up is required for these patients. ACCEPTED MANUSCRIPT Abbreviations: Computed tomography (CT); computed tomography angiography (CTA); digital AC C EP TE D M AN U SC RI PT subtraction angiography (DSA) ACCEPTED MANUSCRIPT Conflict of interest AC C EP TE D M AN U SC RI PT All the authors declare that they have no conflict of interest.