Journal Pre-proof Transient cerebral vasospasm after carotid artery stenting: A case report and literature review Masashi Kuwabara, MD, Toshinori Nakahara, MD, Takafumi Mitsuhara, MD, Koji Shimonaga, MD, Masahiro Hosogai, MD, Kaoru Kurisu, MD, Shigeyuki Sakamoto, MD PII: S1878-8750(19)33001-3 DOI: https://doi.org/10.1016/j.wneu.2019.11.151 Reference: WNEU 13820 To appear in: World Neurosurgery Received Date: 25 September 2019 Accepted Date: 25 November 2019 Please cite this article as: Kuwabara M, Nakahara T, Mitsuhara T, Shimonaga K, Hosogai M, Kurisu K, Sakamoto S, Transient cerebral vasospasm after carotid artery stenting: A case report and literature review, World Neurosurgery (2020), doi: https://doi.org/10.1016/j.wneu.2019.11.151. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. 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Transient cerebral vasospasm after carotid artery stenting: A case report and literature review Masashi Kuwabara, MD1, Toshinori Nakahara, MD2, Takafumi Mitsuhara, MD1, Koji Shimonaga, MD2, Masahiro Hosogai, MD2, Kaoru Kurisu, MD1, and Shigeyuki Sakamoto, MD1 1 Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima-shi, Hiroshima 734-8551, Japan 2 Department of Neurosurgery, Hiroshima City Asa Hospital, 2-1-1 Kabe-minami, Asakita-ku, Hiroshima-shi, Hiroshima 731-0293, Japan 1 Corresponding author: Masashi Kuwabara Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima-shi, Hiroshima 734-8551, Japan Tel: +81-08-2257-5227; Fax: +81-08-2257-5229; Email: m214028@gmail.com 2 Abstract: Background: Cerebral embolism after carotid artery stenting (CAS) is a well-known complication, but cerebral ischemia due to cerebral vasospasm after CAS is rare and has seldom been reported. We describe a patient with transient ischemic complications due to reversible cerebral vasospasm of the middle cerebral artery (MCA) after CAS. Clinical description: A 74-year-old man presented with right hemiparesis by acutely scattered brain infarction in the left cerebral hemisphere. Magnetic resonance angiography (MRA) showed severe stenosis of the left cervical internal carotid artery origin. CAS under a distal filter protection was performed without any intraprocedural complications, but 12 hours later, the patient had aphasia and Gerstmann syndrome. Urgent magnetic resonance image revealed no evidence of an intracranial hemorrhage or new cerebral infarction. However, MRA showed diffuse vasospasm of the left MCA. His symptoms and imaging findings improved gradually by conservative treatment. The 1 patient was discharged without new neurological deficits and recurrent attack in 3 weeks after CAS. Conclusion: In a patient with delayed neurological symptoms after CAS, the possibility of cerebral vasospasm should be kept in mind in order to select appropriate treatment. Key Words: carotid artery stenting, cerebral vasospasm, ischemic complication 2 Introduction: Various complications after carotid artery stenting (CAS) have been reported. These include internal carotid artery (ICA) complications such as intrastent thrombus formation, restenosis, and vascular dissection; neurological complications such as intracranial hemorrhage, hyperperfusion syndrome, or cerebral infarction due to thrombosis or debris from a plaque; and systemic complications such as contrast-induced encephalopathy, myocardial infarction, bradycardic hypotension, and cholesterol embolism6). However, cerebral ischemia due to delayed cerebral vasospasm as a delayed post-CAS complication is rare and has seldom been reported 3,4). We describe a case with reversible cerebral vasospasm of the ipsilateral middle cerebral artery (MCA) after CAS for symptomatic left cervical ICA stenosis, and review literatures of cerebral vasospasm after CAS. Case Report: 3 A 74-year-old man presenting with difficulty moving his right arm was referred to our hospital. Magnetic resonance image (MRI) showed an acute cerebral infarction in the left cerebral hemisphere (Fig. 1A). Head and neck magnetic resonance angiography (MRA) showed left cervical ICA stenosis (Figs. 1B and C). Carotid ultrasound showed an echolucent plaque with a maximum blood flow velocity of 257 cm/sec during systole. Neck CT angiography showed severe stenosis with a little calcification in left cervical ICA. Black-blood T1WI MRI showed high intensity signal in plaque. Single photon emission computed tomography (SPECT) at rest showed significantly reduced cerebral blood flow (CBF) in the left parietal lobe (Fig. 1D). The patient received clopidogrel (75mg/day) and aspirin (100mg/day) orally, and CAS was proposed to prevent recurrent attacks at a later date. CAS procedure was performed using a distal filter protection device. After predilation, stent (Precise PRO RX stent system: Cordis Endovascular, Johnson & Johnson, Miami, FL, USA) was deployed. Postdilation was performed with a 5.5 × 40 mm PTA balloon catheter. Angiogram revealed excellent dilatation (Figs. 2A and B). During and after CAS, no 4 bradycardia, hypotension, seizures, or neurological symptoms developed. Post-CAS angiography also showed no intracranial abnormalities. However, 12 hours after CAS, the patient developed aphasia and Gerstmann syndrome. Urgent cranial MRI did not show abnormal findings such as acute cerebral infarction, but MRA showed poor visualization of the left distal MCA (Fig. 3A). Neck CT angiography showed a good patency in carotid stent, but cranial CT angiography revealed diffuse stenosis of the distal left MCA like MRA (Figs. 3B). These imaging findings suggested that the cause of the neurological symptoms was ischemia of the left cerebral hemisphere due to vasospasm of the left distal MCA. Intravenous edaravone and a continuous intravenous infusion of milrinone and dopamine were immediately started. The patient’s symptoms began to improve from day 2 after CAS. Cranial MRA and contrast CTA showed improved visualization of the distal left MCA (Figs. 3C and D). The symptoms resolved completely day 7 after CAS, and the patient was discharged without new neurological deficits at 3 weeks after CAS. 5 Discussion In post-CAS complications, attention must certainly be paid to possible cerebral embolism from emboli that travel distally during CAS, but about 40% to 70% of ischemic complications are reported to occur a few hours after, rather than during, CAS. This highlights the need to also be alert for delayed ischemic complications3,4). These include cerebral ischemia due to delayed cerebral vasospasm which is rare and has seldom been reported. From our extensive review of the literature, delayed cerebral vasospasm has been reported in only 11 cases, including the present patient, after CAS or a carotid endarterectomy (CEA) (Table 1). This includes 6 cases after CEA and 5 cases after CAS, including 6 men and 5 women ranging in age from 49 to 74 years7-15). Many cases present predominantly with neurological symptoms in the territory supplied by the blood vessels affected by vasospasm. These reports include vasospasm only of the MCA, as in the present patient, whereas others include vasospasm of the anterior cerebral artery (ACA) and posterior cerebral artery (PCA). The time of post-procedure 6 symptom onset has ranged from 12 hours, as in the present patient, to a maximum of 30 days. Seven of the 11 patients had a cerebral infarction. Treatment varied, but most often included a calcium channel blocker. Seven of the 11 patients had complete recovery and a relatively good clinical course. The mechanism of delayed cerebral vasospasm is not well understood. However, several possible mechanisms can be considered based on the literature. The first mechanism is that delayed scattering of small debris or thrombi from a plaque where a stent has been placed can cause vasospasm due to mechanical irritation. Of 111 patients who underwent CAS, Qureshi et al. reported 14 periprocedural ischemic complications, including 4 during the procedure and 10 within 48 hours after the procedure1-4). Based on these findings, Rosenbloom et al. suggested that scattering of small debris and thrombi from a plaque even after stent placement can cause mechanical irritation and lead to vasospasm13). The second mechanism is a reversible cerebral vasoconstriction syndrome (RCVS). RCVS comprises a group of disorders, and its onset is characterized by a severe headache that is also known as a thunderclap headache16-19). Imaging 7 studies show diffuse cerebral vasospasm of a cerebral blood vessel, and clinically, neurological symptoms may occur in the territory supplied by the blood vessels affected by vasospasm. RCVS can occur with pregnancy, certain drugs, hypercalcemia, head trauma, carotid artery dissection, CEA, and CAS13,14). The third mechanism involves chronically insufficient CBF associated with disruption in autoregulation of the cerebral vasculature. A post-procedure increase in CBF might then trigger the onset of vasospasm. The literature has described chronically insufficient CBF associated with disruption in autoregulation of cerebral vasculature in patients with severe ICA stenosis13,15). When CEA or CAS is performed in such patients, transient post-procedure hyperperfusion has occasionally been reported to induce severe vasospasm in sensitive cerebral blood vessels7,8,13-15). In our case, MRA and CTA showed an acute course of cerebral vasospasm of the ipsilateral MCA with reversible changes in a very short time. The patient had an acute course without severe headaches that was not typical for RCVS. Pre-procedure SPECT at rest did show significantly reduced blood flow in the left parietal lobe. We speculated 8 that mechanism of transient cerebral vasospasm in our case was chronically insufficient CBF associated with disruption in autoregulation of the cerebral vasculature because pre-procedure SPECT at rest did show significantly reduced blood flow in the left parietal lobe. Conclusion In a patient with delayed neurological symptoms after CAS, the possibility of cerebral vasospasm should be kept in mind in order to select appropriate treatment. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. 9 Informed consent This article does not contain any studies with human participants performed by any of the authors. 10 References 1. Brott TG, Hobson RW 2nd, Howard G (2010) Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 363: 11-23 2. Yadav JS, Wholey MH, Kuntz RE (2004) Protected carotid artery stenting versus endarterectomy in high-risk patients. N Eng J Med 351: 1493-1501 3. Coutts SB, Hill MD, Hu WY (2003) Hyperperfusion syndrome: toward a stricter definition. Neurosurgery 53: 1053-1058 4. Qureshi AI, Luft AR, Janardhan V (2000) Identification of patients at risk for periprocedural neurological deficits associated with carotid angioplasty and stenting. 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Brick JF, Dunker RO, Gutierrez AR (1990) Cerebral vasoconstriction as a complication of carotid endarterectomy. J Neurosurg 73: 151-153 10. Dagher HN, Shum MK, Campellone JV (2005) Delayed intracranial vasospasm following carotid endarterectomy. Cerebrovasc Dis 20: 205-206 12 11. Lopez-Valdes E, Chang HM, Pessin MS, Caplan LR (1997) Cerebral vasoconstriction after carotid surgery. Neurology 49: 303-304 12. Ohashi T, Okada H, Haraoka R, Oga Y, Nakamura T, Miki T (2012) Intracranial vasospasm following carotid artery stenting. JNET 6: 353 13. Rosenbloom MH, Singhal AB (2007) CT angiography and diffusion-perfusion MR imaging in a patient with ipsilateral reversible cerebral vasoconstriction after carotid endarterectomy. AJNR Am J Neuroradiol 28: 920-922 14. Soltanolkotabi M, Ansari S, Patel B, Shaibani A, Hurley M (2012) Reversible cerebral vasoconstriction syndrome following carotid artery stenting. J Neurointervent Surg 4: 49-50 15. Wu TY, Frith RW, Barber PA (2011) Reversible cerebral vasoconstriction following carotid endarterectomy. J Clin Neurosci 18: 1725-1728, 13 16. Bartynski WS, Boardman JF (2008) Catheter angiography, MR angiography, and MR perfusion in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol 29: 447-455 17. Calabrese LH, Dodick DW, Schwedt TJ (2007) Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 146: 34-44 18. Ducros A, Boukobza M, Porcher R (2007) The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain 130: 3091-3101 19. Fang HY, Kuo YL, Wu CJ (2009) Transient contrast encephalopathy after carotid artery stenting mimicking diffuse subarachnoid hemorrhage: a case report. Catheter Cardiovasc Interv 73: 123-126 14 Figure legends Fig. 1 A. Diffusion-weighted imaging showed scattered high-intensity in the left cerebral hemisphere. B. Cranial MRA showed a decrease in intensity on the left large vessels compared to the right. C. Cervical MRA showed severe stenosis at the origin of the left cervical internal carotid artery (arrow). D. SPECT at rest showed significantly reduced cerebral blood flow in the left parietal lobe (arrow). Fig. 2 A. Preoperative lateral view of digital subtraction angiogram showed severe stenosis in the left ICA. 15 B. Postoperative lateral view of digital subtraction angiogram showed a dilated stenotic lesion after carotid artery stenting. Fig. 3 A. Post-CAS (12 h) MRA showed diffuse poor visualization of the distal left MCA. B. Post-CAS (12 h) contrast CTA showed diffuse poor visualization of the distal left MCA. C. MRA 2 days after starting treatment showed improved visualization of the distal left MCA. D. Contrast CTA day 2 after CAS showed improved visualization of the distal left MCA. 16 1 Table 1. Case Cases of patients with cerebral vasoconstriction following carotid stenting (CAS) or carotid endarterectomy (CEA) Author/ Age year (y)/ Surgery Side of Neurologic surgery symptoms R Confusion, Vasoconstriction Days after Acute Treatment Outcome surgery infarction ACA, MCA 8 No None CR ACA, MCA 7 Yes Corticoster sex 1 Brick JF, 57/M CEA 19901) 2 Lopez V, paranoia 50/M CEA R Numbness 19972) 3 Lopez V, 1997 4 oid 54/F CEA R 2) Dagher Hemianopia, MCA, PCA 8 Yes Verapamil MD nausea 62/M CEA L Aphasia ACA, MCA 5 No Diltiazem CR 54/F CEA L Aphasia, ACA, MCA 2 Yes Nimodipine CR HN, 20053) 5 Rosenblo om MH, 2007 6 7 Teddy , magnesium 58/F CEA R Weakness, YW, visual 20115) blurring Ohashi, 2012 8 numbness 4) 69/M CAS L 6) Soltanolk Aphasia, ACA, MCA, PCA 3 Yes Nimodipine MCA 1 Yes Fasudil weakness 49/F CAS L otabi M, Numbness, CR HCl ACA, MCA, PCA 14 Yes Verapamil CR ACA, MCA 0.5 Yes Argatroban, CR weakness 20127) 9 Arai, 72/M CAS R 20138) 10 Aghaebra Unilateral neglect, 60/F CAS R him A, Headache, dopamine ACA, MCA 30 MCA 0.5 Verapamil weakness 20149) 11 present 74/M case CAS L Aphasia, No agnosia 2015 M: male, F: female, CEA: carotid endarterectomy, CAS: carotid artery stenting, CR: complete recovery, MD: moderate disability, ACA: anterior cerebral artery, MCA: middle cerebral artery, PCA: posterior cerebral artery Milrinone, dopamine CR 54/F 58/F 69/M 49/F 72/M 60/F Rosenbloom MH, 20074) Teddy YW, 20115) Ohashi, 20126) Soltanolkotab i M, 20127) Arai, 20138) Aghaebrahim A, 20149) 5 6 7 8 9 10 CAS CAS CAS CAS CEA CEA CEA R R L L R L L R Headache, weakness Unilateral neglect, Numbness, weakness Aphasia, weakness Weakness, visual blurring Aphasia, numbness Aphasia Hemianopia, nausea Numbness ACA, MCA ACA, MCA ACA, MCA, PCA MCA ACA, MCA, PCA ACA, MCA ACA, MCA MCA, PCA ACA, MCA ACA, MCA Vasoconstriction 30 0.5 14 1 3 2 5 8 7 8 － Yes Yes Yes Yes Yes No Yes Yes No CR CR Argatroban, dopamine － Fasudil hydrochlorid e Verapamil CR CR CR MD － CR Nimodipine Nimodipine, magnesium Diltiazem Verapamil Corticosteroi d None Acute Days after Treatment Outcome surgery infarction 11 CR 62/M Dagher HN, 20053) 4 CEA R Confusion, paranoia Neurologic symptoms present case Milrinone, 74/M CAS L Aphasia, agnosia MCA 0.5 No 2018 dopamine M：male, F：female, CEA：caroted endarterectomy, CAS：caroted artery stenting, CR：complete recovery, MD：moderate desability, ACA：anterior cerebral artery, MCA：middle cerebral artery, PCA：posterior cerebral artery, 54/F Lopez V, 19972) 3 CEA R Side of surgery － 50/M Lopez V, 19972) 2 CEA Surgery Verapamil 57/M Brick JF, 19901) 1 Case Author/year Age/sex Table.1 Cases of patients with cerebral vasoconstriction following carotid stenting (CAS) or carotid endarterectomy (CEA) Fig.1 Fig.2 Fig.3 Abbreviations: 1) CAS: Cerebral embolism after carotid artery stenting 2) MCA: middle cerebral artery 3) MRA: Magnetic resonance angiography 4) ICA: internal carotid artery 5) SPECT: Single photon emission computed tomography 6) CBF: cerebral blood flow 7) CEA: carotid endarterectomy 8) ACA: anterior cerebral artery 9) PCA: posterior cerebral artery 10) RCVS: reversible cerebral vasoconstriction syndrome 11) CTA: computed tomography angiography 12) M: male 13) F: female 14) CR: complete recovery 1 15) MD: moderate disability 2