Ischemia Intracerebral Hemorrhage After Carotid Endarterectomy Associated with Asymptomatic Perioperative Cerebral Ischemia Detected by Cerebral Perfusion Imaging: Case Report Kuniaki Ogasawara, M.D., Takashi Inoue, M.D., Masakazu Kobayashi, M.D., Hidehiko Endo, M.D., Takeshi Fukuda, M.D., and Akira Ogawa, M.D. Department of Neurosurgery, Iwate Medical University, Morioka, Japan Ogasawara K, Inoue T, Kobayashi M, Endo H, Fukuda T, Ogawa A. Intracerebral hemorrhage after carotid endarterectomy associated with asymptomatic perioperative cerebral ischemia detected by cerebral perfusion imaging: case report. Surg Neurol 2004;62:319 –23. BACKGROUND Risk factors for intracerebral hemorrhage following carotid endarterectomy (CEA) include perioperative cerebral ischemia, postoperative cerebral hyperperfusion, and postoperative anticoagulation therapy, and at least 2 of these risk factors are typically present in the context of intracerebral hemorrhage (ICH). CASE DESCRIPTION A 75-year-old man with severe bilateral cervical internal carotid artery stenosis and a minor stroke resulting in left motor weakness underwent a right CEA. The operation was uneventful, and the patient did not experience new neurologic deficits upon recovery from anesthesia. Brain single photon emission computed tomography (SPECT) obtained immediately after CEA showed a perfusion defect in the right parietal lobe and absence of cerebral hyperperfusion. A computed tomography (CT) scan showed no new abnormal findings. Aspirin therapy was instituted postoperatively. On the second postoperative day, the patient experienced abrupt worsening of left hemiparesis, and subsequent CT imaging demonstrated a hematoma in the right parietal lobe. Cerebral hyperperfusion was absent on repeat SPECT. CONCLUSION Perioperative cerebral ischemia can result in intracerebral hemorrhage after CEA even in the absence of cerebral hyperperfusion and/or anticoagulation therapy. Further, cerebral perfusion imaging performed immediately after CEA is a useful modality for the identification of occult cerebral ischemia or hyperperfusion that may lead Address reprint requests to Kuniaki Ogasawara, M.D., Department of Neurosurgery, Iwate Medical University, 19-1 Uchimaru, Morioka, 0208505, Japan. Received September 4, 2003; accepted November 7, 2003. © 2004 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010 –1710 to intracerebral hemorrhage. rights reserved. © 2004 Elsevier Inc. All KEY WORDS Carotid endarterectomy, intracerebral hemorrhage, cerebral ischemia, cerebral perfusion imaging. ntracerebral hemorrhage (ICH) following carotid endarterectomy (CEA) occurs in fewer than 1% of cases but may account for up to one quarter of all postoperative complications [1,4,8 –10,13] and has a high morbidity and mortality rate in communitybased series [4,8 –10,13]. Some characteristics of patients who have had an ICH after CEA have been identified and compared with those in controls. Cerebral hyperperfusion following CEA has been proposed as the main mechanism [1,3,4,9]. Perioperative cerebral ischemic events and postoperative anticoagulation therapy may be other important risk factors [3,4,9,12]. The following case describes a patient with asymptomatic perioperative cerebral ischemia as detected by cerebral perfusion imaging that developed an ICH after CEA. Further, this occurred in the absence of post-CEA hyperperfusion. Regional cerebral blood flow (CBF) was quantitatively measured using single photon emission computed tomography (SPECT) and [123I]N-isopropyl-p-iodoamphetamine [5]. I Case Report A 75-year-old man with severe bilateral cervical internal carotid artery (ICA) stenosis was admitted 0090-3019/04/$–see front matter doi:10.1016/j.surneu.2004.03.001 320 Surg Neurol 2004;62:319 –3 Preoperative magnetic resonance scan showing small infarcts in the cerebral white matter in the posterior portion of the right frontal lobe. 1 for CEA after experiencing a minor stroke that resulted in left motor weakness. The patient’s medical history was significant for hypertension and diabetes mellitus, and his medication profile included aspirin, perindopril, and glibenclamide. Upon admission, a neurologic examination revealed slight left hemiparesis. A magnetic resonance imaging scan demonstrated small infarcts in the cerebral white matter in the posterior portion of the right frontal lobe (Figure 1). Cerebral angiography revealed 85% stenosis of the right cervical ICA and 83% stenosis of the left cervical ICA. Brain SPECT demonstrated reduced CBF in the bilateral cerebral hemispheres (Figure 2 left). Each value was less than the mean—2SD of the control value (Table 1) [5]. Sixty days after onset of the symptoms, the patient underwent a right CEA under general anesthesia. An intraluminal shunt was not used. A single bolus of heparin (5000 units) was given before the right ICA was cross-clamped, and the heparin was reversed using 30 mg of protamine sulfate after declamping of the ICA. The cross-clamping time was Ogasawara et al 28 min. Intraoperative electroencephalographic monitoring revealed no abnormal findings. The operation was uneventful, and the patient did not experience new neurologic deficits upon recovery from anesthesia. SPECT obtained immediately after CEA showed an increase in right cerebral hemisphere CBF (1.3-fold control values, Table 1) except in the right parietal lobe, where a wedge-shaped perfusion defect was noted (Figure 2 middle). Subsequent computed tomography (CT) scan showed no new abnormal findings. Magnetic resonance angiography revealed a widely patent right cervical ICA and no abnormal findings in the main trunks of the intracranial arteries. Although intensive control of blood pressure was not instituted after surgery, postoperative systolic blood pressure ranged from 120 to 140 mm Hg. Aspirin was reinitiated on the first postoperative day, but anticoagulation therapy was not instituted. The patient had an uneventful course until late on the second postoperative day, when he experienced abrupt worsening of his left-side hemiparesis. A CT scan demonstrated a hematoma in the right parietal lobe, corresponding to the wedgeshaped perfusion defect noted on the postoperative SPECT study (Figure 3). Subsequent SPECT showed a large perfusion defect corresponding to the hematoma (Figure 2 right). The value of CBF in the right cerebral hemisphere (excluding the perfusion defect) was essentially unchanged from postoperative values (Table 1). A partial thromboplastin time obtained immediately after the occurrence of ICH was within normal limits. The subsequent clinical course was uneventful, and the patient experienced gradual improvement in his left-side motor function. Discussion Most authors recommend institution of strict control of postoperative blood pressure to prevent hyperperfusion syndrome and ICH [2,9,11,13–15]. In our institution, we measured cerebral perfusion pre- and postoperatively using SPECT in all patients undergoing CEA and utilized antihypertensive medication postoperatively in patients diagnosed with cerebral hyperperfusion [6,7]. In our series of patients, post-CEA hyperperfusion was observed in 14%. While 21% of these patients developed cerebral hyperperfusion syndrome, none experienced intracerebral hemorrhage. Thus, cerebral perfusion imaging was performed immediately after CEA in the present case despite the absence of new neurologic deficits upon recovery from anesthesia. Intracerebral Hemorrhage After CEA Surg Neurol 321 2004;62:319 –3 Serial quantitative cerebral blood flow images using [123I]N-isopropyl-p-iodoamphetamine SPECT. Preoperative SPECT showed reduced cerebral blood flow in the bilateral cerebral hemispheres (left). SPECT performed immediately after surgery showed recovery of perfusion in the right cerebral hemisphere except in the right parietal lobe, where a wedge-shaped perfusion defect was noted (middle). SPECT performed after worsening of left-sided hemiparesis on the second postoperative day demonstrated a large perfusion defect in the right parietal lobe and normal perfusion in the surrounding tissue (right). 2 In the present case, the lack of ischemic changes with cross-clamping on electroencephalography studies and a wedge-shaped perfusion defect on brain SPECT obtained immediately after surgery indicated the presence of perioperative cerebral ischemia likely secondary to cerebral embolism. The SPECT also demonstrated a 1.3-fold increase in ipsilateral cerebral hemisphere CBF when excluding the area of the perfusion defect. Cerebral hyperperfusion after CEA is defined as a CBF increase of 1 ⱖ100% (i.e., a doubling) compared with preoperative values [14]; thus, this patient did not exhibit cerebral hyperperfusion. Henderson et al reviewed the clinical and radiologic characteristics of patients with ICH following CEA and described several risk factors, including cerebral hyperperfusion, perioperative cerebral ischemia and anticoagulation therapy [4]. Further, in that series of patients, at least two of these risk factors were typically present in the context of ICH. Pre- and Postoperative Cerebral Blood Flow* Measured Using Single Photon Emission Computed Tomography BEFORE SURGERY IMMEDIATELY AFTER SURGERY TWO DAYS AFTER SURGERY Right cerebral hemisphere† 27.3 36.0 36.2 Left cerebral hemisphere 28.5 29.6 31.4 *: mL/100g/min; †: except for a perfusion defect. CONTROL (MEAN ⴞ SD) 35.9 ⫾ 4.4 322 Surg Neurol 2004;61:319 –23 Ogasawara et al REFERENCES 3 A CT scan 2 days after surgery showing hemorrhage in the right parietal lobe. In particular, ICH in the setting of a perioperative cerebral ischemic event was always compounded by the cerebral hyperperfusion and/or anticoagulation therapy. Based on these findings, Henderson et al conclude that an intraoperative cerebral ischemic event, in which damage to the microvasculature also occurs, could compound the cascade of events caused by cerebral hyperperfusion following reopening of a tight stenosis. Further, they speculated that the mechanism of ICH could not be solely because of hemorrhagic transformation of an infarct [4]. However, our patient experienced ICH after CEA in the absence of cerebral hyperperfusion or anticoagulation therapy. These findings suggest that perioperative cerebral ischemia caused by cerebral embolism can be a sole cause of ICH after CEA. In the present case, perioperative cerebral ischemia occurring in the right parietal lobe was asymptomatic, and the diagnosis was only established by brain SPECT. Thus, this case demonstrates the utility of cerebral perfusion imaging in the early identification of occult cerebral ischemia or hyperperfusion that may lead to ICH after CEA. 1. Breen JC, Caplan LR, DeWitt LD, Belkin M, Mackey WC, O’Donnell TP. Brain edema after carotid surgery. Neurology 1996;46:175–81. 2. Dalman JE, Beenakkers IC, Moll FL, Leusink JA, Ackerstaff RG. Transcranial Doppler monitoring during carotid endarterectomy helps to identify patients at risk of postoperative hyperperfusion. Eur J Vasc Endovasc Surg 1999;18:222–7. 3. Ferguson GG, Eliasziw M, Barr HW, et al. The North American Symptomatic Carotid Endarterectomy Trial: surgical results in 1415 patients. Stroke 1999;30: 1751–8. 4. Henderson RD, Phan TG, Piepgras DG, Wijdicks EF. Mechanisms of intracerebral hemorrhage after carotid endarterectomy. J Neurosurg 2001;95:964 –9. 5. Ogasawara K, Ito H, Sasoh M, et al. Quantitative measurement of regional cerebrovascular reactivity to acetazolamide using 123I-N-isopropyl-p-iodoamphetamine autoradiography with SPECT: validation study using H215O with PET. J Nucl Med 2003;44:520 –5. 6. Ogasawara K, Konno H, Yukawa H, Endo H, Inoue H, Ogawa A. Transcranial regional cerebral oxygen saturation monitoring during carotid endarterectomy as a predictor of postoperative hyperperfusion. Neurosurgery 2003;53:309 –15. 7. Ogasawara, K, Yukawa, H, Kobayashi, M, et al Prediction and monitoring of cerebral hyperperfusion after carotid endarterectomy by using single-photon emission computerized tomography scanning. J Neurosurg 2003;99:504 –10. 8. Ouriel K, Shortell CK, Illig KA, Greenberg RK, Green RM. Intracerebral hemorrhage after carotid endarterectomy: incidence, contribution to neurologic morbidity, and predictive factors. J Vasc Surg 1999;29: 82–7. 9. Piepgras DG, Morgan MK, Sundt TM Jr, Yanagihara T, Mussman LM. Intracerebral hemorrhage after carotid endarterectomy. J Neurosurg 1988;68:532–6. 10. Pomposelli FB, Lamparello PJ, Riles TS, Craighead CC, Giangola G, Imparato AM. Intracranial hemorrhage after carotid endarterectomy. J Vasc Surg 1988;7:248 – 55. 11. Reigel MM, Hollier LH, Sundt TM Jr, Piepgras DG, Sharbrough FW, Cherry KJ. Cerebral hyperperfusion syndrome: a cause of neurologic dysfunction after carotid endarterectomy. J Vasc Surg 1987;5:628 –34. 12. Schroeder T, Sillesen H, Sorensen O, Engell HC. Cerebral hyperperfusion following carotid endarterectomy. J Neurosurg 1987;66:824 –9. 13. Solomon RA, Loftus CM, Quest DO, Correll JW. Incidence and etiology of intracerebral hemorrhage following carotid endarterectomy. J Neurosurg 1986;64: 29 –34. 14. Sundt TM Jr, Sharbrough FW, Piepgras DG, Kearns TP, Messick JM Jr, O’Fallon WM. Correlation of cerebral blood flow and electroencephalographic changes during carotid endarterectomy, with results of surgery and hemodynamics of cerebral ischemia. Mayo Clin Proc 1981;56:533–43. 15. Yoshimoto T, Houkin K, Kuroda S, Abe H, Kashiwaba T. Low cerebral blood flow and perfusion reserve induce hyperperfusion after surgical revascularization: case reports and analysis of cerebral hemodynamics. Surg Neurol 1997;48:132–9.