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¤CASE REPORT
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A Case of Contrast-Induced Encephalopathy Using Iodixanol Emiliano Chisci, MD, PhD; Francesco Setacci, MD; Gianmarco de Donato, MD; and Carlo Setacci, MD Department of Surgery, Vascular and Endovascular Surgery Unit, University of Siena, Italy.
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Purpose: To document a heretofore unreported complication of the contrast agent iodixanol during an endovascular procedure. Case Report: A 76-year-old woman with a history of coronary artery disease was admitted to the emergency department for recurrent transient ischemic attacks. Before combined percutaneous transluminal coronary angioplasty and carotid artery stenting (CAS) using iodixanol, the patient suffered from concomitant unstable angina and recurrent transient ischemic attacks. The total amount of iodixanol used during the CAS procedure was 300 mL. Contrast-induced encephalopathy, which manifested as aphasia, stupor, and full hemiparesis immediately after the combined procedure, was diagnosed by urgent computed tomography. Treatment was based on anti-edema drugs, and the patient made a complete recovery within 48 hours, without any neurological sequelae. Conclusion: Although previously reported in relation to other types of contrast media, contrast-induced encephalopathy has never been described as a complication of an endovascular procedure using iodixanol. J Endovasc Ther. 2011;18:540–544 Key words: contrast media, endovascular intervention, complication, contrast-induced encephalopathy, carotid artery stenting, percutaneous coronary intervention, concurrent procedures
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Contrast-induced encephalopathy (CIE) has been described during various endovascular interventions,1–10 and neurotoxicity is a wellknown adverse effect of contrast agents, which can cause osmotic disruption of the blood-brain barrier.11 Symptoms include viSee Commentary page 545 sual disturbances, transient cortical blindness, and transient neurological deficits.1–10 Different contrast agents, both ionic and nonionic, were used in the cases reported in the literature, but they were all hyperosmolar in relation to blood.1–10 The particularity of
the case we report here is that CIE occurred despite the use of an isosmolar contrast agent (osmolality of 290 mOsm/kg H2O, the same as blood); to our knowledge, no one has reported CIE in conjunction with the use of an isosmolar contrast agent.
CASE REPORT A 76-year-old right-handed woman was admitted to our emergency department for recurrent transient ischemic attacks (TIA) causing transient aphasia, as well as right facial and brachial hemiparesis (lasting ,24 hours) associated with intermittent chest pain
The authors have no commercial, proprietary, or financial interest in any products or companies described in this article. Address for correspondence and reprints: Emiliano Chisci, Department of Surgery, Vascular and Endovascular Surgery Unit, University of Siena, Viale Bracci, 53100 Siena, Italy. E-mail:
[email protected] ß 2011 by the INTERNATIONAL SOCIETY
OF
ENDOVASCULAR SPECIALISTS
Available at www.jevt.org
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while resting. The patient had suffered from unstable angina for nearly 1 month prior to admission and had been scheduled to have an elective coronary arteriogram a few days later. Physical examination did not show any obvious neurological deficit, and even the non-enhanced computed tomography (CT) scan did not show any recent cerebral ischemia. The electrocardiogram showed subendocardial ischemia, and troponin levels were abnormal (0.9 mg/dL). A color duplex ultrasound scan revealed an ostial, calcified, eccentric .80% stenosis in the left internal carotid artery. The patient had a medical history of coronary artery disease, coronary bypass grafting, hypertension, severe dyslipidemia (treated with statins), peripheral artery disease, slight decrease in renal function (estimated glomerular filtration rate 45 mL/min/1.73 m2), and diabetes. A team of vascular surgeons, cardiologists, and neurologists discussed the case and planned a single-session percutaneous transluminal coronary angioplasty (PTCA) and carotid artery stenting (CAS) procedure. A loading dose of clopidogrel (300 mg) was administered, and aspirin was provided as part of the patient’s chronic therapy. The planned intervention took place on the day after admission. Both procedures were performed through a transfemoral approach with an 8-F short introducer sheath placed into the common femoral artery. A full dose of heparin was given intravenously (5000 units), and the activated clotting time did not exceed 230 seconds during both procedures. During PTCA, multiple lesions at the level of the interventricular artery were treated with 3 bare balloon-expandable stents (Tsunami; Terumo, Tokyo, Japan); this procedure required nearly 200 mL of iodixanol (Visipaque 320 mg l/mL; GE Healthcare, Waukesha, WI, USA). In the subsequent CAS procedure, the left common carotid artery was engaged with a guiding catheter (40u Multipurpose; Boston Scientific, Natick, MA, USA), and extra- and intracranial angiography was performed. A distal embolic protection device (EPI Filter Wire EZ; Boston Scientific) was placed across the lesion, followed by atropine administration (0.5-mg intravenous bolus) and predilation of the ostial
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calcified .80% lesion with a cutting balloon (2.5315 mm; Boston Scientific). A 7330-mm closed-cell stent (Carotid Wallstent; Boston Scientific) was placed because of the symptomatic nature of the lesion. Postdilation was performed using a 5.5320-mm balloon at 8 atmospheres for 10 seconds under a second identical atropine bolus. The total amount of contrast agent used was nearly 300 mL of iodixanol. This procedure was also uneventful until the arterial closure device was being placed, when the patient manifested sudden stupor, aphasia, and full right hemiparesis. At this point, the guidewire was no longer in place, so a non-enhanced CT scan was performed, which showed left (ipsilateral) hemispheric contrast staining of the cerebral sulci and hyperdensity of some subarachnoid spaces due to extravasation of the contrast medium (Figure, A). The diagnosis was a massive left hemisphere CIE. Treatment consisted of intravenous mannitol (125 mg/L 3 3) and a 40-mg intravenous bolus of methylprednisolone on the first day; on the second day, the mannitol was reduced to 2 doses and the methylprednisolone bolus cut in half to 20 mg. On day 3, 1 dose of mannitol was given with a 10-mg bolus of methylprednisolone. Under this regimen, both the symptoms and contrast staining disappeared after 48 hours (Figure, B). The patient recovered uneventfully from the CIE, and neurological and psychometric tests were negative at 30 days and 1 year after the procedure.
DISCUSSION Insofar as we can tell, this is only the third case of CIE after CAS, and neither of the previous cases involved iodixanol. Both were performed in patients suffering from TIAs2,3; one underwent an isolated CAS procdure,2 whereas the other had combined PTCA and CAS,3 as in our case. Both of these cases recovered uneventfully from CIE within 2 to 4 days. Of note, one case was performed using an ionic low osmolar contrast agent (i.e., ioxaglate)2 and the other using a nonionic low osmolar agent (i.e., iohexol).3 The Table offers more details regarding these 2 cases. In cases of CIE reported by cardiologists or neuroradiologists following other endovascular
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Figure ¤ (A) Non-enhanced computed tomography performed immediately after the combined PTCA + CAS procedure. There is left hemispheric contrast staining of the cortical sulci and hyperdensity of some subarachnoid spaces due to extravasation of the contrast agent. The good outcome and quick recovery of the patient is the key point to guide the clinician toward the diagnosis of contrast encephalopathy (CIE). Moreover, in the setting of CIE, another area of the brain may also be involved (e.g., posterior circulation), while in the case of hyperperfusion syndrome (the worst scenario is hemorrhage), the brain damage is exclusively limited to the territory of the treated internal carotid artery. (B) Normal nonenhanced computed tomography at 48 hours documenting complete clearing of the left hemispheric contrast staining.
procedures (but not CAS), the contrast media were either ionic or nonionic agents.1,4–10 To our knowledge, no cases of CIE associated with an isosmolar contrast agent such as iodixanol have been reported to date. This agent’s osmolarity is identical to blood, which
should reduce the risk of osmotic effects and thereafter complications. It may be speculated in this specific case that the large amount of contrast used (300 mL) and the presence of precedent TIAs could have predisposed the patient to CIE and allowed the contrast agent
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¤ TABLE Details of the 2 Cases of Post-CAS Contrast Encephalopathy Reported Thus Far in the Literature Preop Neurological Status
Dangas et al.
Fang et al.3
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2
Symptomatic (TIAs), confusion, hemiparesis Symptomatic (TIAs), hemiparesis
Procedure
Medical Treatment
Ioxeglate (ionic low osmolar, 180 mL)
CAS ACT: 210 s
NA
Complete recovery within 2 days
Iomexol (nonionic low osmolar, 250 mL)
PTCA + CAS ACT: 144 s
NA
Complete recovery within 4 days
Type of Contrast
Outcome
TIA: transient ischemic attack, PTCA: percutaneous transluminal coronary angioplasty, CAS: carotid artery stenting, ACT: activated clotting time.
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to disrupt the blood-brain barrier and concentrate in the brain.11 Of note, the systemic delivery of contrast medium during PTCA did not cause bilateral contrast encephalopathy or any symptoms; only when iodixanol was injected directly in the left internal carotid artery did symptoms appear. We can postulate that in this patient there was a threshold for contrast sensitivity, which was triggered by the iodixanol injected during CAS (after 200 mL during PTCA). This hypothesis is debatable, and any cause-effect relation has not yet been demonstrated. However, the etiology of this CAS complication has to be attributed to the contrast agent owing to (1) the rapid recovery from neurological deficits and (2) because symptoms disappeared completely when contrast staining of the cerebral sulci and hyperdensity of some subarachnoid spaces disappeared. When a contrast agent permeates part of the brain (an entire hemisphere in this patient), it can cause cortical dysfunction by increasing neuronal excitability.9 Although the neuroradiological findings may be impressive (Figure, A), the prognosis of CIE is excellent, and a wait-and-see approach may even be appropriate if symptoms are limited, although the use of anti-edema drugs is nonetheless advisable. If neurological deterioration is significant, intubation and sedation have been used to protect the brain.4 In any case, it is crucial to make a differential diagnosis among CIE and microembolic shower (general slowing of contrast media without evidence of focal filling defects at angiography and cerebral edema at CT), subarachnoid hemorrhage12 (no rapid recovery from neurological deficits, without complete resolution of contrast staining on follow-up CT within 24– 72 hours), and hyperperfusion syndrome (diffuse cerebral edema and effacement of the cortical sulci at CT; brain damage is exclusively limited within the treated artery distribution brain territory), as they require different treatment.1 Neuroradiological imaging is essential in order to make a differential diagnosis. Another point of discussion concerning our case is that concomitant coronary and carotid pathology is a very frequent situation (5% to 15%).13 Unfortunately, there is so far no sufficient evidence to support one specific
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treatment strategy over others. In the meantime, the best revascularization strategy for patients with advanced coronary and carotid disease should be tailored on a case-by-case basis by a multidisciplinary team in highvolume centers.13 Although CIE is a benign complication, and it seems that there is no increased risk during re-exposure, subsequent contrast studies in a patient with a previous CIE should be undertaken with caution.
Conclusion This anecdotal case report shows that even iodixanol, an isosmolar contrast agent, can cause contrast-induced encephalopathy. CIE remains a rare and benign complication following endovascular procedures. Neuroradiological imaging is mandatory to make a differential diagnosis, especially to rule out other more threatening complications that require different treatment.
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8. Torvik A, Walday P. Neurotoxicity of watersoluble contrast media. Acta Radiologica. 1995; 399:221–229. 9. Rama BN, Pagano TV, DelCore M, et al. Cortical blindness after cardiac catheterization: effect of rechallenge with dye. Cathet Cardiovasc Diagn. 1993;28:149–151. 10. Sawaya RA, Hammoud R, Arnaout S, et al. Contrast-induced encephalopathy following coronary angioplasty with iohexol. South Med J. 2007;100:1054–1055.
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11. Muruve DA, Steinman TI. Contrast-induced encephalopathy and seizures in a patient with chronic renal insufficiency. Clin Nephrol. 1996;45:406–409. 12. Sharp S, Stone J, Beach R. Contrast agent neurotoxicity presenting as subarachnoid hemorrhage. Neurology. 1999;52:1503–1505. 13. Roffi M. Management of patients with concomitant severe coronary and carotid artery disease: is there a perfect solution? Circulation. 2007;116:2002–2004.
