Contrast-induced encephalopathy: a complication of coronary angiography Tharanga Geethapriya Fernando ,1 Shanika Nandasiri,2 Sepalika Mendis,1 Sunethra Senanayake,2 Inuka Kishara Gooneratne,2 Rayno Navinan,1 Ambiga Kadiragamanathan,1 Sumudu Wickramasinghe,1 Tharuka Herath ,2 Narmathey Thambirajah,2 Romesh Markus3 1 Cardiology, National Hospital of Sri Lanka, Colombo, Sri Lanka 2 Neurology, National Hospital of Sri Lanka, Colombo, Sri Lanka 3 Department of Neurology, St Vincent’s Hospital, Sydney, Australia Correspondence to Tharanga Geethapriya Fernando, Cardiology, National Hospital of Sri Lanka, Colombo 01000, Sri Lanka; tharangafer nando9@gmail.com Accepted 27 June 2020 © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. To cite: Fernando TG, Nandasiri S, Mendis S, et al. Pract Neurol Epub ahead of print: [please include Day Month Year]. doi:10.1136/ practneurol-2020-002524 ABSTRACT Contrast-induced encephalopathy is a rare idiosyncratic reaction to contrast material. A 56year-old woman with hypertension developed a hemiparesis with confusion and disorientation 3 hours after routine coronary angiography. The procedure had been prolonged, and during it she had received 130 mL of iopromide contrast. A metabolic screen was negative, and cerebral angiography and MR scan of brain were normal. She recovered completely by day 5. Contrastinduced encephalopathy should be considered in patients developing focal neurological deficits following coronary angiography. Patients requiring investigations to exclude acute stroke in this setting should not receive additional intravenous or intra-arterial contrast, although MR with gadolinium appears safe. Better awareness of this complication should avoid potentially harmful interventions such as thrombolysis. INTRODUCTION Coronary angiography and percutaneous coronary intervention are generally considered safe but do have some intrinsic risk. The contrast media used for these procedures potentially have a long list of complications, though recent use of lowosmolar contrast media has made these significantly less likely.1 However, unpredictable idiosyncratic drug reactions still occur; contrast-induced encephalopathy is one such rare phenomenon that can cause a spectrum of focal and generalised neurological disturbances.2 Case report A 52-year-old woman from South Asia, who had hypertension, underwent elective diagnostic coronary angiography due to class III angina with a positive treadmill test. The coronary angiogram involved femoral arterial access with sufficient heparinisation. There was difficult engagement of the coronary vessels, necessitating an extended period of catheter manipulation and administration of at least 130 mL of iopromide contrast. Towards the end of the procedure, and while still on the table, she developed a featureless headache. Three hours after the procedure, she become progressively confused with new onset of left arm and leg weakness. On examination, she was disorientated in time, place and person with a Glasgow Coma Scale score of 14/15 and a leftsided hemiparesis (Medical Research Council grade 3/5 weakness in the left arm and leg). Her left-sided muscle tone was reduced with diminished reflexes, and the plantar response was equivocal. Her disorientation prevented an accurate sensory examination. There was no neglect, aphasia or hemianopia. Her cranial nerve function was largely intact, including normal facial movement and equally sized pupils reactive to light. The remaining examination was normal, including the cardiovascular system. A bedside transthoracic 2D-echocardiogram showed preserved left ventricular function and no left ventricular clots. A 12-lead ECG showed sinus rhythm. A comprehensive metabolic screen was normal, including full blood count, renal function, liver function, clotting profile and random plasma glucose. A noncontrast CT scan of head done within an hour showed cortical and subarachnoid hyper-densities, mainly in the right frontoparieto-occipital areas (figure 1A). Urgent cerebral angiogram and digital subtraction Fernando TG, et al. Pract Neurol 2020;0:1–4. doi:10.1136/practneurol-2020-002524 1 Pract Neurol: first published as 10.1136/practneurol-2020-002524 on 28 August 2020. Downloaded from http://pn.bmj.com/ on August 29, 2020 at University of Rochester Medical Center. Protected by copyright. NEUROLOGICAL RARITIES Figure 1 (A) Urgent non-contrast CT scan of head showing cortical and subarachnoid hyper densities, mainly on the right side of the fronto-parieto-occipital areas. (B) CT scan of head 48 hours later showing resolution of the cortical and subarachnoid hyperdensities. angiography, performed in view of possible early intervention, were normal (figure 2). Because her neurological symptoms had not resolved completely 48 hours following symptom onset (orientation improved but weakness unchanged in both upper and lower limb), we obtained an MR scan of brain, which was normal; the absence of diffusion restriction excluded cerebral ischaemia (figure 3). MR angiogram of the cervical and intracranial vessels (time of flight sequence) was normal, although there was right middle cerebral artery narrowing with reduced flow, probably due to an artefact, especially as the previous digital subtraction angiogram Figure 2 Digital subtraction angiogram (lateral view) showing normal appearances of (A) left middle cerebral artery and (B) right middle cerebral artery. 2 Fernando TG, et al. Pract Neurol 2020;0:1–4. doi:10.1136/practneurol-2020-002524 Pract Neurol: first published as 10.1136/practneurol-2020-002524 on 28 August 2020. Downloaded from http://pn.bmj.com/ on August 29, 2020 at University of Rochester Medical Center. Protected by copyright. NEUROLOGICAL RARITIES Figure 3 MR scan of brain 48 hours following symptom onset, which was normal without diffusion restriction. MR angiogram of the intracranial vessels was normal. had been normal. MR venogram was negative (figure 2). Repeat CT scan of head after 48 hours showed resolution of the previously noted hyper-densities (figure 1B). She gradually recovered, and her neurological deficits had completely resolved by day 5. She remained completely well at outpatient review 1 week later. We made a diagnosis of contrast-induced encephalopathy based on the clinical picture, the temporal relationship to iodinated contrast, normal neuroimaging studies and complete resolution of all symptoms and signs. higher (4%) when using hyperosmolar iodinated media.4 Its pathogenesis is as yet unknown, though there are two likely mechanisms: ► Blood–brain barrier disruption allowing contrast agents to permeate into the central nervous system, causing direct neuronal toxicity. The chemical and physical properties of the contrast agents, especially their ionicity and hyperosmolality, may disrupt the barrier. However, this is controversial, as even non-ionic and iso-osmolar contrast agents may cause similar problems. ► Arterial vasospasm and disruption of the microcirculation of an already impaired cerebral auto-regulatory system.5 6 DISCUSSION Ischaemic stroke following diagnostic coronary angiography and other percutaneous coronary interventions is well recognised and can cause significant morbidity and mortality. The usual mechanisms are embolic, from either clots or dislodgment of atheromatous plaques.3 Contrast-induced encephalopathy following coronary angiography first became apparent in the early 1970s; its usual incidence is relatively low (0.3–1.0%) but is The contrast used in this patient was non-ionic and iso-osmolar, and so arterial vasospasm was most likely here. Neuroimaging can help to identify features that favour contrast-induced encephalopathy and that reflect the possible pathogenesis. CT scan of head may show abnormal cortical and subcortical contrast enhancement, focal hyperdense lesions, enhanced cerebral sulci, cerebral oedema and subarachnoid contrast enhancement mimicking subarachnoid haemorrhage (reflecting extravasation of contrast and vasogenic Fernando TG, et al. Pract Neurol 2020;0:1–4. doi:10.1136/practneurol-2020-002524 3 Pract Neurol: first published as 10.1136/practneurol-2020-002524 on 28 August 2020. Downloaded from http://pn.bmj.com/ on August 29, 2020 at University of Rochester Medical Center. Protected by copyright. NEUROLOGICAL RARITIES oedema). Contrast-induced encephalopathy is associated with vasogenic oedema whereas ischaemic stroke causes cytotoxic oedema. MR studies in contrast-induced encephalopathy may show gyral swelling and hyperintensity on T2-weighted-fluid-attenuated inversion recovery and diffusion-weighted imaging (representing vasogenic oedema), but with normal apparent diffusion coefficient, whereas in stroke, there is diffusion restriction owing to cytotoxic oedema.6 7 Note that the imaging can also be completely normal or may become normal after a short interval.8 The risk factors associated with contrast-induced encephalopathy relate either to the procedure or to the patient. ► Procedure-related factors include the osmolality and volume of contrast administered, and the type of catheterisation and procedure, for example, selective angiography of the internal mammary graft, angiography of the vertebro-basilar system.2 5 ► Patient-related factors include male sex, advanced age, associated comorbidities including hypertension, diabetes mellitus, renal impairment, history of transient ischaemic attacks and history of contrast-induced encephalopathy. Most authors stress that hypertension is an important predisposing factor for contrast-induced encephalopathy, as it may play a role in impairing cerebral autoregulation, especially when chronic.6 The clinical manifestations of contrast-induced encephalopathy include encephalopathy, motor, sensory, speech or visual disturbances, and seizures.4 These typically appear soon after giving contrast and resolve completely within 48–72 hours. This patient had a predisposing history of chronic hypertension, and the procedure was complicated by an extended period of catheterisation and exposure to large volumes of contrast. The clinical evolution was classical, but the delay in recovery could be attributable to the digital subtraction cerebral angiogram, which involved more contrast, nearly 100 mL of iohexol. Contrast-induced encephalopathy usually has a good prognosis although there are rarely reported cases of persistent deficits.6 Supportive care and observation are usually considered sufficient. Key points ► Contrast-induced encephalopathy is a rare complication of procedures that require administration of large amounts of contrast, such as coronary angiography. ► Its clinical features can mimic stroke although it often resolves within 48–72 hours. ► Hypertension predisposes to the evolution of contrast induced encephalopathy. ► Investigations to exclude acute stroke following such procedures should avoid additional intravenous or intra-arterial contrast. Acknowledgements We would like to acknowledge the dedicated nursing staff of the Institute of Cardiology, National Hospital of Sri Lanka, for their dedicated care they provide for the patients with cadiovascular disease. Competing interests None declared. Patient consent for publication Consent obtained directly from patient(s). Provenance and peer review Not commissioned. Externally peer reviewed by Anthony Pereira, London, UK. ORCID iDs Tharanga Geethapriya Fernando http://orcid.org/0000-00034874-305X Tharuka Herath http://orcid.org/0000-0002-4439-4748 REFERENCES CONCLUSION Although contrast-induced encephalopathy is rare, it can mimic stroke and so should be considered following procedures that involve administration of a large volume of contrast. 1 Tavakol M, Ashraf S, Brener SJ. Risks and complications of coronary angiography: a comprehensive review. Glob J Health Sci 2012;4:65–93. 2 Spina R, Simon N, Markus R, et al. Recurrent contrast-induced encephalopathy following coronary angiography. Intern Med J 2017;47:221–4. 3 Khatri P, Kasner SE. Ischemic strokes after cardiac catheterization: opportune thrombolysis candidates? Arch Neurol 2006;63:817–21. 4 Liao MT, Lin TT, Lin LY, et al. Contrast-induced encephalopathy after percutaneous coronary intervention. Acta Cardiologica Sinica 2013;29:277–80. 5 Ting F, Bhat A, Markus R, et al. Contrast-induced encephalopathy post-angiography. Internet J Neurol 2013;16:1. 6 Park JC, Ahn JH, Chang IB, et al. A case of unusual presentation of contrast-induced encephalopathy after cerebral angiography using iodixanol. J Cerebrovasc Endovasc Neurosurg 2017;19:184–8. 7 Donepudi B, Trottier S. A seizure and hemiplegia following contrast exposure: understanding contrast-induced encephalopathy. Case Rep Med 2018;2018:9278526. 8 Sawaya RA, Hammoud R, Arnaout S, et al. Contrast-induced encephalopathy following coronary angioplasty with iohexol. South Med J 2007;100:1054–5. 4 Fernando TG, et al. Pract Neurol 2020;0:1–4. doi:10.1136/practneurol-2020-002524 Pract Neurol: first published as 10.1136/practneurol-2020-002524 on 28 August 2020. Downloaded from http://pn.bmj.com/ on August 29, 2020 at University of Rochester Medical Center. Protected by copyright. NEUROLOGICAL RARITIES