Neurological Sciences https://doi.org/10.1007/s10072-020-04844-1 BRIEF COMMUNICATION Contrast-induced encephalopathy mimicking total anterior circulation stroke: a case report and review of the literature Martina Vigano’ 1 & Vittorio Mantero 1 & Paola Basilico 1 & Christian Cordano 2 & Davide Sangalli 1 & Paolo Reganati 3 & Alessandro Lunghi 3 & Andrea Rigamonti 1 & Andrea Salmaggi 1 Received: 22 June 2020 / Accepted: 17 October 2020 # Fondazione Società Italiana di Neurologia 2020 Abstract Introduction Contrast-induced encephalopathy is a rare and usually reversible entity due to the administration of iodinated contrast. Clinical manifestations include cortical blindness, encephalopathy, seizures and focal neurological deficits. Methods We report the case of a 56-year-old woman who developed global aphasia and right hemiplegia after a cerebral angiography performed for a subarachnoid haemorrhage. A prompt brain MRI resulted negative, while CT scan revealed left cerebral oedema with the cerebral sulci effacement. Complete recovery was observed in 10 days. Discussion Diagnosis of contrast-induced encephalopathy requires a temporal correlation between neurological dysfunction and administration of iodinated contrast. Usually, the symptomatology is transient with a full recovery within 48–72 h. The most common symptom is cortical blindness, while other symptoms have been rarely reported. Only 20 cases previously reported global aphasia and/or hemiplegia or mimed anterior circulation strokes. Prompt brain neuroimaging is essential in order to exclude an alternative diagnosis that requires a distinct therapeutic approach. Keywords Contrast-induced encephalopathy . Iodinated contrast . Reversible encephalopathy . Stroke mimics . Stroke chameleons Introduction Contrast-induced encephalopathy (CIE) is a rare, acute and usually reversible neurological entity associated with intraarterial administration of iodinated contrast. Risk factors seem to be hypertension and renal failure. Clinical manifestations include cortical blindness, encephalopathy, seizures and focal neurological deficits. In most reported cases, the symptoms are reversible and fatal encephalopathy has been rarely reported [1]. * Vittorio Mantero vittorio.mantero@hotmail.com 1 Neurological Department, “A. Manzoni” Hospital, ASST Lecco, Via dell’Eremo 9/11, 23900 Lecco, Italy 2 UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA 3 Neuroradiological Unit, “A. Manzoni” Hospital, ASST Lecco, Lecco, Italy Herein, we describe a patient who suffered from longlasting but fully reversible hemiplegia and global aphasia after a brain angiography. Case report A 56-year-old right-handed woman has admitted to our emergency department for acute onset of intense headache which started in the previous 2 days. She had a history of migraine, renal colic, smoking and previous heroin abuse 20 years earlier. The brain CT scan showed a small interhemispheric posterior-left parafalcine subarachnoid haemorrhage. Cerebral angiography showed two small aneurysms involving the left carotid siphon, the left posterior cerebral artery and the left choroidal artery. After a collegial discussion between neurologists, neuroradiologists and neurosurgeons, these aneurysms were considered incidental, so we decided to treat them later. Ten days after, a second cerebral angiography was performed to exclude the presence of a third aneurism in the area of the haemorrhage. A total of 70 ml of iomeprol (Iomeron® Neurol Sci 300 mg/ml) was administered during the procedure, and no haemorrhage or vasospasm complicated the procedure. However, at the end of the angiography, the patient developed global aphasia and right hemiplegia. A brain MRI with T2, FLAIR and DWI sequences was immediately performed, excluding ischaemic or haemorrhagic events (Fig. 1a). No artery occlusion, dissection or reversible vasospasm was detected on the brain MRI angiography (Fig. 1d). A brain CT scan was performed 4 h later and revealed left cerebral oedema with effacement of the cerebral sulci (Fig. 1b, c). The absence of oedema on MRI is likely due to execution time, immediately after cerebral angiography. The next day she was subjected to cerebrospinal fluid (CSF) examination showing 150 protein/mm3 and normal cell count, and to electroencephalography negative for epileptic seizures. The diagnosis of CIE was performed, and the patient started dexamethasone and compound sodium chloride injection to facilitate the elimination of the contrast agent. A brain CT scan on day 2 showed resolution of cerebral oedema (Fig. 1e, f). The patient presented slow progressive neurological improvement with complete recovery in 10 days. Discussion CIE is a well-known complication of cerebral angiography. The diagnosis requires a temporal correlation (minutes to hours) between administering iodinated contrast and symptoms and signs of neurological dysfunction. Usually, the Fig. 1 Brain MRI (a) and MRA (d) showing normal findings; brain CT scan performed 4 h after symptom onset (b, c) showing left cerebral oedema with effacement of the cerebral sulci; brain CT scan performed 2 days after symptom onset showing resolution of cerebral oedema (e, f) symptomatology is transient with a full recovery within 48– 72 h. Moreover, the diagnosis should not be attributable to other pathological processes [2]. The presentation of CIE is similar to embolic or haemorrhagic complications following angiography. A prompt brain neuroimaging is instrumental to exclude these alternative diagnoses that require a distinct therapeutic approach. DWI images on MRI are important to distinguish cytotoxic from vasogenic oedema, in which diffusion is normal or increased. CIE’s pathogenesis is not completely understood but probably related to temporary disruption of the blood‑brain barrier (BBB) after injection of iodinated contrast. Consequently, hyperosmolality and direct neurotoxicity of contrast media in the extracellular space could further result in cerebral vasogenic oedema [1]. Our patient does not have any one of the known risk factor for CIE; however, the recent subarachnoid haemorrhage could have contributed to the BBB injury, causing endothelial cell damage [3]. CIE has been reported following angiography of various vascular territories (head and neck, coronary, thoracic, abdominal, spinal) and following endovascular aneurysm treatment; anyhow, it is more commonly associated with cerebral or carotid angiography. Many types of iodinated contrast agents are used, and independently of their osmolarity or ionic states can cause CIE. There is no limit dose of iodinated contrast related to CIE, but larger doses are considered a risk factor [4]. CIE’s most common symptom is cortical blindness, probably due to relatively higher permeability of the BBB in the occipital cortex with respect to other areas [2]. Other 68 82 52 82 82 72 51 70 M F M M F Foltys et al. Velden et al. F M Vranckx et al. Zwicker Sila F M Eckel et al. Dangas et al. M M Lantos Uchiyama et al. Fang et al. Guimaraens et al. 80 71 64 - No - Coronary angiography + PCI Hypertension N/A Carotid and coronary Hypertension No angiography + stenting Carotid artery angiography + Hypertension No right internal carotid artery, aneurysm coiling No N/A N/A Yes Hypertension Yes Chronic kidney disease; hypertension Coronary angiography + PCI Chronic kidney disease; hypertension Carotid artery angiography + coiling anterior aneurysm Coronary angiography + internal mammary artery graft Coronary angiography + coronary stenting Carotid artery angiography + stenting 50 180 Iopromide Iopromide Iohexol Iopamidol Iomeprol Iopromide N/A 300 250 260 500 130 Ioversol 280 (Optiray) Ioxaglate Iohexol Iothalamate 12 meglumine Ioxaglate 360 4 days 3 days 4–5 days Clinical resolution CT hyperdensities filling the sulci of both cerebral 40 h hemispheres CT bilateral frontal and parieto-occipital attenua- 1, 5 days tion of the cortex and mild loss of sulci. MRI DWI punctate abnormalities in the left frontal region, right frontoparietal area and cerebellum Cerebral oedema and extravascularly localized 6h contrast media left hemisphere CT contrast enhancement of occipital lobes, 6 days temporal lobes, thalami. (permaMRI T2-hyperintensities at both thalami, occipital nence of lobes and cerebellar hemispheres retrograde amnesia) CT right frontoparietal cortical enhancement and 2 days oedema CT bilateral occipital and left parietal lobe alterations CT left temporo-parieto-occipital alterations CT bilateral occipital, basal ganglia alterations Imaging involvement CT enhancement throughout the left cerebral 7 days cortex and left basal ganglia, diffuse swelling of the left cerebral hemisphere Right hemiparesis CT left frontoparietal-occipital cortical enhance- 2 days ment Gerstmann’s left CT cortical enhancement and oedema in the right 2 days visual field deficit, cerebral hemisphere hemiparesis, right gaze deviation 72 h Right hemiparesis and motor aphasia Aphasia, right-sided hemiparesis Right-sided visual neglect and Wernicke’s aphasia Cortical blindness, aphasia, amnesia, periodic alternating gaze with nystagmus Confusion, left hemiparesis, neglect Visual loss, headache, confusion, right pronator drift and aphasia Right-sided hemiparesis, aphasia Cortical blindness, fluent aphasia Cortical blindness, left hemiparesis Volume Clinical presentation (ml) Diatrizoate 250 meglumine Previous Contrast angiography agent Renal No impairment; hypertension Hypertension No Risk factors Coronary angiography + PCI Hypertension Yes Spinal angiography Carotid artery and aorta angiography Abdominal aorta and renal artery angiography + angioplasty F Utz et al. 74 Sex Age Procedure Previously reported cases of CIE mimicking anterior circulation strokes Study Table 1 Neurol Sci 69 65 73 67 56 F F M M F F Chisci et al. Liao et al. Ruiz-Salas et al. Spina et al. Chen et al. Donepudi et al. Onishi et al. F Present case F Risk factors Chronic N/A kidney disease Hypertension No N/A Yes Yes Yes N/A Hypertension Yes Intracarotid sodium amobarbital procedure (Wada test) Aortic angiography + thoracic Chronic aortic aneurysm repair kidney disease; hypertension Cerebral angiography + Hypertension anterior choroidal artery and posterior communicating artery aneurysms coil embolization Cerebral angiography - Coronary angiography Iomeprol N/A Iodixanol Iopamidol Iopromide N/A Ioversol Iodixanol Iohexol Previous Contrast angiography agent Coronary angiography + PCI Hypertension N/A Carotid and coronary angiography + PCI + carotid artery stenting Coronary angiography Coronary angiography + PCI - PCI percutaneous coronary intervention 39 76 76 M 69 Sex Age Procedure Gurer et al. Wilczewska et al. Study Table 1 (continued) 70 N/A 248 N/A 110 N/A 150 300 100 Global aphasia and right hemiplegia Right-sided hemiparesis and aphasia Consciousness disturbance, global aphasia, cortical blindness, right-sided weakness Aphasia, left-sided hemiparesis Global aphasia, bilateral limb weakness Decrease in consciousness and right hemiplegia Seizure and left-sided hemiplegia Stupor, aphasia, hemiparesis Left-sided hemiparesis, conjugate gaze deviation to the right Stupor, disorientation, left hemiplegia Volume Clinical presentation (ml) 14 days 24 h 12 h 48 h 48 h 6h Clinical resolution CT left cerebral oedema with effacement of the cerebral sulci CT cortical oedema of the left cerebral hemisphere and contrast agent leakage to the subarachnoid space 10 days 24 h CT abnormal hyperdensity and extensive 7 days enhancement of the right cortex, subarachnoid space and basal ganglia MRI left hemispheric oedema CT contrast enhancement of right cerebral hemisphere Normal (CT, MRI) MRI hyperintensity high Frontoparietal regions CT diffuse hyperdense lesion in the right frontoparietal region and two hyperdense lesions in the right parietal lobe and the right basal ganglia Hyperdensity of cerebral sulci and subarachnoid spaces CT hyperdensity of cerebral sulci and right frontal lobe Imaging involvement Neurol Sci Neurol Sci neurological symptoms, including hemiparesis or hemiplegia, speech disturbance, loss of coordination, confusion, seizure and coma, are rare [1]. Persistent deficits and fatal encephalopathy have been rarely reported [1, 5]. Utz reported the first case involving also the anterior circulation in 1988: A patient developed cortical blindness and left hemiparesis as a complication of the abdominal aorta and renal artery angiography with angioplasty [6]. To our knowledge, only 20 cases previously reported global aphasia and/or hemiplegia or mimicked anterior circulation strokes [7–26] (Table 1). The median age of these reported cases is 68.5 years (range 39–82), without prevalence of sex. Arterial hypertension is the most common risk factor being present in 67% of patients, 24% present chronic kidney disease. In the majority of patients, aphasia, hemiparesis/hemiplegia or the combination of two symptoms are reported. Clinical resolution is variable from hours to 14 days, more frequently within 4–5 days. No patient died, and clinical sequelae are described only in one patient (retrograde amnesia). Interestingly, recurrent CIE was described after a new exposure to iodinated contrast [23] in some patients, whereas in other cases, re-injection of contrast medium did not lead to any consequence [27, 28]. The unknown risk of recurrence may represent significant trouble in the management of such patients. Our patient has two potentially treatable aneurysms, so it is crucial to decide the adequate approach considering the risk of CIE recurrence. In our case, after a collegial discussion, we have decided to postpone the treatment of the residual aneurysms, performing a brain MRI with MR angiography in a month. Since the radiological picture was stable, we decided not to treat the patient, continuing with strict follow-up to evaluate a possible neuroradiological or surgical approach. In conclusion, CIE is a rare complication of endovascular procedures due to iodinated contrast extravasation. The low frequency and the variable presentation of this event make the diagnosis difficult. The only way to exclude alternative diagnoses is a prompt brain imaging, crucial to recognize the treatable causes. In a few cases of CIE, permanent neurological dysfunctions may occur; the risk/benefit ratio in rechallenging patients with iodinated contrast must be carefully evaluated, in particular in patients having presented the first episode of CIE. Informed consent References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Author contributions All authors approved the contents of the manuscript and validated the accuracy of the data. Compliance with ethical standards 16. Conflict of interest The authors declare that they have no conflict of interest. 17. Ethical approval Not applicable Not applicable Leong S, Fanning NF (2012) Persistent neurological deficit from iodinated contrast encephalopathy following intracranial aneurysm coiling. A case report and review of the literature. 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