Contrast-induced Encephalopathy after Endovascular Embolization of an Anterior Communicating Artery Aneurysm:Case Report and Literature Review

Lin Zhao,Wen-Jing Zhou,Lu Yang,Yan-Chao Huo,Yao-Ming Xu

1Department of Neurosurgery,Tongliao City Hospital,Inner Mongolia,China.2Tongliao Clinical School of Inner Mongolia Medical University,Inner Mongolia,China.3Department of Neurology,Tongliao City Hospital,Inner Mongolia,Inner Mongolia,China.

Abstract

Keywords:Endovascular embolization,Intracranial aneurysm,Contrast-induced encephalopathy,Neurotoxicity,Adverse event,Neurological intervention

Background

With the development and advancement of neurointerventional technology,the clinical application of contrast agents has increased,and contrast agent-related adverse reactions have gradually drawn attention clinically.Contrast-induced encephalopathy(CIE)is a rare and serious complication among many adverse reactions,most of which occur after surgery.The clinical manifestations mainly include headache,nausea,hemiplegia,epilepsy,cortical blindness,delirium,and confusion[1].There is currently a lack of unified diagnostic criteria and treatment methods for CIE.In this article,we report a case of CIE after intracranial aneurysm embolization and review the related literature.

Clinical data

A 59-year-old woman was admitted to Tongliao Hospital for neurointerventional treatment due to a left anterior communicating artery aneurysm.She had a history of hypertension,which was controlled with regular medication.The contraindications were eliminated after a preoperative examination,and head computed tomography(CT)showed no abnormalities(Figure 1A).After evaluation,interventional embolization was performed.

The operation was completed without complications,and the coil embolization was dense(Figure 1B).After 30 min of observation in the anesthesia recovery room,the patient’s vital signs were stable.She returned to the ward after an unremarkable physical examination.Three hours after the operation,she complained of a headache on the right side accompanied by frequent nausea.During severe attacks,she would vomit a small amount of non-brownish stomach contents and was slightly irritable.Her blood pressure at the time of vomiting was 138/82 mmHg,which increased to 160/100 mmHg after 1 h.She was able to follow instructions for the physical examination,answer questions directly,and had no neurological deficits and dysarthria.Her pupils were not of equal size and deviated to the right(left:right=2.5:4.0 mm).Her left limb muscle strength was grade IV;hence,her muscle tone was normal.The left Babinski sign was negative.Emergency head CT showed no intracranial hemorrhage,obvious brain tissue edema in the right cerebral hemisphere,blurred sulcus/gyrus,or metal artifacts(spring coils)in the left frontal lobe(Figure 1C).(Transcranial Doppler,TCD)examination showed that the main blood vessels in the skull were unobstructed,the blood flow velocity was normal,and there was no indication of high perfusion.The patient was diagnosed with CIE and underwent mannitol dehydration and fluid replacement.She was given hormones,sodium valproate to prevent epilepsy,and nimodipine to prevent cerebral vasospasm and control blood pressure.

Figure 1 Head computed tomography at different time

An urgent blood routine check,biochemistry,and blood coagulation test were performed.Her white blood cell count was 9.76×109/L and percentage of neutrophils was 83.8%;other results were normal.In addition,chest X-ray showed no abnormalities.During the late rounds,the patient had stable vital signs but a poor condition.There was a lack of cooperation in physical examinations,slurred speech despite correct answers,left limb muscle strength of II,and a positive Babinski sign.

In the morning round the next day,the patient’s family members reported that she had a fever of 39°C at 12 am in the morning;she was given physical cooling,which reduced her body temperature to 38°C.Her vital signs were stable,white blood cell count was 18.89×109/L,and neutrophil percentage was 84.6%.She was given antibiotic therapy and piperacillin sodium infusion therapy.

The patient’s condition improved from the previous night.She reported that the right frontotemporal pain was absent during the physical examination.In addition,her pupils were deviated and equal in size(2.5 mm),left limb muscle strength was grade II,and Babinski sign was positive.At11:30,physical examination showed no gaze,pupils of equal size,left limb muscle strength of III,and a positive Babinski sign.Head CT showed that the edema in the right cerebral hemisphere was significantly reduced(Figure 1D).In the afternoon,the patient’s mental state improved,and her symptoms recovered to some extent,but she still experienced a headache with no nausea or vomiting.A physical examination performed at 17:30 showed that there was no gaze,normal eye movements,left limb muscle strength of IV,and a positive Babinski sign.She had a headache on the right side and only consumed a small amount of liquid food.

On the third day at 08:30,the patient was in a good mental state,her headache disappeared,her speech was fluent,and she could eat normally.She stated that she could get out of bed independently at 0:00 in the morning,and her physical strength recovered.Her body temperature was 36.8°C,and there were no signs of damage to the nervous system.She was discharged at 14.00 that day,and she reported no discomfort and repetition of symptoms at a telephonic follow-up 1 week later.

Discussion

In recent years,among the reported cases of contrast agent-related adverse events,CIE has been rarely reported,with an incidence rate of 0.3%-1.0%[2].The risk factors and specific mechanisms underlying CIE have not yet been determined.They are generally considered to be related to the following factors:male sex,advanced age,high blood pressure,diabetes,renal impairment,large amount of contrast agent,and history of adverse reactions to contrast agents[3].A foreign report stated that approximately 50% of patients diagnosed with contrast-induced encephalopathy have a history of hypertension[4].The patient reported in this study was elderly and had a history of hypertension,which is consistent with previous reports.

Pathogenesis

In the literature,several theories on the pathogenesis of CIE exist:(1)Autoimmune response theory:as haptens,contrast agents can bind to the corresponding antibody to cause an antigen-antibody reaction[5].(2)Physical and chemical properties of the contrast agent:the osmotic pressure of the contrast agent is higher than that of plasma.After being injected into the human blood vessel,the contrast agent damages the connection of vascular endothelial cells and interrupts the blood-brain barrier.The hypertonicity of the contrast agent may contribute to the neurotoxicity.Other theories claim that the ability of contrast agents to penetrate the blood-brain barrier may be related to the dose,contact time,anion concentration,and lipophilicity of the contrast agent[6].(3)The osmotic pressures of the contrast agent and the cerebrospinal fluid vary.An increase in intracranial pressure and change in the environment of neurons can affect neuron function[5].(4)Small cerebral vasospasm:Rapid high-pressure injection of contrast agents during cerebrovascular intervention causes cerebral vasospasm and induces transient ischemia due to changes in cerebral hemodynamics [3].(5)Microembolism: contrast agents increase blood viscosity and reduce fluidity,inducing the formation of microthrombi and resulting in neurological damage.(6)Cytotoxicity:the contrast agent is neurotoxic and can directly damage brain cells and cause CIE.

In this report,the contrast agent used was iodixanol,a nonionic iodine contrast agent that generally does not penetrate the blood-brain barrier easily as it is hydrophilic.The osmotic pressure of the contrast agent is equal to that of human plasma.The incidence of adverse reactions is low and the security is higher.Adverse reactions such as nausea,vomiting,lack of appetite,and skin rash have been reported occasionally,but encephalopathy has not been reported yet.Theoretically,if the brain structure is underdeveloped,destroyed,or inflamed due to another etiology,the iodine contrast may cause encephalopathy of the nervous system.It is not clear whether there is a definite correlation between the dose of the contrast agent and encephalopathy.It has been reported that with types of contrast agents(ionic and nonionic)is unrelated.At volumes of approximately 40 ml may induce CIE[7].In the present case,approximately 80 ml of contrast agent was used,which may be one of the causes of CIE.

Clinical manifestations

Spina et al.[3]reported that the diagnosis of CIE should meet the following characteristics of neurological impairment:symptoms manifest within minutes or hours of using the contrast agent;symptoms are generally relieved within 24-48 h;and other intracranial diseases such as ischemic stroke or cerebral hemorrhage,cerebral artery dissection,epilepsy,metabolic diseases,and other drugs are excluded.Embolism (thrombosis or gas) or complications of hemorrhagic cerebrovascular disease after cerebral angiography can be ruled out with imaging examinations[3].Head CT results can be normal or reveal cerebral edema,local cortical enhancement,or high-density shadows similar to those in subarachnoid hemorrhage [8].Previously,asymptomatic patients with cerebral aneurysm embolization for 2 h underwent head CT,which revealed that cortical enhancement and cerebral edema were more common,with an incidence of 23%-54%[9,10].Cortical enhancement and cerebral edema may subside after 24 h.Therefore,the diagnosis of CIE is still a diagnosis of exclusion.After the patient’s illness,no other causes of CIE were found after complete examination.After 30 h of symptom onset,the symptoms were completely relieved after comprehensive treatment.There was no abnormality in the neurological examination,and the diagnostic criteria for CIE were met.

In the present case,the main treatment was mannitol dehydration to lower intracranial pressure,anti-inflammatory drugs,hormone treatment,and prevention of epilepsy and other drugs,supplemented by blood pressure control.The patient recovered quickly and had a good prognosis,but the specific mechanism needs to be elucidated.These findings can serve as a reference for the clinical practice.

The uncertainty in this case was that the patient had a left anterior communicating artery aneurysm.Before treatment,angiography of the right anterior circulation was simply performed through the common carotid artery as required by the routine procedure.The amount of contrast agent used was several times more than that used in the right hemisphere;however,after the onset of symptoms,head CT revealed that the patient’s right hemisphere was significantly swollen and the left hemisphere was not swollen.The possible reason remains uncertain.This phenomenon and the underlying mechanism warrant continued attention and discussion.

There are no effective measures to prevent CIE in clinical practice,and the mechanism of contrast-induced neurotoxicity is complicated and controversial.Under normal circumstances,the blood-brain barrier is intact in patients with unruptured intracranial aneurysms,and it is difficult for the contrast agent to penetrate the blood-brain barrier.However,the possibility of damage to the blood-brain barrier due to the excessive amount of contrast agent cannot be ruled out.In neurointerventional surgery,contrast agents are often injected repeatedly into a single local blood vessel.The cumulative effect of the contrast agent may eventually lead to the destruction of the blood-brain barrier and trigger neurotoxic reactions.

In summary,CIE is an acute and reversible central nervous system dysfunction caused by the use of contrast agents.Although it is very rare clinically,improper treatment may lead to irreversible clinical outcomes and cause alarm to doctors.The clinical manifestations of CIE are complex and diverse.In clinical work,medical staff need to strengthen postoperative management to achieve early detection,diagnosis,and treatment.In particular,for patients at high risk,changes in the patient’s condition should be observed closely after surgery.Sufficient hydration and dilution of the contrast agent during and after surgery may be feasible prevention methods.There is currently no specific clinical treatment for CIE.This report summarizes the literature and the experience of our center.We conclude that such patients can achieve good prognosis through timely and reasonable treatment,and it is necessary to explore the mechanism and etiology of the disease.