The prognosis of most CIE is generally reported to be good with a rapid recovery, and only rare cases with the persistent deficits have been reported [2]. Notably, there were 8 cases of autopsy-proven fatal cerebral oedema due to contrast neurotoxicity in the early stage of angiography [1, 3, 4]. The 8 deaths included 6 infants; 5 of these patients underwent cardiac angiography, and the other 3 received aortography. All fatal cerebral oedema cases reported involved the use of ionic high osmolar contrast agents, and ionic high osmolar contrast agents are no longer used in routine angiography and intervention procedures. The case which we report here may be the first fatal cerebral oedema after DSA using iopamidol. This case highlights the potential for other types of iodinated contrast agents to induce fatal encephalopathy.
The diagnosis of CIE is important, as its presentation may be similar to embolism, and haemorrhagic complications following angiography or endovascular interventions. Typical radiological findings include abnormal cortical contrast enhancement and cerebral oedema, subarachnoid contrast enhancement and striatal contrast enhancement [2, 11]. CT or MRI of the brain helps us to differentiate CIE from haemorrhage or infarct. In the case which we report here, none of the CT scans of the brain after DSA (immediately, 2 days, 9 days and 15 days after the procedure) indicated intracerebral haemorrhage or infarct. Therefore, the possibility of multiple embolisms was not considered in this case. The hyperdense signal in the subarachnoid space in the cerebral CT scans was considered to be due to the severe diffuse cerebral oedema. The hyperdense appearance results from a combination of loss of grey-white differentiation, narrowing and effacement of the subarachnoid spaces, and corresponding engorgement of superficial pial veins [10].
The mechanism of CIE is controversial. The temporary disruption of the blood-brain barrier (BBB) after injection of the iodinated contrast agent is widely accepted [2, 11-15]. Experimental studies have demonstrated that contrast agents can penetrate the altered BBB and that this is dependent on the contact time, anions and dosage [1, 12, 13, 15]. Both the hyperosmolality and chemotoxicity of the contrast agents contribute to the disruption of the BBB. Hyperosmolality of the contrast medium is hypothesised to cause shrinkage of endothelial cells and disrupt tight junctions [12]. Other studies suggest that the alteration of the BBB is due to the physical or chemical effects of the contrast medium on the BBB instead of the hyperosmolality [14]. The expression of endothelin, which can be induced by radiocontrast agents, can increase human brain endothelial cell permeability and has been implicated in the pathophysiology of disorders associated with BBB injury [2, 15].
Studies have indicated that opening of the BBB may be accompanied by brain oedema, resulting from the flux of proteins, electrolytes, and water across the abnormally permeable cerebral vessels into the extracellular space [4]. An idiosyncratic response to small doses of contrast agent, which may be related to the areas of incompleteness of their BBB, has been reported [1]. We postulate that the idiosyncratic response to contrast agents may have contributed to the patient's prolonged and progressive brain oedema. Contrast agents can produce direct neurotoxic effects on the neurons and astrocytes when they penetrate the altered BBB. Experimental studies have shown that ionised contrast agents can severely alter neuronal function when directly introduced into the nervous system [1, 12, 13, 15]. We hypothesised that the direct neurotoxic effect of the contrast agent also contributed to the patient's progressive and fatal brain oedema.
All types of iodinated contrast agents can induce the development of neurotoxicity, but the occurrence of fatal cerebral oedema is very rare. Unfortunately, there is no currently available effective treatment for such a severe fatal CIE. In the case reported by L. Junck and W.H. Marshall [4], the post mortem tissue iodine concentrations were the highest in the urine, serum and kidney. The use of continuous renal replacement therapy and continuous blood purification may be potential treatments for cases of fatal CIE.
In summary, although CIE has typically been associated with benign outcomes in previous studies, we present a case of fatal cerebral oedema after DSA using iopamidol. This case illustrates the potential to cause severe complications, even fatal cerebral oedema, with all types of iodinated contrast agents. The doctors performing angiography and interventions should be aware of this severe potentially harmful effect. The rare occurrence of severe contrast-induced complications renders their prevention very difficult. Further studies are needed to define the risk factors and the mechanism of the iodinated contrast agent neurotoxicity, which may help minimise the occurrence of severe complications.