A case of contrast-induced encephalopathy

Abstract

The differential diagnosis of the patient with encephalopathy is broad and remains a common yet challenging problem for critical care physicians. A case is presented of contrast-induced encephalopathy in an 81-year-old man undergoing a left heart catheterisation after receiving iopamidol, a low-osmolar contrast agent. Immediately after receiving contrast, our patient experienced severe headache, agitation, altered mentation and significant skin hypersensitivity. This rare, acute and reversible neurological disturbance can be associated with administration of intra-arterial, osmotic, iodinated contrast. Although uncommon, it is important to recognise the various presentations, risk factors and treatment of this condition.

Background

Contrast-induced encephalopathy is an interesting and rare cause of encephalopathy that has been described as occurring after coronary or cerebral angiography. This condition has been associated with various neurological presentations including cortical blindness, seizure, encephalopathy, global aphasia, focal neurological deficits and even a chemical meningitis from extravasation of contrast media.^1–10 Symptoms appear within minutes to hours after contrast injection and usually resolve within 72 hours as the contrast material is cleared by the kidney.¹¹ CT imaging of the brain may demonstrate diffuse cortical hyperattenuation similar to subarachnoid haemorrhage although normal brain CT has also been described.^{6 7} MRI findings may include hyperintensity in the cortex on T2, fluid attenuated inversion recovery and diffusion weighted imaging.^{2 3} Here, we describe a case of contrast-induced encephalopathy following coronary angiography using Iopamidol contrast.

Case presentation

An 81-year-old man was admitted for syncope. His medical history was significant for coronary artery disease, abdominal aortic aneurysm, peripheral vascular disease and hypertension. The physical examination was remarkable for a low volume and slow-rising carotid pulse and a loud mid-peaking systolic murmur in the right intercostal space. Further evaluation with transthoracic echocardiogram revealed severe aortic stenosis. While undergoing evaluation for transcatheter aortic valve replacement he had a left heart catheterisation with the administration of 250 mL of Iopamidol. Within 90 min of receiving the iodinated contrast, the patient developed a severe headache with altered mentation, agitation and skin hypersensitivity. He was without noticeable focal deficits. Laboratory findings were unremarkable.

Investigations

A non-contrast CT scan of the head was obtained emergently. The CT demonstrated increased density of the falx and tentorium corresponding to recent contrast administration (figure 1). An MRI obtained 48 hours after the onset of encephalopathy revealed small vessel ischaemia and age-related changes (figure 2). These studies were limited to primarily the brain parenchyma. Early CT angiography, CT venography, MR angiography or MR venography would have allowed for better visualisation of the cerebral vasculature however given the acute change in clinical status and the clinical scenario the aforementioned imaging was pursued.

Figure 1.

CT of the patient demonstrating increased density of the falx and tentorium corresponding to recent contrast administration.

Figure 2.

MRI of the patient demonstrating age-related changes.

Differential diagnosis

In the patient who presents with a constellation of findings that include acute encephalopathy and severe headache, a broad differential of encephalopathy should be considered including infection, vasculitis, subarachnoid haemorrhage, cerebral venous thrombosis, cerebral infarction, hypertensive emergency, reversible cerebral vasoconstriction syndromes and posterior reversible encephalopathy syndrome. His clinical presentation, non-focal neurological examination and brain imaging did not support a diagnosis of infection, vasculitis, subarachnoid haemorrhage, cerebral venous thrombosis or cerebral infarction. A normal blood pressure excluded hypertensive emergency. Reversible cerebral vasoconstriction syndromes were less likely as he did not have recurrent thunderclap headaches and lacked typical risk factors (female gender, pregnancy, younger age and recent exposure to vasoactive agents).¹² Posterior reversible encephalopathy syndrome (PRES) was considered, and there may be overlap in the suspected pathogenesis; however, this patient lacked typical risk factors of uncontrolled hypertension, immunosuppressive therapy or comorbid autoimmune disease.¹³ Additionally, there is only one report of an association of PRES with contrast medium and our patient lacked findings on MRI consistent with this diagnosis such as vasogenic oedema, which typically would have been observed within 48 hours.^{13 14} Given the proximity of the contrast administration to the onset of symptoms, contrast-induced encephalopathy was strongly suspected.

Treatment

Our patient was treated conservatively with intravenous fluids, acetaminophen and non-steroidal anti-inflammatory drugs. His mental status and agitation resolved within 48 hours. His headache improved although it continued for several days before completely resolving.

Outcome and follow-up

At 6-month follow-up, our patient reported ongoing shortness of breath since his transcatheter aortic valve replacement. He denied syncopal episodes and had no recurrence of headache or any neurological deficits. Interesting he did have exposure to arterial contrast while undergoing transcatheter aortic valve replacement. For this, he was hydrated prior to the procedure and a significantly lower volume of 159 mL of Iopamidol without headache or neurological sequela.

Discussion

Although the exact mechanism of contrast-induced encephalopathy remains to be elucidated, it has been postulated that the hyperosmotic properties of contrast media cause disruption of the blood–brain barrier resulting in direct neurotoxicity and cause cerebral oedema.¹⁵ Animal studies have shown that ionic contrast material can cause blood–brain barrier disruption.¹⁶ Hyperosmolarity of the contrast material may have chemical toxicity promoting endocytosis and exocytosis of endothelial cells in addition to causing endothelial cells to shrink and compromise the integrity of tight junctions.¹⁷ Contrast-induced encephalopathy has most commonly been described in the setting of with non-ionic, low osmotic contrast medium although it has also occurred with administration of ionic as well as high osmolar contrast. There has also been a case of this phenomenon with iodixanol, an isosmolar contrast agent.^{18 19} Contrast-induced encephalopathy most commonly affects the parieto-occipital cortex. It is believed that this is due to the posterior circulation being more sensitive to blood pressure changes and at increased susceptibility of damage due to less vascular autoregulation.³ Predisposing factors include large contrast volume (80–400 mL), chronic hypertension, transient ischaemic attack, impaired cerebral autoregulation, impaired renal function, vertebral-basilar arteriography, male gender and previous adverse reactions to contrast.^{2 3 11}

Treatment of contrast-induced encephalopathy is largely supportive, usually involving intravenous hydration; however, anticonvulsants have been used in cases where seizures were present.²⁰ Systemic corticosteroids and osmotic diuretics have been used. Dialysis has been implemented in those with end-stage renal disease.^{3 5 21} Symptoms and neurological deficits occur shortly after contrast administration and typically resolve within 24–48 hours,²¹ but have been described as lasting longer in those with end-stage renal disease even up to 8 days.²² Patients may not necessarily experience contrast-induced encephalopathy if re-exposed to contrast medium, however recurrence has been described.^{19 21 23} Prevention involves hydration prior to contrast administration and using the lowest volume of contrast required.¹¹

Learning points.

• Neurological complications of arterial contrast administration include cortical blindness, seizure, encephalopathy, global aphasia, focal neurological deficits and chemical meningitis.

• Risk factors of contrast-induced encephalopathy include large contrast volume (80–400 mL), chronic hypertension, transient ischaemic attack, impaired cerebral autoregulation, impaired renal function, vertebral-basilar arteriography, male gender and previous adverse reactions to contrast.

• Treatment of contrast-induced encephalopathy is supportive, largely consisting of intravenous hydration however anticonvulsants, osmotic diuretics and dialysis have been described.

• Preventation of contrast-induced encephalopathy included hydration prior to contrast administration and using the lowest amount of contrast needed.