Cortical blindness after contrast-enhanced CT scan in a patient of sarcoidosis - Is it related to posterior reversible encephalopathy syndrome?

Transient cortical blindness (TCB) is a well known but rare complication of administration of contrast agent. In this case report, we present a 53-year-old woman who is a follow-up case of sarcoidosis and developed TCB with focal neurological symptoms following contrast-enhanced computed tomography scan. Magnetic resonance imaging revealed bilateral T2/Flair hyperintensities in parieto-occipital, high frontal, and cerebellar hemispheres with involvement of corpus callosum. Clinically and radiologically patient improved significantly in 4 days. The exact mechanism is still speculative and its possible relationship with posterior reversible encephalopathy syndrome is briefly discussed. The patient's symptoms were presumed to be exacerbated by presence of hypertension, underlying autoimmune disorder, sepsis, and high osmolality of contrast agent. Though there is no definite evidence to suggest that a certain treatment regimen improves the natural history of this disease but control of risk factors can possibly prevent this rare but devastating complication.

Introduction

Transient cortical blindness (TCB) is a well known but rare complication of administration of contrast agent. It was first reported in 1970 following coronary angiography.[1] The incidence of TCB is reported to range from 0.3 to 1% with nonionic contrast agents, but can be as high as 4% when hyperosmolar iodinated contrast agents are used.[2] In this case report, we present a case of TCB following contrast-enhanced computed tomography (CT) scan and discuss its possible relationship to posterior reversible encephalopathy syndrome (PRES).

Case Report

A 53-year-old hypertensive woman presented to the emergency with the complaints of abdominal pain and vomiting. She was a follow-up case of pulmonary sarcoidosis and was on steroid for past 7 months. Ultrasound of abdomen done in the emergency revealed cholelithiasis. Laboratory evaluation revealed anemia (hemoglobin level, 7.9 g/dl) and leukocytosis (TLC, 19,100; DLC P90L10). Other electrolytes, renal and hepatic parameters were normal. Serum amylase (39 IU/l) and lipase (43 IU/l) were normal with ACE (Angiotensin Converting Enzyme) levels of 55 U/l. Contrast enhanced CT of abdomen was performed as pancreatitis was clinically suspected. The contrast (70 ml Omnipaque, 350 mg l/ml) was administered intravenously at the rate of 5 ml/s. CT scan revealed cholelithiasis with no other significant findings. However 15 minutes after the scan, patient complained of headache and bilateral acute onset loss of vision. Extraocular movements were full and pupillary light reflexes were normally present. Fundi were bilaterally normal. Blood pressure recorded at the onset of event was 160/100 mm Hg. She became disoriented over next 30 minutes and appeared to develop Anton syndrome with findings of confusional status, cortical blindness, and denial of symptoms. Neurological examination did not reveal focal abnormality. Magnetic resonance imaging (MRI) performed immediately on 3 T MR Scanner revealed bilateral T2/Flair hyperintensity in parieto-occipital, high frontal, and cerebellar hemispheres with involvement of corpus callosum. Corresponding iso-hypointense T1 signal was noted in these regions. Lesions in splenium, parieto-occipital and centrum semiovale region were hyperintense on diffusion weighted images (DWI) with normal or raised apparent diffusion coefficient (ADC) values [Figure 1]. MR angiography performed simultaneously was unrevealing [Figure 1]. The patient continued to receive steroids with additional hydration therapy and calcium channel antagonists. After 2 hours of the procedure, she developed an episode of generalized tonic-clonic seizure. The next day (12 hours postprocedure), patient developed right hemiparesis with persistence of visual deficit and disoriented state. Over the next 48 hours, patient clinically stabilized with gradual improvement of sensorium and right-sided weakness. Vision also improved as she was able to perceive light and shapes of object. Repeat cranial MRI after 4 days showed significant improvement in parieto-occipital and frontal hyperintensities [Figure 2]. On day 8, her neurological symptoms resolved almost completely with near total resolution of visual symptoms. Follow-up CT scan on day 10 revealed further regression of lesions [Figure 3]. Meanwhile, her respiration deteriorated with development of right lower lobe pneumonia and she was electively ventilated. Patient finally succumbed to sepsis, nosocomial pneumonia, and ventilator-associated complications.

Figure 1

(a) Flair MR images show patchy cortical subcortical hyperintensities in bilateral parieto-occipital, high frontal and splenium of corpus callosum region. No mass effect is noted. (b and c) DWI (b=1000 s/m2) show hyperintensties in the areas of altered signal intensity in Flair image with increased ADC values in the corresponding areas

Figure 2

Follow-up MR flair imaging after 4 days showed improvement in bilateral parieto-occipital and frontal hyperintensities

Figure 3

CT scan on day 10 showed significant resolution of parieto-occipital and frontal changes

Discussion

Sarcoidosis is a multisystem disorder and neurological involvement clinically has been reported in 5% of cases. A typical imaging finding is the basilar meningeal involvement in the form of nodules or plaques showing focal or diffuse thickening on contrast-enhanced MRI scans. Other imaging findings are obstructive or communicating hydrocephalus, enhancing or nonenhancing parenchymal, dural, and bone lesions in the head and spine.[3]

The clinico-radiological profile and the temporal sequences of events in the present case are suggestive of neurotoxic manifestation of contrast agent rather than neurosarcoidosis. Though our patient could not survive through the respiratory complications, neurologically near complete recovery was achieved. TCB was reported in cerebral, vertebral, brachial, aortic arch, renal, and coronary angiography, translumbar aortography and myelography.[2] The onset of TCB occurs from minutes up to 12 hours after angiography and is accompanied by headaches, mental state changes, memory loss, and, sometimes, denial of blindness. Usually significant recovery including vision occurs by 12 hours, although complete recovery may take as long as 5 days.[4] However, neurological complications developing after contrast-enhanced CT scan has been reported in only one case report in the literature.[2] Author reported the case of a 16-year-old male patient with cortical blindness after intravenous application of nonionic contrast agent during CT angiography, but the patient did not have typical imaging finding of TCB.

The mechanism of cerebral injury following contrast administration remains speculative. TCB due to contrast and a syndrome of PRES seems to be related entities. Contrast agents penetrate the blood-brain barrier by opening tight capillary junctions or enhancing endothelial pinocytosis.[5] It then enters the cerebral cortex and adversely affects neuronal membranes. The toxicity is predominantly localized to occipital lobes.

PRES is a neurotoxic state accompanied by a unique brain imaging pattern typically associated with a number of complex clinical conditions including pre-eclampsia/eclampsia, allogeneic bone marrow transplantation, solid organ transplantation, autoimmune diseases, and high-dose cancer chemotherapy. Two theories have historically been proposed, which are as follows: (1) Severe hypertension leads to failed auto-regulation, subsequent hyperperfusion, with endothelial injury/vasogenic edema and (2) vasoconstriction and hypoperfusion leads to brain ischemia and subsequent vasogenic edema.[6] The predominance of posterior hemisphere lesions is explained by a relative lack of protective, sympathetically mediated arteriolar vasoconstriction in the posterior circulation during severe hypertension.[7] Endothelin release has been implicated in the pathophysiology of disorders associated with PRES and has also been shown to increase human brain endothelial cell permeability following administration of radiographic contrast material.[8]

In PRES, CT/MRI typically demonstrate focal regions of symmetric hemispheric edema. The basic PRES pattern resembles the brain watershed zones with parietal and occipital lobes being most commonly affected, followed by the frontal lobes, the inferior temporal-occipital junction, and the cerebellum. Three hemispheric pattern variants may be encountered with similar frequency (holohemispheric, superior frontal sulcal, and primary parietal-occipital). Focal/patchy areas of PRES vasogenic edema may also be seen in the basal ganglia, brain stem, and deep white matter (external/internal capsule).[9] DWI has established that the areas of abnormality represent vasogenic edema with elevated ADC values.[9] Our patient showed radiological distribution characteristic of holohemispheric pattern of PRES with DWI patterns of vasogenic edema. Therefore, the radiology of this case also suggested that the contrast-induced neurotoxicity is pathogenically related to PRES syndrome.

The present case seems to have several predisposing factors for developing neurotoxic complications of contrast agent. In 70 to 80% of patients with PRES, moderate to severe hypertension is observed.[9] Our patient was chronically hypertensive, which predominantly increased the susceptibility to osmotic disruption of blood brain barrier. Bartynski et al. observed that PRES seems to occur in patients with infection, sepsis, and shock (23.6%) with predominance of gram-positive organisms (84%).[10] Therefore, the presence of sepsis was the second important predisposing factor in our patient. Third important is that PRES has been associated with autoimmune disorders like systemic lupus erythematosus, Wegener's granulomatosis, systemic sclerosis, and polyarteritis nodosa in 10.4% of the cases.[10] Sarcoidosis has not been described in the literature as a predisposing factor for PRES, but the systemic autoimmune process probably predisposed our patient to neurotoxicity. Fourth, omnipaque, the contrast material used during the procedure has significantly higher osmolality (780 mosm/kg) when compared with that of the blood (300 mosm/kg) and may also have been a contributing factor to an increase in permeability of the blood-brain barrier, a phenomenon well known to occur with ionic contrast material solutions.[7]

The prevention of this rare complication of contrast can possibly be achieved by control of hypertension, treatment of sepsis, ensuring adequate hydration before administration of contrast, and using low osmolality contrast in a patient with several predisposing factors.

Conclusion

We believe that cortical blindness and neurological worsening in our patient were caused by neurotoxic effect of nonionic contrast media, triggered by hypertension, sarcoidosis, and sepsis. There is no definite evidence to suggest that a certain treatment regimen improves the natural history of this disease, which is usually benign. Knowledge about this complication is crucial as the condition is self-limiting and relatively simple treatment is required for its management.