Posterior Reversible Encephalopathy Syndrome (PRES): A Comprehensive Clinical and Imaging Review with a Case of Cyclosporine-Induced PRES in IgA Nephropathy

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 Posterior Reversible Encephalopathy Syndrome (PRES): A Comprehensive Clinical and Imaging Review with a Case of Cyclosporine-Induced PRES in IgA Nephropathy

Keywords: posterior reversible encephalopathy syndrome, PRES, cyclosporine neurotoxicity, IgA nephropathy, FLAIR MRI, vasogenic edema, neuroimaging, hypertension-related brain injury

Introduction

Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic clinical–radiological entity characterized by acute neurological symptoms and distinctive neuroimaging findings, typically affecting the parieto-occipital regions. Although “reversible” is in its name, delayed recognition or inappropriate management can lead to permanent neurological deficits or death. This posting presents an in-depth expert-level review of PRES, including cause, etiology, pathophysiology, epidemiology, clinical presentation, imaging features, treatment, and prognosis, supported by a real-world case of cyclosporine-induced PRES in a patient with IgA nephropathy.

Case Summary

A 35-year-old male with a known history of IgA nephropathy (Berger’s disease) presented with confusion, blurred vision, and seizures. Two weeks before presentation, he had started cyclosporine therapy for immunosuppression. On examination, his blood pressure was 160/80 mmHg, with somnolence and visual disturbances, but fundoscopy was normal. Brain MRI using fluid-attenuated inversion recovery (FLAIR) sequences revealed vasogenic edema in the cortical and subcortical white matter, predominantly in the posterior brain regions.

Figures

Figure 1: FLAIR MRI slice showing hyperintense signal in the parieto-occipital region, suggestive of vasogenic edema.

Figure 2: Additional FLAIR MRI slice demonstrating bilateral, symmetric cortical-subcortical hyperintensities.

  • Figure 3: Coronal FLAIR MRI view highlighting the extent of posterior white matter involvement.


Cause and Etiology

PRES results from disruption of cerebral autoregulation and blood–brain barrier (BBB) breakdown, leading to vasogenic edema. The most common causes include:

  1. Hypertension – rapid rise in BP overwhelms autoregulation.

  2. Cytotoxic drugs – cyclosporine, tacrolimus, chemotherapy agents.

  3. Autoimmune diseases – systemic lupus erythematosus, vasculitis.

  4. Renal failure – both acute and chronic.

  5. Eclampsia/pre-eclampsia.

In this case, the etiology was cyclosporine-induced neurotoxicity in the background of IgA nephropathy.

Pathophysiology

The pathophysiology of PRES is not fully understood, but two main theories exist:

  1. Hyperperfusion theory: Sudden hypertension exceeds the autoregulatory capacity of cerebral vessels, leading to arteriolar dilation, BBB disruption, and leakage of plasma into the extracellular space, producing vasogenic edema.

  2. Hypoperfusion theory: Cytotoxic injury to vascular endothelium (e.g., from immunosuppressants) causes vasoconstriction, ischemia, and secondary BBB disruption.

In cyclosporine-induced PRES, direct endothelial toxicity and vasoconstriction play dominant roles, even in the absence of severe hypertension.

Epidemiology

  • PRES affects all age groups but is most common in middle-aged adults.

  • Incidence is higher in patients with solid organ transplantation, autoimmune disease, renal failure, or cytotoxic drug exposure.

  • Cyclosporine neurotoxicity occurs in up to 25% of transplant recipients, but PRES is less frequent.

Clinical Presentation

PRES typically presents with acute or subacute onset of:

  • Seizures (in ~75% of cases)

  • Altered mental status (confusion, somnolence, coma)

  • Visual disturbances (blurred vision, hemianopia, cortical blindness)

  • Headache

  • Focal neurological deficits

Our patient presented with confusion, visual impairment, and seizures—a classic PRES triad.

Imaging Features

MRI is the gold standard for diagnosis.

  • FLAIR MRI: Hyperintensities in subcortical white matter of posterior cerebral hemispheres.

  • T2-weighted MRI: High signal intensity in affected regions.

  • Diffusion-weighted imaging (DWI): Differentiates vasogenic from cytotoxic edema.

  • Distribution: Bilateral, symmetric involvement of parieto-occipital lobes; frontal lobes, temporal lobes, cerebellum, and brainstem can also be affected.

In this case:

  • Figures 1–3 show bilateral posterior cortical and subcortical hyperintensities consistent with vasogenic edema.

Treatment

Management principles:

  1. Remove or reduce the causative factor – cyclosporine was discontinued in our patient.

  2. Control blood pressure – gradual BP reduction to avoid ischemia.

  3. Manage seizures – antiepileptic therapy as needed.

  4. Treat underlying conditions – optimize renal function, manage autoimmune disease.

Prognosis

  • With early recognition and management, clinical and radiologic recovery occurs in days to weeks.

  • Delayed diagnosis can lead to ischemia, hemorrhage, or death.

  • Recurrence is possible if precipitating factors are not controlled.

Our patient improved both clinically and radiologically within a week after stopping cyclosporine.

Quiz

1. Which MRI sequence is most useful for detecting vasogenic edema in PRES?
A) T1-weighted imaging
B) T2-weighted imaging
C) FLAIR
D) Gradient-echo imaging

2. Which of the following is not a common cause of PRES?
A) Hypertension
B) Cyclosporine
C) Eclampsia
D) Amyotrophic lateral sclerosis

3. What is the primary mechanism of cyclosporine-induced PRES?
A) Demyelination of cortical neurons
B) Direct endothelial toxicity and vasoconstriction
C) CSF overproduction
D) Axonal degeneration

Answer & Explanation

1. Answer: C) FLAIR. Explanation: FLAIR sequences suppress CSF signal, enhancing the visibility of cortical and subcortical vasogenic edema.

2. Answer: D) Amyotrophic lateral sclerosis.Explanation: ALS is a neurodegenerative disease unrelated to PRES pathogenesis.

3. Answer: B) Direct endothelial toxicity and vasoconstriction. Explanation: Cyclosporine damages vascular endothelium, leading to vasoconstriction, ischemia, and BBB breakdown.

References

[1] Hinchey, J., et al., “A reversible posterior leukoencephalopathy syndrome,” New England Journal of Medicine, vol. 334, no. 8, pp. 494–500, 1996.
[2] Bartynski, W. S., “Posterior reversible encephalopathy syndrome, Part 1: Fundamental imaging and clinical features,” AJNR Am J Neuroradiol, vol. 29, no. 6, pp. 1036–1042, 2008.
[3] Lee, V. H., et al., “Clinical spectrum of reversible posterior leukoencephalopathy syndrome,” Arch Neurol, vol. 65, no. 2, pp. 205–210, 2008.
[4] McKinney, A. M., et al., “Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings,” AJR Am J Roentgenol, vol. 189, no. 4, pp. 904–912, 2007.
[5] Legriel, S., et al., “Posterior reversible encephalopathy syndrome: prognosis and management,” Intensive Care Medicine, vol. 37, no. 6, pp. 1032–1042, 2011.
[6] Fugate, J. E., and Rabinstein, A. A., “Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions,” Lancet Neurology, vol. 14, no. 9, pp. 914–925, 2015.
[7] Roth, C., and Ferbert, A., “The posterior reversible encephalopathy syndrome: what's certain, what's new?” Practical Neurology, vol. 11, no. 3, pp. 136–144, 2011.

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