Posterior Reversible Encephalopathy Syndrome (PRES) Beyond Hypertension: Triggers, Pathophysiology, Management, and Outcomes

Abstract

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a neurovascular disorder characterized by vasogenic edema, most often affecting the parieto-occipital lobes. Although typically reversible, some patients develop lasting neurological sequelae such as cognitive or visual impairment and epilepsy. This review summarizes the current understanding of PRES beyond its classical association with hypertension, emphasizing emerging triggers, mechanisms, and updates in management. Methods: A structured narrative review was conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) framework. Literature was systematically searched in PubMed, Web of Science, and Google Scholar for studies published between January 1996 and June 2025. Fifty-nine relevant publications, including original studies and reviews, were synthesized to integrate evidence on presentation, imaging, pathophysiology, genetics, and management. Results: PRES can be triggered by a broad spectrum of hypertensive and non-hypertensive conditions, such as renal dysfunction, eclampsia, systemic lupus erythematosus, sepsis, and exposure to immunosuppressive agents (e.g., tacrolimus, cyclosporine, rituximab). The syndrome involves multifactorial mechanisms, including endothelial dysfunction, blood–brain barrier disruption, and dysregulated cerebral autoregulation. Emerging data indicate that genetic polymorphisms in endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and aquaporin genes may influence individual susceptibility, although causality remains unconfirmed. Conclusion: PRES is a multifactorial syndrome that extends beyond hypertension. Early recognition, prompt neuroimaging, and targeted management of underlying triggers are critical for improving outcomes. Future studies should focus on clarifying genetic associations, standardizing diagnostic criteria for atypical cases, and optimizing therapeutic strategies through personalized medicine approaches.