Posterior reversible encephalopathy syndrome (PRES) is a reversible clinicoradiologic condition first described by Hinchey et al. in 1996 [¹]. PRES occurs more commonly in females and has been reported in nearly all age groups. It is most frequent among middle-aged adults, with an average age of 44 years [²]. The syndrome is characterized by a range of acute and subacute neurological signs and symptoms accompanied by distinctive neuroimaging findings. Diagnosis is clinico-radiologic, with MRI crucial to confirm the presence and distribution of vasogenic edema [³]. On MRI, PRES typically appears as vasogenic edema involving the white matter of the cerebral hemispheres, predominantly in the posterior regions, including the parieto-occipital lobes bilaterally. Other regions may also be affected, including the temporal and frontal lobes, cerebellum, brainstem, and deep white matter [⁴,⁵]. Symptoms usually develop over several hours to a few days and include headache, confusion, altered mental status, seizures, and visual disturbances [¹]. Patients may also experience lethargy, stupor, or occasionally focal neurological deficits [¹]. Less common manifestations include nystagmus and periodic alternating gaze deviation [⁶,⁷]. PRES is frequently associated with hypertension, particularly in eclampsia, hypertensive encephalopathy, and post-transplant settings involving immunosuppressive agents [⁸]. The primary pathophysiological theory posits that a sudden increase in blood pressure exceeds the brain’s autoregulatory capacity, leading to endothelial injury, fluid leakage, and vasogenic edema [⁹]. However, approximately 30% of patients with PRES are normotensive. This observation supports an alternative hypothesis of direct endothelial toxicity induced by factors such as inflammation, autoimmune disease, sepsis, renal failure, or certain medications [⁸]. Early recognition and management of PRES can significantly improve outcomes and reduce complications [¹⁰]. Clinico-radiologic features are potentially reversible, especially with timely intervention. Diagnosis, therefore, requires a high index of clinical and imaging suspicion to ensure early treatment and a favorable prognosis [¹¹]. This review aims to provide a comprehensive understanding of PRES by exploring diverse etiological triggers beyond hypertension, analyzing proposed pathophysiological mechanisms, and examining the long-term outcomes and risks associated with persistent neurological deficits. It also considers whether the relative frequency of different triggers varies across regions due to differences in healthcare practice and access to care.

An overview of clinical presentation, risk factors, epidemiology, evaluation, differentials, and complications is provided in .

As illustrated in (Figure 1), the incidence of PRES has been documented across multiple U.S. states with notable variation.

Initially, Posterior Reversible Encephalopathy Syndrome (PRES) was thought to occur in the context of severe hypertension, but now, growing evidence has proved the existence of multiple other triggers. The fact that 30% of PRES patients have no hypertension has supported this evidence [⁸]. These triggers include eclampsia or pre-eclampsia, immunosuppressive drugs, sepsis, autoimmune diseases, and rarely, renal failure [¹⁵,¹⁶]. An elevation in the circulatory levels of toxins and cytokines, such as TNF-alpha, IL-1, and IL-6, is provoked by these triggers, causing damage to the blood-brain barrier (BBB) and allowing fluid leakage extravascularly [¹⁷]. More rarely, some rare triggers, such as hypercalcemia, hyperglycemia, and blood transfusion, have been reported. These triggers primarily cause PRES through osmotic shifts, leading to endothelial dysfunction [¹⁸,¹⁹,²⁰].

PRES is a neurologic condition characterized by vasogenic edema most often occurring in the parieto-occipital lobes. Endothelial injury, disruption of the blood-brain barrier (BBB), and loss of cerebral autoregulation are the major pathological factors that contribute to the occurrence of PRES. Depending on the cause, endothelial damage is the primary harm, occurring through several pathways. Acute blood pressure increases that exceed cerebral autoregulation cause physical damage at the endothelium level in early hypertensive PRES, which accounts for 60–80% of patients. Similar to this, endothelial integrity is compromised when immunosuppressants such as tacrolimus are present. This is due to the ability of these medications to block endothelial tight junctions by inhibiting the calcineurin-NFAT signaling pathway and reducing the production of occludin and claudin-5 [³⁸,³⁹,⁴⁰]. Anti-angiogenic factors from the placenta, such as soluble endoglin and sFlt-1, are systemic VEGF antagonists in eclampsia [⁴¹]. After endothelial injury, the BBB can be disrupted in several ways. TNF-alpha, IL-1 beta, and IL-6 are a few inflammatory cytokines known to induce the production of matrix metalloproteinases that dissolve tight junctions and facilitate edema. Hypoalbuminemia has also been implicated as a contributing factor in the development of PRES. Low serum albumin levels (<3 g/dL) have been reported in patients with PRES, which may decrease plasma oncotic pressure and exacerbate vasogenic edema following endothelial injury [⁸,⁴²]. Vasogenic edema is characterized by increased apparent diffusion coefficient (ADC) values on MRI, whereas restricted diffusion indicates cytotoxic injury [⁴³]. Compared to the anterior regions, the posterior circulation has less sympathetic innervation, making it more vulnerable to damage [⁴⁴,²⁶,⁴³]. Recent reports have investigated the de novo mechanism of intravascular permeability through vasopressin-induced V1a receptor recognition. Genetic polymorphisms in endothelial nitric oxide synthase (eNOS) (rs1799983) and endogenous vascular endothelial growth factor (VEGF) (rs699947) may also be associated with PRES. It was reported that systemic lupus erythematosus, an autoimmune-mediated PRES that is seen in approximately 10-15% of cases, may be associated with PRES due to complement activation and immune complex deposition [⁴⁵,⁴⁶].

As described previously, there has been a significant shift in the understanding of PRES over the years, and several hypotheses regarding possible genetic predispositions have been explored; however, none have yet been confirmed. Endothelial dysfunction plays a key role in the proposed pathogenesis of PRES. Polymorphisms in genes coding for endothelial nitric oxide synthase (eNOS) and methylenetetrahydrofolate reductase (MTHFR), which may impair vascular function, have been hypothesized to increase susceptibility to PRES, particularly in conditions such as pre-eclampsia that share overlapping mechanisms [⁴⁷]. Similarly, potential associations between aquaporin-4 (AQP4) gene variants and reduced water permeability, leading to cerebral edema, have been described. Four non-synonymous single-nucleotide variants were identified, suggesting a theoretical role for AQP4 dysfunction in edema-related disorders [⁴⁸]. However, a genomic study by Matiello et al. involving 23 PRES patients did not find supporting evidence [⁴⁹]. Additionally, AQP4-IgG autoantibodies—typically seen in neuromyelitis optica spectrum disorder (NMOSD)—have not been detected in PRES without NMOSD, further supporting the argument against a direct causal link [⁵⁰]. Rarely, PRES-like changes have been observed in recurrent NMOSD with AQP4 autoimmunity, which may reflect a distinct pathogenic process [⁵¹]. Emerging evidence has also suggested a possible role of the arginine vasopressin (AVP) pathway in PRES development, potentially through AVP-mediated cerebral vasoconstriction and endothelial stress. Genetic variants affecting the AVP axis, including genes that encode the hormone, its receptors, or modulators, may contribute to susceptibility; however, confirmatory studies are still required [⁴⁶]. PRES has been reported in association with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and neurolupus [⁵²]. Elevated cytokines such as interleukin-6 (IL-6) and interleukin-10 (IL-10) have been observed in SLE patients who develop PRES [⁵³]. IL-6 may also influence AVP release, providing a mechanistic link between inflammation, vascular regulation, and hormonal response [⁴⁶,⁵⁴]. Furthermore, some reports suggest that immunosuppressive therapy, especially calcineurin inhibitors, may predispose to PRES, partly via AVP-mediated vasoconstrictive mechanisms [⁴⁶,⁵⁵].

The key element for efficient management is the early diagnosis, prompt recognition of signs and symptoms, and differentiation from other similar conditions, such as intracranial hemorrhage. Management strategies are tailored according to the underlying cause of PRES. That’s why the first thing is to identify the trigger and to manage or reverse it. However, most of the cases require ICU care for aggressive management of their symptoms, e.g., seizures and status epilepticus. So, once PRES is suspected, transfer to the intensive care unit should be considered [⁵⁶]. In general, the acute management of PRES is supportive, for example:

Malignant PRES, by definition, is characterized by the presence of coma with a Glasgow Coma Scale (GCS) score of <8, deterioration despite standard management for elevated intracranial pressure, and radiological evidence of edema [⁵⁷]. This condition requires aggressive management that may include mechanical ventilation, transfusion of blood products for reversal of coagulopathy, and corticosteroids for patients with autoimmune disorders. Furthermore, intracranial pressure should be monitored because it may cause obstructive hydrocephalus that requires an external ventricular drain [⁵⁸].

Regarding prognosis, although PRES was initially described as a benign and reversible condition, subsequent studies have shown that it can occasionally be associated with substantial morbidity and even mortality, depending on the underlying etiology and clinical context [⁸,⁵⁹,³⁹]. Many survivors may experience varying degrees of long-term neurological sequelae, including motor impairment, epilepsy, or cognitive dysfunction [⁵⁹,³⁹]. Follow-up imaging frequently reveals residual structural lesions, and the overall outcome depends largely on the rapid identification and management of the precipitating cause [³⁹]. Favorable outcomes are most often observed in cases related to pre-eclampsia or eclampsia, whereas poorer outcomes are linked to delayed recognition, severe encephalopathy, or extensive imaging abnormalities [⁵⁹,³⁹]. Recurrent episodes of PRES have been reported in a small subset of patients, typically those with ongoing systemic or vascular risk factors such as autoimmune disease, renal impairment, or uncontrolled hypertension [³⁹,⁵⁹] . Several clinical and radiological factors have been identified as predictors of poor outcomes in PRES, as reported in prior cohort and imaging-based studies. These include severe encephalopathy, hypertension-related or sepsis-associated PRES, delayed recognition or management of the underlying trigger, and the presence of comorbidities such as renal dysfunction or autoimmune disease. Laboratory abnormalities, such as elevated C-reactive protein, coagulopathy, and metabolic derangements, have also been associated with an unfavorable prognosis [⁸,⁵⁹,⁴⁵]. Radiologically, corpus callosum involvement, extensive cerebral edema, intracerebral or subarachnoid hemorrhage, and restricted diffusion on MRI have been described as adverse prognostic indicators. These findings are summarized narratively in the text rather than in tabular form, given the heterogeneity of reporting across studies [⁵⁹,⁴⁵]. Despite recovery in many patients, structured long-term follow-up remains crucial. Regular neurological and neurocognitive assessments are recommended after discharge to detect delayed sequelae or recurrence. Patients with persistent deficits may benefit from individualized rehabilitation programs that incorporate physiotherapy, occupational therapy, and cognitive rehabilitation. However, no standardized follow-up or rehabilitation protocol currently exists, highlighting a key area for future research.

Although PRES remains a heterogeneous syndrome, several practical points emerge from the current evidence synthesis. First, early clinical recognition and prompt MRI evaluation should be prioritized in any patient presenting with acute seizures, encephalopathy, or visual symptoms, particularly in the presence of hypertension, renal dysfunction, autoimmune disease, or exposure to immunosuppressive agents. Clinicians should maintain a low diagnostic threshold, as timely identification markedly improves outcomes [⁴⁵,¹⁴]. Second, management must be context-specific. In tertiary care centers, access to rapid MRI, neurocritical care units, and multidisciplinary teams (including neurology, nephrology, obstetrics, and intensive care) enables aggressive yet controlled management, including blood pressure titration, seizure prophylaxis, and etiologic treatment. In community or resource-limited hospitals, where MRI or intensive care may be delayed, clinical suspicion combined with CT and supportive measures (gradual BP reduction, removal of triggers, seizure control) remains the cornerstone, with transfer to higher-level care when feasible [¹²,⁴⁵]. Third, education and training are critical. PRES often presents across multiple specialties, such as neurology, internal medicine, nephrology, and obstetrics, and its reversibility depends on early detection. Incorporating PRES recognition algorithms, imaging interpretation workshops, and inter-disciplinary simulation exercises into postgraduate curricula and continuing medical education could bridge the existing awareness gap [³⁶,⁴⁵,²⁹]. Finally, protocols should emphasize multidisciplinary coordination and structured follow-up imaging to detect residual lesions or recurrence, ensuring long-term neurological recovery.

While this review provides an integrated synthesis of the literature on PRES, several limitations should be acknowledged. First, as a narrative review, the study is inherently subject to selection bias despite efforts to ensure comprehensive database coverage and predefined inclusion criteria. The absence of a formal quantitative synthesis or meta-analysis limits the ability to derive pooled effect estimates or assess publication bias. Second, the heterogeneity among included studies, which span different populations, clinical settings, diagnostic criteria, and imaging protocols, may influence the generalizability of the findings. Third, the reliance on English-language publications and exclusion of non-peer-reviewed material may have led to the omission of relevant evidence from other regions. Lastly, variations in reporting standards and retrospective data in many studies limit the causal interpretation and weaken the strength of conclusions. Future prospective and multicenter studies with standardized diagnostic and reporting frameworks are warranted to validate these observations and refine the understanding of PRES subtypes and outcomes.

Beyond its historical association with hypertension, PRES is now recognized as a multifactorial neurovascular condition with diverse etiologies and complex pathophysiology. Although hypertension remains a common precipitating factor, a considerable number of cases occur in normotensive patients, emphasizing the need to explore non-hypertensive mechanisms. PRES encompasses a broad clinical and radiologic spectrum, typically manifesting with vasogenic edema in the parieto-occipital regions, though atypical patterns are not uncommon. Diagnostic challenges persist, particularly in normotensive or atypical presentations, underscoring the importance of maintaining high clinical and imaging suspicion. While several mechanisms have been proposed, the pathogenesis of PRES remains incompletely understood, and emerging genetic hypotheses require further validation. The current evidence base, largely derived from observational, case-based, and heterogeneous studies, supports associations but does not establish definitive causation. Management continues to rely on prompt recognition, supportive care, and treatment of the underlying trigger. Although outcomes are often favorable, neurological morbidity and mortality may occur, especially in severe or delayed cases. Recurrent PRES has also been described in patients with persistent systemic risk factors. Given the heterogeneity and predominantly retrospective nature of existing evidence, future prospective and multicenter studies are needed to better characterize PRES subtypes, confirm genetic and molecular associations, and guide the development of targeted management strategies toward more individualized care.