Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic syndrome resulting from dysfunction of cerebral autoregulation and vascular endothelium. It presents with neurological symptoms such as headache, seizures, altered consciousness, and visual disturbances, against a background of posterior brain edema confirmed by neuroimaging.
Although the name includes “reversible,” “posterior,” and “white matter,” these features are not always present. Lesions may also involve the frontal lobes, temporal lobes, brainstem, and cerebellum, and some cases do not recover. It is also called RPLS (Reversible Posterior Leukoencephalopathy Syndrome).
In 1996, Hinchey et al. first proposed the concept of posterior reversible encephalopathy syndrome. 2)8)
Epidemiology
Ophthalmic importance
Often presents with visual disturbances such as decreased vision, blurred vision, scotomas, visual hallucinations, and cortical blindness. This condition can be a starting point for ophthalmologists in clinical practice.
Neurological findings are reversible in 75–90% of cases, but 10–20% have permanent neurological sequelae. Death occurs in 3–6%, mainly due to intracranial hemorrhage and cerebral edema. 3) It should be noted that the term “reversible” does not apply to all cases.
Symptoms progress rapidly over hours to days.
Vital signs and systemic findings
Ophthalmic findings
Neuroimaging findings (MRI)
Typical findings for each MRI modality are shown below.
| Modality | Typical findings |
|---|---|
| T2/FLAIR | Hyperintensity in the cortex to subcortical white matter of the parietal and occipital lobes |
| DWI | Hypo- to isointensity (reflecting vasogenic edema) |
| ADC map | Hyperintensity (useful for differentiating from cytotoxic edema) |
| Contrast-enhanced MRI | Gyriform contrast enhancement (reflecting BBB disruption) |
In atypical cases, lesions may also involve the frontal lobe, temporal lobe, cerebellum, brainstem, basal ganglia, and spinal cord. 1)
Approximately one-third of patients have blood pressure within the normal range. When endothelial dysfunction is the direct pathogenic mechanism, posterior reversible encephalopathy syndrome can occur without hypertension. 3) Particularly in COVID-19-associated posterior reversible encephalopathy syndrome, only 28.6% of reported cases had hypertension. 2)
Main Triggers
Drug-related
Other risk factors
Hypomagnesemia, uremia, sepsis, hypercalcemia, IVIg for Guillain-Barré syndrome, tumor lysis syndrome
COVID-19 related
SARS-CoV-2 infection can be a direct cause of PRES. Only 28.6% of COVID-19-associated PRES cases had hypertension, suggesting that virus-induced direct endothelial injury is the main cause. 2)
In the WHO pharmacovigilance database, 152 drugs are significantly associated with PRES. 4) The main categories are antineoplastic agents, immunomodulators, and antimicrobials. In particular, immunosuppressants (cyclosporine, tacrolimus), chemotherapeutic agents (cisplatin, bevacizumab), and antimicrobials (metronidazole, fluoroquinolones) are known as representative triggering drugs.
The diagnosis is established when clinical suspicion based on predisposing factors is combined with neuroimaging evidence of brain edema. Actively suspect PRES when symptoms suggestive of occipital or parietal lobe involvement (visual disturbances, seizures, altered consciousness) are present along with triggers. Diagnosis is made by brain MRI or CT, and it is useful to correlate visual field findings and associated neurological symptoms with neuroimaging.
The basis of treatment is rapid intervention through multidisciplinary collaboration (ophthalmologist, neurologist, internist, obstetrician, oncologist).
Removal of Triggers
Top priority: Prompt discontinuation of causative drugs or treatment of the underlying disease.
Drug-induced cases: In antimicrobial-associated PRES, 90% of patients achieve complete or near-complete recovery after drug discontinuation. 4)
Blood Pressure Management
Intravenous medications: Many patients require blood pressure control with intravenous drugs.
Goal: A 20–30% reduction in blood pressure within the first few hours after onset is recommended. 5)
Seizure Management
Antiepileptic drugs: Prevention and treatment are important because frequent seizures worsen cerebral edema.
Examples of medications: Sodium valproate, levetiracetam, lacosamide, etc. 1)2)3)8)
Additional Treatment
Removal of the trigger is the highest priority. The three mainstays of treatment are discontinuation of the causative drug, prompt blood pressure control (reduction of 20–30% in the first few hours), and seizure control with antiepileptic drugs. 5) If cerebral edema is severe, mannitol may be used to lower intracranial pressure. Visual symptoms often recover with appropriate treatment, but continued ophthalmologic follow-up is necessary to monitor visual symptoms.
The central mechanism is disruption of the blood-brain barrier (BBB) due to dysfunction of cerebral autoregulation and vascular endothelium. This leads to vasogenic cerebral edema.
Hyperperfusion theory
Mechanism: Hypertension → failure of cerebral autoregulation → capillary damage → hyperperfusion → vasogenic edema
Features: The posterior circulation has relatively less sympathetic innervation and is more susceptible to hyperperfusion. 3)4)
Endothelial dysfunction theory
Mechanism: Preeclampsia, chemotherapy, etc. directly toxic to endothelium → capillary leakage and BBB disruption → vasoconstriction → hypoperfusion → vasogenic edema
Features: Useful for explaining cases without hypertension (e.g., SLE, chemotherapy).
Ischemia theory
Mechanism: Cerebral ischemia → impaired autoregulation → reactive local vasoconstriction → local hypoperfusion → cytotoxic edema and cerebral infarction
Feature: Useful for explaining cases with cytotoxic edema showing reduced diffusion on DWI.
Vulnerability of the posterior circulation
The reason the occipital and parietal lobes are common sites is that the posterior circulation has relatively sparse sympathetic innervation and is more likely to reach the limits of autoregulation. 3)4)
Mechanism in COVID-19
SARS-CoV-2 binds to ACE2 receptors, reducing ACE2 expression and causing overactivation of the ACE/AngII/AT1 axis. This leads to increased vascular permeability, inflammation, and oxidative stress, resulting in endothelial dysfunction. 2) Furthermore, cytokine storm (IL-1, IL-6, TNF, IFN-γ, VEGF) causes massive release of vasoconstrictors such as thromboxane A2, leading to the development of PRES. 3)
Immune-mediated mechanism
Release of activated T cells and cytokines (histamine, free radicals, nitric oxide), as well as vasoconstrictors such as endothelin-1 and thromboxane A2, also contribute to brain edema formation. 6)
Mechanism in NMOSD-complicated cases
It has been suggested that AQP-4 IgG attacks astrocyte end-feet around cerebral blood vessels, causing damage to BBB components, which may lead to vasogenic edema appearing as PRES. 1)
Wang et al. (2024) reported a case of an 18-year-old female with no classical risk factors (hypertension, renal failure, immunosuppressive drugs) who developed posterior reversible encephalopathy syndrome (PRES) triggered solely by SARS-CoV-2 infection. 2) MRI abnormalities completely resolved 11 days after onset, and normal findings were maintained at 6-month follow-up. Only 28.6% of COVID-19-associated PRES cases had hypertension, suggesting that direct virus-induced endothelial damage is the main cause.
Motolesè et al. (2021) reviewed five cases of hemorrhagic PRES associated with COVID-19. 3) Coagulopathy, endothelial dysfunction, and antithrombotic therapy were identified as factors increasing the risk of hemorrhagic transformation. Prompt discontinuation and reversal of anticoagulation therapy are key to improving outcomes.
Yang et al. (2022) reviewed 14 cases of PRES coexisting with neuromyelitis optica spectrum disorder (NMOSD). 1) Involvement of AQP-4 IgG was suggested, and it has been proposed that PRES may be a special phenotype of NMOSD. Treatment strategies are not standardized, and it is necessary to decide on intensification or reduction of immunotherapy on a case-by-case basis.
In a systematic review of 12 cases by Barba et al. (2024), metronidazole and fluoroquinolones were the most common, each accounting for 33.3%. 4) After drug discontinuation, 90% recovered completely or nearly completely. Serum neurofilament light chain (NfL) is considered a promising biomarker for neurological damage in PRES.
In a review of 16 pediatric SLE cases by Luo et al. (2025), lupus nephritis, high disease activity, and hypertension were identified as major triggers. 6) Cases have been reported in which controlling SLE activity with new therapeutic agents such as telitacicept led to improvement of PRES.
Yang B, Guo L, Yang X, Yu N. The pathogenesis and treatment of posterior reversible encephalopathy syndrome after neuromyelitis optica spectrum disorder: a case report and literature review. BMC Neurology. 2022.
Wang L, Wang Z, Huang R, et al. SARS-CoV-2 may play a direct role in the pathogenesis of posterior reversible encephalopathy syndrome (PRES) associated with COVID-19. Medicine. 2024.
Motolese F, Ferrante M, Rossi M, et al. Posterior Reversible Encephalopathy Syndrome and brain haemorrhage as COVID-19 complication: a review of the available literature. J Neurol. 2021.
Barba L, Carrubba C, Spindler K, et al. Posterior reversible encephalopathy syndrome associated with antibiotic therapy: a case report and systematic review. Neurol Sci. 2024.
Patel SP, Jarbath M, Saravis L, et al. Pheochromocytoma manifesting as cortical blindness secondary to PRES with associated TMA: a case report and literature review. BMC Endocr Disord. 2022.
Luo M, He H, Zhou Q, et al. Juvenile systemic lupus erythematosus complicated with posterior reversible encephalopathy syndrome: a case report and literature review. Orphanet J Rare Dis. 2025.
Dai Y, Liu W, Hong F. Post reversible encephalopathy syndrome attributed to mycophenolate mofetil used in the treatment of SLE: A case report and review of literature. J Int Med Res. 2024.
Grandmougin D, Ehrlich T, Liu Y, et al. A presentation of posterior reversible encephalopathy syndrome after heart transplantation: a case report and review of literature. J Med Case Rep. 2025.
