Beyond the Classic Pattern: Radiologic Insights into the Diverse Presentations of PRES

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome with numerous etiologies, mostly characterized by magnetic resonance imaging (MRI) abnormalities in the posterior cerebral white and gray matter and acute neurological symptoms. To examine the predisposing factors, clinical results, and radiological features of PRES in children diagnosed with malignancy. The study included 20 patients (7 F/13 M) aged 4-16 years at the time of diagnosis who were diagnosed with malignancy and developed PRES during chemotherapy. All the patients were diagnosed as having PRES both clinically and radiographically during chemotherapy. The time from the initiation of the chemotherapy to the onset of PRES ranged from 7-675 days. Hypertension was detected in nine patients, seizure was the most common presenting symptom - had involvement in the occipital and parietal lobes on MRI (n=14)/followed by headache (n=8)/altered consciousness (n=5)/visual impairment (n=4). Hydrocephalus and tentorial herniation were observed in one patient. Most of the lesions on MRI resolved within 10-33 days and the EEG findings within 9 months. Clinical symptoms of PRES also disappeared completely the 5-year Press frequency was found to be 2.48%. PRES may complicate the oncological treatment in children. Hypertension is a leading risk factor for PRES, while it should be kept in mind that the blood pressure may be normal in chemotherapy-induced PRES cases. PRES should be included in the differential diagnosis of all patients receiving chemotherapy and presenting with acute neurological symptoms.

Quiz Page September 2011: A Patient With Postpartum Hypertension and Seizure

Dear Sir, We welcome the comments made by Dr. Donmez regarding etiologic factors in the development of posterior reversible encephalopathy syndrome (PRES), in particular the potential contribution of Epstein barr virus (EBV) infection. A large number of disorders have been described in association with PRES in the pediatric population including solid organ and bone marrow transplantation, renal dysfunction, autoimmunity, sepsis, and chemotherapy with hypertension being observed in up to 88 % of children at symptoms onset [1]. As Dr. Donmez points out, additional underlying factors may incite or potentiate the development of PRES such as viral infection or medication effects. Such factors, in addition to hypertension, vary from case to case but are known to be present in most PRES cases in adults and children [1, 2]. Whether hypertension directly contributes to the development of PRES or is instead a downstream effect of an underlying systemic toxicity that affects both the cerebral vasculature (manifesting characteristic MRI and MRA findings) and the renal vasculature (resulting in hypertension) is unclear. In our case, the patient did have a brief period of hypertension which may or may not have contributed to the development of PRES [3]. Taking a step back, it seems plausible that this patient’s hypertension could be attributed to GuillainBarre syndrome (GBS) through altered autonomic regulation of the sympathetic nervous system [4, 5]. Such amechanism is supported by the extensive involvement of upper cervical nerve roots observed in this case and their contribution to the cervical ganglia [3]. Further, this patient had no prior history of hypertension nor has he experienced hypertension following the resolution of the GBS/ PRES episode. The presence of viral markers of EBV may explain the development of GBS; however, we posit that any specific correlation between Epstein Barr viremia and the development of PRES in our case is less robust than our proposed correlation between GBS and PRES. Although PRES is well known to occur in the setting of infection including viral illness [6], sepsis represents the most common scenario in which the development of PRES has been attributed to an infectious etiology [2]. Thus, it is our opinion that among the potential contributing factors in the cascade leading to PRES in this individual, GBS remains at the forefront. In this regard, we have recently observed a statistically significant correlation between systolic blood pressure at symptoms onset and normalized ADC values in 25 children with PRES further supporting the association between vasogenic edema and hypertension [1]. Attempts to isolate a single etiologic factor in PRES development have failed given that PRES is likely a multi-factorial entity. A better understanding of PRES pathophysiology may be likely gained by viewing PRES as a downstream result of a cascade of events which may alter the blood brain barrier homeostasis [7]. * Giulio Zuccoli giulio.zuccoli@gmail.com

Rituximab‐associated posterior reversible encephalopathy syndrome

Dear Editor, Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic syndrome characterized by predominant parietal and occipital lobe edema that is mainly reversible within a few days.1,2 However, many atypical patterns have been identified.3 Reversibility is not always achieved,3 which exposes a contradiction in this supposedly benign entity. We report the case of a 14-year-old patient who presented with classical signs of PRES, but whose condition evolved into a malignant phenotype. A 14-year-old patient received a renal transplant from a cadaveric donor and took tacrolimus, corticosteroids, and antithymocyte immunoglobulin. On the third day, his renal function had not improved and hemodialysis was started. He then immediately developed headache, vomiting, and experienced a tonic-clonic seizure. His blood pressure (BP) peaked at 240/150 mm Hg. Brain CT revealed bilateral edema in the parieto-occipital regions associated with a small hemorrhagic transformation, representing PRES (Fig. 1A, B, and C). Laboratory tests revealed thrombocytopenia (66,000/µL) and elevated serum creatinine (2.52 mg/dL). Tacrolimus was suspended and sodium nitroprusside was administered, which fully controlled his hypertension. Fig. 1 Brain CT in the first presentation. A: Subcortical edema extends to the parietal and frontal region. B and C: Bilateral occipital edema is demonstrated, with minor hemorrhagic transformation, suggesting posterior reversible encephalopathy syndrome. D, ... On the following day his BP was 147/90 mm Hg but his neurological function had deteriorated. Follow-up brain CT revealed extensive cortical and white-matter edema associated with parenchymatous, subarachnoid, and intraventricular hemorrhage (Fig. 1D, E, and F). Brain death was later confirmed, leading to the suspension of life support. PRES pathophysiology remains a mystery even after almost 20 years since its initial description.1 There are two prevailing hypotheses: cytotoxic and vasogenic.4,5 Eclampsia, renal failure, autoimmune diseases, and chemotherapy treatment and other factors may trigger PRES.1,5 Despite its classically favorable outcome, PRES is associated with direct mortality in 5-15% of cases.6,7 Important prognostic factors within PRES have been suggested, such as the anatomical distribution of edema, hemorrhage, and cytotoxic edema in diffusion-weighted imaging sequences, but they have yet to be proven.7,8 Alhilali et al.7 further analyzed the prognostic factors in PRES and found that hemorrhage, even if minor, is the most relevant factor associated with a poor outcome, which may indicate more extensive endothelial dysfunction. Hefzy et al.6 found that hemorrhagic transformation occurred in 17% of PRES cases, mainly small or petechial hemorrhages (<5 mm) and hematomas, but also subarachnoid and intraventricular bleeding. The rates found in other studies have varied from 6.4% to 19.4%, with mortality reaching 26-29% in this group.6,7 The precipitating illness is usually severe, and PRES may be only a marker of such severity, but novel reports unveil the malignant evolution of this condition.7,8 Although many terms have been used to describe this event,7 malignant PRES seems to best encompass the permanent neurological damage or even death that sometimes accompanies this endothelial breakdown in the brain. The optimal management of PRES has yet to be elucidated.8 Better outcomes in malignant PRES have been attributed to aggressive neurointensive care, decompressive craniectomy, and intracranial pressure management.8 These results are promising, but larger studies are needed to confirm the efficacy of this approach. PRES is usually a benign entity; however, it represents a small outlier in the clinical spectrum of this syndrome. A wider range of neurological disabilities encompasses this syndrome and leads to a malignant evolution, suggesting that a good prognosis cannot be assumed with PRES, but rather its occurrence should prompt immediate action to avoid disability.

Management Strategies for Posterior Reversible Encephalopathy Syndrome (PRES) in Patients Receiving Calcineurin-Inhibitor or Sirolimus Therapy for Hematologic Disorders and Allogeneic Transplantation

Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neurologic condition characterised by specific clinical and radiologic findings. It usually manifests subacutely as insidious onset of headache, visual disturbance, altered consciousness and seizures in association with MRI findings of posterior white matter vasogenic oedema. RPLS has been reported in a wide variety of clinical settings. Hypertension, eclampsia, pre-eclampsia, renal impairment, autoimmune conditions and cytotoxic drugs are all cited as aetiologic variables. RPLS, albeit rare, is an important entity for physicians to be aware of as early recognition, and prompt intervention is critical to ensure resolution of the neurological deficit. We describe the case of a 69-year-old lady who collapsed with seizure activity after receiving carboplatin and etoposide chemotherapy for small cell lung cancer. In our opinion, the clinical and radiological courses are typical of RPLS. RPLS has rarely been reported secondary to this chemotherapy regimen, and the purpose of this report is to add to the literature and highlight the association between RPLS and cytotoxic chemotherapy.

The diagnosis of posterior reversible encephalopathy syndrome

The diagnosis of posterior reversible encephalopathy syndrome

Preeclampsia and Cerebrovascular Disease.

Reversible posterior leukoencephalopathy syndrome (PRES) is a relatively uniform clinical and neuroradiologic manifestation of central nervous system toxicity. The clinical features are headache, altered mental status, and visual disturbances. PRES is often associated with arterial hypertension but it is most usually related to drug toxicity. In fact, it has been related to immunosupressants, cytotoxic, and new antineoplastic-targeted therapies such as sorafenib, sunitinib, bevacizumab, bortezomib, rituximab, and etanercept. We describe a most unusual case of nonconvulsive status epilepticus related to PRES induced by cetuximab in a patient with metastatic squamous cell carcinoma of the penis. This case emphasizes that in any patient receiving treatment with anti-epidermal growth factor receptor agents and showing a compatible clinical syndrome, PRES should be suspected. We also review the clinical and neuroradiologic features of PRES, discuss its' pathogenesis, and highlight the importance of rapid recognition and withdrawal of the causative agent.

The aim of our study is to determine the clinical predictors and the differential diagnosis of posterior reversible encephalopathy syndrome (PRES) in patients presenting with acute neurological symptoms and risk factors for PRES. Using the diagnostic algorithm for PRES from Fugate and Rabinstein (Lancet Neurol 14(9):914–925, 1), we carried out a retrospective study on 220 patients, presenting with acute neurological symptoms such as seizures, encephalopathy, headache, visual disturbances or other focal neurological signs that appear in the clinical setting of risk factors such as hypertension/blood pressure fluctuations, chemotherapy, renal failure, autoimmune disorders, or eclampsia, in whom imaging of the brain was performed to exclude PRES. Seventeen percent of patients had a radiologically confirmed diagnosis of PRES. Univariable logistic regression showed a significant association between PRES and epileptic seizures, encephalopathy, hypertension, chemotherapy and renal failure. Multivariable logistic regression of acute neurological symptoms and risk factors showed a significant association of epileptic seizures, encephalopathy, visual disturbances, hypertension and chemotherapy with PRES. Using these variables to predict PRES yielded a discriminative ability (AUC) equal to 0.793. Diagnoses when PRES was not confirmed included primary or secondary headaches (26%), toxic-metabolic encephalopathy (21%), vascular pathology (12%) and other less frequent disorders. Epileptic seizures, encephalopathy, visual disturbances, hypertension, renal failure and chemotherapy were the best clinical predictors of PRES, while headache, immune suppression and autoimmune disease were not useful for the clinical diagnosis of PRES in our study.

Posterior reversible encephalopathy syndrome (PRES) is an acute neurological condition characterized by a spectrum of clinical and radiological features. It is most often associated with severe hypertension, renal dysfunction, autoimmune disease, sepsis, and exposure to cytotoxic or immunosuppressive agents. Although increasingly recognized in emergency and critical care practice, its pathophysiology remains incompletely understood and diagnostic challenges frequently delay treatment. Reported mortality ranges from 10 to 19%, and up to 40–44% of patients experience persistent neurological deficits or residual radiologic lesions, highlighting its clinical relevance. The clinical manifestations of PRES range from seizures, headache, and visual disturbance to confusion and reduced consciousness. Seizures occur in as many as 60–90% of cases, particularly in younger populations. Magnetic resonance imaging is the diagnostic modality of choice, revealing characteristic vasogenic edema, most prominently in the posterior cerebral regions, although atypical patterns are frequently observed. Misdiagnosis remains common due to overlap with stroke, encephalitis, and other acute neurological syndromes. Management is primarily supportive and directed at controlling the underlying precipitant. Blood pressure stabilization, withdrawal or adjustment of offending agents, and short-term antiseizure therapy form the cornerstone of treatment. Although most patients show clinical and radiologic recovery within weeks, complications such as intracranial hemorrhage, infarction, or recurrent PRES may occur. Special populations including pediatric, obstetric, and transplant patients require tailored evaluation and management strategies due to distinct risk profiles. Emerging research highlights endothelial dysfunction, blood–brain barrier disruption, and immune-mediated injury as central mechanisms. Investigations into biomarkers, advanced neuroimaging techniques, and targeted therapeutic approaches are opening opportunities for earlier detection and improved outcomes. PRES is reversible in many cases yet remains a potentially life-threatening syndrome with substantial morbidity and mortality. Early recognition, systematic neuroimaging, and rapid correction of precipitating factors are essential to optimizing outcomes. Future advances will depend on deeper mechanistic insight, validation of prognostic biomarkers, and development of standardized, evidence-based management protocols to guide care across diverse patient populations.

Posterior reversible encephalopathy syndrome (PRES) refers to a clinicoradiological entity with characteristic features on neuroimaging and nonspecific symptoms comprising headache, confusion, visual disturbances, and seizures. This syndrome may occur in diverse situations, including the taking of cytotoxic and immunosuppressive drugs, hypertensive encephalopathy, and eclampsia. The lesions in PRES are thought to be due to vasogenic edema that occurs predominantly in the posterior cerebral hemispheres, and are reversible with appropriate management. We present herein the case of a female with sickle cell (SC) disease who presented with this syndrome without any of the common risk factors. A 57-year-old woman presented to the emergency room with confusion and behavioral changes of sudden onset. Her medical history included a SC disease and supraventricular tachycardia for which she was being treated with flecainide, atenolol, and aspirine. On the day before admission, the patient presented with a SC vaso-occlusive crisis with diffuse pain in both lower limbs. The examination upon admission revealed confusion, temporo-spatial disorientation, behavioral disorders, dysarthria, phasic disorders, a discrete right motor deficit, and psycho-motor slowing. She complained of leg pain, her blood pressure was 139/89 mm Hg, and there was no fever. Laboratory tests revealed normal renal function and serum electrolytes, but impaired liver function. Her hemoglobin and platelet count were 8.8 g/dL and 74,000/mm3, respectively, and her white blood cell count was elevated at 11,000/mm3. Lumbar puncture findings were normal; blood, urine cultures, and serology tests (HIV, human T-lymphotropic virus, syphilis, herpes, hepatitis C, leptospirosis, Lyme) produced negative results, hepatitis B, cytomegalovirus and Epstein-Barr virus serologies were in favor past healed infections. Brain MRI revealed multiple bithalamic, biparietal, bitemporal, bifrontal, and cerebellar subcortical high signal intensity lesions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted sequences (Fig. 1A). Apparent diffusion coefficient mapping revealed a high signal indicative of the presence of vasogenic edema. Control MRI performed after 15 days revealed complete resolution of the bithalamic lesions and all other lesions (Fig. 1B). The patient's clinical status also normalized spontaneously. Fig. 1 A: Brain axial fluid-attenuated inversion recovery MRI-sequence showing bithalamic, biparietal, and bifrontal hyperintense signals. B: MRI control performed 15 days later, showing disappearance of the presenting radiological features. The case described herein is thus far unique in that while lesions in PRES usually involve mainly the parieto-occipital lobes, in this case the lesions also involved both thalami, the cerebellum, and the temporal and frontal lobes. The diagnosis of PRES was confirmed by the radiological features disappearing at follow-up MRI performed 15 days later. The originality of this case also lies in the very rare cases of PRES described in SC patients being associated with severe acute chest syndrome, uncontrolled hypertension, renal failure, or pulmonary infection,1,2,3 which was not the case in the present patient. In those previously described cases, PRES was attributed to abrupt elevation of blood pressure, or blood volume. It is possible that our patient presented with relative hypertension, since SC patients generally have a lower blood pressure than non-SC controls. Reversible posterior leukoencephalopathy syndrome (RPLS) was described by Hinchey et al.4 in patients with hypertension, eclampsia, renal failure, or with immunosuppressor treatments. The syndrome includes headache, transient neurological symptoms, visual changes, seizures, or altered consciousness, with MRI revealing subcortical edema in the posterior regions of the cerebral hemispheres without infarction; these clinical and radiological findings are reversible with control of blood pressure or withdrawal of immunosuppressive therapy. Since the gray matter can also be involved, the term RPLS has been replaced by PRES. The pathophysiology of PRES remains a matter of debate. One hypothesis is that severe hypertension in these patients causes impaired cerebrovascular autoregulation, vasodilatation, and vasogenic edema, while another is that toxicity of immunosuppressive drugs (e.g., tacrolimus or cyclosporine) leads to impaired endothelial homeostasis. However, PRES appears ultimately to be related to endothelial dysfunction that leads to cerebro-vascular autoregulation impairment and vasogenic edema.2 Since endothelial dysfunction is thought to play part in the cerebrovascular disease observed in SC anemia, SC patients may have an increased risk of developing PRES.2 In addition to more classical neurological complications of SC disease, such as ischemic strokes, silent cerebral infarcts, intracerebral hemorrhages or seizures, PRES may also be evoked in patients presenting with acute neurological changes, even in the absence of risk factors, as in our case.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition characterised by acute neurological symptoms and typical magnetic resonance imaging findings. It is commonly associated with hypertension, renal dysfunction, autoimmune conditions, and exposure to certain systemic anti-cancer therapy (SACT) agents. Although PRES has been reported with several chemotherapeutic drugs, its occurrence shortly after the first dose of single-agent weekly paclitaxel is exceptionally rare and not well-documented. We report the case of a 61-year-old female with metastatic breast cancer who developed acute confusion, focal seizures, and a reduced Glasgow Coma Scale (GCS) shortly after receiving her first dose of weekly paclitaxel (80 mg/m²) for visceral crisis. Prior to chemotherapy, she had no history of hypertension, neurological disease, or chronic kidney disease. Following paclitaxel administration, she developed transient hypertension and rapid neurological deterioration. The CT scan was normal. MRI confirmed findings consistent with PRES, showing bilateral parieto-occipital cortical-subcortical signal changes. Paclitaxel was withheld, and she was medically managed (antihypertensive, antiepileptic treatment, and corticosteroids), leading to gradual recovery. This case highlights PRES as a rare but serious potential complication of single-agent paclitaxel therapy. Clinicians should maintain a high index of suspicion for PRES in patients presenting with new-onset neurological symptoms following chemotherapy, as early recognition and prompt management are essential for a favourable outcome.