Chemotherapy-associated hemorrhagic posterior reversible encephalopathy syndrome (PRES) with considerations for circle of Willis variants on cerebral blood flow and autoregulation: A case report.

RATIONALE: Hodgkin lymphoma, a lymphatic system cancer, is treated by chemotherapy, radiation therapy, and hematopoietic stem cell transplantation. Posterior reversible encephalopathy syndrome (PRES) is a rare neurotoxic effect associated with several drugs and systemic conditions. This case study emphasizes the potential risks of intensive chemotherapy regimens and postulates the impact of the circle of Willis variants on the heterogeneity of hemispheric lesions in PRES. PATIENT CONCERNS: A 42-year-old woman diagnosed with stage IIA nodular sclerosing Hodgkin lymphoma and chronic thrombocytopenia presented after 6 years of initial diagnosis and 4 years post-haploidentical transplant. She underwent planned chemotherapy with ifosfamide, carboplatin, and etoposide. DIAGNOSES: She developed an alteration in her mental status. A computerized tomography scan and angiogram of the head and neck revealed findings consistent with PRES and a left fetal-type posterior cerebral artery with an aplastic A1 segment of the left anterior cerebral artery. One hour later she was found comatose with clinical sequelae of an uncal herniation. INTERVENTIONS: Subsequent events led to emergent intubation, and administration of 23.4% hypertonic saline. A repeat computerized tomography scan showed a right intraparenchymal hemorrhage with fluid-fluid levels measuring up to 4.7 cm, bilateral subarachnoid hemorrhage, right uncal herniation, and 15 mm of leftward midline shift. She emergently underwent a right decompressive hemi-craniectomy. OUTCOMES: An magnetic resonance imaging of the brain demonstrated bilateral cytotoxic edema involving the parieto-occipital lobes. Despite interventions, the patient's neurological condition deteriorated, leading to a declaration of brain death on the 8th day. LESSONS: This case underscores the importance of recognizing the severe neurological complications, including PRES, associated with chemotherapeutic treatments in Hodgkin lymphoma. PRES may also be exacerbated by coagulopathies such as thrombocytopenia in this case. The circle of Willis variants may influence cerebral blood flow, autoregulation, and other factors of hemodynamics, leading to increased susceptibility to both radiographic lesion burden and the worst clinical outcomes.

Pediatric posterior reversible encephalopathy syndrome: Can MR imaging features predict outcomes in non-oncologic patients?

PURPOSE: Identify MR features predictive of poor outcomes in non-oncologic pediatric PRES. METHOD: A six-year search of all non-oncologic pediatric patients with clinical and MR features of PRES was performed. Modified Rankin scores were used to classify clinical outcomes into good versus poor, then clinical and MR features were compared among groups. Univariate and multivariate analysis was performed to identify MR predictors of poor outcomes for various imaging features, and p-values < 0.05 were considered statistically significant. RESULTS: One hundred and forty-one patients (mean age 10.1 ± 3.0 years, male to female ratio 1:1.1) were included. Clinically, nephrotic syndrome (p = 0.03), focal deficits (p = 0.04), longer hospitalization (p < 0.001), and mechanical ventilation (p < 0.001) were significantly associated with poor outcomes. Univariate analysis revealed that deep grey matter nuclei (OR = 5.29, 95 % CI: 1.6-18.0) and cerebellar edema patterns (OR = 3.49, 95 % CI: 1.3-9.5), cytotoxic edema (OR = 63.6, 95 % CI:16.5-244.2), hemorrhage (OR = 16.58, 95 % CI: 4.3-64.2), and severe PRES patterns (OR = 11.0, 95 % CI: 3.5-34.7) on MR were all significantly associated with poor outcomes (p-values = 0.008 and 0.014, <0.001, <0.001, and < 0.001, respectively). This remained true for cytotoxic edema (OR = 84.26, 95 % CI: 17.3-410.9, p-value < 0.001) and hemorrhage (OR = 44.56, 95 % CI: 6.9-289.7, p-value < 0.001) on multivariate analysis. CONCLUSION: Diffusion restriction and hemorrhage on initial MR scans were the two independent predictors of poor outcomes in non-oncologic pediatric patients.

Experimental Models of Posterior Reversible Encephalopathy Syndrome: A Review From Pathophysiology to Therapeutic Targets.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by nonspecific symptomatology (eg, headache, visual disturbances, encephalopathy, and seizures) and classically cortical and subcortical vasogenic edema predominantly affecting the parietooccipital region. PRES etiologies are usually dichotomized into toxic PRES (eg, antineoplastic drugs, illicit drugs) and clinical condition-associated PRES (eg, acute hypertension, dysimmune disorders). Although the pathophysiology of PRES remains elusive, 2 main pathogenic hypotheses have been suggested: cerebral hyperperfusion due to acute hypertension and cerebral hypoperfusion related to endothelial dysfunction. Research into the pathogenesis of PRES has emerged through the development of animal models in the last decade. The motivation for developing a suitable PRES model is 2-fold: to fill in knowledge gaps of the pathophysiological mechanisms involved, and to open new perspectives for clinical assessment of pharmacological targets to improve therapeutic management of PRES. All current models of PRES have a hypertensive background, on which other triggers (acute hypertension, inflammatory, drug toxicity) have been added to address specific facets of PRES (eg, seizures). The initial model consisted in inducing a reduced uterine perfusion pressure that mimics preeclampsia, a leading cause of PRES. More recently, a model of stroke-prone spontaneously hypertensive rats on high-salt diet, originally developed for hypertensive small vessel disease and vascular cognitive impairment, has been studied in PRES. This review aims to discuss, depending on the research objective, the benefits and limitations of current experimental approaches and thus to define the desirable characteristics for studying the pathophysiology of PRES and developing new therapies.

[Posterior reversible encephalopathy syndrome in children with hematological diseases]. / Sindrom zadnei obratimoi entsefalopatii u detei s zabolevaniyami sistemy krovi.

OBJECTIVE: To assess risk factors (RF) and severity grade of Posterior reversible encephalopathy syndrome (PRES) in children with hematological diseases. MATERIAL AND METHODS: We analyzed cases of PRES in children during chemotherapy (CT) and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We estimated the following RF: arterial hypertension, steroid therapy, CT, immunosuppressive therapy (IST), infection and renal injury. RESULTS: Thirty-five cases of PRES occurred in 32 patients (8 after allo-HSCT and 27 during CT) were included in this study. In the most of cases (94.3%), there were 2 and more RF. An increase in blood pressure level (88.6%), CT and IST (82.8%) administration, steroid therapy (71.4%) were the most significant for PRES development. Infectious process and the decline in renal function played a lesser role in this syndrome (31.4% and 14%). At the initial presentation of PRES, there were seizures (94.3%), a decrease of consciousness (28.6%), headache, vision disturbances and stomachache (20%). In the most of cases (91.4%), the 2nd and 3d grade according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) were observed. Brain magnetic resonance imaging (MRI) revealed the vasogenic edema of temporal (88.6%), occipital (74.3%), frontal (40%) lobes and the cerebellum (22.9%) more often than the cytotoxic edema (p=0.03). The cytotoxic edema was observed in the thalamus and the basal ganglia (2.9%) more often than in other parts of the brain (p<0.01). CONCLUSION: The majority of PRES cases are caused by more than two RF. Arterial hypertension does not have a leading role among its causes. There is a significant correlation between the grade of PRES according to CTCAE 5.0 score and RF number (p<0.05).

Capecitabine-induced posterior reversible encephalopathy syndrome (PRES) in a patient with gastric adenocarcinoma.

Posterior reversible encephalopathy syndrome (PRES) is characterised by encephalopathy, visual disturbances and seizures, accompanied by radiological parieto-occipital oedema. Immunosuppressive and immunomodulatory drugs are risk factors. While capecitabine-induced PRES cases are rare, this report details a young woman with advanced gastric adenocarcinoma on capecitabine. She exhibited symptoms of nausea, vomiting and abdominal pain before developing hypertension, drowsiness and a seizure. Brain MRI revealed parieto-occipital hyperintense areas indicative of PRES. Suspending capecitabine led to a gradually improved mental state. Prompt recognition and treatment of PRES offer reversibility, often achievable through dose reduction or discontinuation of the causative drug.

Golimumab-induced posterior reversible encephalopathy syndrome (PRES): a case-based review.

Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state which is characterized by seizures, headache, visual disturbances, paresis, and altered mental status. Golimumab is anti-tumor necrosis factor-α inhibitor (anti-TNF-α) that can be used in the treatment of rheumatologic diseases. Here, we present a patient who had developed PRES after golimumab treatment for ankylosing spondylitis (AS). A 45-year-old female patient was admitted to the emergency service with a newly onset severe headache, loss of vision in both eyes, and two generalized tonic-clonic seizures that lasted for 3 to 4 min. The patient had the diagnoses of AS for 12 years and hypertension for 3 years and receiving golimumab and carvedilol. The patient was diagnosed with PRES based on the current clinical and diffusion cranial magnetic resonance imaging (MRI) findings. On suspicion of being the trigger of this situation, golimumab was stopped. After starting anti-convulsant therapy and controlling blood pressure, the neurological findings recovered rapidly and no seizures were seen. Control MRI images, in the first month's visit, were normal. Although chemotherapeutic agents are well-known causes of PRES, there are few reported cases with anti-TNF-α agents in the literature. To our knowledge, this is the first case that developed PRES after golimumab. Demyelinating diseases are the most frightening neurologic complication of anti-TNF-α treatment; however, PRES should come to mind in patients presenting with neurological symptoms.

Pediatric posterior reversible encephalopathy syndrome: Age related clinico-radiological profile and neurologic outcomes.

BACKGROUND: The aim of this study was to analyze the characteristics of pediatric posterior reversible encephalopathy syndrome (PRES) to determine clinical and radiologic differences between younger and older age groups, and to identify risk factors for development of any neurologic sequelae. METHODS: The study cohort consisted of confirmed pediatric PRES patients in a tertiary care university hospital from January, 2015, to December, 2020. Demographic and clinical properties, radiological manifestations, and neurologic outcomes were noted. Children aged ≤6 years were compared with those older than 6 years and factors affecting neurologic outcomes were evaluated. RESULTS: The most common underlying diseases were oncological (37%) and kidney diseases (29%). Epileptic seizures were the most frequent symptoms at initial clinical presentation. The regions in the brain that were most commonly involved were the occipital region (n = 65, 96%), the parietal region (n = 52, 77%), and the frontal lobe (n = 35, 54%). Magnetic resonance imaging (MRI) findings were consistent with atypical patterns in most of the study cohort (71%). Patients with unfavorable clinical outcomes (n = 13, 19.1%) had longer initial seizure times and longer encephalopathy times, lower leucocyte and absolute neutrophil counts, and lower neutrophil to lymphocyte ratios. No relationship was found between MRI findings, involvement patterns, and neurologic outcomes. CONCLUSIONS: No clinically specific differences between two different age groups were found. Atypical imaging manifestations of pediatric PRES in our study had an incidence that was as high as those found in earlier adult studies. Multivariate logistic regression analysis showed that the initial neutrophil to lymphocyte ratio, absolute neutrophil counts, and white cell counts could not predict poor neurologic outcomes.

Posterior Reversible Leucoencephalopathy Syndrome: Case Series, Comments, and Diagnostic Dilemma.

PURPOSE OF REVIEW: To report a series of patients with clinical and radiological features suggestive of posterior reversible encephalopathy syndrome (PRES) related to diverse etiologies emphasizing its pathophysiological basis. RECENT FINDINGS: Posterior reversible encephalopathy syndrome (PRES) may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury induced by ischemia from a vasoconstrictive response to rising blood pressure or toxins/cytokines. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. Diagnosis of PRES in some circumstances can be challenging and structural imaging may not be sufficient to distinguish it from other differential diagnostic considerations like ADEM. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Such techniques are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease. Eight patients with PRES resulting from different etiologies varying from pre-eclampsia/eclampsia, post-partum headache with seizures, neuropsychiatric systemic lupus erythematosus, snake bite, Dengue fever with encephalopathy, alcoholic liver cirrhosis with hepatic encephalopathy, and lastly reversible cerebral vasoconstriction syndrome (RCVS). Additionally, a diagnostic dilemma between PRES and acute disseminated encephalomyelitis (ADEM) was notable in one patient. Some of these patients did not have or only very transiently had arterial hypertension. PRES may underlie the clinical conundrum of headache, confusion, altered sensorium, seizures, and visual impairment. PRES need not necessarily be always associated with high blood pressure. Imaging findings may also be variable. Both clinicians and radiologists need to familiarize themselves with such variabilities.

Posterior reversible encephalopathy syndrome triggered by FLOT (5-fluorouracil, oxaliplatin, docetaxel, and calcium levofolinate) chemotherapy and thrombocytopenia (docetaxel and cisplatin) chemotherapy.

INTRODUCTION: Posterior reversible encephalopathy syndrome is a clinical and imaging syndrome characterized by endothelial dysfunction, blood-brain barrier disruption, and vasogenic edema. The common clinical symptoms of posterior reversible encephalopathy syndrome include headache, altered consciousness, visual disturbances, and seizures, among which headache and seizures are the most common. The classic imaging patterns usually reveal vasogenic edema. CASE REPORT: We describe the case of a middle-aged woman with gastric cancer. She was under treatment by fluorouracil, leucovorin, oxaliplatin, and docetaxel regimen and thrombocytopenia regimen after tumor progression, but developed unconsciousness, irritability, and headache shortly after initiation of treatment. Her magnetic resonance imaging in our hospital shows abnormal signals in bilateral frontal parietal occipital lobes with hyperintensities on T2-weighted magnetic resonance imaging and fluid-attenuated inversion recovery imaging, accompanied by the increased value of apparent diffusion coefficient. And T1-weighted images illustrate hypointense foci, with increased diffusion-weighted imaging signals. MANAGEMENT AND OUTCOME: After admission, she was treated to control blood pressure, reduce brain edema, expand blood vessels, improve consciousness, and symptomatic support treatment. 3 days after the onset of the disease, her headache symptoms and state of consciousness gradually improved, and her blood pressure can be controlled at about 130/80 mmHg. DISCUSSION: This is the first report that posterior reversible encephalopathy syndrome is caused by a thrombocytopenia regimen, and our case highlights the pathogenic role of a thrombocytopenia regimen in posterior reversible encephalopathy syndrome. However, the association between the thrombocytopenia regimen and previous fluorouracil, leucovorin, oxaliplatin, and docetaxel regimens needs further study.

Posterior reversible encephalopathy syndrome following cervical spine surgery: insights from an interesting case.

A 14-month child presenting with complaints of spastic paraplegia was diagnosed with C6-D1 intramedullary cyst. A cysto-subarachnoid shunt was performed; the patient was clinically stable in the immediate post-operative period. On post-operative day 2, the patient developed multiple episodes of generalized tonic-clonic seizures (GTCS) with altered sensorium, NCCT head revealed bilateral diffuse parieto-occipital hypodensities. MRI brain showed on T2WI and FLAIR, diffuse hyperintensities in bilateral parieto-occipital region suggestive of posterior reversible encephalopathy syndrome (PRES). The patient never experienced hypertensive episodes and was treated with anti-epileptics. The patient's symptoms improved and repeat MRI after 10 weeks revealed normal signal intensity in bilateral parieto-occipital areas. PRES after spinal surgeries is very rare and more so in pediatric cases, CSF hypotension may contribute to PRES in such cases.

Pontine lesion in hyperglycemic crises: Relevance to osmotic demyelination syndrome and posterior reversible encephalopathy syndrome.

We herein describe a case of type 1 diabetes that presented with a pontine lesion during two hyperglycemic crises accompanied by marked fluctuations in serum osmotic pressure and blood pressure. Magnetic resonance imaging showed swollen pons with osmotic demyelination syndrome characteristics accompanying cytotoxic edema at the first crisis. The involvement of vasogenic edema was also assumed in the second crisis. Neurological symptoms were milder than magnetic resonance imaging findings. The patient recovered after 7 days without sequelae in both crises. Based on these findings, a pontine lesion needs to be considered in patients with poorly controlled diabetes showing rapid metabolic and blood pressure changes, as observed in hyperglycemic crises. Cytotoxic edema leading to osmotic demyelination syndrome and vasogenic edema caused by vascular endothelial cell damage might both be involved in the pathogenesis of a pontine lesion.

Is decompressive craniectomy necessary in malignant posterior reversible encephalopathy syndrome with brain edema caused uncal herniation? A case report of reversible coma without surgical decompression.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is considered a benign entity and is usually reversible with only medical management, but persistent neurologic deficits and disability or death can occur without adequate treatment. Favorable outcomes have been associated with surgical decompression in malignant-type PRES in which hemorrhagic transformation or brain stem compression has developed. CASE DESCRIPTION: Here we report a case of malignant PRES in a 61-year-old female of Asian descent in which the disease rapidly progressed to coma and a near-fatal condition with uncal herniation caused by severe brain edema; however, this patient achieved a dramatic recovery without surgical decompression. CONCLUSION: After reviewing previous reports regarding malignant PRES, we propose that hemorrhagic transformation is a crucial indicator for surgical decompression and an important prognostic factor in malignant PRES.

Clinical features and outcomes of children admitted to the pediatric intensive care unit due to posterior reversible encephalopathy syndrome.

OBJECTIVE: The aim of this study is to analyze the clinical features, neuroimaging findings and outcomes of the children admitted to our tertiary pediatric intensive care unit (PICU) due to posterior reversible encephalopathy syndrome (PRES). METHODS: This was a retrospective study where the hospital records of children admitted to PICU due to PRES between January 1, 2011 and January 1, 2021 were reviewed. RESULTS: We enrolled 14 patients with a median age of 8 years (IQR 2.2-14.2) to study. Eight (57 %) patients were male. All patients had comorbid illnesses such as hemophagocytic lymphohistiocytosis in 3, Β-cell acute lymphoblastic leukemia in 2, and different diagnosis in other patients as one one. Three patients had cardiac arrest, 9 patients had seizures, 5 patients had SE, 12 patients had altered mental status, 8 patients had hypertensive crisis, 1 patient had visual impairment. Thirteen patients had occipital involvement, 11 had parietal involvement, 4 had temporal involvement, 1 had thalamic involvement, 2 had cerebellar involvement, 1 had involvement of the corpus callosum, 1 had brainstem involvement, 1 had hippocampus involvement and 1 had involvement of the basal ganglia. Fourteen patients had supratentorial involvement while 3 had infratentorial involvement. Electroencephalogram was performed for 7 patients, out of which 6 revealed encephalopathy. Median PICU LOS was 19.5 days (IQR 13.2-49.2, minimum 2 - maximum 84 days). Five patients had neurologic sequelae. Four (28.5 %) patients died and ten patients survived. CONCLUSION: Co-occurence of hypertension and seizures should prompt consideration of PRES and urgent neuroimaging, particularly in patients on immunosuppressants or chemotherapeutics. Hypertension should be addressed aggressively in patients with PRES. Electroencephalographic monitoring should be performed if there is suspicion of SE or nonconvulsive SE. Despite its usually good prognosis, PRES can cause serious morbidity and mortality with delay in diagnosis or treatment.

Mepolizumab-Induced Posterior Reversible Encephalopathy Syndrome (PRES), a new patient report.

BACKGROUND: Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic state characterized by seizures, headache, vision change, paresis, and altered mental status. PRES has an important place in medicine due to the wide variety of causative diseases, infections, and medications that precipitate its mysterious onset. Although exposure to medications, particularly immunosuppressants, cancer chemotherapy, and biologic drugs, is a common occurrence in patients who develop PRES, Mepolizumab has never before been associated. CASE PRESENTATION: This report of a 67-year-old male patient outlines the first reported case of Mepolizumab-induced PRES in the literature. CONCLUSIONS: Treatment of severe asthma, asthma-exacerbations, and diseases such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss) with Mepolizumab is rapidly gaining popularity ever since the drug's recent FDA-approval. This report aims to raise awareness of this potentially life-threatening and previously unreported side effect of Mepolizumab since early identification of the causative agent is the key to preventing the severe neurologic disability and possible death that may occur from the delayed treatment of PRES.

Posterior reversible encephalopathy syndrome after first rituximab transfusion for treatment of granulomatosis with polyangiitis.

A woman in her 60s developed acute onset headache, blurry vision and encephalopathy a few hours after rituximab infusion, given to treat granulomatosis with polyangiitis. CT scan showed oedema in the posterior circulation area suggesting the diagnosis of posterior reversible encephalopathy syndrome, and an MRI confirmed it. After being treated with aggressive blood pressure control and other supportive measures, her symptoms improved over 3-4 days. This case highlights the need for awareness and early recognition of this rare but serious adverse effect of rituximab. CT scan can be helpful in diagnosis (also to rule out bleeding), but the MRI provides the most accurate diagnosis.