Analysis of drug-induced posterior reversible encephalopathy syndrome using the food and drug administration adverse drug events reporting system database.

OBJECTIVE: In this retrospective pharmacovigilance study, we gathered data on drug-induced posterior reversible encephalopathy syndrome (PRES). Our goal was to identify the primary suspect drugs in PRES by analyzing the Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHODS: We identified and analyzed reports of PRES listed in the FAERS database between 2004 and 2021. Using the reporting odds ratio and 95% confidence interval, we evaluated the safety signals for each of the drugs associated with PRES. RESULTS: We reviewed 11,077 reports of adverse events corresponding to PRES. The primary suspect drug categories were antineoplastics, immunosuppressants, and glucocorticoids. PRES was 24.77% more likely to occur in females than in males. Drug-induced PRES usually occurs in individuals with cancer, those who have undergone an organ/stem cell transplant, and those with autoimmune conditions. CONCLUSION: Our results show that the drugs most commonly suspected to cause PRES were antineoplastics, immunosuppressants, and glucocorticoids. Future studies are needed to illuminate the pathophysiological alterations that underlie PRES. In the meantime, prescribers and patients should be made aware of the potential risks of PRES associated with pharmaceutical therapy, and the summaries of product characteristics for individual drugs should be updated to include this information.

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.

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.

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.

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma.

Anti-GD2 monoclonal antibodies (mAb) improve the prognosis of high-risk neuroblastoma (HR-NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second-line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti-GD2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long-term survival in this vulnerable age group. Thirty-three HR-NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized-3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb-related long-term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post-mAb treatments included chemotherapy, radiotherapy, and anti-NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse-free post-mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti-GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70-100 mg/m2 /cycle). HR-NB in infants proved to be highly curable.

[Posterior reversible encephalopathy syndrome during nilotinib treatment for chronic myeloid leukemia].

Here we present the case of a 50-year-old woman with chronic myeloid leukemia who received nilotinib as initial treatment. After about 2 years of nilotinib therapy, she developed headache, blurred vision, impaired consciousness, and marked hypertension. Posterior reversible encephalopathy syndrome (PRES) was diagnosed, and was strongly suspected to be a vascular adverse event caused by nilotinib. Nilotinib was withheld and the patient was treated with antihypertensive drugs under ventilator management. Her symptoms resolved quickly. The most likely cause of PRES is systemic arterial hypertension and endothelial dysfunction due to direct injury leading to dysfunction at the level of the blood-brain barrier, along with the resultant vasogenic edema. PRES has been reported with some tyrosine kinase inhibitors, but this is the first case of PRES during nilotinib 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.

PRES-like leukoencephalopathy presenting with status epilepticus associated with Brentuximab Vedotin treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by acute neurological symptoms with typical imaging features, primarily in the territories of the brain supplied by the posterior circulation, probably due to vasogenic edema. Both clinical and imaging features are generally reversible. We report a 13-year-old girl affected by Nodular Sclerosis Classical Hodgkin Lymphoma stage IIIB into complete remission, with a recurrence and autologous bone-marrow transplantation, who has been treated with an anti-CD30 monoclonal antibody, brentuximab-vedotin. The girl has suddenly presented a convulsive status epilepticus, that needed intubation and sedation. Therefore, an IV therapy with levetiracetam was started. Furthermore, the girl has presented high blood pressure and reduced kidney function. Brain MRI demonstrated a diffuse PRES-like disease, that went into regression after the first week. After another week, the girl presented a new prolonged generalized tonic clonic convulsive episode, that needed intubation and sedation and an association of clobazam and levetiracetam: a new brain MRI showed a recurrence of PRES-like lesions in addition to some signs of leukoencephalopathy with brain lactate accumulation on 1H-MRS, due to cerebral energetic failure. The girl also presented a refractory arterial hypertension. After 45 days of ICU hospitalization the patient has been discharged and followed up with neurological examinations. Brain MRI and brain 1H-MRS, 5 months after patient's discharge, showed incomplete regression of cerebral white matter signal abnormalities with MRS normalization.

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes.

Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.

Posterior reversible encephalopathy syndrome associated with use of Atezolizumab for the treatment of relapsed triple negative breast cancer.

Posterior reversible encephalopathy syndrome (PRES) is a complex neurological disorder with multiple clinical manifestations including headaches, seizures, and altered mental status. It is associated with many conditions including malignancy and medications including chemotherapy and immunotherapy. We report the case of a 56-year old female with a history of advanced triple negative breast cancer treated with atezolizumab (a PD-L1 inhibitor), paclitaxel and ipatasertib (investigational AKT inhibitor), who developed hypertension, confusion, and imaging findings consistent with PRES.

Eclampsia with RCVS: Postpartum seizure provoked by methergine.

BACKGROUND: Eclampsia is a pregnancy complicationcharacterized bygeneralized tonic-clonicconvulsions.Not all seizures in pregnancy are eclamptic, and othercauses include epilepsy, infection,stroke,tumor, and ruptured aneurysm. CASE: A 19-year-old G1P0 presentedinlabor at term. She had a generalized tonic-clonicseizure one hour aftervaginaldelivery for which she received methergine for uterine atony. Seizure activity resolved with lorazepam and magnesium sulfate for presumed eclampsia.Brain imaging revealedvasoconstriction of theleftposterior cerebral artery and blood in the subarachnoid space,andshewas diagnosed with eclampsia with reversible cerebral vasoconstrictive syndrome (RCVS). CONCLUSION: RCVS isapregnancy-related cause of seizure that should remain on the differential for any patient presenting with a seizure in the peripartum period, especially with use of vasoconstrictive agents. Management is controversial but involves calcium channel blockers and magnesium sulfate, as well as avoidance of vasoconstrictive agents.

Rare anti-VEGFR therapy-induced toxicity and long-term response to immunotherapy in a rare non-clear cell renal cell carcinoma patient.

Advanced non-clear cell renal cell carcinoma (nccRCC) has a poor prognosis and clinical data on the therapeutic options currently available, including immunotherapy, are generally limited highlighting an unmet clinical need. Moreover, the onset of rare adverse events raises the need of a better therapeutic management of limited treatment options. We report the clinical case of a 63-year-old man with the diagnosis of metastatic mucinous tubular and spindle cell carcinoma, a rare nccRCC, with sarcomatoid differentiation who developed two episodes of posterior reversible encephalopathy syndrome (PRES) to first-line sunitinib. It appeared after 5 months the start of the targeted therapy and reappeared at the reintroduction of the therapy. PRES is a rare and unusual adverse event to anti-vascular endothelial growth factor receptor (VEGFR) therapies, which is characterized by acute neurological disorders along with typical changes on neurological imaging, especially MRI. Moreover, this rare histotype of RCC experienced a long-term response to immunotherapy which is lasting more than 2 years. This clinical case is interesting for its rarity as a rare neurological adverse event developed twice in a rare type of RCC which also experienced an unusual long-term benefit to immunotherapy.

Posterior Reversible Encephalopathy Syndrome in the Setting of Asparaginase-associated Pancreatitis in 2 Pediatric Patients With Acute Leukemia.

Asparaginase, a critical component of current pediatric acute leukemia treatment protocols, is associated with a number of serious side effects, one of which is pancreatitis. Pancreatitis can result in significant morbidity and mortality from necrosis, pseudocyst formation, hemorrhage, systemic inflammation, intestinal perforation, and sepsis. Another rare complication of pancreatitis is posterior reversible encephalopathy syndrome, likely mediated by systemic inflammation secondary to pancreatic autodigestion and proinflammatory cytokine-mediated vascular endothelial damage. Here, we review this association in the literature and report 2 pediatric patients with leukemia who developed posterior reversible encephalopathy syndrome in the setting of asparaginase-associated pancreatitis.

The first two cases of posterior reversible encephalopathy syndrome (PRES) secondary to conventional transcatheter arterial chemoembolization of hepatocellular carcinoma.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a very rare complication secondary to transcatheter arterial chemoembolization (TACE). Only two patients with liver metastasis have been reported. We report for the first time two cases of hepatocellular carcinoma (HCC) patients occurred PRES secondary toTACE. CASE PRESENTATION: The two patients with HCC developed headache, epilepsy, expressive aphasia, visual impairment and loss of consciousness, 11 and 3 h after conventional TACE (c-TACE) surgery. One patient experienced raised blood pressure during and after TACE, accompanied by a significant elevated creatinine. The magnetic resonance imaging (MRI) of the two patients showed multiple abnormal signals in the brain, mainly located in the white matter region. Combined with the clinical symptoms and MRI findings, PRES was diagnosed. Their symptoms and MRI changes improved significantly in the next two weeks. CONCLUSION: The PRES in this report is chemoembolization-associated syndrome, which might be related to the use of chemotherapy agents during TACE. And if neurological symptoms occur after TACE, patients should be closely monitored to exclude PRES.

Posterior reversible encephalopathy syndrome in a patient with Richter's syndrome on combination DA-R-EPOCH chemotherapy regimen: a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic entity characterized by headaches, altered mental status, seizures, visual loss, and a characteristic imaging pattern in brain magnetic resonance images. The exact etiology and pathogenesis of this condition are not yet fully elucidated. CASE PRESENTATION: A 72-year-old White man presented with 2 weeks of low-grade fever and chills, night sweats, fatigue, dysphagia, and new-onset rapidly increasing cervical lymphadenopathy. He had a history of chronic lymphocytic leukemia with transformation to diffuse large B-cell lymphoma for which he was started on dose-adjusted rituximab, etoposide, prednisone vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Shortly after treatment initiation, the patient developed severe airway obstruction due to cervical lymphadenopathy that required emergency intubation. A few days later, the cervical lymphadenopathy and the status of the airway improved, and sedation was consequently weaned off to plan for extubation. However, the patient did not recover consciousness and developed generalized refractory seizures. Brain magnetic resonance imaging revealed edema in the cortical gray and subcortical white matter of the bilateral occipital and inferior temporal lobes, consistent with PRES. CONCLUSIONS: Posterior reversible encephalopathy syndrome refers to a neurological disorder and imaging entity characterized by subcortical vasogenic edema in patients who develop acute neurological signs and symptoms of a usually reversible nature in different settings, including chemotherapy. Despite its name, PRES is not always fully reversible, and permanent sequelae can persist in some patients. Clinicians should be aware of the possible association between chemotherapy and PRES to ensure early recognition and timely treatment.

Delayed Gemcitabine-Induced Posterior Reversible Encephalopathy Syndrome.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiographic syndrome that has been expanding rapidly in the world of clinical medical oncology and hematology. In this article, we provide a unique patient case of delayed gemcitabine-induced PRES. BRIEF CASE REPORT: A 60-year-old African American female with significant past medical history of ER+/PR+/HER2- invasive ductal carcinoma of the left breast is seen in the medical oncology clinic with vague, mild complaints of lightheadedness. She had progressed on multiple lines of chemotherapy and was ultimately switched to gemcitabine. One month after her third dose of gemcitabine, she developed acute vision loss and soon developed generalized tonic-clonic seizure. Extensive workup was unrevealing other than PRES and she slowly improved with supportive care and withdrawal of the medication. DISCUSSION: Multiple case reports have described PRES in the context of combination chemotherapy with gemcitabine and a platinum agent in the treatment of gastrointestinal malignancies. With growing evidence, this case is consistent with the hypothesis that gemcitabine as monotherapy has a direct association with PRES. This case highlights a unique aspect in that PRES can occur at a delayed time interval, much further than the expected hours to days after the previous treatment.

Uterine sarcoma with posterior reversible encephalopathy syndrome associated with pazopanib.

WHAT IS KNOWN AND OBJECTIVE: Our objective is to report on a case of posterior reversible encephalopathy syndrome associated with pazopanib. CASE DESCRIPTION: A 64-year-old patient with uterine sarcoma developed PRES 3 days after pazopanib was initiated. After the discontinuation of pazopanib, the symptoms of PRES improved. WHAT IS NEW AND CONCLUSION: The first report worldwide to describe a patient with uterine sarcoma experiencing PRES caused by pazopanib. Patients with uterine sarcoma may experience PRES, even in the early phase of pazopanib therapy.