Posterior Reversible Encephalopathy Syndrome In Patient Research Articles

Posterior reversible encephalopathy syndrome post stem cell transplantation in sickle cell disease: case series and literature review.

Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression. This is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances. During ten years follow-up (2011-2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions (p = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence (p = 0.006), size (p = 0.016) and number (p = 0.005) of CMBs. PRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.

Risk factors of posterior reversible encephalopathy syndrome in patients with preeclampsia or eclampsia: A retrospective review.

<p>Posterior reversible encephalopathy syndrome (PRES) is characterized by vasogenic edema, usually reversible, with the prominent involvement of the parietal and occipital lobes. The exact etiopathogenesis leading to PRES is unknown. Because signs of eclampsia and preeclampsia in neuroimaging often overlap and manifest as PRES, we aimed to evaluate whether demographic, clinical, and laboratory parameters predict PRES in patients with preeclampsia or eclampsia.<br><br></p>. <p>213 pre-eclampsia or eclampsia patients with cranial imaging were retrospectively examined. We recorded the patients&rsquo; demographic information, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), hemogram, biochemical indicators, clinical symptoms, and imaging features.</p>. <p>Of all patients, 69% (n = 147) had preeclampsia while 31% (n = 66) had eclampsia, and 24.4% (n = 53) were diagnosed with PRES. The mean age of patients who developed PRES was 25.81 &plusmn; 6.07 years and thus significantly less than that of patients who did not develop PRES (p = .000). Patients with PRES had significantly higher mean SBP (p = .015), DBP (p = .009), and MAP (p = .003) than patients without PRES, along with significantly higher aspartate aminotransferase (ASAT; p = .001), alanine aminotransferase (ALAT; p = .001) blood urea nitrogen (BUN; p = .001), white blood cell (WBC; p = .003), neutrophil (p = .001), and hemoglobin (Hb; p = .027) levels, but significantly lower albumin (p = .000) levels.</p>. <p>Age, high blood pressure, and BUN, neutrophil, and WBC levels were predictors of the development of PRES in patients with preeclampsia and eclampsia. Early neuroimaging considering those predictors should be performed to diagnose PRES in patients with preeclampsia and eclampsia.</p>.

Predictors of Posterior Reversible Encephalopathy Syndrome (PRES) in Women With Pre-eclampsia/Eclampsia: A Retrospective Analysis.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological entity characterized by acute neurological symptoms with reversible subcortical vasogenic brain edema. One of the most common risk factors is pre-eclampsia/eclampsia. This study aimed to compare the clinical and radiological characteristics of PRES with those without PRES in patients with pre-eclampsia/eclampsia and attempts to find independent predictors of PRES. This was a single-center, retrospective study. Fifty-three female patients admitted to the Department of Obstetrics & Gynaecology, AIIMS Rishikesh between 2018 and 2021 with severe pre-eclampsia/eclampsia were included. Brain imaging was done to confirm the diagnosis of PRES. Baseline characteristics between patients whose imaging was suggestive and not suggestive of PRES were compared. Fifty-three patients with pre-eclampsia/eclampsia were included in the analysis. The median age and period of gestation of the study population were 28 (range 19-37) years and 36.6 (range 24.2-41.5) weeks respectively. Twelve patients (22.6%) had eclampsia, and 41 (87.4%) had pre-eclampsia of which 28 (52.8%) had severe pre-eclampsia. Twelve patients were diagnosed with PRES. Patients with PRES were significantly younger with a median age of 23 [range 20-30 vs 29 (range 19-37; p = 0.005) years], and more likely to be primiparous (91.7% vs 36.6%; p < 0.001) compared to those without PRES. PRES was significantly more common in patients with eclampsia. Of 12 patients with eclampsia, nine (75%) had evidence of PRES. The maternal and fetal outcome,however, wassimilar in both groups. Patients with PRES were more likely to have poor sensorium compared to those without PRES (83.3% vs 5.3%; p < 0.01). Eclampsia was found in the independent predictor of PRES (odds ratio, OR 20.9; 95% confidence interval, CI 3.0-147.0, p = 0.02). In this study, patients with PRES were younger and significantly more likely to be primiparous and have eclampsia compared to those without PRES. Headache followed by seizures and altered sensorium were the most common clinical manifestations and subcortical white matter hyperintensities involving fronto-parieto-occipital lobes were the most common radiological finding. Eclampsia emerged as an independent risk factor for PRES.

Posterior Reversible Encephalopathy in Sepsis-Associated Encephalopathy: Experience from a Single Center.

Sepsis-associated encephalopathy (SAE) is frequently encountered in sepsis and is often accompanied by neuroimaging findings indicating ischemia, hemorrhage, and edema. Posterior reversible encephalopathy syndrome (PRES) has been vastly underrecognized in previously reported cohorts of patients with sepsis and SAE. Our aim was to determine the prevalence and distinguishing clinical, neuroimaging, and electroencephalography features of PRES in SAE. In this prospective observational study, patients with radiologically identified PRES were selected from a consecutively enrolled cohort of 156 patients with SAE and assessed for neurological outcome using the extended Glasgow Outcome Scale for 12months. Patients with SAE and PRES and other types of brain lesions were compared in terms of clinical and diagnostic workup features. Fourteen of 156 patients (8.9%) were determined to be radiologically compatible with PRES, whereas 48 patients displayed other types of acute brain lesions. Patients with PRES often showed lesions in atypical regions, including frontal lobes, the corpus callosum, and the basal ganglia. Source of infection was mostly gram-negative bacteria originating from pneumonia or intraabdominal infections. Patients with PRES were not different from other patients with SAE with brain lesions in terms of features of sepsis and neurological outcome. However, patients with PRES showed increased prevalence of seizures and intraabdominal source of infection. PRES is highly prevalent in SAE, often encompasses unusual brain regions, and usually presents with generalized seizures. Patients with SAE and PRES do not appear to have distinguishing clinical and diagnostic workup features. However, generalized seizures may serve as warning signs for presence of PRES in patients with SAE.

Posterior reversible encephalopathy syndrome seen in a case of acu tepost-streptococcal glomerulonephritis: a case report

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological condition that involves the acute onset of headache, confusion, optical impairments, and seizures with accompanying vasogenic edema on brain imaging. Here is a 12 years old male patient presented with complaints of swelling in the face and legs, headache and vomitings. He had a history of fever, sore throat and tonsillitis 12 days back. On physical examination weight and height of the patient was between 25-50th percentile, BP was 142/92 mmHg (&gt;99th centile), he had pretibial +2 edema and periorbitol edema. At presentation urine analysis showed haematuria, proteinuria at nephritic level, elevated urea and creatinine, increased ASO titre, low C3 and C4 levels. After admission, he had an episode of convulsion when BP was 162/98 mm hg. Magnetic resonance imaging brain showed bilateral occipital, parietal, frontal cortex and subcortical white matter T2/Fluid-attenuated inversion recovery (FLAIR) hyperintensitie, suggestive of PRES. EEG was found to be normal. MRI was found to be normal in the first month after starting on antihypertensive and anticonvulsive treatment. In the first year of the follow-up, the blood pressure, neurological examination and urinalysis findings were found to be normal. Thus, it is suggested that early diagnosis of PRES in patients with clinical features and prompt treatment will prevent permanent neurologic sequale.

Posterior Reversible Encephalopathy Syndrome Following Intracranial Hypotension Due to Cerebrospinal Fluid (CSF) Leakage: A Report of Two Cases

Posterior reversible encephalopathy syndrome (PRES) in cases of intracranial hypotension is a life-threatening condition. Early suspicion, appropriate treatment, and tight control of possible contributing factors that may facilitate PRES in cerebrospinal fluid (CSF) leak patients may bring a more favorable outcome, lowering the morbidity and mortality rate.Two cases of PRES with features of intracranial hypotension are presented.We also discussed the possible pathogenesis of PRES in patients with intracranial hypotension. We emphasize the importance of the early diagnosis and treatment of ICH by repairing the leakage and further prompt attention to tight blood pressure control in those patients to avoid PRES development.

Posterior reversible encephalopathy syndrome during management of hematological disorders

Background Posterior reversible encephalopathy syndrome (PRES) is a disorder of reversible subcortical vasogenic brain edema with acute neurological symptoms. Diagnosis of PRES is based on exclusion, and treatment consists of symptomatic management. Aims To study the clinical features, radiological findings, and outcomes of PRES in patients with hematological disorders. Patients and methods Case files of patients diagnosed with PRES from January 2016 to November 2019 were reviewed. PRES was diagnosed based on clinical features and MRI findings. Primary diagnosis, clinical history, vital signs, laboratory parameters, treatment summary, and neuroimaging findings were recorded. Results A total of 16 patients were diagnosed with PRES. Their median age was 7 years (range, 2–25 years). A total of 12 patients had acute lymphoblastic leukemia, who were on induction phase, two patients had aplastic anemia, and one each had acute myeloid leukemia and beta-thalassemia major. All patients had hypertension and 15 had seizures as initial presentation of PRES. Overall, 12 patients had bilateral subcortical white matter hyperintensity on T2 in occipital and parietal lobes on MRI. All patient recovered, except one, who had residual neurological deficit. All patients were restarted on the disease therapy once the patients were stabilized. No recurrences were observed. Conclusion Early recognition of PRES may help initiate timely treatment and reduce morbidity and mortality. Implicating agents may be withheld during the symptomatic period. Its management is symptomatic, and therapy may be restarted once patient is clinically stable. Its prognosis is favorable, but some patients may have residual neurological deficit.

Posterior reversible encephalopathy syndrom u dítěte s ulcerózní kolitidou

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical-neuroradiological entity with acute onset, defined as a vasogenic brain edema associated with neurotoxic impairment. We report the case of an eight-year-old boy with severe ulcerative colitis and celiac disease, who was treated with infliximab and azathioprine. On the 10th day after infliximab administration, a 45-minute unconsciousness developed with generalized convulsions and pupil miosis, accompanied by arterial hypertension. The boy was treated with anticonvulsants and antihypertensives. The state of consciousness improved ad integrum. Magnetic resonance imaging (MRI) of the brain revealed symmetric areas of high-intensity signal involving occipital and fronto-parietal lobes. Lumbar puncture was negative. Repeat MRI, seven days from the onset, showed resolution of the previous changes. The condition was assessed as PRES that developed as a complication of treatment (infliximab, azathioprine) in a patient with active ulcerative colitis. The case indicates a possible risk of developing PRES in patients with uncompensated inflammatory bowel disease, receiving immunosuppressive and/or bio­logical treatment and/or developing arterial hypertension

Posterior reversible encephalopathy syndrome in the emergency department: A single center retrospective study.

Posterior Reversible Encephalopathy Syndrome (PRES) and the related term Reversible Posterior Leukoencephalopathy Syndrome (RPLS) denote a constellation of clinical symptoms paired with key radiological findings. These symptoms may include headache, altered mental status, visual changes, and seizures. PRES is a rare condition and remains a challenging diagnosis to make in the emergency department. Data on risk factors and clinical presentation are limited, and there is no recent literature-supported diagnostic criteria. Our primary objective was to identify initial symptoms, clinical presentation, and risk factors that should guide the emergency clinician to consider a diagnosis of PRES. A secondary objective was to identify associations between risk factors and the outcomes of mortality and ICU admissions. This was a retrospective, observational study that evaluated patients seen in the Emergency Department (ED) in an urban tertiary care center with the diagnosis of PRES or RPLS from 1/1/2008 to 1/1/2018. The Health System's Electronic Medical Record was used to collect data. Search criteria included any patient diagnosed with Posterior Reversible Encephalopathy Syndrome (PRES) or Reversible Posterior Leukoencephalopathy Syndrome (RPLS), and excluded patients under 18 years of age, transfer patients, or patients that were not evaluated in our emergency department. We identified 98 patients based on our initial search criteria. After a chart review, 27 patients met our predefined eligibility criteria. In patients with confirmed diagnosis of PRES, the majority were female (70%) and 37% were either on an immunomodulator or undergoing chemotherapy at the time of presentation. 67% of patients presented with altered mental status, 41% had a focal neurologic deficit, and 37% had a witnessed seizure prior to diagnosis. Headache (48%), nausea (33%), and vision changes (30%) were the next most common reported symptoms. The majority of patients were hypertensive at time of presentation (82%) and many had a past medical history of hypertension (78%); twelve were given anti-hypertensive medications. 33% of the patients were admitted to the ICU and 26% died. There were no statistical associations found between documented ED interventions and the outcome of mortality. PRES is difficult to identify and diagnose in the emergency department. Significant risk factors such as female gender, hypertension, and those currently undergoing active immunotherapy/chemotherapy are associated with PRES. Common presenting complaints and exam findings include headache, altered mental status, and neurologic deficits. Emergency providers should consider PRES in patients presenting with altered mental status with significant risk factors, especially with neurologic deficits for which stroke has been ruled out.

Rituximab‐associated posterior reversible encephalopathy syndrome

Rituximab‐associated posterior reversible encephalopathy syndrome

Clinical Profile and Outcome of Posterior Reversible Encephalopathy Syndrome in Hemodialysis Patients.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiologic entity characterized by headache, altered level of consciousness, seizures, visual disturbances, and reversible vasogenic subcortical edema. Hypertension and renal failure are well known principal risk factors for the development of PRES. However, risk factors and outcome of PRES has not been studied in patients on maintenance hemodialysis (MHD). The objective of this study is to characterize the factors predisposing to the development of PRES in patients on MHD. We performed a retrospective analysis in patients of MHD who were diagnosed with PRES between August 1, 2013, and July 31, 2015. Those with a history of cerebrovascular accidents/stroke, and epilepsy were excluded. We analyzed the clinical details, course, and laboratory data. One year follow-up data were noted in recurrence of PRES and mortality. A total of 18 patients were included for the final analysis. Of these, 13 (72%) patients were males. Majority of these patients were young and mean age was 21.1 years (6–50 years). Most of the PRES episodes developed shortly after initiation of MHD with mean duration of 2 months after initiation of MHD (1 month–3 years). All 18 patients had resistant hypertension. Eight (45%) patients had infection at the time of PRES episodes. Four patients had catheter-related bloodstream infection, 1 had pneumonia and 3 patients were recently diagnosed with pulmonary tuberculosis. Four (22%) patients developed recurrence of PRES and all these episodes developed within 2 months of index event. Seven (39%) patients underwent renal transplantation, and all received triple immune suppression and had uncontrolled hypertension in the perioperative period. However, none of these patients developed PRES after transplantation. All these patients had been maintaining stable graft function in the follow-up. All episodes of PRES were of generalized tonic–clonic seizure type and 6 of them presented as status epilepticus. None of them had any neurological sequel and no mortality at the end of 1 year. PRES is not uncommon in patients on MHD. Uncontrolled hypertension and infection are common predisposing factors. Renal transplantation is safe and not adversely affected by prior episodes of PRES in MHD.

Posterior Reversible Encephalopathy Syndrome after Hematopoietic Cell Transplantation in Children with Hemoglobinopathies

Posterior reversible encephalopathy syndrome (PRES) is a serious adverse event associated with calcineurin inhibitors used for graft-versus-host disease (GVHD) prophylaxis. We compared the incidence of PRES in children with thalassemia (n = 222, 1.4 to 17.8 years old) versus sickle cell disease (SCD; n = 59, 2 to 17 years old) who underwent hematopoietic cell transplantation from HLA-matched siblings or alternative donors and analyzed the risk factors for PRES. Overall, 31 children developed calcineurin inhibitor-related PRES (11%), including 30 patients with seizures and 1 patient without seizures. PRES incidence was significantly higher in SCD patients (22%; 95% confidence interval [CI], 10% to 32%) than in thalassemia patients (8%; 95% CI, 5% to 12%;P = .002). In multivariate analysis, factors associated with PRES were hypertension (hazard ratio [HR], 5.87; 95% CI, 2.57 to 13.43; P = .0001), SCD (HR, 2.49; 95% CI, 1.25 to 4.99; P = .009), and acute GVHD (HR 2.27; 95% CI, 1.06 to 4.85; P = .031). In the entire cohort overall survival (OS) was significantly higher in patients without versus with PRES (90% versus 77%; P = .02). In a subgroup analysis that including matched sibling transplants, OS and disease-free survival (DFS) were similar in thalassemia patients without PRES (92% and 88%, respectively) and with PRES (82% and 73%, respectively), whereas SCD patients with PRES had significantly lower OS (67%) and DFS (67%) than patients without PRES (94% and 94%, respectively; P = .008). Thus, SCD patients had a significantly higher incidence of PRES than thalassemia patients, and hypertension and GVHD were the 2 main risk factors for PRES in patients with hemoglobinopathies. Although PRES did not significantly influence survival in patients with thalassemia, patients with SCD had significantly lower survival after PRES.

The clinical characteristics of posterior reversible encephalopathy syndrome in patients with chronic renal failure.

Few studies have investigated posterior reversible encephalopathy syndrome (PRES) in patients with chronic renal failure (CRF). The present study analyzed the clinical manifestations, laboratory examinations and imaging features of PRES in patients with CRF. A total of 42 patients with CRF with or without PRES were recruited in the current retrospective case-control study. Patient data taken prior to the onset of PRES in patients with CRF and PRES (n=21) were collected and analyzed. At the same time, data from patients with CRF but without PRES (n=21) were also analyzed. Brain magnetic resonance imaging (MRI) scans were collected from patients in the PRES group. The mean blood pressure of patients in the PRES group was significantly higher than that of the control group (systolic blood pressure: 172±15 mmHg vs. 135±14 mmHg, P<0.01; diastolic blood pressure: 95±16 mmHg vs. 64±13 mmHg, P<0.01). Furthermore, compared with the control group, mean serum albumin (Alb) and hemoglobin (Hb) concentrations in the PRES group were significantly lower (Alb: 29.1±5.3 g/l vs. 34.6±6.1 g/l, P=0.001; Hb: 74±16 g/l vs. 89±28 g/l, P=0.037). By contrast, mean LDH concentration was significantly higher in the PRES group (LDH: 336±141 U/l vs. 235±89 U/l, P=0.004). In the PRES group, 24 h urine volume was significantly lower in the PRES group than in the control group (24 h urine volume: 651±520 ml vs. 982±518 ml, P=0.046). No significant differences in levels of serum potassium (4.5±0.6 mmol/l vs. 4.4±0.5 mmol/l, P=0.377), sodium (138.3±4.9 mmol/l vs. 139.0±6.8 mmol/l, P=0.325), calcium (2.0±0.24 mmol/l vs. 1.9±0.24 mmol/l, P=0.673), alanine aminotransferase; (24±14 U/l vs. 18±8 U/l, P=0.975); aspartate aminotransferase (29±11 U/l vs. 24±9 U/l, P=0.619) and uric acid (448±148 µmol/l vs. 378±116 µmol/l, P=0.599) were found between the two groups. PRES is a relatively common nervous system complication arising in patients with CRF. Certain biochemical markers, including Hb and Alb, may be associated with PRES. Diagnosing PRES is difficult as computed tomography (CT) brain scans may be normal and MRI scans, which are more sensitive than CT scans at diagnosing PRES, are not always performed in patients with CRF. Thus, brain MRI scans should be taken first in such patients when PRES is suspected.

Incidence of Posterior Reversible Encephalopathy Syndrome in Eclamptic and Patients With Preeclampsia With Neurological Symptoms

(Am J Obstet Gynecol. 2016; 215(2):239.e1–239.e5) Posterior reversible encephalopathy syndrome (PRES) has been reported numerous times in patients with eclampsia, but has also been occasionally reported in patients with preeclampsia. PRES is a syndrome in which the affected patients are observed to have reversible vasogenic brain edema in addition to acute neurological symptoms such as seizures, impaired consciousness, and visual disturbances. The purpose of this study was to assess the incidence of PRES in patients with preeclampsia and eclampsia and establish any pathophysiological backgrounds they may share through a comparison of clinical and radiologic characteristics.

Early Recognition and Management of Posterior Reversible Encephalopathy Syndrome: A Newly Recognized Complication in Patients Receiving Tyrosine Kinase Inhibitors.

Adult patients with cancer receiving antineoplastic, targeted, and other immunosuppressive therapies are at risk for severe side effects. Studies link posterior reversible encephalopathy syndrome (PRES) with immunosuppressants used for patients undergoing transplantation, as well as select tyrosine kinase inhibitors (TKIs) and other targeted therapies used in patients with cancer. PRES is a reversible condition with early recognition and management; however, permanent neurologic toxicities have been reported. This article aims to educate oncology nurses on signs, symptoms, and management of PRES in patients receiving TKIs. The literature was reviewed to develop an educational session about causes, manifestations, pathophysiology, and management of PRES. Using a case study and flipped classroom model, staff participated in an online lecture and concept engagement exercise. Education for nurses included frequent neurologic and mental status assessments, blood pressure monitoring with mean arterial blood pressure goal, and seizure precautions. Nursing knowledge was evaluated with pre- and post-testing. Evaluation revealed improved knowledge in recognizing and managing patients with PRES related to TKIs. The flipped classroom approach was perceived as a valuable tool for busy staff nurses.

Cyclosporine-Induced Posterior Reversible Encephalopathy Syndrome in a Patient with Pemphigus Vulgaris.

Dear Editor: Cyclosporine is an immunosuppressive drug originally isolated from Tolypocladium inflatum in 19701. Here, we report a case of cyclosporine-induced posterior reversible encephalopathy syndrome (PRES) in a patient with pemphigus vulgaris. A 41-year-old Korean woman who had no underlying disease except pemphigus vulgaris was admitted to the emergency room owing to a sudden onset of severe headache, nausea, vomiting, and vision loss. A few minutes after admission, she presented with generalized tonic-clonic convulsive movement and became confused. Transient hypertension (160/100 mmHg) accompanied the episode. Laboratory tests showed leukocytosis (17.9×109/L) with neutrophilia (92.2%); cerebrospinal fluid was normal. Multiple ill-defined high-signal enhanced lesions were visible in the cortex and subcortical white matter of the bilateral parieto-occipital lesion on a T2-weighted brain magnetic resonance imaging (MRI) (Fig. 1A). Six months earlier, the patient presented with highly crusted vegetating lesions on her lower lip (Fig. 2A) as well as several flaccid blisters and scaly crusted erosions on her trunk (Fig. 2B). Histopathological examination showed suprabasal acantholysis (Fig. 2C), and a direct immunofluorescence study on the perilesional dorsal skin showed intercellular epidermal IgG deposition (Fig. 2D). Therefore, she was diagnosed with pemphigus vulgaris. Initially, the patient received prednisolone 100 mg/day for 2 weeks and tapered for 4 months; this was followed by cyclosporine 200 mg/day (4 mg/kg) for 2 months. We considered acute hypertension and cyclosporine administration as possible causes of the convulsive encephalopathy. Cyclosporine was discontinued immediately, and conservative therapy was administered. The patient showed a complete clinical recovery in 6 weeks, and signal enhancement also decreased on follow-up brain MRI (Fig. 1B). Cyclosporine is rarely reported to cause PRES; its association with cyclosporine was first described by Adams et al.2 in 1987. PRES is characterized by clinical symptoms including headache, mental confusion, vomiting, visual disturbance, and multiple generalized tonic-clonic seizures; it is associated with characteristic radiological abnormalities in the posterior area of the cerebral white matter3. In addition to immunosuppressive or cytotoxic drugs, reported causes of PRES also include acute hypertension, infection, autoimmune disease, eclampsia, and pre-eclampsia3. Although the pathophysiology of PRES remains unclear, several mechanisms have been proposed. Cyclosporine has a direct toxic effect on vascular endothelial cells, causing them to release endothelin, prostacyclin, and thromboxane; these may cause microthrombi and also damage the blood-brain barrier3. Many PRES cases have been reported in organ and bone marrow transplant recipients receiving high-dose cyclosporine4. However, in the present case, the patient had been taking low-dose cyclosporine 4 mg·kg-1·day-1 and had no associated risk factors for neurotoxicity. We finally diagnosed the patient with PRES because of her favorable response to cyclosporine discontinuation and the ultimately near-full reversal of encephalopathy. Thus, the possibility of PRES in patients taking even low-dose cyclosporine who present with neurologic symptoms should be emphasized. Physicians should rapidly diagnose this disease and withdraw the causative drug(s), because delayed diagnosis could lead to permanent sequelae. Fig. 1 (A) Axial T2-weighted magnetic resonance imaging (MRI) showing an area of high signal intensity in the bilateral white matter of the posterior parieto-occipital area. (B) Six weeks later, axial T2-weighted MRI showing significant improvement after cyclosporine ... Fig. 2 (A) Highly crusted vegetating lesions on the lower lip. (B) Several flaccid blisters and scaly crusted erosions are distributed on her trunk. (C) Separation of the epidermis above the basal layer and scattered acantholytic cells (H&E, ×200). ...

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

▪Background: Posterior reversible encephalopathy syndrome (PRES) is a potentially life-threatening complication of therapy with calcineurin inhibitors (CNI). Medications in this class include tacrolimus (Tac) and cyclosporine A (CSA). Sirolimus (Siro), an inhibitor of the mammalian target of rapamycin (mTOR) complex, may also be associated with PRES. These therapies are generally used in the management of patients with severe aplastic anemia (SAA), to prevent or treat graft-versus-host disease following allogeneic hematopoietic cell transplantation (alloHCT), or to prevent rejection of solid organ allografts. PRES is associated with hypertension and symptomatic features include headaches, seizures, and occasionally, intracranial hemorrhage or ischemic strokes. Classical findings on magnetic resonance imaging (MRI) studies include leukoencephalopathy with vasogenic edema in the occipital cerebrum. Diffusion restriction is observed on diffusion-weighted imaging. Management of CNI/Siro-associated PRES has not been well-studied.Methods: We performed a single-institution retrospective review of all patients identified to have possible PRES on MRI between October 2000 and February 2014. Patients were identified by searching a database of all neuroimaging studies performed at our institution during this time period for the terms: PRES, posterior reversible encephalopathy, or reversible posterior leukoencephalopathy. Radiography studies were reevaluated for this study to uniformly collect data regarding imaging features. Medical chart review was conducted to determine patient features at diagnosis, management decisions with focus on medication changes, and outcomes.Results: Our review identified 191 patients who underwent 236 MRI studies that demonstrated findings suggesting a possible diagnosis of PRES. On medical record review, pertinent clinical data were available for 167 patients, of whom 93 (56%) were deemed to have a clinical diagnosis consistent with PRES. Amongst this cohort, 27 patients (29%) were diagnosed with PRES while taking a CNI or Siro – 22 (81%) were receiving Tac, 4 (15%) were receiving CSA, and 1 patient (3.7%) was receiving Siro at diagnosis. The median age at PRES diagnosis was 52 (range 7 - 68), with no apparent association between age and the occurrence of CNI/Siro-associated PRES. Indications for CNI/Siro therapy included: alloHCT (19%), SAA (3.7%), systemic lupus erythematosus (7.4%), and solid organ transplantation (70%). Symptomatic features and physical signs at diagnosis of CNI/Siro-associated PRES included: hypertension (74%), seizure (52%), headache (44%), intracranial hemorrhage (22%), and cerebrovascular accident (15%). Presentation with these symptoms was not significantly different between CNI/Siro-associated PRES and other forms of PRES (p = 0.36, 0.48, 0.88, 0.97, and 0.44, respectively). The median time from initiation of CNI/Siro therapy to onset of PRES was 22 days (range 1 - 1924). Only 3 patients (11%) discontinued CNI/Siro therapy at PRES diagnosis and did not resume, whereas 12 (44%) continued the same medication, 10 (37%) were changed to alternative CNI (Tac-to-CSA or CSA-to-Tac) therapy, and 2 (7.4%) were changed from CNI to Siro. Two patients experienced recurrent PRES following these initial management decisions. All other patients continued therapy without recurrence.Conclusions: CNI/Siro therapy, mostly in the setting of allogeneic hematopoietic cell or solid organ transplantation, was associated with roughly one-third of PRES cases at our institution. Management of CNI/Siro-associated PRES has not been well studied, and the low incidence of this complication is prohibitive to the implementation of prospective studies. In this retrospective review, we evaluated the management strategies and outcomes of patients who developed PRES while receiving CNI/Siro therapy. The vast majority of patients (77%) tolerated continuation of the same CNI or changing to alternative CNI therapy. An additional 11% tolerated conversion from CNI to Siro. The recurrence rate with continuation of CNI/Siro therapy was low at 2/24 (8.3%) and no patients experienced fatal complications of PRES, suggesting this management strategy is safe. Additional analyses are underway to determine whether clinical or radiographic features may help predict the recurrence of PRES in patients who continue CNI/Siro therapy. DisclosuresOff Label Use: Off-label use of tacrolimus, cyclosporine, and sirolimus for immune prophylaxis in hematopoietic cell transplant patients is discussed..

Elevation of serum lactate dehydrogenase at posterior reversible encephalopathy syndrome onset in chemotherapy-treated cancer patients

The pathophysiology of posterior reversible encephalopathy syndrome (PRES) is incompletely understood; however, an underlying state of immune dysregulation and endothelial dysfunction has been proposed. We examined alterations of serum lactate dehydrogenase (LDH), a marker of endothelial dysfunction, relative to the development of PRES in patients receiving chemotherapy. A retrospective Institutional Review Board approved database of 88 PRES patients was examined. PRES diagnosis was confirmed by congruent clinical diagnosis and MRI. Clinical features at presentation were recorded. Serum LDH values were collected at three time points: prior to, at the time of, and following PRES diagnosis. Student’s t-test was employed. LDH values were available during the course of treatment in 12 patients (nine women; mean age 57.8years [range 33–75years]). Chemotherapy-associated PRES patients were more likely to be normotensive (25%) versus the non-chemotherapy group (9%). LDH levels at the time of PRES diagnosis were higher than those before and after (p=0.0263), with a mean difference of 114.8 international units/L. Mean time intervals between LDH measurement prior to and following PRES diagnosis were 44.8days and 51.4days, respectively. Mean elapsed time between last chemotherapy administration and PRES onset was 11.1days. In conclusion, serum LDH, a marker of endothelial dysfunction, shows statistically significant elevation at the onset of PRES toxicity in cancer patients receiving chemotherapy. Our findings support a systemic process characterized by endothelial injury/dysfunction as a factor, if not the prime event, in the pathophysiology of PRES.

A novel homozygous GLUT9 mutation cause recurrent exercise-induced acute renal failure and posterior reversible encephalopathy syndrome

Renal hypouricemia (RHU) is an autosomal recessive hereditary disease characterized by impaired renal urate reabsorption and subsequent profound hypouricemia. There are two types of RHU, type 1 and type 2, caused by the loss-of-function mutation of SLC22A12 and SLC2A9 genes, respectively. RHU predisposes affected people to exercise-induced acute renal failure (EIARF), posterior reversible encephalopathy syndrome (PRES) and nephrolithiasis. A Chinese patient had experienced three episodes of EIARF and one episode of PRES. The investigations showed profound hypouricemia and significantly increased renal excretion of UA. Cranial magnetic resonance imaging showed communicating hydrocephalus. Renal biopsy displayed interlobular artery intimal thickening with reduction of lumen and acute tubulointerstitial injury. The mutational analysis revealed a homozygous splice-site mutation in the SLC2A9 gene encoding glucose transporter 9. The patient was diagnosed as RHU type 2 caused by a loss-of-function mutation of the SLC2A9 gene. Consequently, he was strictly prohibited from strenuous exercise. During the 5-year follow-up, EIARF and PRES never recurred. Strenuous exercise may induce systemic (including renal and cerebrovascular) vasoconstriction eventually resulting in EIARF and PRES in patients with RHU. To our knowledge, this is the first report of a homozygous splice-site mutation in the SLC2A9 gene, renal arteriolar chronic lesion, concurrence of RHU and communicating hydrocephalus.

Tacrolimus Associated Posterior Reversible Encephalopathy Syndrome – A Case Series and Review

Tacrolimus is an immunosuppressive drug mainly used to lower the risk of transplant rejection in individuals who are post solid organ or hematopoietic transplantation. It is a macrolide which reduces peptidyl-propyl isomerase activity and inhibits calcineurin, thus inhibiting T-lymphocyte signal transduction and interleukin-2 (IL-2) transcription. It has been associated with Posterior Reversible Encephalopathy Syndrome (PRES), a disease of sudden onset that can present as a host of different symptoms, depending on the affected area of the brain. While infectious causes of encephalopathy must always be entertained, the differential diagnosis should also include PRES in the appropriate context. We report three cases of PRES in patients with acute myeloid leukemia (AML) placed on tacrolimus after receiving a bone marrow transplant (BMT). The focus of this review is to enhance clinical recognition of PRES as it is related to an adverse effect of Tacrolimus in the setting of hematopoietic transplantation.