Posterior Reversible Encephalopathy Syndrome in Pediatric Hematopoietic Stem Cell Transplantation with Beta Major Thalassemia: The Association between the PRES Occurrence and Class of Beta Major Thalassemia.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive curative option for ß-major thalassemia patients (ß-MT). Posterior reversible encephalopathy syndrome (PRES) is a pervasive neurological complication which typically occurs following HSCT. ß-MT patients are prone to a higher PRES incidence due to long-term immunosuppression; thus, it is imperative that these patients are closely monitored for PRES after HSCT. PATIENTS AND METHODS: We included 148 pediatric patients with ß-MT who underwent HSCT between March 2015 and August 2022 in Children's Medical Center. Patients in this study were divided into two groups. The association between PRES and class of ß-MT and other risk factors were assessed and the overall survival rate was determined. RESULTS: Fourteen out of 112 patients (12%) with class I and II ß-MT developed PRES. However, PRES occurred in 11 out of 36 patients (30.5%) with ß-MT-III. Our results indicated that there was a significant association between class III ß-MT and the occurrence of (P = .004). Additionally, acute graft-versus-host disease (aGVHD) occurred in 80% and 44.7% of patients in the PRES and non-PRES groups, respectively (P = .001). The results of the Kaplan-Meier analysis revealed that the 5-year overall survival (OS) was 75.6% in the PRES group versus 95% in the non-PRES group, which was statistically significant (P = .001). CONCLUSION: Based on our results, pediatric ß-MT III patients are at a higher risk of developing PRES. Additionally, pediatric ß-MT patients with a history of aGVHD, regardless of disease class, are more likely to develop PRES. Considering these results, PRES has a higher chance of being the etiology of symptoms and should be considered more often in these 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.

Postoperative Posterior Reversible Encephalopathy Syndrome after Coronary Artery Bypass Surgery.

Null.

[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).

Neurologic Complications in Patients With Lymphoreticular Malignancy: A Descriptive Cohort Study.

OBJECTIVES: The objectives of this study were to study the spectrum of neurologic complications in children with lymphoreticular malignancy (acute lymphoblastic leukemia, Hodgkin, and non-Hodgkin lymphoma) at diagnosis and during treatment and to determine the etiology of these complications. MATERIALS AND METHODS: In this descriptive cohort study, conducted between November 2018 and March 2020, 204 children with a diagnosis of lymphoreticular malignancy were enrolled. The baseline investigations were done in all the cases. Those who developed neurological symptoms were evaluated with cerebrospinal fluid examination and radiologic and electrophysiologic studies as per indication and were managed according to standard management guidelines. RESULTS: Of the 204 patients, 30 (14.7%) developed neurological complications. The majority of these complications (n=20/30; 87%) occurred during the intensive chemotherapy period. Common complications included acute methotrexate neurotoxicity (n=7), vincristine-induced neurotoxicity (n=7), central nervous system (CNS) relapse (n=4), and posterior reversible encephalopathy syndrome (n=2). L-asparaginase-induced thrombosis (n=1), intramedullary compression syndrome (n=1), CNS infection (n=2), CNS hemophagocytic lymphohistiocytosis (n=1), and steroid-induced myopathy (n=1) were also observed. The complications resolved in 21/30 (70%) patients after receiving appropriate treatment while the neurological complication persisted in 2/30 (6.7%) patients. Three patients (10%) abandoned the treatment, and 4 (13.3%) patients expired. CONCLUSIONS: Neurologic complications in patients with lymphoreticular malignancy are quite variable, having common presenting symptoms but varying imaging abnormalities. By close follow-up and effective treatment, the morbidity and mortality of these complications can be minimized.

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 in children with acute lymphoblastic leukemia during remission induction chemotherapy: a single-center retrospective study.

BACKGROUND: This study investigated the clinical characteristics, cranial magnetic resonance imaging (MRI) features, MRI follow-up, and prognosis of children with acute lymphoblastic leukemia (ALL) who developed posterior reversible encephalopathy syndrome (PRES) during remission induction chemotherapy. METHODS: We analyzed the age, gender, PRES symptoms and signs, cranial MRI findings, therapeutic effect, and prognosis of children with ALL who developed PRES during chemotherapy from January 2010 to December 2013 at the Hematology Oncology Center of Beijing Children's Hospital. Changes in cranial MRI findings were analyzed, and intelligence (IQ) and cognitive function were evaluated using the Wechsler Scale and the Wisconsin Card Score Test after the children completed chemotherapy. RESULTS: There were 850 children with newly diagnosed ALL in this period; 13 (1.5%), 6 boys and 7 girls, developed PRES. All were diagnosed as B-cell ALL. The median age at PRES onset was 7 years (2-11 years). The median day of PRES onset was day 28 (day 17-34) of remission induction chemotherapy. Of the 13 children with PRES onset and seizures, 4 had visual disturbances and 2 had consciousness disturbances. Cranial MRI showed hyperintensity in the subcortical white matter on T2-weighted axial and fluid-attenuated inversion recovery (FLAIR) images. The lesion locations were as follows: occipital lobe, 12 (92.3%) patients; frontal lobe, 7 (53.8%) patients; temporal lobe, 5 (38.4%) patients; parietal lobe, 3 (23.1%) patients; and cerebellum, 1 (7.7%) patient. There were 8 (61.5%) patients with vasogenic edema and 5 (38.5%) with cytotoxic edema. After treatment, all children recovered within one month, when their PRES symptoms were relieved, they continued to receive chemotherapy. However, 1 child (1.07%) died of severe central nervous system infection one year after PRES treatment, and 3 (25%) had recurrent seizures and were diagnosed with epilepsy after three months of PRES treatment. Their cranial MRIs showed cytotoxic edema, which was acute stage on day 15, with aggravated lesions on cranial MRI. The cranial MRI lesions returned to normal at one month in 3 (23.1%) patients, at three months in 6 (46.1%) patients, at one year in 8 (61.5%) patients, and at two years in 12 (92.3%) patients. The 12 surviving children all returned to school, and their full-scale, verbal, and performance IQs were normal, with no significant differences in intelligence or cognitive function compared with children with ALL without PRES during the same period. CONCLUSIONS: PRES can occur during remission induction chemotherapy treatment of children with ALL, but the incidence is low. Cranial MRI can be used for diagnosis and to characterize lesions. The children recover about a month after treatment, and cranial MRI lesions return to normal within two years. The time for complete resolution of MRI lesions differs, and children with cytotoxic edema have worse prognosis with sequelae, such as epilepsy, which requires close monitoring. PRES does not affect intelligence or cognitive development.

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.

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.

Posterior reversible encephalopathy syndrome after lung transplantation: Risk factors and management.

INTRODUCTION: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation. METHODS: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19). RESULTS: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES. CONCLUSION: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.

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.

Factors affecting hospitalization, imaging severity, and complications in posterior reversible encephalopathy syndrome.

PURPOSE: Assess factors in posterior reversible encephalopathy syndrome (PRES) related to intensive care unit (ICU) admissions, mechanical ventilation, and length of stay (LoS). METHODS: Retrospectively, we collected clinical, biochemical, and imaging data of PRES patients. MRI studies were assessed for imaging severity, and complications, including restricted diffusion and hemorrhage. Univariate and multivariate regression analyses were performed for factors associated with ICU admission, mechanical ventilation, and LoS. We assessed for association between clinical and biochemical factors and imaging severity grading systems and complications. RESULTS: We had 57 subjects with mean ± SD age of 56.3 ± 14.5 years and 68.3% were females. In 60 cases, 36.7% had hypertension, 23.3% had chronic renal disease, 18.3% had sepsis, 16.7% were on active chemotherapy, 10% underwent hematopoietic stem cell transplantation (HSCT), 10% with active cancer, 6.7% were eclampsia/preeclampsia, and 1.7% had radiotherapy. We had 17 (26.6%) grade 1, 26 (46.8%) grade 2, 17 (26.6%) grade 3 PRES based on vasogenic edema extent, and 28 (46.7%) severe PRES (≥ 5 areas) cases. 19 (31.7%) had restricted diffusion with hemorrhage in 19 (31.7%) cases. On multivariate analysis, ICU admissions showed significant association with hypertension (OR = 5.57, 95% CI: 0.96-32.23; p = 0.05), and raised INR (OR = 119, 95% CI: 1.1-1244.3; p = 0.04); LoS with HSCT, mean arterial pressure (MAP), intraparenchymal hematoma, and sepsis; and extent of vasogenic edema with restricted diffusion (OR = 4.31, 95% CI: 1.5-12.33; p < 0.01). CONCLUSION: In summary, PRES with hypertension and elevated INR are associated with ICU admissions. HSCT, MAP, intraparenchymal hematoma, and sepsis correlated with LoS. Imaging severity grading based on vasogenic edema extent may be better due to association with restricted diffusion.

Posterior Reversible Encephalopathy Syndrome After Epilepsy Surgery Alerted by Low-Processed Electroencephalography Levels: A Case Report.

The development of posterior reversible encephalopathy syndrome (PRES) in a patient undergoing epilepsy surgery without perioperative hypertension is uncommon. A young man having epilepsy surgery with normal blood pressures had an unexplained drop in his processed electroencephalogram (pEEG) levels intraoperatively. This alerted and prompted us to search for the cause. A postoperative electroencephalogram (EEG) confirmed a diffuse slowing of cortical waves. The intraoperative findings of pEEG, magnetic resonance imaging (MRI), and EEG postoperatively prompted a diagnosis of PRES. The patient was managed conservatively and had a full recovery. This case report highlights the role of brain electrical activity monitors in PRES.

Anaesthetic management of large meningioma excision complicated by Takotsubo and posterior reversible encephalopathy.

A 47-year-old woman with a history of a pulsatile headache, photophobia, dizziness and blurred vision was diagnosed with a massive expansive meningioma and proposed for surgical excision. During surgery, the patient began to show progressive haemodynamic instability with extreme hypotension and severe arrhythmia that only responded to epinephrine. With the continuity of haemodynamic instability, ST segment elevation and great amount of blood loss, the surgery was postponed. The follow-up brain CT scan showed evidence of posterior reversible encephalopathy syndrome and cardiac catheterisation diagnosed as Takotsubo syndrome. The patient remained sedated under aminergic support and was admitted to a cardiac intensive care unit. After clinic stabilisation, the patient underwent two more surgical procedures with special attention paid to monitoring haemodynamic stability, blood loss and cardiac output. After 70 days of admission, the patient was discharged with moderate visual impairment and follow-up consultations in neurosurgery and cardiology.

[Posterior reversible encephalopathy syndrome (PRES) as a presentation of AL amyloidosis]. / Síndrome de encefalopatía posterior reversible (PRES) como forma de presentación de una amiloidosis AL.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity linked to multiple aetiologies with similar neuroimaging findings. Its incidence is unknown, and its pathogenesis is multifactorial, encompassing phenomena of endothelial dysfunction and cerebral flow autoregulation, inter alia. There is a wide variety of associated conditions, the most frequent being hypertension, eclampsia, and immunosuppressive therapy, along with other drugs, autoimmune diseases, and even uraemia. We present the case of a reversible posterior encephalopathy syndrome secondary to renal involvement as a debut form of AL amyloidosis.