Original Article

Posterior Reversible Encephalopathy Syndrome in Children With Hematologic Malignancies

Journal of Child Neurology 1-7 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815578525 jcn.sagepub.com

Ma´rcio Tavares, MD1, Mavilde Arantes, MD2, Se´rgio Chacim, MD1, Anto´nio Campos Ju´nior, MD3, Armando Pinto, MD4, Jose´ Ma´rio Mariz, MD1, Teresa Sonin, MD5, and Susana Pereira, MD5

Abstract Since its original description 2 decades ago, posterior reversible encephalopathy syndrome has been reported in children with several predisposing conditions. Epidemiologic data of posterior reversible encephalopathy syndrome in children with hematologic malignancies is still scarce. Herein, we describe the clinical and radiologic features along with the outcome and follow-up of posterior reversible encephalopathy syndrome complicating the treatment of children with hematologic malignancies. Ten patients with a median age of 6.3 years were diagnosed with posterior reversible encephalopathy syndrome. Six of them were undergoing chemotherapy and the remaining 4 were at 37, 52, 78, and 857 days after allogenic hematopoietic stem cell transplant. The median follow-up was 27.6 months. Even though follow-up imaging showed complete resolution of abnormalities in those 10 children, 2 developed secondary epilepsy. Despite accurate diagnosis of posterior reversible encephalopathy syndrome and immediate intervention, neurologic sequelae may still develop. Thus, a close follow-up should be considered in all patients. Keywords neurologic complications, hematologic malignancies, allogenic hematopoietic stem-cell transplant, children, epilepsy Received November 02, 2014. Received revised December 21, 2014. Accepted for publication February 24, 2015.

Posterior reversible encephalopathy syndrome is a clinicalradiologic disorder first described by Hinchey et al in 1996. This syndrome was originally characterized, clinically, by seizures, consciousness impairment, headache and visual disturbance, and, radiologically, by vasogenic edema that involved predominantly posterior white matter and resolved without any sequelae.1 Radiologic findings of posterior reversible encephalopathy syndrome have been explored with the increasing availability of magnetic resonance imaging (MRI), along with its clinical course.2,3 Recently, the risk of neurologic impairment and the recognition of vasogenic edema in other locations than parieto-occipital have challenged the definition of posterior reversible encephalopathy syndrome, which persists however as the accepted term. Posterior reversible encephalopathy syndrome has been reported in children with hematologic malignancies, even though its underlying pathophysiologic mechanisms remain unclear.4-7 Neurologic events are not rare in children with malignant conditions, and other possible complications need to be differentiated from posterior reversible encephalopathy syndrome: central nervous system infection, stroke, metabolic causes (such as hyponatremia), central nervous system involvement of the malignancy, and methotrexate-related encephalopathy.8,9 Posterior reversible

encephalopathy syndrome is reversible when it is expediently recognized and the causative factor is removed. Failure to do so may result in symptom progression, prolonged hospitalization, unnecessary invasive procedures, permanent neurologic injury, and death.10,11 Epidemiologic data of posterior reversible encephalopathy syndrome in children with hematologic malignancies is still scarce. We aimed to describe the clinical and radiologic features along with the outcome and follow-up of a cohort of

1

Department of Onco Hematology, Portuguese Institute of Oncology, Porto, Portugal 2 Division of Neuro Radiology, Department of Radiology, Portuguese Institute of Oncology, Porto, Portugal 3 Bone Marrow Transplant Unit, Portuguese Institute of Oncology, Porto, Portugal 4 Department of Pediatrics, Portuguese Institute of Oncology, Porto, Portugal 5 Department of Neurology, Portuguese Institute of Oncology, Porto, Portugal Corresponding Author: Ma´rcio Tavares, MD, Servic¸o de Onco-Hematologia, Instituto Portugueˆs de Oncologia do Porto, Rua Doutor Anto´nio Bernardino Almeida, Porto 4200-072, Portugal. Email: [email protected]

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patients who developed posterior reversible encephalopathy syndrome during their treatment course at our institution.

Material and Methods Study Subjects We searched retrospectively the pediatric report database at our institution from January 2008 to December 2013 for patients with hematologic malignancies who developed neurologic events during their treatment course. During this period, 117 pediatric allogenic hematopoietic stem cell transplants were performed at the Bone Marrow Transplant Unit. Posterior reversible encephalopathy syndrome was established based on the presence of seizures, consciousness impairment, visual disturbance, or headache associated with a brain MRI scan showing variable degrees of vasogenic edema. A final cohort of 10 patients was identified.

Clinical Evaluation The following information was collected from the cohort’s medical records: demographic data, previous medical history, current comorbidities and drug treatment, details of clinical and radiologic presentation, and outcome of the neurologic disorder. Blood pressure and hemoglobin values at the onset of posterior reversible encephalopathy syndrome were sought. Hypertension was defined as a systolic or diastolic blood pressure exceeding the 95th percentile for age, sex, and height. Anemia was defined as a hemoglobin concentration or red blood mass cell less than 5th percentile for age, sex, and height. According to our protocol, every child presenting with neurologic signs, prolonged alteration in consciousness, and/or unexplained seizures performs an urgent cranial computed tomographic imaging and is evaluated by a neurologist. Electroencephalogram (EEG) is performed in children with deep coma, prolonged post-ictal state, or persistent neurologic manifestations despite normal or nonspecific imaging features. Patients with severe impairment of consciousness are transferred to a pediatric intensive care unit for mechanical ventilation or clinical and operative monitoring and return to the nursery when clinically stable.

MRI Imaging Brain MRI is the key investigation for the diagnosis of posterior reversible encephalopathy syndrome, and it was performed on an urgent basis. The MRI was performed at 1.5 Tesla. All studies included axial T1- and T2 -weighted images, fluid-attenuated inversion recovery images, diffusion-weighted imaging sequences, apparent diffusion coefficient maps, T2*-weighted gradient echo sequences, and contrast-enhanced T1-weighted sequences. Imaging features were assessed as recommended in the literature2,3: location (left/right hemisphere; frontal, parietal, occipital and/or temporal edema; striatum, pallidum, thalamus, hypothalamus, mesencephalon, pons, cerebellum, corpus callosum), topographic edema pattern (predominant parietooccipital, predominant superior frontal sulcus, holohemispheric watershed and central), edema grading [grade 1 (mild): limited cortex and white matter edema with or without limited deep white matter extension, grade 2 (moderate): white matter and cortex edema with limited ventricle surface extension, grade 3 (severe): diffuse, widely confluent white matter and cortex edema with extensive ventricle contact or ventricle deformity], diffusivity of lesions (reduced or increased apparent diffusion coefficient), presence of hemorrhage, and contrast enhancement.

Patient Follow-Up Follow-up brain MRI was carried out in all patients for evaluation of reversibility of edematous brain areas and/or development of residual lesions. Our neurologists monitored all patients on regular office visits.

Statistical Analysis Descriptive statistics were used in this study.

Results Population Ten patients (6 girls and 4 boys) were diagnosed with posterior reversible encephalopathy syndrome. Median ages at the time of diagnosis of hematologic malignancy and posterior reversible encephalopathy syndrome were 6.3 (8 months to 12.4 years) and 8.5 (1.4-12.5 years) years, respectively. Primary diagnoses were acute lymphoblastic leukemia (n ¼ 5), acute myeloid leukemia (n ¼ 2), Hodgkin lymphoma (n ¼ 1), Burkitt lymphoma (n ¼ 1), and hemophagocytic lymphohistiocytosis secondary to myelodysplastic syndrome (n ¼ 1). At onset, 4 patients were undergoing first-line chemotherapy. Another 4 patients were at 37, 52, 78, and 857 days from bone marrow transplant (3 matched unrelated and 1 umbilical cord blood). The patient with Hodgkin lymphoma was undergoing chemotherapy as relapsed treatment. The patient with hemophagocytic lymphohistiocytosis was undergoing chemotherapy as relapsed treatment but had performed an umbilical cord blood transplant 34 months before. All bone marrow transplant recipients presented graft-versus-host disease and were receiving a calcineurin inhibitor (cyclosporine or tacrolimus).

Clinical Features Table 1 summarizes patients’ demographic data, clinical features at the onset of posterior reversible encephalopathy syndrome, and the outcome. Seizure was the initial sign in 9 (90%) patients. Altered mental status and headache were presented in 5 (50%) and 3 (30%) patients, respectively. Two patients (20%) complained of severe abdominal pain preceding posterior reversible encephalopathy syndrome. Nine (90%) patients were hypertensive and 1 had normal blood pressure. Three children were receiving antihypertensive drugs at the onset of posterior reversible encephalopathy syndrome. The mean hemoglobin value was 10.6 g/dL, and anemia was identified in 7 (70%) patients. Electroencephalogram reports were available in 2 patients: one showed focal slowing waves (patient no. 1) and the other generalized dysrhythmic waves (patient no. 4).

Neuroimaging Features Brain computed tomography was performed in 9 patients: 5 were normal or had nonspecific findings and the remaining 4 showed bilateral diffuse cortico-subcortical low-density

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F

M

F

M M F

F M

3

4

5

6 7 8

9 10

8.1 ALL-B 8.4 ALL-T

5.5 Burkitt lymphoma 12.4 ALL-B Phþ 8.8 ALL-B 9.6 MDS, HLH

6.3 ALL-B

U-BMT/TCL, CCT U-BMT/TCL, CCT

ND U-BMT/TCL UCB/CyA

ND

ND

12.5 AML-M3 ND 10.5 Hodgkin ND lymphoma 1.4 AML-M7 UCB/CyA, MMF

Allo-HSCT/ Immunosuppression

ESPHALL None Etoposide, CyA, dexamethasone None None

LMB 2001–COP

EORTC 58951

None

APL 2000 DHAP

Chemotherapy

Hypertension 142/99

141/95 BP >P95þ20% 120/84

159/105

155/90

170/110

149/85 133/98

BP (mm Hg)

9.3 12.2

14.2 12.5 11.4

9.2

8.9

9.1

9.9 9.6

Hg (g/ dL)

Seizures, consciousness impairment, visual disturbance Abdominal pain, unresponsiveness Seizures, unresponsiveness, hemiparesis Abdominal pain, seizures, headache Seizures, headache Seizures, consciousness impairment, hemiparesis Seizures, headache Seizures, consciousness impairment, nystagmus

Seizures, hemiparesis Seizures

Clinical symptoms

No Yes

No Yes No

No

Yes

No

No No

34.2 0.5

45.8 8.0 4.5

51.3

7.4

52.3

40.0 5.3

Deceased Alive Deceased Epilepsy Alive Deceased

Alive

Alive Epilepsy Alive

Alive Deceased

ICU Follow-up admission (mo) Outcome

Abbreviations: ALL, acute lymphoblastic leukemia; allo-HSCT, allogenic hematopoietic stem cell transplant; AML, acute myeloid leukemia; BP, blood pressure; CCT, corticosteroid; CyA, cyclosporine; F, female; Hg, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; ICU, intensive care unit; M, male; MDS, myelodysplastic syndrome; MMF, mycophenolate mofetil; ND, not done; TCL, tacrolimus; U-BMT, unrelated bone marrow transplant; UCB, umbilical cord blood transplant.

F F

1 2

Patient Age Primary no. Gender (y) diagnosis

Table 1. Demographic Data, Clinical Features, and Outcome of 10 Children With Hematologic Malignancies That Developed Posterior Reversible Encephalopathy Syndrome.

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Table 2. Radiologic Findings of 10 Children With Hematologic Malignancies That Developed Posterior Reversible Encephalopathy Syndrome. Radiologic item Edema location

Distribution pattern

Edema grading ADC Enhancement

n (%) Parietal Occipital Frontal Temporal Cerebellum Thalamus Holohemispheric watershed Parieto-occipital Superior frontal sulcus Mild Moderate Increased Reduced None Pathological

10 8 7 6 2 1 6 3 1 9 1 8 2 9 1

(100) (80) (70) (60) (20) (10) (60) (30) (10) (90) (10) (80) (20) (90) (10)

Abbreviation: ADC, attenuated diffusivity coefficient.

areas. Brain MRI was performed in 10 patients. Table 2 summarizes brain MRI features of posterior reversible encephalopathy syndrome. Figure 1 shows the 3 most common topographic edema distribution patterns in our population. Parietal edema was encountered in all patients. Occipital, frontal, and temporal edema was seen in 80%, 70%, and 60% of patients, respectively. Cerebellar and thalamic involvement was found in 20% and 10% of patients, respectively. No patient presented edema in the striatum, pallidum, hypothalamus, mesencephalon, pons, or corpus callosum. Several topographic imaging patterns of posterior reversible encephalopathy syndrome have been described previously in the literature.2,3 Holohemispheric watershed pattern (60%) was the most frequently found (Figure 1a). Parieto-occipital (Figure 1b) and superior frontal sulcus (Figure 1c) patterns were encountered in 30% and 10% of patients, respectively. Central pattern was not observed. Regarding the extent of edematous brain areas, 9 patients showed edema grade 1 (90%) and 1 patient showed edema grade 2. No patient showed edema grade 3. Foci or areas with reduced apparent diffusion coefficient were observed in only 20% of patients. Increased apparent diffusion coefficient values were observed in 80% of patients. Pathologic contrast enhancement was observed in only 1 patient, having a leptomeningeal distribution. No patient showed hemorrhagic events associated with posterior reversible encephalopathy syndrome. Location, topographic edema pattern, and diffusivity of lesions did not predict admission to intensive care unit or development of secondary epilepsy.

Management and Outcome Three patients were admitted to the pediatric intensive care unit and 2 of them required intubation and mechanical ventilation. These 3 patients recovered totally from neurologic deficits and were transferred back to the general ward in less than 24 hours.

During the acute event, all patients received antiepileptic therapy: 9 patients received valproate sodium and 1 received levetiracetam. Nine patients (90%) were discharged home and 1 patient died in hospital of disseminated viral disease (patient no. 10). Those 9 patients were followed up for an average of 27.6 months (4.5-52.3 months). Follow-up imaging was performed in those 9 patients and complete resolution of vasogenic edema was documented in all. Patients undergoing chemotherapy at the onset of posterior reversible encephalopathy syndrome resumed and completed their treatment plan. Two patients developed secondary epilepsy and were maintained on antiepileptic therapy. For 5 patients, antiepileptic therapy was withdrawn after an average of 5.4 months (2.7-14.2 months), and they did not develop recurrent seizures. The remaining 2 patients were reducing antiepileptic therapy at the time of last appointment. Recurrence of posterior reversible encephalopathy syndrome was not observed in any case. Three patients died during follow-up, all of infectious complications: pneumonia (n ¼ 2) and catheter-related infection (n ¼ 1).

Discussion Posterior reversible encephalopathy syndrome is a heterogeneous entity that has been reported in children with several malignant and nonmalignant predisposing conditions. In the largest European cohort of children with posterior reversible encephalopathy syndrome described in the literature, renal insufficiency was the most common primary disorder, with only 3 patients having hematologic malignancies.3 Our study described the clinical-radiologic features and the outcome of 10 patients with hematologic malignancies, highlighting that we report the first case study of children with Hodgkin lymphoma who developed posterior reversible encephalopathy syndrome during chemotherapy for relapsed disease. Multiple factors contribute to the high risk of posterior reversible encephalopathy syndrome in children with hematologic malignancies, namely, hypertension, high-dose multidrug cytotoxic chemotherapy, transplantation, graft-versus-host disease, and immunosuppressants. Anemia is present in more than 90% of patients with hematologic malignancies and may also contribute to posterior reversible encephalopathy syndrome as was recently shown.12 High-dose multidrug cytotoxic chemotherapy has been reported as an important cause of posterior reversible encephalopathy syndrome in children with either hematologic or oncologic diseases.13,14 Although posterior reversible encephalopathy syndrome may complicate the treatment of hematologic malignancies in any stage of chemotherapy, the risk is highest with more intensive regimens (induction chemotherapy for acute lymphoblastic leukemia and relapsed chemotherapy for other malignancies). Two patients presented with severe abdominal pain, an unexpected symptom that has been infrequently reported in the literature.7 Acute elevation of blood pressure and gastrointestinal complaints may reflect autonomic nervous system dysfunction and be warning signs of posterior reversible encephalopathy syndrome in children undergoing intensive

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Figure 1. Three topographic edema distribution patterns in posterior reversible encephalopathy syndrome observed in the present study: (A) holohemispheric watershed pattern, (B) predominant parieto-occipital pattern, (C) predominant superior frontal sulcus pattern.

chemotherapy. We look forward for larger cohorts to confirm this association. Clinicians may be reluctant in resuming chemotherapy after the acute neurologic event. In the present cohort, all patients completed their treatment protocol and no case of posterior reversible encephalopathy syndrome recurrence was noticed, corroborating the findings of other authors.12,14,15 Thus, we believe there is no need to suspend chemotherapy or avoid intrathecal and radiation therapy when they’re recommended by therapeutic protocols. Posterior reversible encephalopathy syndrome is a significant clinical problem in the setting of bone marrow or stem cell transplantation. The incidence of posterior reversible encephalopathy syndrome at our cohort was 4.3%. The risk is highest during the first 100 days after transplant but persists for several months.16-18 All bone marrow transplant recipients had graftversus-host disease and were receiving immunosuppressants (tacrolimus or cyclosporine), suggesting that both factors predispose to posterior reversible encephalopathy syndrome. Two opposing mechanisms may explain the pathophysiology underlying posterior reversible encephalopathy syndrome. One mechanism by which children with hematologic malignancies develop posterior reversible encephalopathy syndrome involves the direct toxic effect of transplantation, cancer chemotherapy, immunosuppressants, anemia, and graft-versus-host disease on the cerebrovascular endothelium.19-21 The endothelium possesses intrinsic vasodilator properties, but endothelial injury leads to vascular instability and local vasoconstriction, with downstream hypoperfusion.22 These reactions result in blood-brain barrier dysfunction with vasogenic edema.12,23 Data supporting this mechanism have been reported. A recent study involving MRI angiography in children with posterior reversible encephalopathy syndrome showed multifocal narrowing in the posterior cerebral circulation.24 The second hypothesis suggests that the acute elevation of blood pressure overcomes the limit of cerebral autoregulation, leading to the breakdown of the blood-brain barrier, hyperperfusion, and leakage of fluid into the brain with subsequent vasogenic edema.

This hypothesis is supported by the high prevalence of hypertension in children with posterior reversible encephalopathy syndrome irrespective of its etiology.15,24,25 In our opinion, both mechanisms are equally relevant to our cancer patients. Our treatment strategy combined general measures with the correction of the underlying cause. Important aspects were (1) reduction of the causative drug (steroids) or change to an alternative one (tacrolimus to cyclosporine or vice versa), (2) aggressive management of blood pressure, and (3) treatment of seizures (valproate sodium or levetiracetam). Antiepileptic therapy is difficult to manage in these patients and there are no firm recommendations regarding drugs of choice and duration of therapy. Morris et al13 recommended gradual withdrawal of antiepileptic therapy within 3 to 6 months in uncomplicated patients. Patients with abnormal findings in brain MRI have a high risk of epilepsy and benefit from a longer regimen (12 months). We managed to withdraw antiepileptic therapy successfully in 5 patients, and another 2 were reducing treatment at the time of their last appointments. Our results add to the emerging clinical and radiologic data challenging the classical definition of posterior reversible encephalopathy syndrome. First, it presents with a variety of MRI findings. Although the most common location of vasogenic edema in our cohort was the parieto-occipital region of both cerebral hemispheres, atypical locations such as the cerebellum and thalamus were seen in 10% to 20% of the cases. However, there appears to be no predictive correlation between MRI findings and the outcome of posterior reversible encephalopathy syndrome. Second, it can have an aggressive behavior and be eventually fatal. Up to 30% of children diagnosed with posterior reversible encephalopathy syndrome are admitted to an intensive care unit for mechanical ventilation and/or organ support.12,26 In a group of 27 consecutive children, 5 developed life-threatening complications (cerebral hemorrhage, transforaminal cerebellar herniation, and refractory status epilepticus) and 2 of them died.11 Third, a significant number of children develop chronic clinical and radiographic sequelae. Two children

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in our cohort developed chronic epilepsy. We did not observe persistent edema and/or structural residua on follow-up MRI, but they have been well documented by other authors.2,3,27 In a series of 11 children with cancer, 3 developed chronic epilepsy even though follow-up MRI was abnormal in only 1 patient. Recurrence of posterior reversible encephalopathy syndrome is rare, and it has been reported most frequently in patients with systemic hypertension as the primary etiology.24,28,29 Systemic hypertension has been found in more than two-thirds of children with hematologic malignancies, but only a minority is under treatment.30 Recognizing pediatric hypertension is challenging. On the one hand, it is defined by age, gender, and height and, on the other, elevations in blood pressure are frequently regarded as mild and transient. At our cohort, only 3 of 9 children with hypertension were receiving antihypertensive drugs. In fact, children are more vulnerable to cerebral dysfunction than adults under systemic hypertension because they have a narrower range of autoregulation in cerebral blood flow.31 Health care providers become more sensitive to high blood pressure after a neurologic emergency. We speculate that intensive monitoring of blood pressure and treatment of hypertension after posterior reversible encephalopathy syndrome may have prevented its recurrence at our cohort. Our study has some limitations. First, patients were selected from the pediatric report database, which may have biased our results and some cases may have been missed. Second, our cohort is small and heterogeneous, which may mitigate the interpretation of the results. Finally, we could not make confirmative conclusions because no control sample of patients was used.

Conclusions Pediatric patients with hematologic malignancies have a high risk of neurologic complications, namely, posterior reversible encephalopathy syndrome. Pediatric oncologists should consider posterior reversible encephalopathy syndrome in every patient presenting with altered mental status, seizures, hypertension, and acute severe abdominal pain during cancer treatment. Better recognition and serious consideration for treatment should be given to hypertension in children with hematologic malignancies. Brain MRI plays an important role in the diagnosis of posterior reversible encephalopathy syndrome and should be performed on an urgent basis. In spite of accurate diagnosis and immediate intervention by a multidisciplinary team (neurologist, pediatric oncologist, neuroradiologist, and intensivist), neurologic sequelae may still develop. Thus, we recommend a close follow-up even in patients with complete clinical and radiologic recovery in the short term. Further understanding of posterior reversible encephalopathy syndrome will lead to optimal management of these patients. Acknowledgment This study was performed at the Department of Pediatrics, Portuguese Institute of Oncology, Porto, Portugal.

Author Contributions MT collected and organized the data and wrote the first manuscript (including the first draft). MA reviewed the neuroimaging findings. ACJ, AP, TS and SP cared for the patients. MA, SC, JMM, and SP provided their support and mentorship. All authors verified the results and revised the final manuscript.

Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval The Institutional Ethical Committee at the Portuguese Institute of Oncology, Porto, reviewed and approved this study (CES.194/014).

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21. Schots R, Kaufman L, Van Riet I, et al. Proinflammatory cytokines and their role in the development of major transplantrelated complications in the early phase after allogeneic bone marrow transplantation. Leukemia. 2003;17:1150-1156. 22. Stanimirovic D, Satoh K. Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation. Brain Pathol. 2000;10:113-126. 23. Staykov D, Schwab S. Posterior reversible encephalopathy syndrome. J Intensive Care Med. 2012;27:11-24. 24. Singh RR, Ozyilmaz N, Waller S, et al. A study on clinical and radiological features and outcome in patients with posterior reversible encephalopathy syndrome (PRES). Eur J Pediatr. 2014;173: 1225-1231. 25. Ishikura K, Hamasaki Y, Sakai T, et al. Posterior reversible encephalopathy syndrome in children with kidney diseases. Pediatr Nephrol. 2012;27:375-384. 26. Chen TH, Chiou SS, Lin WC, et al. Posterior reversible encephalopathy syndrome in critically ill children: a case series. Intensive Care Med. 2013;39:155-156. 27. Stevens CJ, Heran MKS. The many faces of posterior reversible encephalopathy syndrome. Br J Radiol. 2012;85:1566-1575. 28. Roth C, Ferbert A. Posterior reversible encephalopathy syndrome: long-term follow-up. J Neurol Neurosurg Psychiatry. 2010;81: 773-777. 29. Li R, Mitchell P, Dowling R, Yan B. Is hypertension predictive of clinical recurrence in posterior reversible encephalopathy syndrome? J Clin Neurosci. 2013;20:248-252. 30. Louis CU, Butani L. High blood pressure and hypertension in children with newly diagnosed acute leukemia and lymphoma. Pediatr Nephrol. 2008;23:603-609. 31. Jones BV, Egelhoff JC, Patterson RJ. Hypertensive encephalopathy in children. Am J Neuroradiol. 1997;18:101-106.

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Posterior Reversible Encephalopathy Syndrome in Children With Hematologic Malignancies.

Since its original description 2 decades ago, posterior reversible encephalopathy syndrome has been reported in children with several predisposing con...
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