Multifactorial Posterior Reversible Encephalopathy Syndrome in Children: Clinical, Laboratory, and Neuroimaging Findings

Abstract

The aim of this study was to investigate the association of neuroimaging, clinical, and laboratory findings in children with different underlying diseases who developed posterior reversible encephalopathy syndrome (PRES). All consecutive pediatric patients referred to our institute between 2000 and 2017 were retrospectively evaluated for newly diagnosed PRES. Clinical data, medical history, and therapies administered at the time of PRES and laboratory findings were reviewed as the magnetic resonance imaging (MRI) obtained at PRES presentation and during follow-up. Statistics included Mann–Whitney U, Chi-square, and Fisher's exact tests. A total of 39 pediatric patients (25 males, median age = 8.8 years) with a confirmed diagnosis of PRES were included. The patients were divided into four groups based on the underlying disease: (1) patients with hemato-oncological diseases not transplanted (n = 15, 38.5%), (2) who underwent hematopoietic stem cell transplantation (HSCT; n = 12, 30.8%), (3) affected by renal (n = 8, 20.5%), and (4) by autoimmune diseases (n = 4, 10.2%). Hemato-oncological patients and those undergoing HSCT presented a higher incidence of involvement of deep gray matter structures and hemorrhagic lesions when compared with patients with renal and autoimmune disorders (p = 0.036 and p = 0.036, respectively). No differences emerged among different groups of patients regarding presenting PRES symptoms, arterial blood pressure, laboratory findings, and extent of MRI abnormalities and these parameters did not show association with outcome.

In conclusion, in pediatric patients with different diseases who develop PRES, involvement of deep gray matter structures and hemorrhagic lesions are more common in hemato-oncological patients and those undergoing HSCT. Clinical and radiologic outcome is favorable independently of clinical data and extent of MRI abnormalities.

Keywords

posterior reversible encephalopathy syndrome - pediatric patients - magnetic resonance imaging

Ethical Approval

This retrospective study was approved by our institutional review board (Regional Ethics Committee of Liguria, Genoa, Italy-28REG2017).

Authors' Contributions

All authors have contributed to the manuscript in significant ways, have reviewed, and agreed upon the manuscript content

Publication History

Received: 09 May 2020

Accepted: 31 May 2020

Article published online:
05 August 2020

• References

• 1 Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015; 14 (09) 914-925
• 2 Gao B, Lyu C, Lerner A, McKinney AM. Controversy of posterior reversible encephalopathy syndrome: what have we learnt in the last 20 years?. J Neurol Neurosurg Psychiatry 2018; 89 (01) 14-20
• 3 Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol 2017; 264 (08) 1608-1616
• 4 Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 2008; 29 (06) 1036-1042
• 5 Kastrup O, Schlamann M, Moenninghoff C, Forsting M, Goericke S. Posterior reversible encephalopathy syndrome: the spectrum of MR imaging patterns. Clin Neuroradiol 2015; 25 (02) 161-171
• 6 Karia SJ, Rykken JB, McKinney ZJ, Zhang L, McKinney AM. Utility and significance of gadolinium-based contrast enhancement in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol 2016; 37 (03) 415-422
• 7 Gavrilovici C, Miron I, Voroneanu L, Bădărau S, Stârcea M. Posterior reversible encephalopathy syndrome in children with kidney disease. Int Urol Nephrol 2017; 49 (10) 1793-1800
• 8 Masetti R, Cordelli DM, Zama D. et al. PRES in children undergoing hematopoietic stem cell or solid organ transplantation. Pediatrics 2015; 135 (05) 890-901
• 9 de Laat P, Te Winkel ML, Devos AS, Catsman-Berrevoets CE, Pieters R, van den Heuvel-Eibrink MM. Posterior reversible encephalopathy syndrome in childhood cancer. Ann Oncol 2011; 22 (02) 472-478
• 10 Won SC, Kwon SY, Han JW, Choi SY, Lyu CJ. Posterior reversible encephalopathy syndrome in childhood with hematologic/oncologic diseases. J Pediatr Hematol Oncol 2009; 31 (07) 505-508
• 11 Rossi A, Morana G, Gandolfo C, Severino M. Neuroradiology of chemotherapeutic. Neurotoxicity in children. Neuroradiol J 2010; 23 (02) 183-190
• 12 Faraci M, Lanino E, Dini G. et al. Severe neurologic complications after hematopoietic stem cell transplantation in children. Neurology 2002; 59 (12) 1895-1904
• 13 Banerjee JS, Heyman M, Palomäki M. et al. Posterior reversible encephalopathy syndrome: risk factors and impact on the outcome in children with acute lymphoblastic leukemia treated with nordic protocols. J Pediatr Hematol Oncol 2018; 40 (01) e13-e18
• 14 Anastasopoulou S, Eriksson MA, Heyman M. et al. Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia: Clinical characteristics, risk factors, course, and outcome of disease. Pediatr Blood Cancer 2019; 66 (05) e27594
• 15 Khan RB, Sadighi ZS, Zabrowski J, Gajjar A, Jeha S. Imaging patterns and outcome of posterior reversible encephalopathy syndrome during childhood cancer treatment. Pediatr Blood Cancer 2016; 63 (03) 523-526
• 16 Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. AJNR Am J Neuroradiol 2002; 23 (06) 1038-1048
• 17 Siebert E, Spors B, Bohner G, Endres M, Liman TG. Posterior reversible encephalopathy syndrome in children: radiological and clinical findings - a retrospective analysis of a German tertiary care center. Eur J Paediatr Neurol 2013; 17 (02) 169-175
• 18 Raj S, Overby P, Erdfarb A, Ushay HM. Posterior reversible encephalopathy syndrome: incidence and associated factors in a pediatric critical care population. Pediatr Neurol 2013; 49 (05) 335-339
• 19 Zama D, Masetti R, Cordelli DM. et al. Risk factor analysis of posterior reversible encephalopathy syndrome after allogeneic hematopoietic SCT in children. Bone Marrow Transplant 2014; 49 (12) 1538-1540
• 20 Hefzy HM, Bartynski WS, Boardman JF, Lacomis D. Hemorrhage in posterior reversible encephalopathy syndrome: imaging and clinical features. AJNR Am J Neuroradiol 2009; 30 (07) 1371-1379
• 21 Cordelli DM, Masetti R, Ricci E. et al. Life-threatening complications of posterior reversible encephalopathy syndrome in children. Eur J Paediatr Neurol 2014; 18 (05) 632-640
• 22 Carreras E, Diaz-Ricart M. The role of the endothelium in the short-term complications of hematopoietic SCT. Bone Marrow Transplant 2011; 46 (12) 1495-1502
• 23 Penack O, Socié G, van den Brink MR. The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation. Blood 2011; 117 (16) 4181-4189
• 24 Palomo M, Diaz-Ricart M, Carbo C. et al. Endothelial dysfunction after hematopoietic stem cell transplantation: role of the conditioning regimen and the type of transplantation. Biol Blood Marrow Transplant 2010; 16 (07) 985-993
• 25 Palomo M, Diaz-Ricart M, Carbo C. et al. The release of soluble factors contributing to endothelial activation and damage after hematopoietic stem cell transplantation is not limited to the allogeneic setting and involves several pathogenic mechanisms. Biol Blood Marrow Transplant 2009; 15 (05) 537-546
• 26 McKinney AM, Short J, Truwit CL. et al. Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 2007; 189 (04) 904-912
• 27 Moon SN, Jeon SJ, Choi SS. et al. Can clinical and MRI findings predict the prognosis of variant and classical type of posterior reversible encephalopathy syndrome (PRES)?. Acta Radiol 2013; 54 (10) 1182-1190
• 28 Schwartz RB, Mulkern RV, Gudbjartsson H, Jolesz F. Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to pathogenesis. AJNR Am J Neuroradiol 1998; 19 (05) 859-862