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Neuropediatrics
DOI: 10.1055/a-2627-2045
Review Article

Evaluating Risk Factors for Lethality in Posterior Reversible Encephalopathy Syndrome following Hematopoietic Stem Cell Transplantation in Pediatric Patients: A Systematic Review and Individual Participant Data Meta-analysis

Mohammadreza Padooiy Nooshabadi 
1   Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Hossein Akbarnataj Bishe
1   Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Seyyed Amir Yasin Ahmadi
2   Department of Community and Family Medicine, Preventive Medicine and Public Health Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
,
Marzieh Eshagh
1   Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Maryam Behfar
1   Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Leila Jafari
1   Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
,
Amir Ali Hamidieh
1   Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Funding None.
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Abstract

Hematopoietic stem cell transplantation (HSCT) is frequently the sole curative treatment for a range of hematologic and nonhematologic disorders. One of the most notable neurological complications associated with HSCT is posterior reversible encephalopathy syndrome (PRES), which affects approximately 1 to 10% of pediatric recipients. Although usually reversible, PRES can lead to serious morbidity and lethality. This systematic review and individual participant data (IPD) meta-analysis aims to evaluate risk factors for lethality and characterize the clinical course of PRES in pediatric HSCT patients.

Studies reporting PRES in pediatric HSCT recipients with data on outcomes and risk factors were included. Data were sourced from PubMed, Web of Science, Scopus, and Embase (last search: October 20, 2024). IPD were extracted from articles or requested from corresponding authors. Risk of bias was assessed using the Newcastle–Ottawa Scale. A one-stage IPD meta-analysis evaluated associations between risk factors and lethality and descriptive analyses reported the clinical course of PRES in the included population.

Among 175 pediatric patients with PRES across 15 studies, the mean age was 8.68 years, and 64.8% were male. PRES occurred on average 73.08 days post-HSCT presenting with seizures (90.3%), hypertension (87.8%), altered mental status (31.9%), headache (28.5%), visual disturbances (27.1%), and atypical presentations (24.3%). Neuroimaging findings indicated that 12.3% of cases involved only anterior or posterior brain circulation, while most (75.4%) demonstrated dual circulation involvement, with bilateral cerebral involvement observed in 89.8% of patients. The overall lethality rate was 32.5%. The meta-analysis reported an overall prevalence of 7% for PRES among pediatric recipients of HSCT. The IPD meta-analysis revealed no significant associations between lethality and factors such as age (p = 0.590), sex (p = 0.516), atypical PRES presentations (p = 0.642), or the specific cerebral circulation involved (p = 0.758). Conversely, acute graft-versus-host disease demonstrated a trend toward statistical significance for association with lethality (p = 0.056). Additionally, underlying malignant disease (odds ratio [OR]: 2.635, 95% confidence interval [95% CI]: 1.256–5.529, p = 0.01), the use of cord blood as a cell source (OR: 5.692, 95% CI: 1.241–26.109, p = 0.025), and transplantation from an unrelated donor (OR: 4.948, 95% CI: 2.176–11.249, p < 0.001) were significantly associated with increased lethality risk.

Malignant underlying disease, cord blood transplantation, and unrelated donors significantly increase lethality risk in pediatric HSCT recipients with PRES. These findings underscore the importance of tailored management strategies to identify and monitor at-risk pediatric HSCT recipients.

Keywords

posterior reversible encephalopathy syndrome - hematopoietic stem cell transplantation - pediatric recipients - posttransplant complications - treatment-related neurologic complications - risk factors for lethality

Supplementary Material



Publikationsverlauf

Eingereicht: 06. März 2025

Angenommen: 03. Juni 2025

Artikel online veröffentlicht:
18. Juni 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 2008; 29 (06) 1036-1042
    CrossrefPubMedSuche in Google Scholar
  • 2 Hinchey J, Chaves C, Appignani B. et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334 (08) 494-500
    Suche in Google Scholar
  • 3 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
    Suche in Google Scholar
  • 4 Gümüş H, Per H, Kumandaş S, Yikilmaz A. Reversible posterior leukoencephalopathy syndrome in childhood: report of nine cases and review of the literature. Neurol Sci 2010; 31 (02) 125-131
    Suche in Google Scholar
  • 5 Ghosh PS, Hupertz V, Ghosh D. Neurological complications following pediatric liver transplant. J Pediatr Gastroenterol Nutr 2012; 54 (04) 540-546
    PubMedSuche in Google Scholar
  • 6 Ghosh PS, Kwon C, Klein M, Corder J, Ghosh D. Neurologic complications following pediatric renal transplantation. J Child Neurol 2014; 29 (06) 793-798
    PubMedSuche in Google Scholar
  • 7 Geevasinga N, Cole C, Herkes GK, Barnett Y, Lin J, Needham M. Sickle cell disease and posterior reversible leukoencephalopathy. J Clin Neurosci 2014; 21 (08) 1329-1332
    PubMedSuche in Google Scholar
  • 8 Lee G, Lee SE, Ryu KH, Yoo ES. Posterior reversible encephalopathy syndrome in pediatric patients undergoing treatment for hemophagocytic lymphohistiocytosis: clinical outcomes and putative risk factors. Blood Res 2013; 48 (04) 258-265
    PubMedSuche in Google Scholar
  • 9 Faraci M, Lanino E, Dini G. et al. Severe neurologic complications after hematopoietic stem cell transplantation in children. Neurology 2002; 59 (12) 1895-1904
    PubMedSuche in Google Scholar
  • 10 Hashmi SK. Basics of hematopoietic cell transplantation for primary care physicians and internists. Prim Care 2016; 43 (04) 693-701
    PubMedSuche in Google Scholar
  • 11 Santos MM, Tannuri AC, Gibelli NE. et al. Posterior reversible encephalopathy syndrome after liver transplantation in children: a rare complication related to calcineurin inhibitor effects. Pediatr Transplant 2011; 15 (02) 157-160
    PubMedSuche in Google Scholar
  • 12 Cordelli DM, Masetti R, Zama D. et al. Etiology, characteristics and outcome of seizures after pediatric hematopoietic stem cell transplantation. Seizure 2014; 23 (02) 140-145
    PubMedSuche in Google Scholar
  • 13 Habetz K, Ramakrishnaiah R, Raina SK, Fitzgerald RT, Hinduja A. Posterior reversible encephalopathy syndrome: a comparative study of pediatric versus adult patients. Pediatr Neurol 2016; 65: 45-51
    PubMedSuche in Google Scholar
  • 14 Hun M, Tian J, Xie M. et al. Analysis of risk factors associated with poor outcome in posterior reversible encephalopathy syndrome after treatment in children: systematic review and meta-analysis. Front Neurol 2020; 11: 938
    PubMedSuche in Google Scholar
  • 15 Tambasco N, Mastrodicasa E, Salvatori C. et al. Prognostic factors in children with PRES and hematologic diseases. Acta Neurol Scand 2016; 134 (06) 474-483
    PubMedSuche in Google Scholar
  • 16 Stewart LA, Clarke M, Rovers M. et al; PRISMA-IPD Development Group. Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD statement. JAMA 2015; 313 (16) 1657-1665
    CrossrefPubMedSuche in Google Scholar
  • 17 Jafari L, Behfar M, Tabatabaie S. et al. 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. Clin Transplant 2024; 38 (01) e15164
    PubMedSuche in Google Scholar
  • 18 Wells GA, Shea B, O'Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute; 2010 . Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
    PubMedSuche in Google Scholar
  • 19 Chen B, Benedetti A. Quantifying heterogeneity in individual participant data meta-analysis with binary outcomes. Syst Rev 2017; 6 (01) 243
    PubMedSuche in Google Scholar
  • 20 Behfar M, Babaei M, Radmard AR. et al. Posterior reversible encephalopathy syndrome after allogeneic stem cell transplantation in pediatric patients with Fanconi anemia, a prospective study. Biol Blood Marrow Transplant 2020; 26 (12) e316-e321
    PubMedSuche in Google Scholar
  • 21 Hamidieh A, Jafari L, Kashani H. et al, eds. The effect of posterior reversible encephalopathy syndrome after hematopoietic stem cell transplantation in pediatric patients with beta-major thalassemia. Bone Marrow Transplant; 2023. Springer Nature, England.
    Suche in Google Scholar
  • 22 Gaziev J, Marziali S, Paciaroni K. et al. Posterior reversible encephalopathy syndrome after hematopoietic cell transplantation in children with hemoglobinopathies. Biol Blood Marrow Transplant 2017; 23 (09) 1531-1540
    PubMedSuche in Google Scholar
  • 23 Li XY, Huang K, Zhou DH. et al. Severe hypertension is an independent risk factor for posterior reversible encephalopathy syndrome post-hematopoietic cell transplantation in children with thalassemia major. Clin Transplant 2019; 33 (01) e13459
    PubMedSuche in Google Scholar
  • 24 Majumdar S, Robertson Z, Robinson A, Starnes S, Iyer R, Megason G. Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience. Bone Marrow Transplant 2010; 45 (05) 895-900
    PubMedSuche in Google Scholar
  • 25 Atça AÖ, Erok B, Aydoğdu S. Neuroimaging findings of posterior reversible encephalopathy syndrome (PRES) following haematopoietic stem cell transplantation in paediatric recipients. BMC Pediatr 2021; 21 (01) 445
    PubMedSuche in Google Scholar
  • 26 Cordelli DM, Masetti R, Bernardi B. et al. Status epilepticus as a main manifestation of posterior reversible encephalopathy syndrome after pediatric hematopoietic stem cell transplantation. Pediatr Blood Cancer 2012; 58 (05) 785-790
    PubMedSuche in Google Scholar
  • 27 Grioni D, Pavan F, Prunotto G, Canonico F, Grandi C, Rovelli A. Should posterior reversible encephalopathy syndrome be mainly considered an epileptic disorder? Results of a sequential neurophysiological study in a pediatric cohort. Neuropediatrics 2017; 48 (02) 72-78
    PubMedSuche in Google Scholar
  • 28 Kapoor R, Simalti A, Kumar R. et al. PRES in pediatric HSCT: a single-center experience. J Pediatr Hematol Oncol 2018; 40 (06) 433-437
    PubMedSuche in Google Scholar
  • 29 Kim SJ, Im SA, Lee JW. et al. Predisposing factors of posterior reversible encephalopathy syndrome in acute childhood leukemia. Pediatr Neurol 2012; 47 (06) 436-442
    Suche in Google Scholar
  • 30 Lee Y-J, Yum M-S, Kim E-H. et al. Clinical characteristics of transplant-associated encephalopathy in children. J Korean Med Sci 2017; 32 (03) 457-464
    PubMedSuche in Google Scholar
  • 31 Shkalim-Zemer V, Konen O, Levinsky Y. et al. Calcineurin inhibitor-free strategies for prophylaxis and treatment of GVHD in children with posterior reversible encephalopathy syndrome after stem cell transplantation. Pediatr Blood Cancer 2017; 64 (11) e26531
    PubMedSuche in Google Scholar
  • 32 Straathof K, Anoop P, Allwood Z. et al. Long-term outcome following cyclosporine-related neurotoxicity in paediatric allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 2017; 52 (01) 159-162
    PubMedSuche in Google Scholar
  • 33 Tavares M, Arantes M, Chacim S. et al. Posterior reversible encephalopathy syndrome in children with hematologic malignancies. J Child Neurol 2015; 30 (12) 1669-1675
    PubMedSuche in Google Scholar
  • 34 Wang Y, Zheng Y, Wen J. et al. Cyclosporine A-related neurotoxicity after haploidentical hematopoietic stem cell transplantation in children with hematopathy. Ital J Pediatr 2021; 47 (01) 83
    PubMedSuche in Google Scholar
  • 35 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg 2021; 88: 105906
    CrossrefPubMedSuche in Google Scholar
  • 36 Bartynski WS, Zeigler ZR, Shadduck RK, Lister J. Pretransplantation conditioning influence on the occurrence of cyclosporine or FK-506 neurotoxicity in allogeneic bone marrow transplantation. AJNR Am J Neuroradiol 2004; 25 (02) 261-269
    PubMedSuche in Google Scholar
  • 37 Server A, Bargalló N, Fløisand Y, Sponheim J, Graus F, Hald JK. Imaging spectrum of central nervous system complications of hematopoietic stem cell and solid organ transplantation. Neuroradiology 2017; 59 (02) 105-126
    PubMedSuche in Google Scholar
  • 38 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
    PubMedSuche in Google Scholar
  • 39 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
    PubMedSuche in Google Scholar
  • 40 Jordão M, Raimundo P, Jacinto R. et al. Etiology and clinical characteristics of pediatric non-neoplastic posterior reversible encephalopathy: systematic review. Porto Biomed J 2022; 7 (03) e147
    PubMedSuche in Google Scholar
  • 41 Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol 2017; 264 (08) 1608-1616
    CrossrefPubMedSuche in Google Scholar
  • 42 Roth C, Ferbert A. The posterior reversible encephalopathy syndrome: what's certain, what's new?. Pract Neurol 2011; 11 (03) 136-144
    Suche in Google Scholar
  • 43 Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015; 14 (09) 914-925
    CrossrefPubMedSuche in Google Scholar
  • 44 Siebert E, Bohner G, Endres M, Liman TG. Clinical and radiological spectrum of posterior reversible encephalopathy syndrome: does age make a difference? A retrospective comparison between adult and pediatric patients. PLoS One 2014; 9 (12) e115073
    CrossrefPubMedSuche in Google Scholar
  • 45 Chen Z, Zhang G, Lerner A, Wang AH, Gao B, Liu J. Risk factors for poor outcome in posterior reversible encephalopathy syndrome: systematic review and meta-analysis. Quant Imaging Med Surg 2018; 8 (04) 421-432
    PubMedSuche in Google Scholar
  • 46 Siegal D, Keller A, Xu W. et al. Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance. Biol Blood Marrow Transplant 2007; 13 (11) 1369-1379
    PubMedSuche in Google Scholar
  • 47 Félix C, Nunes N, Florêncio A. et al. On the pathways of an imperfect chameleon: posterior reversible encephalopathy syndrome. Am J Emerg Med 2016; 34 (02) 322-324
    PubMedSuche in Google Scholar