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Original Article
Thoracic Surgery Connective tissue disease is associated with the risk of posterior reversible encephalopathy syndrome following lung transplantation in Korea
Tae Jung Kim1,2orcid, Hyun Joo Lee2,3orcid, Samina Park3orcid, Sang-Bae Ko1,2orcid, Soo-Hyun Park4orcid, Seung Hwan Yoon1orcid, Kwon Joong Na3orcid, In Kyu Park3orcid, Chang Hyun Kang3orcid, Young Tae Kim3orcid, Sun Mi Choi5orcid, Jimyung Park5orcid, Joong-Yub Kim5orcid, Hong Yeul Lee2orcid

DOI: https://doi.org/10.4266/acc.003384
Published online: January 7, 2025

1Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

2Department of Critical Care Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

3Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

4Department of Neurology, Soonchunhyang University Seoul Hospital, Seoul, Korea

5Department of Pulmonology and Critical Care Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Corresponding author: Hyun Joo Lee Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-4913 Fax: +82-2-764-3664 E-mail: hjleedr@gmail.com
• Received: September 5, 2024   • Revised: November 13, 2024   • Accepted: November 14, 2024

© 2025 The Korean Society of Critical Care Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background
    Posterior reversible encephalopathy syndrome (PRES) is a rare complication of lung transplantation with poorly understood risk factors and clinical characteristics. This study aimed to examine the occurrence, risk factors, and clinical data of patients who developed PRES following lung transplantation.
  • Methods
    A retrospective analysis was conducted on 147 patients who underwent lung transplantation between February 2013 and December 2023. The patients were diagnosed with PRES based on the clinical symptoms and radiological findings. We compared the baseline characteristics and clinical information, including primary lung diseases and immunosuppressive therapy related to lung transplantation operations, between the PRES and non-PRES groups.
  • Results
    PRES manifested in 7.5% (n=11) of the patients who underwent lung transplantation, with a median onset of 15 days after operation. Seizures were identified as the predominant clinical manifestation (81.8%, n=9) in the group diagnosed with PRES. All patients diagnosed with PRES recovered fully. Patients with PRES were significantly associated with connective tissue disease-associated interstitial lung disease (45.5% vs. 18.4%, P=0.019, odds ratio=9.808; 95% CI, 1.064–90.38; P=0.044). Nonetheless, no significant variance was observed in the type of immunotherapy, such as the use of calcineurin inhibitors, blood pressure, or acute renal failure subsequent to lung transplantation.
  • Conclusions
    PRES typically manifests shortly after lung transplantation, with seizures being the predominant initial symptom. The presence of preexisting connective tissue disease as the primary lung disease represents a significant risk factor for PRES following lung transplantation.
  • Key Words: autoimmune disease; connective tissue disease; lung transplantation; posterior reversible encephalopathy syndrome
Posterior reversible encephalopathy syndrome (PRES) is an infrequent neurological complication that can develop after solid organ transplantation (SOT). PRES is characterized by acute or subacute neurological manifestations, including headaches, seizures, visual disturbances, or altered mental status, often accompanied by vasogenic edema on brain imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI) [1-3]. The prognosis of PRES is generally favorable, with typically reversible clinical and radiological abnormalities [2-5]. The reported incidence of PRES following SOT ranges from 0.4% to 6%, with variations in occurrence based on the specific type of solid organ transplanted [6-10].
The precipitating factors associated with PRES include elevated blood pressure, renal failure, infection or sepsis, preeclampsia or eclampsia, autoimmune diseases, and the use of immunosuppressive or cytotoxic drugs, particularly calcineurin inhibitors. Previous research on PRES following SOT has primarily consisted of case reports or studies focusing on the clinical features of PRES following transplantation, with limited scope [10-13]. Additionally, a few studies have explored variances in perioperative risk factors and clinical features between patients who developed PRES and those who did not following lung transplantation [13,14]. Hence, this study aimed to examine and compare the risk factors and clinical characteristics of patients who experienced PRES and those who did not following lung transplantation.
Study Population
This study was approved by the Institutional Review Board of Seoul National University Hospital (No. H-2302-135-1408). The board waived the requirement for obtaining informed consent from the patients because of the retrospective nature of the study. A retrospective cohort analysis was conducted on a consecutive series of lung transplant recipients between February 2013 and December 2023 at our institution. A cohort of 147 patients who underwent single and double lung transplantation was included in the analysis.
Baseline Characteristics and Clinical Information
Baseline characteristics, including age, sex, and clinical data, were extracted from the medical records and cohort data. Clinical data, including body mass index (kg/m2), primary lung diseases, and comorbidities, such as hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, and prior stroke, were collected. Relevant laboratory data, such as blood urea nitrogen and creatinine levels, were obtained before lung transplantation.
Clinical Information Associated with Transplantation
The total cohort of patients included in the study was stratified into two distinct groups: PRES and non-PRES groups. We assessed the patients’ perioperative clinical data associated with lung transplantation. Various data points were collected, including details on the transplanted organs (single or double lung, co-transplantation with other organs), donor age and sex, intraoperative variables (operative time and estimated blood loss), induction therapy, types of immunosuppressive agents administered after transplantation, and continuous renal replacement therapy (CRRT) during the postoperative period. Laboratory data, such as blood urea nitrogen, creatinine levels, and levels of calcineurin inhibitors, particularly tacrolimus, were collected on the day of PRES onset and 15 days after transplantation in the non-PRES group. Regarding sedative therapy, we investigated the types of sedative drugs used for light sedation, including remifentanil, dexmedetomidine, midazolam, propofol, and morphine. The total amount of the drugs, including midazolam, propofol, and morphine administered before and after surgery was examined. We analyzed the sedative therapy administered at the time of PRES in the PRES group and on the 15th day after surgery in the group without PRES. The primary outcome under investigation was PRES, characterized by neurological symptoms, including headache, seizure, vision changes, altered mental status, and other focal neurological deficits, along with complete or partial manifestation of the typical PRES pattern on brain MRI [1-3]. Additionally, we analyzed the duration of stay in both the intensive care unit (ICU) and hospital and the rate of in-hospital mortality among the patients included in the study.
Statistical Analysis
Descriptive statistics were used to analyze the data, encompassing measures, such as mean, median, standard deviation, range, and interquartile range (IQR) for continuous variables, as well as frequencies and percentages for categorical variables. Group comparisons between patients with and without PRES were performed using Student t-test or Mann-Whitney U-test for continuous variables, and appropriate statistical tests, such as Pearson's chi-square or Fisher's exact test for categorical variables. The associations between clinical factors and the incidence of PRES after lung transplantation were assessed through logistic regression analyses. Variables that demonstrated statistical significance at a level of P<0.1 in the univariate analyses, as well as clinically important variables, were selected for adjusting the multivariate analysis. Statistical significance was established with a two-sided P-value of <0.05. All analyses were performed using the IBM SPSS software version 29.0 (IBM Corp.).
Baseline Characteristics
Of the total 147 participants (40.8% females) with a mean age of 53.2 years, 11 (7.5%) experienced PRES following lung transplantation (Figure 1). The baseline characteristics are summarized in Table 1. The PRES group exhibited a younger age profile and a higher proportion of females compared with the non-PRES group, although these differences were not statistically significant. In terms of primary lung disease, the prevalence of connective tissue disease-related interstitial lung disease was notably higher (45.5%) in the PRES group than that in the non-PRES group (18.4%, P=0.019) (Table 1). Of the 147 patients, 95.2% underwent double- lung transplantation. Patients with PRES were more likely to undergo single lung transplantation and co-transplantation with other organs than those without PRES (P=0.009). No significant differences in comorbidities or baseline renal function were observed between the groups, as shown in Table 1.
Perioperative Clinical Characteristics in Relation to the Development of PRES
The overall operation duration, estimated blood loss, and intraoperative total blood transfusion were comparable between the two groups (Table 2). Regarding post-transplantation induction therapy, the use of anti-thymocyte globulin therapy was notably greater in the PRES group (P=0.045) (Table 2). Nonetheless, no significant differences were observed in the types of initial immunosuppressants used, with 99.3% of the patients receiving tacrolimus as a calcineurin inhibitor. In addition, renal function and CRRT in the postoperative stage were similar between the two groups. Regarding sedative therapy administered during the pre- and post-transplantation periods, no significant variations were observed in the types of sedative medications used or total dosages administered. None of the patients in the PRES group received midazolam or propofol after lung transplantation (Table 2, Supplementary Table 1). The length of ICU and hospital stay was extended for the PRES group; however, the in-hospital mortality rate was not statistically significant, despite being relatively low (Table 2). In the multivariable analysis, connective tissue disease-related interstitial lung disease as a primary lung disease was independently related to the PRES following lung transplantation (odds ratio [OR], 9.808; 95% CI, 1.064–90.386; P=0.044) (Supplementary Table 2).
In clinical presentations (Table 3), the median onset of PRES symptoms occurred at 15 days (IQR, 5–27 days) after lung transplantation. Of the total patients with PRES, 81.8% experienced PRES within 1 month of transplantation. Symptoms observed at the initial presentation included seizures (n=9, 81.8%), altered mental status (n=4, 36.4%), headache (n=3, 27.3%), and visual field defects (n=1, 9.1%). Tacrolimus levels were within the normal range in all but two patients (case 3, case7). At the onset of PRES, the blood pressure was within the normal range (systolic blood pressure ≤140 mm Hg) in eight patients (72.7%) and mildly elevated in three patients (27.3%). After the PRES event, immunosuppressants were maintained at lower target levels in 54.5% (n=6) of the patients and were switched in 45.5% (n=5) of the patients (Table 3). During hospitalization, all patients demonstrated improvement in their symptoms.
In this study, the prevalence of PRES in patients undergoing lung transplantation was 7.5%. The presence of underlying connective tissue disease has been linked to the development of PRES. However, no significant correlation between renal dysfunction and immunosuppressant use after lung transplantation has been reported. Post-transplantation PRES predominantly manifests in the early stages, typically within the first month after transplantation. Furthermore, the prognosis for PRES is favorable, with complete recovery.
Neurological complications are frequently observed following lung transplantation; however, PRES is infrequent in lung transplant recipients. The prevalence of PRES following lung transplantation in our investigation exceeded the previously reported rates of 1%–2% in the prior studies [13,15,16]. The median onset time of PRES following lung transplantation was 15 days, with seizures being the most prevalent symptom, consistent with the findings of previous studies [9,12-16]. The duration between transplantation and PRES manifestation was comparatively shorter in lung transplant recipients of this study than in recipients of solid organ transplants in previous studies [10,13,15-18]. Previous studies have shown that the onset of PRES following transplantation typically occurs within an average of one month, with a maximum duration up to 1 year. Clinical factors such as rejection, hypertension, renal impairment, and elevated calcineurin inhibitors such as tacrolimus levels have been proposed as potential etiologies for PRES [1,3,4,19-21]. However, this did not identify any statistically significant differences in these factors between the two groups post-transplantation. Instead, the presence of underlying connective lung disease emerged as a significant important factor related to the occurrence of PRES following lung transplantation patients. Therefore, this factor may contribute to an earlier onset of PRES compared to the durations reported in prior studies following transplantation. Furthermore, the type and total dosage of sedatives administered during the perioperative period, such as midazolam and propofol, did not demonstrate a significant impact on PRES.
In our investigation, we observed a significant association between the development of PRES and the presence of connective tissue disease as the primary lung condition. The proportion of connective tissue disorders was found to be higher than that reported in other documented studies [9,13,14,22]. Approximately 50% of the patients diagnosed with PRES exhibit a medical background of autoimmune disorders, such as systemic sclerosis, rheumatic arthritis, Sjogren’s syndrome, endothelial dysfunction, vasculopathy, and autonomic dysfunction, which are associated with autoantibodies and have been linked to the development of PRES in connective tissue diseases [1,14,19,23-27]. In connective tissue diseases, endothelial dysfunction associated with autoimmune disorders may increase susceptibility to the development of PRES, particularly following the administration of immunosuppressive therapies, even in normotensive patients with normal renal function [23-27].
In the management of PRES, early diagnosis and prompt treatment are essential. It is important to emphasize that PRES necessitates immediate diagnosis, with a treatment strategy to minimize the risk of recurrences. A fundamental component of treatment involves the removal of precipitating factors, which includes the reduction of blood pressure, modification of immunosuppressive therapies, management of renal function, and the administration of antiseizure medications for patients who experience seizures [1-3,23-28]. Furthermore, about 80%–90% of patients with PRES recovered completely within 8–10 days, although some patients needed several weeks to achieve full revery. Despite a favorable outcome, 10%–20% of patients experienced permanent neurological sequelae associated with neurological injury following PRES [1-3,18-21]. Regarding immunosuppressive therapy after the occurrence of PRES, there is currently no standardized approach to immunosuppressive therapy. The treatment approach may differ based on the clinical setting and could involve temporary cessation of medication for a specific duration, followed by reinstatement, dosage adjustments, or switching to an alternative immunosuppressive agent. Considering neurological symptoms recovery after cessation of calcineurin inhibitors, it could be a risk factor regardless of trough level. These decisions were made at the discretion of individual clinicians [5,12,13,15-18,20,25-28]. In our study, approximately 50% of the participants temporarily discontinued the medication and resumed the same treatment, whereas the remaining 50% transitioned to an alternative medication, consistent with the findings of prior studies [5,12,13,15-18,20,25-28]. In this study, regardless of the immunosuppressive therapy, neurological symptoms resolved in all patients with PRES. The length of hospitalization and ICU stay for PRES patients tends to be prolonged. However, the higher frequency of extracorporeal membrane oxygenation treatment administered prior to lung transplantation in PRES patients (Table 1) suggests that the severity of the patient's condition may have impacted the length of hospital stay.
This study had some limitations. First, unquantified bias was present because of the retrospective nature of the study. Second, the analysis in this study may have been constrained by the small sample size and use of data from a single center. Third, we did not conduct a comprehensive analysis of all operative data, particularly fluctuations in blood pressure throughout the procedure, which could potentially be linked to PRES.
In conclusion, PRES is a rare neurological disorder that manifests after lung transplantation. Our study demonstrated that individuals with connective tissue disease-associated interstitial lung disease were at a higher risk of developing PRES. No significant association was observed between PRES and tacrolimus levels, renal function, or hypertension. Hence, clinicians should consider these factors when treating patients with such characteristics following lung transplantation. Further multicenter studies involving larger cohorts are necessary to identify the independent associations between risk factors and PRES after lung transplantation.
▪ Our study demonstrated that individuals with connective tissue disease-associated interstitial lung disease were at a higher risk of developing posterior reversible encephalopathy syndrome.
▪ Post-transplantation posterior reversible encephalopathy predominantly manifests in the early stages, typically within the first month after transplantation.
▪ The prognosis for posterior reversible encephalopathy is favorable, with complete recovery.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

FUNDING

None.

ACKNOWLEDGMENTS

None.

AUTHOR CONTRIBUTIONS

Conceptualization: TJK, HJL. Data curation: all authors. Formal analysis: TJK, HJL. Methodology: TJK, HJL. Project administration: HJL. Visualization: TJK, HJL. Writing – original draft: TJK, HJL. Writing – review & editing: TJK, HJL. All authors read and agreed to the published version of the manuscript.

Supplementary materials can be found via https://doi.org/10.4266/acc.00338.
Supplementary Table 1.
Total dose of sedative drugs during perioperative period
acc-003384-Supplementary-Table-1.pdf
Supplementary Table 2.
Association between clinical factors and PRES following lung transplantation
acc-003384-Supplementary-Table-2.pdf
Figure 1.
Flow diagram of the included patients. PRES: posterior reversible encephalopathy syndrome.
acc-003384f1.jpg
Table 1.
Baseline characteristics of the included patients
Variable PRES (n=11, 7.5%) Non-PRES (n=136, 92.5%) P-value
Age (yr) 40.8±23.1 54.2±15.9 0.087
Female 7 (63.6) 53 (39.0) 0.976
BMI (kg/m2) 20.3±5.4 20.3±4.1
Primary lung disease 0.019
 IPF 1 (9.1) 50 (44.1)
 ILD/ARDS 1 (9.1) 21 (15.4)
 CTD-related ILD 5 (45.5) 25 (18.4)
 GVHD 2 (18.2) 17 (12.5)
 COPD/bronchiectasis 0 8 (5.9)
 Others 2 (18.2) 5 (3.7)
Comorbidity
 Hypertension 1 (9.1) 40 (29.4) 0.292
 Diabetes mellitus 0 22 (16.2) 0.371
 Dyslipidemia 1 (9.1) 30 (22.1) 0.459
 Coronary artery disease 0 (0.0) 14 (10.3) 1.000
 Previous stroke 0 6 (4.4) 1.000
Preoperative period
 ECMO bridge 5 (45.5) 46 (33.8) 0.515
 Sedation 0.346
  None 7 (63.6) 84 (61.8)
  Light sedation 2 (18.2) 13 (9.6)
  Midazolam 0 9 (6.6)
  Propofol 0 18 (13.2)
  Midazolam & propofol 1 (9.1) 4 (2.9)
  Morphine with or without midazolam or propofol 1 (9.1) 8 (5.9)
 BUN, preoperative (mg/dl) 18.5 (8.0) 17.1 (12.2) 0.721
 Cr, preoperative (mg/dl) 0.7 (0.2) 0.7 (0.4) 0.811
Intraoperative period
 Transplantation organ 0.009
  Double lung 8 (72.7) 132 (97.1)
  Single lung 1 (9.1) 2 (1.5)
  Heart + lung 1 (9.1) 2 (1.5)
  Liver + lung 1 (9.1) 0
 Donor age (yr) 39.3±15.8 37.2±14.4 0.644
 Donor female 7 (63.6) 59 (43.4) 0.222

Values are presented as mean±standard deviation or number (%).

PRES: posterior reversible encephalopathy syndrome; BMI: body mass index; IPF: idiopathic pulmonary fibrosis; ILD: interstitial lung disease; ARDS: acute respiratory distress syndrome; CTD: connective tissue disease; GVHD: graft versus host disease; COPD: chronic obstructive pulmonary disease; ECMO: extracorporeal membrane oxygenation; BUN: blood urea nitrogen; Cr: creatinine.

Table 2.
Clinical characteristics related to perioperative stage
Variable PRES (n=11, 7.5%) Non-PRES (n=136, 92.5%) P-value
Intraoperative period
 Operation time (min) 421.2±126.6 468.8±109.2 0.171
 EBL (ml) 1,775±1,144 2,874±3,505 0.327
 Transfusion
  RBC, pack 2 (2–11) 6 (4–10) 0.191
  PC, unit 6 (0–6) 6 (0–12) 0.760
  FFP, pint 3 (1–7) 3 (1–6) 0.862
Postoperative period
 Induction 0.045
  Basiliximab 9 (81.8) 133 (97.8)
  ATG 2 (18.2) 3 (2.2)
 Initial Immune suppressant 1.000
  Tacrolimus+MMF+steroid 10 (90.9) 123 (90.4)
  Tacrolimus+steroid 1 (9.1) 12 (8.8)
  MMF+steroid 0 1 (0.7)
 Postoperative BUN (mg/dl) 24.3 (9.0) 24.9 (16.7) 0.895
 Postoperative Cr (mg/dl) 0.5 (0.2) 0.7 (0.5) 0.214
 Sedation 0.166
  None 1 (9.1) 2 (1.5)
  Light sedation 4 (36.4) 83 (61.0)
  Midazolam 2 (18.2) 23 (16.9)
  Propofol 4 (36.4) 22 (16.2)
  Midazolam & propofol 0 3 (2.2)
  Morphine with or without midazolam or propofol 0 3 (2.2)
 Sedation at the time of PRES or on 15 days after TPL 0.594
  None 8 (72.7) 110 (80.9)
  Light sedation 3 (27.3) 21 (15.4)
  Midazolam or propofol 0 5 (3.7)
 CRRT 5 (45.5) 43 (31.6) 0.340
 Tacrolimus level 12.2 (7.6) 12.5 (5.9) 0.890
 Post-TPL ICU length of stay (day) 19 (13–29) 10 (7–16.8) 0.008
 Post-TPL hospital length of stay (day) 83 (60–157) 49 (30–96.3) 0.017
 In-hospital mortality 1 (9.1) 23 (16.9) 0.693

Values are presented as mean±standard deviation or median (interquartile range), or number (%).

PRES: posterior reversible encephalopathy syndrome; EBL: estimated blood loss; RBC: red blood cell; PC: platelet concentrate; FFP: fresh frozen plasma; ATG: anti-thymocyte globulin; MMF: mycophenolate mofetil; BUN: blood urea nitrogen; Cr: creatinine; TPL: transplantation; CRRT: continuous renal replacement therapy; ICU: intensive care unit.

Table 3.
Clinical characteristics in patients with PRES
Case no. Sex/age (yr) Primary lung disease Type of TPL Onset after TPL (day) Neurologic symptom Blood pressure (mm Hg) Mg (mEq/l) CNI, trough (ng/ml) Immune suppressant after PRES
1 F/48 CTD-ILD (systemic sclerosis) BL 5 Seizure 140/102 1.6 TAC Temporary discontinuation of TCA and maintaining TCA
8.3
2 F/62 CTD-ILD (Sjogren) BL 190 Headache, drowsiness, seizure 142/91 1.7 CsA Temporary discontinuation of CsA and maintaining CsA
108
3 F/39 CTD-ILD (systemic sclerosis) BL 15 Seizure 149/109 1.3 TAC Temporary discontinuation of TCA and maintaining TCA
27
4 F/62 CTD-ILD (rheumatoid arthritis) BL 3 Seizure 103/76 2.0 TAC Changing to CsA
4
5 M/62 CTD-ILD (dermatomyositis) BL 84 Nausea, headache, seizure 126/96 1.1 TAC Changing to CsA
12.6
6 F/61 COVID ARDS BL 5 Seizure 169/98 1.6 TAC Changing to CsA
8.1
7 F/59 IPF SL 12 Drowsiness 120/86 1.2 TAC Temporary discontinuation of TCA and maintaining TCA
17.5
8 M/20 GVHD SL 7 Drowsiness, aphasia, seizure 127/78 1.3 TAC Changing to CsA
8.4
9 M/5 GVHD BL+liver 22 Altered mental status 106/78 1.8 TAC Temporary discontinuation of TCA and maintaining TCA
10.9
10 M/6 PPH BL 27 Seizure 104/60 1.4 TAC Temporary discontinuation of TCA and Maintaining TCA
14.6
11 F/25 PPH BL+heart 15 Headache, visual field defect seizure 118/72 1.2 TAC Changing to other immune suppressant
10.9

PRES: posterior reversible encephalopathy syndrome; TPL: transplantation; Mg: magnesium; CNI: calcineurin inhibitor; CTD: connective tissue disease; ILD: interstitial lung disease; BL: both lung; TAC: tacrolimus; CsA: cyclosporin; COVID: coronavirus disease; ARDS: acute respiratory distress syndrome; IPF: idiopathic pulmonary fibrosis; SL: single lung; GVHD: graft versus host disease; PPH: primary pulmonary hypertension.

  • 1. Geocadin RG. Posterior reversible encephalopathy syndrome. N Engl J Med 2023;388:2171-8.ArticlePubMed
  • 2. Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015;14:914-25.ArticlePubMed
  • 3. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494-500.ArticlePubMed
  • 4. Ando Y, Ono Y, Sano A, Fujita N, Ono S. Posterior reversible encephalopathy syndrome: a review of the literature. Intern Med 2022;61:135-41.ArticlePubMedPMC
  • 5. Burnett MM, Hess CP, Roberts JP, Bass NM, Douglas VC, Josephson SA. Presentation of reversible posterior leukoencephalopathy syndrome in patients on calcineurin inhibitors. Clin Neurol Neurosurg 2010;112:886-91.ArticlePubMed
  • 6. Besenski N, Rumboldt Z, Emovon O, Nicholas J, Kini S, Milutinovic J, et al. Brain MR imaging abnormalities in kidney transplant recipients. AJNR Am J Neuroradiol 2005;26:2282-9.PubMedPMC
  • 7. de Groen PC, Aksamit AJ, Rakela J, Forbes GS, Krom RA. Central nervous system toxicity after liver transplantation: the role of cyclosporine and cholesterol. N Engl J Med 1987;317:861-6.ArticlePubMed
  • 8. Katabathina V, Menias CO, Pickhardt P, Lubner M, Prasad SR. Complications of immunosuppressive therapy in solid organ transplantation. Radiol Clin North Am 2016;54:303-19.ArticlePubMed
  • 9. Mateen FJ, Dierkhising RA, Rabinstein AA, Van De Beek D, Wijdicks EF. Neurological complications following adult lung transplantation. Am J Transplant 2010;10:908-14.ArticlePubMedPDF
  • 10. Bartynski WS, Tan HP, Boardman JF, Shapiro R, Marsh JW. Posterior reversible encephalopathy syndrome after solid organ transplantation. AJNR Am J Neuroradiol 2008;29:924-30.ArticlePubMedPMC
  • 11. Arimura FE, Camargo PC, Costa AN, Teixeira RH, Carraro RM, Afonso JE, et al. Posterior reversible encephalopathy syndrome in lung transplantation: 5 case reports. Transplant Proc 2014;46:1845-8.ArticlePubMed
  • 12. Kemna MS, Shaw DW, Kronmal RA, Ameduri RK, Azeka E, Bradford TT, et al. Posterior reversible encephalopathy syndrome (PRES) after pediatric heart transplantation: a multi-institutional cohort. J Heart Lung Transplant 2023;42:218-25.Article
  • 13. Yavuz G, Heck S, Sienel W, Irlbeck M, Kneidinger N, Michel S, et al. Posterior reversible encephalopathy syndrome after lung transplantation: risk factors and management. Clin Transplant 2023;37:e14850. ArticlePubMedPDF
  • 14. Bottiger B, Klapper J, Esposito V, Hashmi N, Berger M, Smith P, et al. Posterior reversible encephalopathy syndrome after lung transplant: clinical characteristics and outcomes. J Heart Lung Transplant 2018;37:S252-3.Article
  • 15. Yamagishi H, Chen-Yoshikawa TF, Date H. Basiliximab for posterior reversible encephalopathy syndrome after lung transplantation. Eur J Cardiothorac Surg 2017;52:823-4.PubMed
  • 16. Shigemura N, Sclabassi RJ, Bhama JK, Gries CJ, Crespo MM, Johnson B, et al. Early major neurologic complications after lung transplantation: incidence, risk factors, and outcome. Transplantation 2013;95:866-71.PubMed
  • 17. Parvex P, Pinsk M, Bell LE, O'Gorman AM, Patenaude YG, Gupta IR. Reversible encephalopathy associated with tacrolimus in pediatric renal transplants. Pediatr Nephrol 2001;16:537-42.ArticlePubMedPDF
  • 18. Wu Q, Marescaux C, Wolff V, Jeung MY, Kessler R, Lauer V, et al. Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation. Eur Neurol 2010;64:169-77.ArticlePubMedPDF
  • 19. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 2008;29:1036-42.ArticlePubMedPMC
  • 20. Hinduja A. Posterior reversible encephalopathy syndrome: clinical features and outcome. Front Neurol 2020;11:71.ArticlePubMedPMC
  • 21. Gamez J, Salvado M, Martinez-de La Ossa A, Deu M, Romero L, Roman A, et al. Influence of early neurological complications on clinical outcome following lung transplant. PLoS One 2017;12:e0174092. ArticlePubMedPMC
  • 22. Jeong YH, Kim DK, Choi S. Current status of lung transplantation in Korea. Curr Chall Thorac Surg 2022;4:4.Article
  • 23. Triplett JD, Kutlubaev MA, Kermode AG, Hardy T. Posterior reversible encephalopathy syndrome (PRES): diagnosis and management. Pract Neurol 2022;22:183-9.ArticlePubMed
  • 24. Rahmanzadeh R, Rahmanzade R, Zabihiyeganeh M. Posterior reversible encephalopathy syndrome in a patient with mixed connective tissue disease: a case report. J Med Case Rep 2016;10:145.ArticlePubMedPMCPDF
  • 25. Granata G, Greco A, Iannella G, Granata M, Manno A, Savastano E, et al. Posterior reversible encephalopathy syndrome: insight into pathogenesis, clinical variants and treatment approaches. Autoimmun Rev 2015;14:830-6.ArticlePubMed
  • 26. Min L, Zwerling J, Ocava LC, Chen IH, Putterman C. Reversible posterior leukoencephalopathy in connective tissue diseases. Semin Arthritis Rheum 2006;35:388-95.ArticlePubMed
  • 27. Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc 2010;85:427-32.PubMedPMC
  • 28. Anghel D, Tanasescu R, Campeanu A, Lupescu I, Podda G, Bajenaru O. Neurotoxicity of immunosuppressive therapies in organ transplantation. Maedica (Bucur) 2013;8:170-5.PubMedPMC

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      Connective tissue disease is associated with the risk of posterior reversible encephalopathy syndrome following lung transplantation in Korea
      Image
      Figure 1. Flow diagram of the included patients. PRES: posterior reversible encephalopathy syndrome.

      Figure 1.

      Connective tissue disease is associated with the risk of posterior reversible encephalopathy syndrome following lung transplantation in Korea
      Variable PRES (n=11, 7.5%) Non-PRES (n=136, 92.5%) P-value
      Age (yr) 40.8±23.1 54.2±15.9 0.087
      Female 7 (63.6) 53 (39.0) 0.976
      BMI (kg/m2) 20.3±5.4 20.3±4.1
      Primary lung disease 0.019
       IPF 1 (9.1) 50 (44.1)
       ILD/ARDS 1 (9.1) 21 (15.4)
       CTD-related ILD 5 (45.5) 25 (18.4)
       GVHD 2 (18.2) 17 (12.5)
       COPD/bronchiectasis 0 8 (5.9)
       Others 2 (18.2) 5 (3.7)
      Comorbidity
       Hypertension 1 (9.1) 40 (29.4) 0.292
       Diabetes mellitus 0 22 (16.2) 0.371
       Dyslipidemia 1 (9.1) 30 (22.1) 0.459
       Coronary artery disease 0 (0.0) 14 (10.3) 1.000
       Previous stroke 0 6 (4.4) 1.000
      Preoperative period
       ECMO bridge 5 (45.5) 46 (33.8) 0.515
       Sedation 0.346
        None 7 (63.6) 84 (61.8)
        Light sedation 2 (18.2) 13 (9.6)
        Midazolam 0 9 (6.6)
        Propofol 0 18 (13.2)
        Midazolam & propofol 1 (9.1) 4 (2.9)
        Morphine with or without midazolam or propofol 1 (9.1) 8 (5.9)
       BUN, preoperative (mg/dl) 18.5 (8.0) 17.1 (12.2) 0.721
       Cr, preoperative (mg/dl) 0.7 (0.2) 0.7 (0.4) 0.811
      Intraoperative period
       Transplantation organ 0.009
        Double lung 8 (72.7) 132 (97.1)
        Single lung 1 (9.1) 2 (1.5)
        Heart + lung 1 (9.1) 2 (1.5)
        Liver + lung 1 (9.1) 0
       Donor age (yr) 39.3±15.8 37.2±14.4 0.644
       Donor female 7 (63.6) 59 (43.4) 0.222
      Variable PRES (n=11, 7.5%) Non-PRES (n=136, 92.5%) P-value
      Intraoperative period
       Operation time (min) 421.2±126.6 468.8±109.2 0.171
       EBL (ml) 1,775±1,144 2,874±3,505 0.327
       Transfusion
        RBC, pack 2 (2–11) 6 (4–10) 0.191
        PC, unit 6 (0–6) 6 (0–12) 0.760
        FFP, pint 3 (1–7) 3 (1–6) 0.862
      Postoperative period
       Induction 0.045
        Basiliximab 9 (81.8) 133 (97.8)
        ATG 2 (18.2) 3 (2.2)
       Initial Immune suppressant 1.000
        Tacrolimus+MMF+steroid 10 (90.9) 123 (90.4)
        Tacrolimus+steroid 1 (9.1) 12 (8.8)
        MMF+steroid 0 1 (0.7)
       Postoperative BUN (mg/dl) 24.3 (9.0) 24.9 (16.7) 0.895
       Postoperative Cr (mg/dl) 0.5 (0.2) 0.7 (0.5) 0.214
       Sedation 0.166
        None 1 (9.1) 2 (1.5)
        Light sedation 4 (36.4) 83 (61.0)
        Midazolam 2 (18.2) 23 (16.9)
        Propofol 4 (36.4) 22 (16.2)
        Midazolam & propofol 0 3 (2.2)
        Morphine with or without midazolam or propofol 0 3 (2.2)
       Sedation at the time of PRES or on 15 days after TPL 0.594
        None 8 (72.7) 110 (80.9)
        Light sedation 3 (27.3) 21 (15.4)
        Midazolam or propofol 0 5 (3.7)
       CRRT 5 (45.5) 43 (31.6) 0.340
       Tacrolimus level 12.2 (7.6) 12.5 (5.9) 0.890
       Post-TPL ICU length of stay (day) 19 (13–29) 10 (7–16.8) 0.008
       Post-TPL hospital length of stay (day) 83 (60–157) 49 (30–96.3) 0.017
       In-hospital mortality 1 (9.1) 23 (16.9) 0.693
      Case no. Sex/age (yr) Primary lung disease Type of TPL Onset after TPL (day) Neurologic symptom Blood pressure (mm Hg) Mg (mEq/l) CNI, trough (ng/ml) Immune suppressant after PRES
      1 F/48 CTD-ILD (systemic sclerosis) BL 5 Seizure 140/102 1.6 TAC Temporary discontinuation of TCA and maintaining TCA
      8.3
      2 F/62 CTD-ILD (Sjogren) BL 190 Headache, drowsiness, seizure 142/91 1.7 CsA Temporary discontinuation of CsA and maintaining CsA
      108
      3 F/39 CTD-ILD (systemic sclerosis) BL 15 Seizure 149/109 1.3 TAC Temporary discontinuation of TCA and maintaining TCA
      27
      4 F/62 CTD-ILD (rheumatoid arthritis) BL 3 Seizure 103/76 2.0 TAC Changing to CsA
      4
      5 M/62 CTD-ILD (dermatomyositis) BL 84 Nausea, headache, seizure 126/96 1.1 TAC Changing to CsA
      12.6
      6 F/61 COVID ARDS BL 5 Seizure 169/98 1.6 TAC Changing to CsA
      8.1
      7 F/59 IPF SL 12 Drowsiness 120/86 1.2 TAC Temporary discontinuation of TCA and maintaining TCA
      17.5
      8 M/20 GVHD SL 7 Drowsiness, aphasia, seizure 127/78 1.3 TAC Changing to CsA
      8.4
      9 M/5 GVHD BL+liver 22 Altered mental status 106/78 1.8 TAC Temporary discontinuation of TCA and maintaining TCA
      10.9
      10 M/6 PPH BL 27 Seizure 104/60 1.4 TAC Temporary discontinuation of TCA and Maintaining TCA
      14.6
      11 F/25 PPH BL+heart 15 Headache, visual field defect seizure 118/72 1.2 TAC Changing to other immune suppressant
      10.9
      Table 1. Baseline characteristics of the included patients

      Values are presented as mean±standard deviation or number (%).

      PRES: posterior reversible encephalopathy syndrome; BMI: body mass index; IPF: idiopathic pulmonary fibrosis; ILD: interstitial lung disease; ARDS: acute respiratory distress syndrome; CTD: connective tissue disease; GVHD: graft versus host disease; COPD: chronic obstructive pulmonary disease; ECMO: extracorporeal membrane oxygenation; BUN: blood urea nitrogen; Cr: creatinine.

      Table 2. Clinical characteristics related to perioperative stage

      Values are presented as mean±standard deviation or median (interquartile range), or number (%).

      PRES: posterior reversible encephalopathy syndrome; EBL: estimated blood loss; RBC: red blood cell; PC: platelet concentrate; FFP: fresh frozen plasma; ATG: anti-thymocyte globulin; MMF: mycophenolate mofetil; BUN: blood urea nitrogen; Cr: creatinine; TPL: transplantation; CRRT: continuous renal replacement therapy; ICU: intensive care unit.

      Table 3. Clinical characteristics in patients with PRES

      PRES: posterior reversible encephalopathy syndrome; TPL: transplantation; Mg: magnesium; CNI: calcineurin inhibitor; CTD: connective tissue disease; ILD: interstitial lung disease; BL: both lung; TAC: tacrolimus; CsA: cyclosporin; COVID: coronavirus disease; ARDS: acute respiratory distress syndrome; IPF: idiopathic pulmonary fibrosis; SL: single lung; GVHD: graft versus host disease; PPH: primary pulmonary hypertension.

      Table 1.

      Table 2.

      Table 3.

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