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Brain MRI imaging markers associated with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis

  • Magnetic Resonance
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European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To investigate the association of brain MRI and clinical variables with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis (CNS-HLH).

Methods

Clinical and brain MRI data of children with CNS-HLH from January 2012 to March 2022 were reviewed retrospectively. Patients were divided into the deceased group and the surviving group. The intergroup differences of seven brain MRI variables, twelve clinical variables, and underlying diseases were studied.

Results

One hundred and fourteen patients were included in this study, consisting of 59 who died and 55 who survived. The included clinical variables did not show statistically independent correlation with patients’ deaths. For MRI variables, a multivariate analysis demonstrated restricted diffusion of lesion (OR = 9.64, 95% CI: 3.39–27.43, p < 0.001) and count of affected brain regions (CABR) (OR = 1.24, 95% CI: 1.03–1.49, p = 0.02) were independent risk factors for death. ROC curve showed CABR (AUC = 0.79, 95% CI: 0.70–0.87, p < 0.001) is highly predictive for mortality with an optimal cutoff value of 4.5 (sensitivity 76%, specificity 73%). For HLH subtypes, familial HLH (F-HLH, OR = 9.90, 95% CI: 2.01–48.87, p = 0.005) and immune-compromise-related HLH (IC-HLH, OR = 4.95, 95% CI: 1.40–17.46, p = 0.01) presented statistically stronger association with death than infection-related HLH. F-HLH and IC-HLH preferred to have large lesions, restricted diffusion, and more brain regions involved than other subtypes.

Conclusion

Brain MRI features exhibit independent prediction for mortality in children with CNS-HLH, and HLH subtypes pose effects on patient outcomes and brain MRI findings.

Clinical relevance statement

The number of affected brain regions and diffusion restriction of lesion exhibit significant correlation with mortality in children diagnosed with CNS-hemophagocytic lymphohistiocytosis, and may serve as candidate MRI markers for the prediction of the disorder’s severity.

Key Points

• The brain MRI markers, restricted diffusion of lesion and count of affected brain regions, significantly correlated with death.

• Familial and immune-compromise-related hemophagocytic lymphohistiocytosis presented statistically stronger association with death than infection-related subtype.

• Brain MRI is potential in death-predicting for children with central nervous system involvement of hemophagocytic lymphohistiocytosis.

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Abbreviations

ADC:

Apparent diffusion coefficient

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DPVL:

Diffuse parenchymal volume loss

DWI:

Diffusion-weighted imaging

HLH:

Hemophagocytic lymphohistiocytosis

F-HLH:

Familial hemophagocytic lymphohistiocytosis

I-HLH:

Infection-related hemophagocytic lymphohistiocytosis

IC-HLH:

Immune-compromise-related hemophagocytic lymphohistiocytosis

MRI:

Magnetic resonance imaging

R-HLH:

Rheumatological hemophagocytic lymphohistiocytosis

SI:

Signal intensity

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Funding

This study has received funding from the National Natural Science Foundation of China (81301300), Chongqing Science and Technology Foundation, and Chongqing Science and Technology Commission (cstc2018jscx-msybX0069 and cstc2016 shmszx130009).

Author information

Authors and Affiliations

  1. Department of Radiology, The Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Er Lu, Yuzhong District, Chongqing, 400000, China

    Wei Ma, Wei Li, Sijie Gao & Ye Xu

  2. Department of Radiology, The People’s Hospital of Yubei District of Chongqing City, Yubei District, Chongqing, 400000, China

    Wei Ma, Yan Huang & Yuan Fang

  3. Department of Emergency, Children’s Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400000, China

    Liang Zhou

  4. Department of Neurology, Children’s Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400000, China

    Xiujuan Li

  5. Department of Hematology, Children’s Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400000, China

    Jie Yu

Authors
  1. Wei Ma
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  3. Wei Li
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  9. Ye Xu
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Corresponding author

Correspondence to Ye Xu.

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Guarantor

The scientific guarantor of this publication is Ye Xu, email: yexu@cqmu.edu.cn., address: Department of Radiology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Er Lu, Yuzhong District, Chongqing 400000, China.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the institutional review board.

Ethical approval

Institutional review board approval was obtained. The institutional review board of Children’s Hospital of Chongqing Medical University approved the study (protocol number: 2019–87), and the written informed consent was waived for this retrospective analysis.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in our previous study [1].

1. Ma W, Li XJ, Li W, Xiao L, Ji XJ, Xu Y (2021) MRI findings of central nervous system involvement in children with haemophagocytic lymphohistiocytosis: correlation with clinical biochemical tests. Clin Radiol 76(2):159.e9-159.e17.

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• retrospective

• case–control study

• performed at one institution

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Ma, W., Zhou, L., Li, W. et al. Brain MRI imaging markers associated with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis. Eur Radiol 34, 873–884 (2024). https://doi.org/10.1007/s00330-023-10147-8

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  • DOI: https://doi.org/10.1007/s00330-023-10147-8

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