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Cerebellar peduncle damage in Langerhans cell histiocytosis-associated neurodegenerative disease revealed by diffusion tensor imaging

  • Diagnostic Neuroradiology
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Abstract

Purpose

To confirm the hypothesis that brain white matter damage is involved in the pathogenesis and disease progression of Langerhans cell histiocytosis (LCH)-associated neurodegenerative disease (ND), we aimed to analyze pediatric patients with LCH using diffusion tensor imaging (DTI).

Methods

We enrolled 33 patients with LCH and obtained 33 DTI datasets. Using DTI-based tractography, fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured in the cerebral and cerebellar white matter tracts. The participants were divided into three groups—non-ND, ND without clinical symptoms (r-ND), and ND with clinical symptoms (c-ND)—according to their clinical status during the examination with DTI. We compared the DTI parameters in white matter tracts were compared among the three groups.

Results

In the order of non-ND, r-ND, and c-ND groups, the FA in superior cerebellar peduncle (SCP) and middle cerebellar peduncle (MCP) significantly decreased, the ADC, AD, and RD of MCP, and the RD of SCP were significantly elevated (FA-SCP; p < 0.001, FA-MCP; p = 0.026, ADC-MCP; p < 0.001, AD-MCP; p = 0.002, RD-MCP; p = 0.003, and RD-SCP; p = 0.018). Furthermore, in the simple linear regression analysis, the FA, ADC, AD, and RD values in the MCP and the FA value in the SCP were significantly influenced by the presence of neurological symptoms and ND findings on MRI (all p < 0.001).

Conclusion

In LCH-ND, we identified microstructural damage in the SCP and MCP. DTI parameters in these tracts may help monitor LCH-ND; therefore, future studies are required to validate these results in a large cohort.

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Data availability

The clinical information and DTI parameters for each patient that led to the results presented in this study can be downloaded from the Harvard Database Repository at https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/URF4IU.

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Acknowledgements

We are grateful to the study participants and their families. We thank Koji Sakai at the Department of Radiology, Kyoto Prefectural University of Medicine, for advice and guidance on the use of the Trackvis and Diffusion toolkit software and Kengo Yoshii at the Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, for statistical advice. We would like to thank Editage (http://www.editage.com) for English language editing.

Funding

This study was supported by the Japan Agency for Medical Research and Development (Grant/Award Number: JP20ck0106605h0001), the research fund of NPO Heart Link working project (Niigata, Japan), and Takeda Science Foundation (2019).

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Authors and Affiliations

  1. Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan

    Tomohiko Imai, Tatsuji Hasegawa, Satoshi Sakaue, Toshihiko Imamura & Tomoko Iehara

  2. Departments of Pediatrics, Shiga University of Medical Science, Shiga, Japan

    Kenichi Sakamoto

  3. Departments of Pediatrics, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Yoko Shioda

  4. Departments of Radiology, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Yoshiyuki Tsutsumi

  5. Departments of Pediatrics, Showa Inan General Hospital, Komagane, Japan

    Akira Morimoto

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  1. Tomohiko Imai
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Contributions

TH, KS, YS, SS, TI, AM, and TI devised this study design. KS and YS contributed to the acquisition of clinical information and YT contributed to the acquisition and interpretation MRI. KS and YS acquired fundings. TI analyzed and interpreted the MRI and diffusion tensor image data and wrote the paper. All coauthors discussed the relationship between the clinical information and the analyzed data.

Corresponding author

Correspondence to Tatsuji Hasegawa.

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The authors have no conflicts of interest to declare.

Ethics approval

This study was approved by the Ethics Review Committees of the Kyoto Prefectural University of Medicine and the National Center for Child Health and Development (ERB-C-1312).

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The attending physician obtained written informed consent from the patients or their parents.

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Imai, T., Sakamoto, K., Hasegawa, T. et al. Cerebellar peduncle damage in Langerhans cell histiocytosis-associated neurodegenerative disease revealed by diffusion tensor imaging. Neuroradiology 66, 43–54 (2024). https://doi.org/10.1007/s00234-023-03249-z

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