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. 2025 Jun;32(6):e70249.
doi: 10.1111/ene.70249.

Quantitative Brain MRI Analysis in Neurodegenerative Langerhans Cell Histiocytosis

Chooyoung Baek  1 , Lucas Rincon de la Rosa  2 , Ilyes Aliouat  3 , Loup Guichard  4 , Eva Pappa  5 , Loic Le Guennec  6 , Lucia Nichelli  7 , Aude Sangare  8 , Marie-Odile Habert  4 , Eleonore Bayen  9 , Antoine Del Cul  10 , Karima Mokhtari  11 , Fleur Cohen-Aubart  12 , Julien Haroche  12 , Sébastien Héritier  13 , Jean Donadieu  13 , Khê Hoang-Xuan  1 , Agusti Alentorn  1 , Ahmed Idbaih  1
Affiliations

Quantitative Brain MRI Analysis in Neurodegenerative Langerhans Cell Histiocytosis

Chooyoung Baek et al. Eur J Neurol. 2025 Jun.

Abstract

Background: Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) is a severe central nervous system involvement complicating LCH. ND-LCH is characterized by a cerebellar ataxia, pyramidal signs, pseudobulbar palsy, cognitive impairment, and behavioral disturbances. Cerebellar atrophy, the most common MRI finding, has been widely described in the literature. However, the natural history of volumetric changes in the cerebellum has never been examined. In this study, we aim to perform a quantitative analysis of cerebellar atrophy in ND-LCH patients compared to a control cohort.

Methods: MRI of patients with ND-LCH was compared to those of controls. An automated cerebellum analysis was performed using the Volbrain software (CERES) and a linear regression analysis was used to score the severity of cerebellar atrophy over time.

Results: We retrospectively analyzed the follow-up MRI of 16 adult patients with ND-LCH compared to those of 22 control patients. We examined an average of four MRIs per patient over a median follow-up period of six years. All patients with ND-LCH exhibit global and cortical cerebellar atrophy over time. The average atrophy rate is -1.86 cm3/year (range - 5.90 to 0.34) and is heterogeneous between patients. All cerebellar lobules are affected by atrophy.

Conclusion: Longitudinal quantitative MRI analysis of the cerebellum in ND-LCH: (i) is feasible, (ii) confirms significant global and cortical cerebellar atrophy in patients with ND-LCH over time, (iii) estimates the rate of cerebellar atrophy, and (iv) could be useful as a therapeutic endpoint in a clinically slow-progressing disease. Further studies are needed to validate our findings.

Keywords: Langerhans cell histiocytosis; central nervous system; cerebellum; magnetic resonance imaging; neurodegenerative Langerhans cell histiocytosis.

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Conflict of interest statement

Ahmed Idbaih: Outside this work travel funding: Carthera, Leo Pharma, Novocure; research grants: Transgene, Sanofi, Servier, and Nutritheragene; consulting: Novocure, Novartis, Polytone Laser, Leo Pharma, and Boehringer Ingelheim.

Figures

FIGURE 1
FIGURE 1
Example of cerebellar atrophy seen in ND‐LCH patients. Sagittal T1‐weighted images show cerebellar atrophy worsening between the time of inclusion (A, 23 years old) and at the final follow‐up period of six years (B, 29 years old), while ND‐LCH has already been diagnosed at the age of 11.
FIGURE 2
FIGURE 2
Box plot showing the change over time in the cerebellum total volume (A) and the cerebellum gray matter (B) in ND‐LCH patients. ***p < 0.001 (Student's t‐test). Horizontal bars correspond to the means. (C) Volumetric changes during the follow‐up (n = 16).
FIGURE 3
FIGURE 3
Cerebellum total volume ratio over time for each patient. (A) Cerebellum total volume decrease rate calculated for each patient. mean ± SEM (standard error of mean). (B) Cerebellum total volume evolution during the follow‐up period for each patient is represented as a ratio compared to year 1.
FIGURE 4
FIGURE 4
Representation of cerebellar atrophy values in ND‐LCH patients compared to controls. (A) Example of cerebellum segmentation using the CERES pipeline in Volbrain software [11], in coronal and sagittal view. (B) Atrophy values in each cerebellar lobule, in a coronal view. Color scale represents atrophy values in each lobule.
See this image and copyright information in PMC

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