Volumetric hippocampal changes in glioblastoma: a biomarker for neuroplasticity?

Abstract

Purpose: The pleiotropic effect of gliomas on the development of cognitive disorders and structural brain changes has garnered increasing interest in recent years. While it is widely accepted that multimodal therapies for brain cancer can foster cognitive impairment, the direct effect of gliomas on critical cognitive areas before anti-tumor therapies is still controversial. In this study, we focused on the effect of IDH1 wild-type glioblastoma on the human hippocampus volume.

Methods: We carried out a case-control study using voxel-based morphometry assessment, analyzed with the Computational Anatomy Toolbox software. Glioblastoma diagnosis was performed according to the latest 2021 WHO classification. Due to stringent inclusion criteria, 15 patients affected by IDH1 wild type glioblastoma were included and compared to 19 age-matched controls.

Results: We observed a statistically significant increase in the absolute mean hippocampal volume (p = 0.017), as well as in the ipsilateral (compared to the lesion, p = 0.027) and the contralateral hippocampal volumes (p = 0.014) in the group of patients. When the data were normalized per total intracranial volume, we confirmed a statistically significant increase only in the contralateral hippocampal volume (p = 0.042).

Conclusions: To the best of our knowledge, this is the first study to explore hippocampal volumetric changes in a cohort of adult patients affected by IDH1 wild-type glioblastoma, according to the latest WHO classification. We demonstrated an adaptive volumetric response of the hippocampus, which was more pronounced on the side contralateral to the lesion, suggesting substantial integrity and resilience of the medial temporal structures before the initiation of multimodal treatments.

Keywords: Glioblastoma; Hippocampus; Neuroplasticity; VBM.

Fig. 1

On the left, the example of a glioblastoma with minimal local mass effect and perilesional edema. On the right, the presence of hippocampal-sparing, which constituted a strict inclusion criterium in order to ensure reliable pre-processing analysis

Fig. 2

The effect of glioma on the hippocampal volume. Box plots showing both the mean absolute and normalized ipsilateral and contralateral hippocampal volume of patients compared to the mean hippocampal value of controls. The square indicates the mean value of the group, the horizontal line indicates the median. The mean absolute values are expressed in cm³, while the normalized values are calculated as the ratio of absolute value to TIV. Created with BioRender.com.