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Updated: Apr 5, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
In vivo evidence of hippocampal dentate gyrus expansion in multiple sclerosis
Maria A Rocca1,2, Giulia Longoni1,2, Elisabetta Pagani1
1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Abstract:
Using MR-based radial mapping, we assessed morphological alterations of the hippocampal dentate gyrus (DG) in patients with relapse-onset multiple sclerosis (MS). We analyzed different stages of the disease and the association of DG alterations with hippocampal-related cognitive functions. Using high-resolution morphological imaging, hippocampal radial mapping analysis was performed in 28 relapsing-remitting (RR), 34 secondary progressive, and 26 benign MS patients and 28 healthy controls (HC). Between-groups differences of DG radial distance (from surface points to the central core of the hippocampus) and correlations with clinical, neuropsychological, and radiological measures were evaluated using surface-based mesh modeling. Compared with HC, all MS clinical phenotypes revealed a larger radial distance of the DG, which was more marked on the left side. Radial distance enlargement was more pronounced in RRMS patients compared with the other disease clinical phenotypes and was inversely correlated to disease duration. Radial distance enlargement was correlated with higher T2 lesion volume and a better cognitive performance in RRMS and with a poor cognitive performance in secondary progressive and benign MS patients. Surface expansion of the DG might represent an inflammation-induced neurogenic (reactive) process of the subgranular zone of the hippocampus primarily aimed at rescuing the functional competence of hippocampal circuitry.
Insights
Multiple sclerosis (MS) patients show altered dentate gyrus (DG) morphology, with larger radial distances observed across all disease types. This expansion may reflect an inflammatory response aimed at preserving cognitive function.
Area of Science:
- Neuroimaging
- Neuroscience
- Neurology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system.
- The hippocampal dentate gyrus (DG) plays a crucial role in memory and cognitive functions.
- Morphological changes in the DG may be associated with cognitive decline in MS.
Purpose of the Study:
- To assess morphological alterations of the hippocampal dentate gyrus (DG) in patients with different clinical phenotypes of multiple sclerosis (MS).
- To investigate the association between DG alterations and cognitive functions across various MS stages.
- To explore the relationship between DG morphology, disease duration, and radiological markers in MS.
Main Methods:
- High-resolution magnetic resonance (MR)-based radial mapping was employed to analyze DG morphology.
- Surface-based mesh modeling was used to evaluate DG radial distance in relapsing-remitting (RRMS), secondary progressive (SPMS), benign MS (BMS) patients, and healthy controls (HC).
- Correlations between DG radial distance and clinical, neuropsychological, and radiological measures were assessed.
Main Results:
- All MS phenotypes exhibited enlarged DG radial distance compared to HC, more pronounced on the left side.
- Radial distance enlargement was greatest in RRMS patients and inversely correlated with disease duration.
- Enlarged DG radial distance correlated with higher T2 lesion volume and better cognitive performance in RRMS, but with poorer cognitive performance in SPMS and BMS.
Conclusions:
- Surface expansion of the DG in MS patients may represent an inflammation-induced reactive neurogenic process.
- This DG alteration might be an adaptive mechanism to preserve hippocampal circuitry function.
- The differential correlation of DG changes with cognitive performance across MS phenotypes highlights disease-specific pathomechanisms.
