In vivo evidence of hippocampal dentate gyrus expansion in multiple sclerosis.
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.
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Maria A
MA
Rocca
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Giulia
G
Longoni
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Elisabetta
E
Pagani
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Giacomo
G
Boffa
Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Bruno
B
Colombo
Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Mariaemma
M
Rodegher
Neuroimmunology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Gianvito
G
Martino
Department of Neuroradiology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Andrea
A
Falini
Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Giancarlo
G
Comi
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.|Department of Neurology, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Massimo
M
Filippi
D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D018891:Dentate Gyrus / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
cognition; dentate gyrus; hippocampus; inflammation; multiple sclerosis; neurogenesis; radial mapping; volumetric MRI