Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1

Vincent V Planche (1) , Ismail Koubiyr (1) , José E. Romero (2) , José V. Manjon (2) , Pierrick Coupé (3, 4) , Mathilde Deloire (5) , Vincent Dousset (6) , Bruno Brochet (5) , Aurélie Ruet (6) , Thomas Tourdias (6)

1 UB - Université de Bordeaux
2 UPV - Universitat Politècnica de València = Universitad Politecnica de Valencia = Polytechnic University of Valencia
3 LaBRI - Laboratoire Bordelais de Recherche en Informatique
4 PICTURA - Patch-based processing for medical and natural images
5 Service de neurologie [Bordeaux]
6 Neuroinflammation: imagerie et thérapie de la sclérose en plaques

Background: Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. Method: We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Partic- ipants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. Results: At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume signifi- cantly smaller than controls (p<.01). After one year, CA4/dentate gyrus atrophy worsened (26.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, 25.6%, p < .001 and 26.2%, p < .01, respectively). CA4/ dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R2 5 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/den- tate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2- lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not cor- related with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß 5 0.87, p < .05). Conclusion: The hippocampal degenerative process spread from dentate gyrus to CA1 at the ear- liest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance.

Domaines: Neurobiologie; Imagerie

Vincent V Planche, Ismail Koubiyr, José E. Romero, José V. Manjon, Pierrick Coupé, et al.. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1. Human Brain Mapping, 2018, 39 (4), pp.1814-1824. ⟨10.1002/hbm.23970⟩. ⟨hal-01808401⟩