Extra-hippocampal subcortical limbic involvement predicts episodic recall performance in multiple sclerosis.
BACKGROUND
Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging.


RESULTS
34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R(2) = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R(2) = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency.


CONCLUSIONS
These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.
Division of Radiological and Imaging Sciences, University of Nottingham, Nottingham, United Kingdom. rob.dineen@nottingham.ac.uk
Robert A
RA
Dineen
Christopher M
CM
Bradshaw
Cris S
CS
Constantinescu
Dorothee P
DP
Auer
D000328:Adult; D016880:Anisotropy; D005260:Female; D020712:Fornix, Brain / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008326:Mammillary Bodies / Q000473:pathology / Q000503:physiopathology; D008569:Memory Disorders / Q000503:physiopathology*; D011939:Mental Recall / Q000502:physiology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology / Q000503:physiopathology*; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D012044:Regression Analysis; D015203:Reproducibility of Results; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology