Hippocampal and Deep Gray Matter Nuclei Atrophy Is Relevant for Explaining Cognitive Impairment in MS: A Multicenter Study.
The structural MR imaging correlates of cognitive impairment in multiple sclerosis are still debated. This study assessed lesional and atrophy measures of white matter and gray matter involvement in patients with MS acquired in 7 European sites to identify the MR imaging variables most closely associated with cognitive dysfunction.



Brain dual-echo, 3D T1-weighted, and double inversion recovery scans were acquired at 3T from 62 patients with relapsing-remitting MS and 65 controls. Patients with at least 2 neuropsychological tests with abnormal findings were considered cognitively impaired. Focal WM and cortical lesions were identified, and volumetric measures from WM, cortical GM, the hippocampus, and deep GM nuclei were obtained. Age- and site-adjusted models were used to compare lesion and volumetric MR imaging variables between patients with MS who were cognitively impaired and cognitively preserved. A multivariate analysis identified MR imaging variables associated with cognitive scores and disability.



Twenty-three patients (38%) were cognitively impaired. Compared with those with who were cognitively preserved, patients with MS with cognitive impairment had higher T2 and T1 lesion volumes and a trend toward a higher number of cortical lesions. Significant brain, cortical GM, hippocampal, deep GM nuclei, and WM atrophy was found in patients with MS with cognitive impairment versus those who were cognitively preserved. Hippocampal and deep GM nuclei atrophy were the best predictors of cognitive impairment, while WM atrophy was the best predictor of disability.



Hippocampal and deep GM nuclei atrophy are key factors associated with cognitive impairment in MS. These MR imaging measures could be applied in a multicenter context, with cognition as clinical outcome.
From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.).|Center for Radiology and MRI of Clinical Center of Serbia (D.D.), Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
D
0000-0002-2970-6125
D
Damjanovic
From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.).
P
0000-0001-5390-2655
P
Valsasina
From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.).|Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
M A
0000-0003-2358-4320
MA
Rocca
Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy.
M L
0000-0001-6909-623X
ML
Stromillo
MRI Center "SUN-FISM" (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte," Naples, Italy.|I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
A
0000-0002-2203-6237
A
Gallo
Department of Neurology (C.E., F.F.).|Division of Neuroradiology (C.E.), Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria.
C
0000-0001-9764-7617
C
Enzinger
Department of Radiology and Nuclear Medicine (H.E.H.), MS Centre Amsterdam, VU University Medical Centre, Amsterdam, Netherlands.
H E
0000-0002-5039-1359
HE
Hulst
Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
A
0000-0002-2132-6750
A
Rovira
NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.
N
0000-0002-6414-5589
N
Muhlert
Department of Neurological and Behavioural Sciences (M.L.S., N.D.S.), University of Siena, Siena, Italy.
N
0000-0003-4930-7639
N
De Stefano
MRI Center "SUN-FISM" (A.G., A.B.), Second University of Naples and Institute of Diagnosis and Care "Hermitage-Capodimonte," Naples, Italy.|I Division of Neurology (A.G., A.B.), Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
A
0000-0002-7202-4445
A
Bisecco
Department of Neurology (C.E., F.F.).
F
0000-0001-8155-7799
F
Fazekas
Magnetic Resonance Unit (A.R., M.J.A.), Department of Radiology and MS Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
M J
0000-0003-0626-5555
MJ
Arévalo
NMR Research Unit (N.M., T.A.Y.), Queen Square MS Centre, University College London Institute of Neurology, London, UK.
T A
0000-0003-3295-0628
TA
Yousry
From the Neuroimaging Research Unit (D.D., P.V., M.A.R., M.F.) filippi.massimo@hsr.it.|Department of Neurology (M.A.R., M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
M
0000-0002-5485-0479
M
Filippi
D000328:Adult; D001284:Atrophy / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D015999:Multivariate Analysis
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