Objectives: Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS.Methods: Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains.Stepwise linear regression was used to predict average cognition in the patient group.Results: Most deep GM volumes were reduced in patients, with larger effects on average in men (Ϫ11%) than in women (Ϫ6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R 2 ϭ 0.31), while lesion volume was not a significant predictor in the model. Conclusions:Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS. Neurology ® 2012;79:1754-1761 GLOSSARY BRB-N ϭ Brief Repeatable Battery for Neurological disease; DGM ϭ deep gray matter; DMT ϭ disease-modifying therapy; EDSS ϭ Expanded Disability Status Scale; GLM ϭ general linear model; GM ϭ gray matter; MS ϭ multiple sclerosis; NBV ϭ normalized whole brain volume; NCGMV ϭ normalized cortical gray matter volume; NDGMV ϭ normalized deep gray matter volume; NGMV ϭ normalized total gray matter volume; NWMV ϭ normalized total white matter volume; RRMS ϭ relapsingremitting multiple sclerosis; WM ϭ white matter.Atrophy of the gray matter (GM) and white matter (WM) is frequently found in multiple sclerosis (MS), 1,2 and can be reliably measured with MRI.3 Although already present in early stages, GM atrophy becomes much more dominant in the progressive phase of the disease. 4 As the clinical relevance and the specific histopathologic substrate of GM atrophy in MS is not well known, it is the subject of many recent studies. 5,6 While the relationship between brain atrophy and clinical measures has been investigated extensively in the past, 7 how atrophy relates to cognition is only recently becoming clearer. -11As cognitive dysfunction is common and present in all stages of the disease, 12-15 exploring the relationship between atrophy and cognition could provide valuable new information.As most studies that focus...

In MS, areas in the ventral stream and sensorimotor cortex appear to become less central in the entire functional network of the brain, which is associated with clinico-cognitive dysfunction. The thalamus, however, displays increased connectivity with these areas. These findings may aid in further elucidating the function of functional reorganization processes in MS.

Classically multiple sclerosis (MS) has been regarded as an auto‐immune disease of the white matter in the central nervous system leading to severe disability over the course of several decades. Current therapeutic strategies in MS are mostly based on either immune suppression or immune modulation. Although effective in decreasing relapse frequency and severity as well as delaying disease progression, MS pathology ensues nonetheless. In the last decade it became evident that gray matter pathology plays an important role in disease progression and helps explaining certain aspects of MS‐related disability such as cognitive decline. Conventional MRI outcome measures commonly used in clinical trials are sufficient to demonstrate an anti‐inflammatory drug‐effect but lack pathological specificity and are poor to moderate predictors of disability. In this article, we review new insights in gray matter pathology and functional reorganization in MS and how these novel fields in MS research may validate and establish new MRI outcome measures, aid in the development of new therapeutic strategies for neuroprotection and neurorepair, and may lead to development of novel predictive measures of disability and disease progression in MS. J. Magn. Reson. Imaging 2012; 36:1–19. © 2012 Wiley Periodicals, Inc.

The purpose of this study was to evaluate quality parameters, metabolite concentrations and concentration ratios, and to investigate the reproducibility of quantitative proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of selected white and gray matter regions of healthy adults. 2D-quantitative short-TE (1)H-MRSI spectra were obtained at 1.5T from the healthy human brain. Subjects (n = 12) were scanned twice with an interval of six months. Absolute metabolite concentrations were obtained based on coil loading, taking into account differences in sensitivity of the phased-array head coil. Spectral quality parameters, absolute metabolite concentrations, concentration ratios, and their reproducibility were determined and compared between time-points using a repeated measures general linear model. The quality of the spectra of selected brain areas was good, as determined by a mean spectral linewidth between 4.8 and 7.3 Hz (depending on the region). No significant differences between the two time-points were observed for spectral quality, concentrations, or concentration ratios. The mean intrasubject coefficient of variation (CoV) varied between 4.0 and 8.5% for total N-acetylaspartate, 7.2 and 10.8% for total creatine, 5.9 and 9.8% for myo-inositol, and 8.0 and 13.3% for choline, and remained below 20% for glutamate. CoV was generally lower when concentration ratios were considered. The study shows that longitudinal quantitative short-TE (1)H-MRSI generates reproducible absolute metabolite concentrations in healthy human white and gray matter. This may serve as a background for longitudinal clinical studies in adult patients.

BACKGROUND AND PURPOSE:The considerable clinical effect of natalizumab in patients with relapsing-remitting multiple sclerosis might be explained by its possible beneficial effect on axonal functioning. In this longitudinal study, the effect of natalizumab on absolute concentrations of total N-acetylaspartate, a marker for neuronal integrity, and other brain metabolites is investigated in patients with relapsing-remitting multiple sclerosis by using MR spectroscopic imaging.