The relationship between whole brain volume and disability in multiple sclerosis: A comparison of normalized gray vs. white matter with misclassification correction (original) (raw)
Related papers
Grey matter volume in a large cohort of MS patients: relation to MRI parameters and disability
2011
Background: Although grey matter damage in multiple sclerosis is currently recognized, determinants of grey matter volume and its relationship with disability are not yet clear. Objectives: The objectives of the study were to measure grey and white matter volumes across different disease phenotypes; identify MRI parameters associated with grey matter volume; and study grey and white matter volume as explanatory variables for clinical impairment. Methods: This is a cross-sectional study in which MRI data of 95 clinically isolated syndrome, 657 relapsing-remitting, 125 secondary-progressive and 50 primary-progressive multiple sclerosis patients from three centres were acquired. Grey and white matter volumes were determined, together with T2 and T1 lesion volumes. Physical disability was assessed with the Expanded Disability Status Scale, cognitive impairment with the Paced Auditory Serial Addition Task. Data were analysed using multiple regression. Results: Grey matter volume was lower in relapsing-remitting patients (mean [SD]: 0.80 [0.05] L) than in clinically isolated syndrome patients (0.82 [0.05] L), and even greater relative atrophy was found in secondary-progressive patients (0.77 [0.05] L). In contrast, white matter volume in secondary-progressive patients was comparable to that in relapsingremitting patients. Grey matter volume was the strongest independent predictor of physical disability and cognitive impairment, and was associated with both T2 and T1 lesion volume. Conclusions: Our findings show that grey matter volume is lower in secondary-progressive than in relapsing-remitting disease. Grey matter volume explained physical and cognitive impairment better than white matter volume, and is itself associated with T2 and T1 lesion volume.
Brain atrophy and lesion load in a large population of patients with multiple sclerosis
Neurology, 2005
To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. Methods: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). Results: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. Conclusions: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.
Brain, 2005
We have recently reported brain atrophy in the early stages of primary progressive multiple sclerosis (PPMS), affecting both grey and white matter (GM and WM). However, to date no clinical or radiological predictors of GM and WM atrophy have been identified. The aim was to investigate short-term changes in GM and WM volumes and to assess the predictive value of demographic, clinical and radiological variables in order to gain a better understanding of the pathological substrate underlying these changes. Thirty-one subjects with PPMS within 5 years of symptom onset were studied at baseline and after 1 year. At baseline, patients underwent neurological examination and were scored on the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite. They had 3D inversion-prepared fast spoiled gradient recalled (FSPGR), dual-echo and triple-dose post-contrast T1weighted spin echo MRI scans. Proton density and enhancing lesion loads were determined. The 3DFSPGR sequence was repeated after 1 year and brain volume changes were calculated using two techniques, SPM99 (statistical parametric mapping) and SIENA (structural image evaluation, using normalization, of atrophy). Stepwise linear regression models were applied to baseline variables to identify independent predictors of atrophy development. Using SPM99, a decrease in brain parenchymal fraction (À1.03%; P < 0.001) and GM fraction (À1.49%; P < 0.001) was observed. The number of enhancing lesions independently predicted decrease in brain parenchymal fraction (P = 0.019) and decrease in WM fraction (P = 0.002). No independent predictors of GM fraction decrease were found. A mean brain volume change of À0.63% (range À4.27% to +1.18%; P = 0.002) was observed using SIENA, which was independently predicted by EDSS (P = 0.004). Global and GM atrophy can be detected over a 1-year period in early PPMS. The former may be predicted by the degree of inflammation, while the latter seems to be independent of it. SIENA and SPM-based methods appear to provide complementary information.
Association between brain volume and disability over time in multiple sclerosis
Multiple Sclerosis Journal - Experimental, Translational and Clinical
Background Most previous multiple sclerosis (MS) brain atrophy studies using MS impact scale 29 (MSIS-29) or symbol digit modalities test (SDMT) have been cross-sectional with limited sets of clinical outcomes. Objectives To investigate which brain and lesion volume metrics show the strongest long-term associations with the expanded disability status scale (EDSS), SDMT, and MSIS-29, and whether MRI-clinical associations vary with age. Methods We acquired MRI and clinical data from a real-world Swedish MS cohort. FreeSurfer and SPM Lesion Segmentation Tool were used to obtain brain parenchymal, cortical and subcortical grey matter, thalamic and white matter fractions as well as T1- and T2-lesion volumes. Mixed-effects and rolling regression models were used in the statistical analyses. Results We included 989 persons with MS followed for a median of 9.3 (EDSS), 10.1 (SDMT), and 9.3 (MSIS-29) years, respectively. In a cross-sectional analysis, the strength of the associations of the M...
Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study
American Journal of Neuroradiology, 2018
BACKGROUND AND PURPOSE: Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes. MATERIALS AND METHODS: Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models. RESULTS: Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures (P Ͻ .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures (P Յ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS (P Յ .01), coupled with thalamic susceptibility changes (P ϭ .05). CONCLUSIONS: Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS. ABBREVIATIONS: DD ϭ disease duration; DGM ϭ deep gray matter; DMT ϭ disease-modifying treatment; EDSS ϭ Expanded Disability Status Scale; FA ϭ fractional anisotropy; HC ϭ healthy controls; LL ϭ lesion load; MD ϭ mean diffusivity; PMS ϭ progressive MS; QSM ϭ Quantitative Susceptibility Mapping; rCBV ϭ relative CBV; RRMS ϭ relapsing-remitting MS
Cognitive impairment may result in significant disability in patients with Multiple Sclerosis (MS). Previous Magnetic Resonance Imaging (MRI) studies on cognition in MS were mainly based on measures of gross brain involvement. This study, using voxel-based morphometry (VBM), aims to investigate associations between the regional distribution of grey matter (GM) damage and cognitive performance in patients with MS. Eighteen MS patients underwent an extensive neuropsychological battery and MRI, including T2-weighted scans and T1-weighted volumes. A group of 18 healthy individuals were also investigated by MRI and served as controls for the VBM. A cross-sectional analysis was first performed, to assess the pattern of regional GM atrophy in MS patients. Then, the impact of regional GM damage on patients' neuropsychological performance was investigated by multiple regression analyses in the patient group. Correlations between global indexes of brain damage and neuropsychological measures were also assessed for comparison with previous literature. The comparison between MS patients and healthy controls revealed a widespread pattern of regional GM atrophy. Consistent with previous studies, associations were found between neuropsychological scores, and global brain atrophy and T2-lesion volumes. Critically, significant associations were found between scores on the Symbol Digit Modalities test and Long Delay Cued Recall on the California Verbal Learning Test, and regional GM volumes in well localized areas of the prefrontal, parietal, temporal, and insular cortex. This study confirms that global assessments of brain damage correlate with measures of cognitive impairment in MS. Interestingly, VBM contributes to clarify those brain regions that more likely determine the cognitive deficits observed in patients. These findings clarify the pathophysiology of cognitive impairment in MS, and propose measures which could be considered for longitudinal monitoring of patients.
Clinical Relevance of Brain Volume Measures in Multiple Sclerosis
CNS Drugs, 2014
Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceeding throughout the disease course, may be an accurate measure of neurodegeneration and tissue damage. There are a number of magnetic resonance imaging-based methods for determining global or regional brain volume, including cross-sectional (e.g. brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore
NeuroImage, 2008
To assess regional grey matter (GM) changes in a large cohort of multiple sclerosis (MS) patients with different clinical phenotypes, using voxelbased morphometry (VBM) and their correlation with the extent of global and regional T2 lesion volumes (LV), we acquired conventional MRI scans from 71 MS patients with different clinical phenotypes (26 with relapsing-remitting [RR] MS, 27 with secondary progressive [SP] MS and 18 with primary progressive [PP] MS), 28 patients with a clinically isolated syndrome (CIS) suggestive of MS, and 21 controls. No GM loss was found in CIS patients. Compared to CIS patients, those with RRMS had a significant GM loss in the right pre and postcentral gyri. Compared to RRMS, SPMS patients had a significant GM loss in several regions of the fronto-parieto-temporo-occipital lobes, the cerebellum and superior and inferior colliculus, bilaterally, and deep GM structures. Compared to PPMS, SPMS patients had a significant GM loss in the postcentral gyrus, the cuneus, the middle occipital gyrus, the thalamus, the cerebellum, and the superior and inferior colliculus. In all MS groups, regional GM loss was strongly/moderately correlated with brain T2 LV. In SPMS and PPMS patients, a correlation was found between cortical regional GM loss and T2 LV of the corresponding or adjacent lobes. In MS patients, GM volume loss follows different patterns of regional distribution according to the clinical phenotype of the disease, is likely secondary to the presence and topography of focal WM inflammatory-demyelinating lesions, and is more evident in the progressive forms of the disease.
Deep grey matter volume loss drives disability worsening in multiple sclerosis
Objective: Grey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. Methods: We analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], 125 primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard deviation [SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-E...