Association Between Thoracic Spinal Cord Gray Matter Atrophy and Disability in Multiple Sclerosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Schlaeger R
PROVIDER: S-EPMC6002864 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
Publications
Association Between Thoracic Spinal Cord Gray Matter Atrophy and Disability in Multiple Sclerosis.
Schlaeger Regina R Papinutto Nico N Zhu Alyssa H AH Lobach Iryna V IV Bevan Carolyn J CJ Bucci Monica M Castellano Antonella A Gelfand Jeffrey M JM Graves Jennifer S JS Green Ari J AJ Jordan Kesshi M KM Keshavan Anisha A Panara Valentina V Stern William A WA von Büdingen H-Christian HC Waubant Emmanuelle E Goodin Douglas S DS Cree Bruce A C BA Hauser Stephen L SL Henry Roland G RG
JAMA neurology 20150801 8
<h4>Importance</h4>In multiple sclerosis (MS), upper cervical cord gray matter (GM) atrophy correlates more strongly with disability than does brain or cord white matter (WM) atrophy. The corresponding relationships in the thoracic cord are unknown owing to technical difficulties in assessing GM and WM compartments by conventional magnetic resonance imaging techniques.<h4>Objectives</h4>To investigate the associations between MS disability and disease type with lower thoracic cord GM and WM area ...[more]
Similar Datasets
Project description:In multiple sclerosis (MS), cerebral gray matter (GM) atrophy correlates more strongly than white matter (WM) atrophy with disability. The corresponding relationships in the spinal cord (SC) are unknown due to technical limitations in assessing SC GM atrophy. Using phase-sensitive inversion recovery (PSIR) magnetic resonance imaging, we determined the association of the SC GM and SC WM areas with MS disability and disease type.A total of 113 MS patients and 20 healthy controls were examined at 3T with a PSIR sequence acquired at the C2/C3 disk level. Two independent, clinically masked readers measured the cord WM and GM areas. Correlations between cord areas and Expanded Disability Status Score (EDSS) were determined. Differences in areas between groups were assessed with age and sex as covariates.Relapsing MS (RMS) patients showed smaller SC GM areas than age- and sex-matched controls (p = 0.008) without significant differences in SC WM areas. Progressive MS patients showed smaller SC GM and SC WM areas compared to RMS patients (all p ? 0.004). SC GM, SC WM, and whole cord areas inversely correlated with EDSS (rho: -0.60, -0.32, -0.42, respectively; all p ? 0.001). The SC GM area was the strongest correlate of disability in multivariate models including brain GM and WM volumes, fluid-attenuated inversion recovery lesion load, T1 lesion load, SC WM area, number of SC T2 lesions, age, sex, and disease duration. Brain and spinal GM independently contributed to EDSS.SC GM atrophy is detectable in vivo in the absence of WM atrophy in RMS. It is more pronounced in progressive MS than RMS and contributes more to patient disability than SC WM or brain GM atrophy.
| S-EPMC5316412 | biostudies-literature
Project description:ObjectiveWe sought to characterize spinal cord atrophy along the entire spinal cord in the major multiple sclerosis (MS) phenotypes, and evaluate its correlation with clinical disability.MethodsAxial T1-weighted images were automatically reformatted at each point along the cord. Spinal cord cross-sectional area (SCCSA) were calculated from C1-T10 vertebral body levels and profile plots were compared across phenotypes. Average values from C2-3, C4-5, and T4-9 regions were compared across phenotypes and correlated with clinical scores, and then categorized as atrophic/normal based on z-scores derived from controls, to compare clinical scores between subgroups. In a subset of relapsing-remitting cases with longitudinal scans these regions were compared to change in clinical scores.ResultsThe cross-sectional study consisted of 149 adults diagnosed with relapsing-remitting MS (RRMS), 49 with secondary-progressive MS (SPMS), 58 with primary-progressive MS (PPMS) and 48 controls. The longitudinal study included 78 RRMS cases. Compared to controls, all MS groups had smaller average regions except RRMS in T4-9 region. In all MS groups, SCCSA from all regions, particularly the cervical cord, correlated with most clinical measures. In the RRMS cohort, 22% of cases had at least one atrophic region, whereas in progressive MS the rate was almost 70%. Longitudinal analysis showed correlation between clinical disability and cervical cord thinning.ConclusionsSpinal cord atrophy was prevalent across MS phenotypes, with regional measures from the RRMS cohort and the progressive cohort, including SPMS and PPMS, being correlated with disability. Longitudinal changes in the spinal cord were documented in RRMS cases, making it a potential marker for disease progression. While cervical SCCSA correlated with most disability and progression measures, inclusion of thoracic measurements improved this correlation and allowed for better subgrouping of spinal cord phenotypes. Cord atrophy is an important and easily obtainable imaging marker of clinical and sub-clinical progression in all MS phenotypes, and such measures can play a key role in patient selection for clinical trials.
| S-EPMC8131917 | biostudies-literature
Project description:The aim of this study was to explore possible changes in whole brain gray matter volume (GMV) after spinal cord injury (SCI) using voxel-based morphometry (VBM), and to study their associations with the injury duration, severity, and clinical variables. In total, 21 patients with SCI (10 with complete and 11 with incomplete SCI) and 21 age- and sex-matched healthy controls (HCs) were recruited. The 3D high-resolution T1-weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Disease duration and American Spinal Injury Association (ASIA) Scale scores were also obtained from each patient. Voxel-based morphometry analysis was carried out to investigate the differences in GMV between patients with SCI and HCs, and between the SCI sub-groups. Associations between GMV and clinical variables were also analyzed. Compared with HCs, patients with SCI showed significant GMV decrease in the dorsal anterior cingulate cortex, bilateral anterior insular cortex, bilateral orbital frontal cortex (OFC), and right superior temporal gyrus. No significant difference in GMV in these areas was found either between the complete and incomplete SCI sub-groups, or between the sub-acute (duration <1 year) and chronic (duration >1 year) sub-groups. Finally, the GMV of the right OFC was correlated with the clinical motor scores of left extremities in not only all SCI patients, but especially the CSCI subgroup. In the sub-acute subgroup, we found a significant positive correlation between the dACC GMV and the total clinical motor scores, and a significant negative correlation between right OFC GMV and the injury duration. These findings indicate that SCI can cause remote atrophy of brain gray matter, especially in the salient network. In general, the duration and severity of SCI may be not associated with the degree of brain atrophy in total SCI patients, but there may be associations between them in subgroups.
| S-EPMC5408078 | biostudies-literature
Project description:OBJECTIVE:Gray 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 analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 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 seven European centers. 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-EDSS progression. RESULTS:SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). INTERPRETATION:This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210-222.
| S-EPMC5838522 | biostudies-literature
Project description:Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability. The purpose of this study is to describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability. A cross-sectional study of 164 patients with complete MRIs was used. In each case the spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale ?4.0) was adjusted for age, disease duration and sex using logistic regression. A total of 125/164 (73 %) MS patients had spinal cord lesions (sSCLs, 57 %; LESCLs, 19 %), but only 11 (7 %) had OSMS. LESCLs were associated with disability (p < 0.0001), longer disease duration (p < 0.0001) and MS (n = 21 vs. n = 10 OSMS; p < 0.0001). LESCLs were also associated with the greatest risk to disability (OR 7.3, 95 % CIs 1.9-26.5; p = 0.003; sSCLs OR 2.5, 95 % CIs 0.9-7.1; p = 0.09) compared with noSCLs. LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.
| S-EPMC3816004 | biostudies-literature
Project description:ObjectiveTo determine if patients with post-polio syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient-reported functional decline.MethodsTwenty patients diagnosed with PPS (March of Dimes criteria) and 20 age- and sex-matched healthy controls (HC) underwent 3T axial 2D-rAMIRA magnetic resonance imaging at the intervertebral disc levels C2/C3-C6/C7, T9/T10 and the lumbar enlargement level (Tmax ) (0.5 × 0.5 mm2 in-plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self-reported fatigue, depression and pain measures were assessed.ResultsPost-polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p = 0.001), C4/C5 (p < 0.001), C5/C6 (p = 0.004) and Tmax (p = 0.041) compared to HC. SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain and depression. SCGM areaTmax together with age and sex explained 68% of ankle dorsiflexion strength variance. No associations were found with age at or time since infection. Patients reporting PPS-related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity.ConclusionsPatients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS-related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases.
| S-EPMC9310958 | biostudies-literature
Project description:ImportanceMultiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown.ObjectiveTo understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS.Design, setting, and participantsIn this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014.Main outcomes and measuresVoxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores).ResultsAmong the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations.Conclusions and relevanceThese biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.
| S-EPMC6415681 | biostudies-literature
Project description:ObjectiveThe clinicoradiologic paradox, or disconnect between clinical and radiologic findings, is frequently encountered in multiple sclerosis (MS), particularly in the spinal cord (SC), where lesions are expected to cause clinical impairment. We aimed to assess whether quantitative diffusion tensor and magnetization transfer imaging measures in the SC can distinguish MS cases of comparable lesion burdens with high and low disability.MethodsOne hundred twenty-four patients with MS underwent 3-T cervical SC MRI and were categorized into 4 subgroups according to SC lesion count and disability level. Regions of interest circumscribed the SC cross-section axially between C3 and C4. Cross-sectional area, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (?(?)), parallel diffusivity (?(?)), and magnetization transfer ratio (MTR) were calculated. Differences between patient subgroups were assessed using t tests and linear regression.ResultsFA, MD, ?(?), ?(?), MTR, and SC cross-sectional area were more abnormal in the high- vs low-disability subgroup of patients with low lesion counts (p < 0.05). MRI measures (except ?(?) and MTR) were more abnormal in the high- vs low-disability subgroup of patients with high lesion counts (p < 0.05). In age- and sex-adjusted comparisons of high- vs low-disability subgroups, all MRI measures retained differences in the low-lesion subgroup, except ?(?), whereas only FA, MD, and ?(?) retained differences in the high-lesion subgroup.ConclusionsIn this cross-sectional study of patients with MS, quantitative MRI reflects clinically relevant differences beyond what can be detected by conventional MRI. Our findings support the utility of quantitative MRI in clinical settings, where accurate measurement of disease burden is becoming increasingly critical for assessing treatment efficacy.
| S-EPMC3589285 | biostudies-literature
Project description:BACKGROUND:The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear. OBJECTIVE:To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS. METHODS:A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for??6?months prior to baseline and had at least one follow-up MRI while on DMTs in the same category. RESULTS:A total of 86 DMT epochs (DMT-H: n?=?32; DMT-L: n?=?54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4?years. Annualized rates of thalamic (-0.15% vs -0.81%; p?=?0.001) and putaminal (-0.27% vs -0.73%; p?=?0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume. CONCLUSION:DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.
| S-EPMC6689465 | biostudies-literature
Project description:Background and purposeModifications of magnetic susceptibility have been consistently demonstrated in the subcortical gray matter of MS patients, but some uncertainties remain concerning the underlying neurobiological processes and their clinical relevance. We applied quantitative susceptibility mapping and longitudinal relaxation rate relaxometry to clarify the relative contribution of atrophy and iron and myelin changes to deep gray matter damage and disability in MS.Materials and methodsQuantitative susceptibility mapping and longitudinal relaxation rate maps were computed for 91 patients and 55 healthy controls from MR images acquired at 3T. Applying an external model, we estimated iron and myelin concentration maps for all subjects. Subsequently, changes of deep gray matter iron and myelin concentration (atrophy-dependent) and content (atrophy-independent) were investigated globally (bulk analysis) and regionally (voxel-based and atlas-based thalamic subnuclei analyses). The clinical impact of the observed MRI modifications was evaluated via regression models.ResultsWe identified reduced thalamic (P < .001) and increased pallidal (P < .001) mean iron concentrations in patients with MS versus controls. Global myelin and iron content in the basal ganglia did not differ between the two groups, while actual iron depletion was present in the thalamus (P < .001). Regionally, patients showed increased iron concentration in the basal ganglia (P ≤ .001) and reduced iron and myelin content in thalamic posterior-medial regions (P ≤ .004), particularly in the pulvinar (P ≤ .001). Disability was predicted by thalamic volume (B = -0.341, P = .02), iron concentration (B = -0.379, P = .005) and content (B = -0.406, P = .009), as well as pulvinar iron (B = -0.415, P = .003) and myelin (B = -0.415, P = .02) content, independent of atrophy.ConclusionsQuantitative MRI suggests an atrophy-related iron increase within the basal ganglia of patients with MS, along with an atrophy-independent reduction of thalamic iron and myelin correlating with disability. Absolute depletions of thalamic iron and myelin may represent sensitive markers of subcortical GM damage, which add to the clinical impact of thalamic atrophy in MS.
| S-EPMC8324266 | biostudies-literature