Gray matter is targeted in first-attack multiple sclerosis.
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ABSTRACT:
SUBMITTER: Schutzer SE
PROVIDER: S-EPMC3769274 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Publications
Gray matter is targeted in first-attack multiple sclerosis.
Schutzer Steven E SE Angel Thomas E TE Liu Tao T Schepmoes Athena A AA Xie Fang F Bergquist Jonas J Vécsei László L Zadori Denes D Camp David G DG Holland Bart K BK Smith Richard D RD Coyle Patricia K PK
PloS one 20130910 9
The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify protein ...[more]
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Project description:BACKGROUND:Coordinated patterns of gray matter morphology can be represented as networks, and network disruptions may explain cognitive dysfunction related to multiple sclerosis (MS). OBJECTIVE:To investigate whether single-subject gray matter network properties are related to impaired cognition in MS. METHODS:We studied 148 MS patients (99 female) and 33 healthy controls (HC, 21 female). Seven network parameters were computed and compared within MS between cognitively normal and impaired subjects, and associated with performance on neuropsychological tests in six cognitive domains with regression models. Analyses were controlled for age, gender, whole-brain gray matter volumes, and education level. RESULTS:Compared to MS subjects with normal cognition, MS subjects with cognitive impairment showed a more random network organization as indicated by lower lambda values (all p < 0.05). Worse average cognition and executive function were associated with lower lambda values. Impaired information processing speed, working memory, and attention were associated with lower clustering values. CONCLUSION:Our findings indicate that MS subjects with a more randomly organized gray matter network show worse cognitive functioning, suggesting that single-subject gray matter graphs may capture neurological dysfunction due to MS.
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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.
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Project description:ObjectiveThis study aimed to investigate longitudinal deep gray matter (DGM) shape changes and their relationship with measures of clinical disability and white matter lesion-load in a large multiple sclerosis (MS) cohort.Materials and methodsA total of 230 MS patients (179 relapsing-remitting, 51 secondary progressive; baseline age 44.5 ± 11.3 years; baseline disease duration 12.99 ± 9.18) underwent annual clinical and MRI examinations over a maximum of 6 years (mean 4.32 ± 2.07 years). The DGM structures were segmented on the T1-weighted images using the "Multiple Automatically Generated Templates" brain algorithm. White matter lesion-load was measured on T2-weighted MRI. Clinical examination included the expanded disability status scale, 9-hole peg test, timed 25-foot walk test, symbol digit modalities test and paced auditory serial addition test. Vertex-wise longitudinal analysis of DGM shapes was performed using linear mixed effect models and evaluated the association between average/temporal changes of DGM shapes with average/temporal changes of clinical measurements, respectively.ResultsA significant shrinkage over time of the bilateral ventrolateral pallidal and the left posterolateral striatal surface was observed, whereas no significant shape changes over time were observed at the bilateral thalamic and right striatal surfaces. Higher average lesion-load was associated with an average inwards displacement of the global thalamic surface with relative sparing on the posterior side (slight left-side predominance), the antero-dorso-lateral striatal surfaces bilaterally (symmetric on both sides) and the antero-lateral pallidal surface (left-side predominance). There was also an association between shrinkage of large lateral DGM surfaces with higher clinical motor and cognitive disease severity. However, there was no correlation between any DGM shape changes over time and measurements of clinical progression or lesion-load changes over time.ConclusionsThis study showed specific shape change of DGM structures occurring over time in relapse-onset MS. Although these shape changes over time were not associated with disease progression, we demonstrated a link between DGM shape and the patients' average disease severity as well as white matter lesion-load.
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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.
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Project description:Previous imaging studies assessing the relationship between white matter (WM) damage and matter (GM) atrophy have raised the concern that Multiple Sclerosis (MS) WM lesions may affect measures of GM volume by inducing voxel misclassification during intensity-based tissue segmentation. Here, we quantified this misclassification error in simulated and real MS brains using a lesion-filling method. Using this method, we also corrected GM measures in patients before comparing them with controls in order to assess the impact of this lesion-induced misclassification error in clinical studies. We found that higher WM lesion volumes artificially reduced total GM volumes. In patients, this effect was about 72% of that predicted by simulation. Misclassified voxels were located at the GM/WM border and could be distant from lesions. Volume of individual deep gray matter (DGM) structures generally decreased with higher lesion volumes, consistent with results from total GM. While preserving differences in GM volumes between patients and controls, lesion-filling correction revealed more lateralised DGM shape changes in patients, which were not evident with the original images. Our results confirm that WM lesions can influence MRI measures of GM volume and shape in MS patients through their effect on intensity-based GM segmentation. The greater effect of lesions at increasing levels of damage supports the use of lesion-filling to correct for this problem and improve the interpretability of the results. Volumetric or morphometric imaging studies, where lesion amount and characteristics may vary between groups of patients or change over time, may especially benefit from this correction.
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| S-EPMC6689465 | biostudies-literature
Project description: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.To investigate the associations between MS disability and disease type with lower thoracic cord GM and WM areas using phase-sensitive inversion recovery magnetic resonance imaging at 3 T, as well as to compare these relationships with those obtained at upper cervical levels.Between July 2013 and March 2014, a total of 142 patients with MS (aged 25-75 years; 86 women) and 20 healthy control individuals were included in this cross-sectional observational study conducted at an academic university hospital.Total cord areas (TCAs), GM areas, and WM areas at the disc levels C2/C3, C3/C4, T8/9, and T9/10. Area differences between groups were assessed, with age and sex as covariates.Patients with relapsing MS (RMS) had smaller thoracic cord GM areas than did age- and sex-matched control individuals (mean differences [coefficient of variation (COV)]: 0.98 mm2 [9.2%]; P?=?.003 at T8/T9 and 0.93 mm2 [8.0%]; P?=?.01 at T9/T10); however, there were no significant differences in either the WM area or TCA. Patients with progressive MS showed smaller GM areas (mean differences [COV]: 1.02 mm2 [10.6%]; P?<?.001 at T8/T9 and 1.37 mm2 [13.2%]; P?<?.001 at T9/T10) and TCAs (mean differences [COV]: 3.66 mm2 [9.0%]; P?<?.001 at T8/T9 and 3.04 mm2 [7.2%]; P?=?.004 at T9/T10) compared with patients with RMS. All measurements (GM, WM, and TCA) were inversely correlated with Expanded Disability Status Scale score. Thoracic cord GM areas were correlated with lower limb function. In multivariable models (which also included cord WM areas and T2 lesion number, brain WM volumes, brain T1 and fluid-attenuated inversion recovery lesion loads, age, sex, and disease duration), cervical cord GM areas had the strongest correlation with Expanded Disability Status Scale score followed by thoracic cord GM area and brain GM volume.Thoracic cord GM atrophy can be detected in vivo in the absence of WM atrophy in RMS. This atrophy is more pronounced in progressive MS than RMS and correlates with disability and lower limb function. Our results indicate that remarkable cord GM atrophy is present at multiple cervical and lower thoracic levels and, therefore, may reflect widespread cord GM degeneration.
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