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Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.

ABSTRACT: 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.

SUBMITTER: Sotirchos ES

PROVIDER: S-EPMC6689465 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.

Sotirchos Elias S ES Gonzalez-Caldito Natalia N Dewey Blake E BE Fitzgerald Kathryn C KC Glaister Jeffrey J Filippatou Angeliki A Ogbuokiri Esther E Feldman Sydney S Kwakyi Ohemaa O Risher Hunter H Crainiceanu Ciprian C Pham Dzung L DL Van Zijl Peter C PC Mowry Ellen M EM Reich Daniel S DS Prince Jerry L JL Calabresi Peter A PA Saidha Shiv S

Multiple sclerosis (Houndmills, Basingstoke, England) 20190211 3

<h4>Background</h4>The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear.<h4>Objective</h4>To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS.<h4>Methods</h4>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 w ...[more]

PMID: 30741108

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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.

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.

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Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.

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Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.

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