MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis.
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SUBMITTER: York EN
PROVIDER: S-EPMC8643503 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purposeSusceptibility MR imaging contrast variations reflect alterations in brain iron and myelin content, making this imaging tool relevant to studies of multiple sclerosis lesion heterogeneity. In this study, we aimed to characterize the relationship of high-field, susceptibility contrasts in multiple sclerosis lesions to clinical outcomes.Materials and methodsTwenty-four subjects with multiple sclerosis underwent 7T MR imaging of the brain, disability examinations, and a fatigue inventory. The inverse of T2* relaxation time (R2*), frequency, and relative susceptibility (from quantitative susceptibility mapping) were analyzed in 306 white matter lesions.ResultsMost lesions were hypointense on R2* (88% without a rim, 5% with). Lesions that were hyperintense on quantitative susceptibility mapping were more frequent in relapsing-remitting than in progressive multiple sclerosis (54% versus 35%, P = .018). Hyperintense lesion rims on quantitative susceptibility maps were more common in progressive multiple sclerosis and patients with higher levels of disability and fatigue. Mean lesion R2* was inversely related to disability and fatigue and significantly reduced in progressive multiple sclerosis. Relative susceptibility was lower in lesions in progressive multiple sclerosis (median, -0.018 ppm; range, -0.070 to 0.022) than in relapsing-remitting MS (median, -0.010 ppm; range, -0.062 to 0.052; P = .003).ConclusionsA progressive clinical phenotype and greater disability and fatigue were associated with lower R2* and relative susceptibility values (suggestive of low iron due to oligodendrocyte loss) and rimmed lesions (suggestive of chronic inflammation) in this multiple sclerosis cohort. Lesion heterogeneity on susceptibility MR imaging may help explain disability in multiple sclerosis and provide a window into the processes of demyelination, oligodendrocyte loss, and chronic lesion inflammation.
| S-EPMC4983536 | biostudies-literature
Project description:BackgroundInfections are discussed as risk factor for multiple sclerosis (MS) development and relapses. This may lead to decreased vaccination frequency in newly diagnosed patients.ObjectiveThe aim of this study was to evaluate the relation of MS diagnosis to subsequent vaccination frequency.MethodsBased on German ambulatory claims data from 2005 to 2019, regression models were used to assess the relation of MS diagnosis (n = 12,270) to vaccination. A cohort of patients with MS was compared to control cohorts with Crohn's disease, psoriasis, and without these autoimmune diseases (total n = 198,126) in the 5 years after and before diagnosis.ResultsPatients with MS were less likely to be vaccinated compared to persons without the autoimmune diseases 5 years after diagnosis (odds ratio = 0.91, p < 0.001). Exceptions were vaccinations against influenza (1.29, p < 0.001) and pneumococci (1.41, p < 0.001). Differences were strong but less pronounced after than before diagnosis (p < 0.001). The likelihood of vaccination was also lower compared to patients with Crohn's disease or psoriasis.ConclusionsPatients with MS were not adequately vaccinated despite guideline recommendations. Increasing awareness about the importance of vaccination is warranted to reduce the risk of infection, in particular, in patients with MS receiving immunotherapies.
| S-EPMC10687801 | biostudies-literature
Project description:Quantitative MRI (qMRI) probes the microstructural properties of the central nervous system (CNS) by providing biophysical measures of tissue characteristics. In this work, we aimed to (i) identify qMRI measures that distinguish histological lesion types in postmortem multiple sclerosis (MS) brains, especially the remyelinated ones; and to (ii) investigate the relationship between those measures and quantitative histological markers of myelin, axons, and astrocytes in the same experimental setting. Three fixed MS whole brains were imaged with qMRI at 3T to obtain magnetization transfer ratio (MTR), myelin water fraction (MWF), quantitative T1 (qT1), quantitative susceptibility mapping (QSM), fractional anisotropy (FA) and radial diffusivity (RD) maps. The identification of lesion types (active, inactive, chronic active, or remyelinated) and quantification of tissue components were performed using histological staining methods as well as immunohistochemistry and immunofluorescence. Pairwise logistic and LASSO regression models were used to identify the best qMRI discriminators of lesion types. The association between qMRI and quantitative histological measures was performed using Spearman's correlations and linear mixed-effect models. We identified a total of 65 lesions. MTR and MWF best predicted the chance of a lesion to be remyelinated, whereas RD and QSM were useful in the discrimination of active lesions. The measurement of microstructural properties through qMRI did not show any difference between chronic active and inactive lesions. MWF and RD were associated with myelin content in both lesions and normal-appearing white matter (NAWM), FA was the measure most associated with axon content in both locations, while MWF was associated with astrocyte immunoreactivity only in lesions. Moreover, we provided evidence of extensive astrogliosis in remyelinated lesions. Our study provides new information on the discriminative power of qMRI in differentiating MS lesions -especially remyelinated ones- as well as on the relative association between multiple qMRI measures and myelin, axon and astrocytes.
| S-EPMC10580009 | biostudies-literature
Project description:INTRODUCTION:Progressive brain atrophy, development of T1-hypointense areas, and T2-fluid-attenuated inversion recovery (FLAIR)-hyperintense lesion formation in multiple sclerosis (MS) are popular volumetric data that are often utilized as clinical outcomes. However, the exact clinical interpretation of these volumetric data has not yet been fully established. METHODS:We enrolled 42 consecutive patients with MS who fulfilled the revised McDonald criteria of 2010. They were followed-up for more than 3 years from onset, and cross-sectional brain volumetry was performed. Patients with no brain lesions were excluded in advance from this study. For the brain volumetric data, we evaluated several parameters including age-adjusted gray-matter volume atrophy, age-adjusted white-matter volume atrophy, and T2-FLAIR lesion volume. The numbers of T1-hypointense and T2-FLAIR-hyperintense areas were also measured along the same timeline. The clinical data pertaining to disease duration, expanded disability status scale (EDSS), and MS severity score (MSSS) at the timing of volumetry were collected. RESULTS:Among the 42 patients with MS and brain lesions, the number of T1-hypointensity (rho = 0.51, p<0.001), gray-matter atrophy (rho = 0.40, p<0.01) and white-matter atrophy (rho = 0.49, p<0.001) correlated with the EDSS. T1-hypointensity count divided by FLAIR lesion volume correlated with the MSSS (rho = 0.60, p<0.001). Meanwhile, counts or volumes of FLAIR-hyperintense lesions were associated only with the times of past relapses, and did not correlate with present neurological disability level or ongoing disease activity. These findings were consistent regardless of the presence of spinal cord lesions. CONCLUSION:Numbers of T1-hypointensities and brain atrophy equally indicated the current neurological disability in MS. The number of T1-hypointensities divided by FLAIR lesion volume represented the clinical severity. The size or number of FLAIR lesions reflected earlier relapses but was not a good indicator of neurological disability or clinical severity.
| S-EPMC7122737 | biostudies-literature
Project description:In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes into the CNS mediating demyelination and tissue destruction. In the periphery, monocytes are divided into three subsets depending on expression of CD14 and CD16, representing different stages of activation and differentiation. To investigate their involvement in MS, peripheral blood mononuclear cells (PBMCs) from 61 patients with incipient, untreated MS and 22 symptomatic control (SC) patients as well as 6 patients with radiologically isolated syndrome (RIS) were characterized ex vivo. In addition, paired serum and cerebrospinal fluid (CSF) samples were analyzed with a panel of biomarkers. In PBMC samples, we demonstrate decreased levels of nonclassical monocytes with a concomitant significant decrease of human endogenous retrovirus (HERV) H3 envelope epitopes on this monocyte subset compared with SC and RIS. The observed HERV expression is present on nonclassical monocytes irrespective of MS and thus presumably a result of the inflammatory activation. For the other surface markers analyzed, we found significantly decreased expression between classical and nonclassical monocytes. In matched samples of CSF a highly significant increase in levels of soluble markers of activation and inflammation is shown, and notably this is not the case for the serum samples. Of the soluble markers investigated, interleukin (IL)-12/IL-23p40 had the highest discriminatory power in differentiating patients with MS from SC and RIS, almost comparable to the immunoglobulin G index.
| S-EPMC7496724 | biostudies-literature
Project description:BackgroundThe medical system in the United States has been riddled with insurance restrictions used by insurance companies to limit health care costs. The effects of insurance restrictions on patients receiving disease-modifying therapies for multiple sclerosis (MS) have not been specifically studied.MethodsA retrospective cross-sectional study of 52 individuals recently diagnosed with MS at a tertiary neurology clinic was conducted to measure the association between prior authorization (PA) duration and other variables of interest. The Cox proportional hazards model was used to determine likelihood of approval. Further analysis included multivariable logistic regression to assess the influence of variables of interest on the initial decision from the insurance company and the effect of the PA on disease activity.ResultsOf 52 PAs, 50% were initially denied. An initial denial decreased the likelihood of approval by 98% (HR, 0.02; 95% CI, <0.01-0.09; P < .001). The odds of denial for oral medications (odds ratio [OR], 4.91; 95% CI, 1.33-21.52; P = .02) and infusions (OR, 8.35; 95% CI, 1.10-88.77; P = .05) were significantly higher than for injections. Medicaid had higher odds of denial compared with commercial insurance (OR, 4.51; 95% CI, 1.13-22.01; P = .04). An initial denial by insurance significantly increased the likelihood of disease activity (OR, 6.18; 95% CI, 1.33-44.86; P = .03).ConclusionsInsurance restrictions delay necessary treatments, increase the likelihood of disease activity, and rarely change the approved disease-modifying therapy. Reducing PAs may lead to improved outcomes for patients with MS.
| S-EPMC10779716 | biostudies-literature
Project description:This series represents samples of multiple myeloma patients with bone lytic lesion by MRI. Keywords = multiple myeloma Keywords = osteolytic lesions Keywords = MRI Keywords = osteoblast Keywords = mesenchymal stem cell Keywords = Wnt signaling Keywords = DKK1 Keywords: other
2004-01-01 | GSE754 | GEO
Project description:BackgroundNon-Hispanic Black and Hispanic persons with MS (pwMS) are more likely to experience rapid disease progression and severe disability than non-Hispanic White pwMS; however, it is unknown how the initiation of high-efficacy disease-modifying therapies (DMTs) differs by race/ethnicity. This real-world study describes DMT treatment patterns in newly diagnosed pwMS in the United States (US) overall and by race/ethnicity.MethodsThis retrospective analysis used the US Optum Market Clarity claims/electronic health records database (January 2015-September 2020). pwMS who were first diagnosed in 2016 or later and initiated any DMT in the two years following diagnosis were included. Continuous enrollment in the claims data for ≥ 12 months before and ≥ 24 months after diagnosis was required. Treatment patterns 2 years after diagnosis were analyzed descriptively overall and by race/ethnicity.ResultsThe sample included 682 newly diagnosed and treated pwMS (non-Hispanic Black, n = 99; non-Hispanic White, n = 479; Hispanic, n = 35; other/unknown race/ethnicity, n = 69). The mean time from diagnosis to DMT initiation was 4.9 months in all pwMS. Glatiramer acetate and dimethyl fumarate were the most common first-line DMTs in non-Hispanic Black (28% and 20% respectively) and Hispanic pwMS (31%, 29%); however, glatiramer acetate and ocrelizumab were the most common in non-Hispanic White pwMS (33%, 18%). Use of first-line high-efficacy DMTs was limited across all race/ethnicity subgroups (11-29%), but uptake increased in non-Hispanic Black and White pwMS over the study period.ConclusionUse of high-efficacy DMTs was low across all race/ethnicity subgroups of newly diagnosed pwMS in the US, including populations at a greater risk of experiencing rapid disease progression and severe disability.
| S-EPMC10730787 | biostudies-literature
Project description:Background and purposeDetecting incidence and enlargement of lesions is essential in monitoring the progression of MS. In clinical trials, lesion load is observed by manually segmenting and comparing serial MR images, which is time consuming, costly, and prone to inter- and intraobserver variability. Subtracting images from consecutive time points nulls stable lesions, leaving only new lesion activity. We propose SuBLIME, an automated method for segmenting incident lesion voxels.Materials and methodsWe used logistic regression models incorporating multiple MR imaging sequences and subtraction images from consecutive longitudinal studies to estimate voxel-level probabilities of lesion incidence. We used T1-weighted, T2-weighted, FLAIR, and PD volumes from a total of 110 MR imaging studies from 10 subjects.ResultsTo assess the performance of the model, we assigned 5 subjects to a training set and the remaining 5 to a validation set. With SuBLIME, lesion incidence is detected and delineated in the validation set with an AUC of 99% (95% CI [97%, 100%]) at the voxel level.ConclusionsThis fully automated and computationally fast method allows sensitive and specific detection of lesion incidence that can be applied to large collections of images. Using the explicit form of the statistical model, SuBLIME can easily be adapted to cases when more or fewer imaging sequences are available.
| S-EPMC3554794 | biostudies-literature
Project description:RationalePatients with myasthenia gravis may also have comorbid autoimmune diseases. Since both myasthenia gravis and neuromyelitis optica spectrum disease are mediated by antibodies, they are likely to occur together. However, since multiple sclerosis is an autoimmune disease that is not mediated by a specific antibody, it has fewer immune mechanisms in common with myasthenia gravis than neuromyelitis optica spectrum disease. We encountered a case of newly developed multiple sclerosis in a patient with myasthenia gravis.Patient concernsA 46-year-old man was diagnosed with ocular myasthenia gravis 6 years ago and had been taking pyridostigmine to control his symptoms.DiagnosisThe patient developed right optic neuritis, and multiple sclerosis was suspected based on the brain magnetic resonance imaging findings. However, the required diagnostic criteria were not met.InterventionsDisease-modifying therapy was not initiated, and clinical progression of the disease was monitored.OutcomesOne year after the onset of optic neuritis, the patient developed myelitis and was diagnosed with multiple sclerosis, prompting treatment with disease-modifying therapy.LessonsWhen optic neuritis occurs in patients with myasthenia gravis, careful evaluation is necessary while considering the possibility that it may be the first symptom of a demyelinating central nervous system disease. Therefore, it is important to conduct shorter-interval monitoring and symptom screening for patients with neurological autoimmune diseases, such as myasthenia gravis, even if multiple sclerosis is not initially suspected, to achieve early detection of multiple sclerosis.
| S-EPMC8878705 | biostudies-literature