Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis

2017 ◽  
Vol 89 (2) ◽  
pp. 205-210 ◽  
Author(s):  
Kim A Meijer ◽  
Anand J C Eijlers ◽  
Jeroen J G Geurts ◽  
Menno M Schoonheim
Keyword(s):  
Multiple Sclerosis ◽  
Functional Connectivity ◽  
Grey Matter ◽  
Neuropsychological Testing ◽  
Regional Analysis ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Deep Grey Matter ◽  
Post Hoc ◽  
The Brain

ObjectiveFunctional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages.MethodsA cohort of 121 patients with early relapsing–remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes.ResultsPatients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability.ConclusionIncreased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease.

scholarly journals Characteristics of lesional and extra-lesional cortical grey matter in relapsing–remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study

2015 ◽  
Vol 22 (2) ◽  
pp. 150-159 ◽  
Author(s):  
Özgür Yaldizli ◽  
Matteo Pardini ◽  
Varun Sethi ◽  
Nils Muhlert ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Fractional Anisotropy ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Study ◽  
Magnetisation Transfer ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Cortical Grey Matter

Background: In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. Objective: To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. Methods: Seventy-two people with MS (46 relapsing–remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. Results: Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. Conclusion: Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability.

scholarly journals Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732097213 ◽  
Author(s):  
Dana Horáková ◽  
Aaron Boster ◽  
Antonio Bertolotto ◽  
Mark S Freedman ◽  
Isabel Firmino* ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Lesion ◽  
Functional System ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Kaplan Meier ◽  
Relapsing Remitting ◽  
Core Study ◽  
Few Data ◽  
Post Hoc

Background Few data exist concerning conversion to secondary progressive MS in patients treated with disease-modifying therapies. Objective Determine the proportion of alemtuzumab-treated patients converting from relapsing-remitting to secondary progressive MS during the CARE-MS core and extension studies. Methods Patients ( N = 811) were analyzed post hoc for secondary progressive MS conversion. Optimal conversion definition: Expanded Disability Status Scale (EDSS) score ≥4, pyramidal functional system score ≥2, and confirmed progression over ≥3 months including confirmation within the functional system leading to progression, independent of relapse. Results Over 6.2 years median follow-up, 20 alemtuzumab-treated patients converted (Kaplan-Meier estimate, 2.7%; 95% confidence interval, 1.8%–4.2%). Sensitivity analysis accounting for dropouts showed similar results (3%), as did analyses using alternative definitions with different EDSS thresholds and/or confirmation periods, and analysis of core study subcutaneous interferon beta-1a-treated patients who received alemtuzumab in the extension. Patients converting to secondary progressive MS were older, and had higher EDSS scores and greater brain lesion volumes at baseline, but did not need additional alemtuzumab or other therapies. Conclusions The 6-year conversion rate to secondary progressive MS was low for alemtuzumab-treated patients, supporting further study of the role alemtuzumab may play in reducing risk of secondary progression. ClinicalTrials.gov identifiers: NCT00530348, NCT00548405, NCT00930553.

Deep grey matter MRI abnormalities and cognitive function in relapsing-remitting multiple sclerosis

2015 ◽  
Vol 234 (3) ◽  
pp. 352-361 ◽  
Author(s):  
Laëtitia Debernard ◽  
Tracy R. Melzer ◽  
Sridhar Alla ◽  
Jane Eagle ◽  
Saskia Van Stockum ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Function ◽  
Grey Matter ◽  
Relapsing Remitting ◽  
Deep Grey Matter ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

scholarly journals Effects of Venous Angioplasty on Cerebral Lesions in Multiple Sclerosis: Expanded Analysis of the Brave Dreams Double-Blind, Sham-Controlled Randomized Trial

2019 ◽  
Vol 27 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Paolo Zamboni ◽  
Roberto Galeotti ◽  
Fabrizio Salvi ◽  
Alessia Giaquinta ◽  
Carlo Setacci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Grading System ◽  
Cerebral Lesions ◽  
Double Blind ◽  
Positive Effects ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Venous Angioplasty ◽  
Post Hoc

Purpose: To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI). Materials and Methods: The Brave Dreams trial ( ClinicalTrials.gov identifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a post hoc assessment, venograms of patients who underwent venous angioplasty were graded as “favorable” (n=38) or “unfavorable” (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared. Results: Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005). Conclusion: Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Post hoc analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.

scholarly journals Short-term MRI measurements as predictors of EDSS progression in relapsing-remitting multiple sclerosis: grey matter atrophy but not lesions are predictive in a real-life setting

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2442 ◽  
Author(s):  
Johanna von Gumberz ◽  
Mina Mahmoudi ◽  
Kim Young ◽  
Sven Schippling ◽  
Roland Martin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Real Life ◽  
Phase 2 ◽  
Short Term ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Grey Matter Atrophy

BackgroundMagnetic resonance imaging (MRI) is the best biomarker of inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so far but the association with disability is weak. Appearance of new MRI-lesions is used to evaluate response to immunotherapies in individual patients as well as being the most common primary outcome in phase-2 trials. Measurements of brain atrophy show promising outcomes in natural cohort studies and some phase-2 trials. From a theoretical perspective they might represent irreversible neurodegeneration and be more closely associated with disability. However, these atrophy measurements are not yet established as prognostic factors in real-life clinical routine. High field MRI has improved image quality and resolution and new methods to measure atrophy dynamics have become available.ObjectiveTo investigate the predictive value of MRI classification criteria in to high/low atrophy and inflammation groups, and to explore predictive capacity of two consecutive routine MRI scans for disability progression in RRMS in a real-life prospective cohort.Methods82 RRMS-patients (40 untreated, 42 treated with immunotherapies, mean age 40 years, median Expanded Disability Status Scale (EDSS) of 2, underwent two clinically indicated MRI scans (3 Tesla) within 5–14 months, and EDSS assessment after a mean of 3.0 (1.5–4.2) years. We investigated the predictive value of predefined classifications in low/high inflammatory and atrophy groups for EDSS progression (≥1.5 if baseline EDSS = 0, ≥1.0 if baseline EDSS <5, ≥0.5 for other) by chi-square tests and by analysis of variance (ANOVA). The classifications were based on current scientific or clinical recommendation (e.g., treatment response criteria). Brain atrophy was assessed with three different methods (SIENA, SIENAX, and FreeSurfer). Post-hoc analyses aimed to explore clinical data and dynamics of MRI outcomes as predictors in multivariate linear and logit models.ResultsProgression was observed in 24% of patients and was independent from treatment status. None of the predefined classifications were predictive for progression. Explorative post-hoc analyses found lower baseline EDSS and higher grey matter atrophy (FreeSurfer) as best predictors (R2= 0.29) for EDSS progression and the accuracy was overall good (Area under the curve = 0.81).ConclusionBeside EDSS at baseline, short-term grey matter atrophy is predictive for EDSS progression in treated and untreated RRMS. The development of atrophy measurements for individual risk counselling and evaluation of treatment response seems possible, but needs further validation in larger cohorts. MRI-atrophy estimates from the FreeSurfer toolbox seem to be more reliable than older methods.

Deep grey matter T2 hypo-intensity in patients with paediatric multiple sclerosis

2011 ◽  
Vol 17 (6) ◽  
pp. 702-707 ◽  
Author(s):  
Antonia Ceccarelli ◽  
Maria A Rocca ◽  
Elisabetta Perego ◽  
Lucia Moiola ◽  
Angelo Ghezzi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Caudate Nucleus ◽  
Grey Matter ◽  
Lesion Volume ◽  
Longitudinal Assessment ◽  
Paediatric Patients ◽  
Relapsing Remitting ◽  
Left Caudate ◽  
Deep Grey Matter ◽  
Dual Echo

Objective: T2 hypo-intensity on magnetic resonance imaging scans is thought to reflect pathological iron deposition in the presence of disease. In this pilot study, we evaluated the utility of the quantification of T2 hypo-intensities in paediatric patients by estimating deep grey matter (DGM) T2 hypo-intensities in paediatric patients with multiple sclerosis (MS) or clinically isolated syndromes (CIS), and their changes over 1 year. Methods: A dual-echo sequence was obtained from 45 paediatric patients (10 with CIS, 35 with relapsing–remitting MS, 8 with an onset of the disease before the age of 10 and 37 during adolescence) and 14 age-matched healthy controls (HC). Eleven patients were reassessed both clinically and with MRI after 1 year. Normalized T2 intensity in the basal ganglia and thalamus was quantified. Results: At baseline, DGM T2 intensity was similar between paediatric patients and HC in all the structures analysed, except for the head of the left caudate nucleus ( p = 0.001). DGM T2 intensity of the head of the left caudate nucleus was similar between paediatric CIS and RRMS patients, but it was reduced in adolescent-onset paediatric patients versus HC ( p = 0.002). In all patients, DGM T2 intensity of the head of the left caudate nucleus was correlated with T2 lesion volume ( r = −0.39, p = 0.007). DGM T2 intensity in all the structures analysed with longitudinal assessment remained stable over the follow-up in the cohort of patients. Conclusions: The quantification of DGM T2 intensity in paediatric patients may provide surrogate markers of neurodegeneration. In paediatric MS, DGM is likely to be affected by iron-related changes, which are likely to be, at least partially, secondary to WM damage.

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