scholarly journals 7T MRI cerebral leptomeningeal enhancement is common in relapsing-remitting multiple sclerosis and is associated with cortical and thalamic lesions

2019 ◽  
Vol 26 (2) ◽  
pp. 177-187 ◽  
Author(s):  
Jonathan Zurawski ◽  
Shahamat Tauhid ◽  
Renxin Chu ◽  
Fariha Khalid ◽  
Brian C Healy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Three Dimensional ◽  
Leptomeningeal Enhancement ◽  
Meningeal Inflammation ◽  
Relapsing Remitting ◽  
Fluid Attenuated Inversion Recovery ◽  
Thalamic Lesions ◽  
Remitting Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Meningeal inflammation may contribute to gray matter (GM) involvement in multiple sclerosis (MS) and is proposed to manifest as magnetic resonance imaging (MRI) leptomeningeal enhancement (LME). Objective: To investigate how LME relates to GM lesions in relapsing-remitting multiple sclerosis (RRMS) at 7T. Methods: A total of 30 RRMS subjects (age (mean ± standard deviation (SD)): 44.0 ± 11.3 years, 93% on disease-modifying treatment) and 15 controls underwent gadolinium-enhanced three-dimensional (3D) MP2RAGE (magnetization-prepared 2 rapid gradient-echo) and fluid-attenuated inversion recovery (FLAIR) MRI. LME, cortical lesions (CLs), thalamic lesions (TLs), and white matter (WM) lesions were expert-quantified. Wilcoxon rank-sum, two-sample t-tests, Spearman correlations, and regression models were employed. Results: Two-thirds (20/30) of MS subjects and 1/15 controls (6.7%) had LME. LME+ MS subjects had 2.7 ± 1.5 foci, longer disease duration (14.9 ± 10.4 vs. 8.1 ± 5.7 years, p = 0.028), increased CL number (21.5 ± 12.6 vs. 5.5 ± 5.0, p < 0.001) and volume (0.80 ± 1.13 vs. 0.13 ± 0.13 mL, p = 0.002), and increased TL number (3.95 ± 2.11 vs. 0.70 ± 1.34, p < 0.001) and volume (0.106 ± 0.09 vs. 0.007 ± 0.01 mL, p < 0.001) versus LME– subjects. LME focus number correlated more highly with CL ( rs = 0.50, p = 0.01) and TL ( rs = 0.81, p < 0.001) than WM lesion ( rs = 0.34, p > 0.05) volume. Similar LME–CL number associations were observed in unadjusted and WM lesion–adjusted comparisons (both p < 0.001). Conclusion: Cerebral LME is common in RRMS at 7T and is independently associated with GM injury. We hypothesize that cerebrospinal fluid (CSF)-related inflammation links cortical and thalamic injury.

scholarly journals Fluid-Attenuated Inversion Recovery Signal Intensity as a Predictor of Gadolinium Enhancement in Relapsing-Remitting Multiple Sclerosis

2018 ◽  
Vol 20 (2) ◽  
pp. 62-66 ◽  
Author(s):  
Mihail Guranda ◽  
Marco Essig ◽  
Ariane Poulin ◽  
Reza Vosoughi
Keyword(s):  
Multiple Sclerosis ◽  
Area Under The Curve ◽  
Quantitative Model ◽  
Inversion Recovery ◽  
Gadolinium Enhancement ◽  
Relapsing Remitting ◽  
Fluid Attenuated Inversion Recovery ◽  
Remitting Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Magnetic resonance imaging (MRI) is used to diagnose and monitor disease activity in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to explore the association of “ultrabright” axial fluid-attenuated inversion recovery (FLAIR) lesions with gadolinium enhancement in patients with RRMS using qualitative and quantitative approaches. Methods: MRIs from patients with RRMS from 2010 to 2015 were reviewed. Two radiologists independently identified ultrabright lesions on axial FLAIR sequences. The contrast-to-noise ratio (CNR) was measured for ultrabright and control lesions. Results: Of 301 lesions included in the study, 77 (26%) were identified by both radiologists as ultrabright. Interrater agreement was moderate (κ = 0.77, P &lt; .001). Lesions identified by both radiologists as ultrabright demonstrated an association with gadolinium enhancement (χ21 = 30.8, P &lt; .001) but were not associated with MRI magnet strength (χ21 = 0.24, P = .65). Higher CNR values were associated with gadolinium enhancement for 1.5-T studies (OR, 1.05; 95% CI, 1.02–1.07; P = .001) and 3-T studies (OR, 1.02; 95% CI, 1.02–1.03; P &lt; .001). Diagnostic accuracy of the quantitative model was good for 1.5-T studies (area under the curve, 0.79; 95% CI, 0.68–0.9; P &lt; .001) and 3-T studies (area under the curve, 0.78; 95% CI, 0.73–0.84; P &lt; .001). Positive predictive value of 100% was obtained for CNR values of 92 for 1.5-T and 184 for 3-T studies. Conclusions: Qualitatively and quantitatively identified ultrabright axial FLAIR lesions are significantly associated with gadolinium enhancement.

scholarly journals Safety and efficacy of cladribine tablets in patients with relapsing–remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study

2017 ◽  
Vol 24 (12) ◽  
pp. 1594-1604 ◽  
Author(s):  
Gavin Giovannoni ◽  
Per Soelberg Sorensen ◽  
Stuart Cook ◽  
Kottil Rammohan ◽  
Peter Rieckmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Placebo Treatment ◽  
Extension Study ◽  
Safety And Efficacy ◽  
Relapsing Remitting ◽  
Clinical Benefits ◽  
Remitting Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Grade 3 ◽  
Relapsing Remitting Multiple Sclerosis

Background: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing–remitting multiple sclerosis (MS). Objective: To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. Methods: In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. Results: A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0–1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. Conclusion: Cladribine tablets treatment for 2 years followed by 2 years’ placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.

scholarly journals Probiotic helminth administration in relapsing–remitting multiple sclerosis: a phase 1 study

2011 ◽  
Vol 17 (6) ◽  
pp. 743-754 ◽  
Author(s):  
JO Fleming ◽  
A Isaak ◽  
JE Lee ◽  
CC Luzzio ◽  
MD Carrithers ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Phase 1 ◽  
Human Study ◽  
Probiotic Treatment ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
The Mean ◽  
Remitting Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. Objective: To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Methods: Five subjects with newly diagnosed, treatment-naive relapsing–remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. Results: The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. Conclusion: TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

scholarly journals Safety and efficacy of helminth treatment in relapsing-remitting multiple sclerosis: Results of the HINT 2 clinical trial

2017 ◽  
Vol 25 (1) ◽  
pp. 81-91 ◽  
Author(s):  
John Fleming ◽  
Gianna Hernandez ◽  
Leslie Hartman ◽  
Jane Maksimovic ◽  
Sara Nace ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Magnetic Resonance Imaging ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Remitting Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Disease Modifying Treatment ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Regulatory Lymphocytes ◽  
Versus Treatment

Background: The hygiene hypothesis suggests that microbial replacement may be therapeutic in allergic and autoimmune diseases. Nevertheless, the results of helminth treatment, including in multiple sclerosis (MS), have been inconclusive. Objective: To assess safety and brain magnetic resonance imaging (MRI) activity in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral administration of ova from the porcine whipworm, Trichuris suis (TSO). Methods: A total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in a baseline versus treatment (BVT) controlled prospective study. MRI scans were performed during 5 months of screening-observation, 10 months of treatment, and 4 months of post-treatment surveillance. Results: No serious symptoms or adverse events occurred during treatment. For the cohort, there was a trend consistent with a 35% diminution in active lesions when observation MRIs were compared to treatment MRIs ( p = 0.08), and at the level of individuals, 12 of 16 subjects improved during TSO treatment. T regulatory lymphocytes were increased during TSO treatment. Conclusion: TSO is safe in RRMS subjects. Potentially favorable MRI outcomes and immunoregulatory changes were observed during TSO treatment; however, the magnitude of these effects was modest, and there was considerable variation among the responses of individual subjects.

scholarly journals ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis

2016 ◽  
Vol 23 (5) ◽  
pp. 686-695 ◽  
Author(s):  
Samia J Khoury ◽  
James Rochon ◽  
Linna Ding ◽  
Margie Byron ◽  
Kristin Ryker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Double Blind ◽  
Costimulatory Blockade ◽  
Neuroinflammatory Disease ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Remitting Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Costimulatory blockade of T lymphocytes with the CTLA4-Ig fusion protein abatacept could be an effective treatment for the immune-mediated neuroinflammatory disease relapsing-remitting multiple sclerosis (RRMS). Objective: To evaluate efficacy and safety of abatacept in RRMS. Methods: ACCLAIM (A Cooperative Clinical Study of Abatacept in Multiple Sclerosis) was a Phase II, randomized, double-blind, placebo-controlled, multi-center trial. In all, 65 of 123 planned participants with RRMS were randomized to monthly intravenous infusions of abatacept or placebo for 24 weeks in a 2:1 ratio, switched to the opposite treatment at 28 weeks, and received their final dose of study medication at 52 weeks. Enrollment was closed early due to slow accrual. The primary endpoint was the mean number of new gadolinium-enhancing (Gd+) lesions obtained on magnetic resonance imaging (MRI) scans performed every 4 weeks. Results: No statistically significant differences were observed in mean number of new Gd+ MRI lesions between the abatacept and placebo groups. No statistically significant differences were observed in other MRI and clinical parameters of RRMS disease activity. Abatacept was well tolerated. Conclusion: The ACCLAIM study did not demonstrate efficacy of abatacept in reducing the number of new Gd+ MRI lesions, or clinical measures of disease activity in RRMS.

scholarly journals Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies

2019 ◽  
Vol 26 (13) ◽  
pp. 1719-1728 ◽  
Author(s):  
Bart Van Wijmeersch ◽  
Barry A Singer ◽  
Aaron Boster ◽  
Simon Broadley ◽  
Óscar Fernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Post Hoc Analysis ◽  
Brain Volume Loss ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: Alemtuzumab is administered as two annual courses for relapsing–remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen. Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers). Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension. Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1–2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: −0.67% (CARE-MS I); −0.47% (CARE-MS II)) declined after Course 2 (Year 6: −0.24%; −0.13%). Conclusion: Early relapsers’ outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit. ClinicalTrials.gov registration numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553.

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