scholarly journals Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy

2021 ◽  
pp. jnnp-2021-326164
Author(s):  
Chenyu Wang ◽  
Joshua Barton ◽  
Kain Kyle ◽  
Linda Ly ◽  
Yael Barnett ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual System ◽  
Contrast Sensitivity ◽  
Reference Group ◽  
Lesion Volume ◽  
Early Improvement ◽  
T2 Lesions ◽  
Specific Effects ◽  
Secondary Endpoints ◽  
Partial Lesion

ObjectiveTo investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visual pathway as a model.MethodsWe monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients commencing alemtuzumab for relapsing MS, and a reference group of 20 healthy controls (HCs), over 24 months. Change in mfVEP latency was the primary endpoint; change in optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity over the course of the study were secondary endpoints.ResultsIn patients, we observed a mean shortening of mfVEP latency of 1.21 ms over the course of the study (95% CI 0.21 to 2.21, p=0.013), not altered by correction for age, gender, disease duration or change in OR T2 lesion volume. Mean mfVEP latency in the HC group increased over the course of the study by 0.72 ms (not significant). Analysis of chronic OR T2 lesions (patients) showed an increase in normalised fractional anisotropy and axial diffusivity between baseline and 24 months (both p<0.01). Mean Mars letter contrast sensitivity was improved at 24 months vs baseline (p<0.001), and driven by an early improvement, in both patients and HC.ConclusionWe found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a ‘permissive’ local milieu; or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-structure specific effects of therapy and inform the design of future phase 2 MS remyelination trials.

scholarly journals Natalizumab versus fingolimod for patients with active relapsing-remitting multiple sclerosis: results from REVEAL, a prospective, randomised head-to-head study

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e038861
Author(s):  
Helmut Butzkueven ◽  
Stephanie Licata ◽  
Douglas Jeffery ◽  
Douglas L Arnold ◽  
Massimo Filippi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cumulative Probability ◽  
T2 Lesions ◽  
Parallel Group ◽  
Relapsing Remitting ◽  
Patients At Risk ◽  
Secondary Endpoints ◽  
Remitting Multiple Sclerosis ◽  
Intent To Treat ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo directly compare the efficacy of natalizumab and fingolimod in patients with active relapsing-remitting multiple sclerosis.MethodsThis phase 4, randomised, rater- and sponsor-blinded, prospective, parallel-group, clinic-based head-to-head study was conducted at 43 sites in nine countries. Patients were randomised (1:1) to intravenous natalizumab 300 mg every 4 weeks or oral fingolimod 0.5 mg once daily for ≤52 weeks. Enrolment-related early study termination precluded assessment of the primary endpoint (evolution of new on-treatment gadolinium-enhancing (Gd+) lesions to persistent black holes). Unplanned exploratory analyses of secondary endpoints evaluated the effects of treatment on the development of new T1 Gd+ lesions and new/newly enlarging T2 lesions, lesion volumes and relapse outcomes.ResultsThe intent-to-treat population comprised 108 patients (natalizumab, n=54; fingolimod, n=54); 63 completed ≥24 weeks of treatment. Due to the limited numbers of events and patients at risk, MRI and relapse outcomes were reported over up to 24 and 36 weeks, respectively. The mean number of new T1 Gd+ lesions was numerically lower with natalizumab than with fingolimod by 4 weeks; accumulation rates were 0.02 and 0.09 per week, respectively, over 24 weeks (p=0.004). The cumulative probability of developing ≥1 lesion at 24 weeks was 40.7% with natalizumab versus 58.0% with fingolimod (HR=0.60; 95% CI 0.31–1.16; p=0.126); the corresponding probabilities for ≥2 lesions were 11.5% vs 48.5% (HR=0.25; 95% CI 0.09–0.68; p=0.007). No significant between-group differences were observed for the other MRI outcomes at 24 weeks. The cumulative probability of relapse over follow-up was 1.9% with natalizumab versus 22.3% with fingolimod (HR=0.08; 95% CI 0.01–0.64; p=0.017). Adverse events were consistent with known safety profiles.ConclusionsThese results suggest that natalizumab is more efficacious than fingolimod in reducing multiple sclerosis relapses and T1 Gd+ lesion accumulation in patients with active disease.Trial registration numbersNCT02342704; EUCTR2013-004622-29-IT; Post-results.

Contrast sensitivity in relapsing–remitting multiple sclerosis assessed by sine-wave gratings and angular frequency stimuli

2014 ◽  
Vol 31 (6) ◽  
pp. 381-386 ◽  
Author(s):  
JÁKINA G. VIEIRA-GUTEMBERG ◽  
LIANA C. MENDES-SANTOS ◽  
MELYSSA K. CAVALCANTI-GALDINO ◽  
NATANAEL A. SANTOS ◽  
MARIA LÚCIA DE BUSTAMANTE SIMAS
Keyword(s):  
Multiple Sclerosis ◽  
Visual System ◽  
Contrast Sensitivity ◽  
Sine Wave ◽  
Angular Frequency ◽  
Control Group ◽  
Spatial Frequencies ◽  
Relapsing Remitting ◽  
The One ◽  
Sine Wave Gratings

AbstractPrevious studies have shown that multiple sclerosis (MS) affects the visual system, mainly by reducing contrast sensitivity (CS), a function that can be assessed by measuring contrast sensitivity function (CSF). To this end, we measured both the CSF for sine-wave gratings and angular frequency stimuli with 20 participants aged between 21 and 44 years, of both genders, with normal or corrected to normal visual acuity. Of these 20 participants, there were 10 volunteers with clinically defined MS of the relapsing–remitting clinical form, with no history of optic neuritis (ON), as well as 10 healthy volunteers who served as the control group (CG). We used a forced-choice detection paradigm. The results showed reduced CS to both classes of stimuli. Differences were found for sine-wave gratings at spatial frequencies of 0.5, 1.25, and 2.5 cycles per degree (cpd) (P < 0.002) and for angular frequency stimuli of 4, 24, and 48 cycles/360° (P < 0.05). On the one hand, comparing the maxima of the respective CSFs, the CS to angular frequency stimuli (24 cycles/360°) was 1.61-fold higher than that of the CS to vertical sine-wave gratings (4.0 cpd) in the CG; for the MS group, these values were 1.55-fold higher. On the other hand, CS in the MS group attained only 75% for 24 cycles/360° and 78% for 4.0 cpd of the 100% CS estimates found for the CG at the peak frequencies. These findings suggest that MS affects the visual system, mostly at its maximum contrast sensitivities. Also, since angular frequencies and sine-wave gratings operate at distinct levels of contrast in the visual system, MS seems to affect CS at both high and low levels of contrast.

scholarly journals Lesion symptom map of cognitive–postural interference in multiple sclerosis

2017 ◽  
Vol 24 (5) ◽  
pp. 653-662 ◽  
Author(s):  
Serena Ruggieri ◽  
Fulvia Fanelli ◽  
Letizia Castelli ◽  
Nikolaos Petsas ◽  
Laura De Giglio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dual Task ◽  
Postural Sway ◽  
Brain Mri ◽  
Quiet Standing ◽  
Lesion Volume ◽  
T2 Lesions ◽  
Lesion Symptom Mapping ◽  
Magnetic Resonance Imaging Mri ◽  
Function Relationship

Objective: To investigate the disease-altered structure–function relationship underlying the cognitive–postural interference (CPI) phenomenon in multiple sclerosis (MS). Methods: We measured postural sway of 96 patients and 48 sex-/age-matched healthy controls by force platform in quiet standing (single-task (ST)) while performing the Stroop test (dual-task (DT)) to estimate the dual-task cost (DTC) of balance. In patient group, binary T2 and T1 lesion masks and their corresponding lesion volumes were obtained from magnetic resonance imaging (MRI) of brain. Normalized brain volume (NBV) was also estimated by SIENAX. Correlations between DTC and lesion location were determined by voxel-based lesion symptom mapping (VLSM) analyses. Results: Patients had greater DTC than controls ( p < 0.001). Among whole brain MRI metrics, only T1 lesion volume correlated with DTC ( r = −0.27; p < 0.01). However, VLSM analysis did not reveal any association with DTC using T1 lesion masks. By contrast, we found clusters of T2 lesions in distinct anatomical regions (anterior and superior corona radiata, bilaterally) to be correlated with DTC ( p < 0.01 false discovery rate (FDR)-corrected). A multivariable stepwise regression model confirmed findings from VLSM analysis. NBV did not contribute to fit the model. Conclusion: Our findings suggest that the CPI phenomenon in MS can be explained by disconnection along specific areas implicated in task-switching abilities and divided attention.

scholarly journals Comparing the Safety and Efficacy of Ziferon and Betaferon in Patients With Remitting- Relapsing Multiple Sclerosis

2020 ◽  
Author(s):  
Mohammad Reza Gheini ◽  
Mohammad Ali Sahraian ◽  
Amir Reza Azimi ◽  
Naser Mmoghadasi ◽  
Mahmud Abdoli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Safety Profile ◽  
Lesion Volume ◽  
Cumulative Number ◽  
Efficacy And Safety ◽  
T2 Lesions ◽  
Number Of Patients ◽  
Significant Difference ◽  
Magnetic Resonance Imaging Mri

Background: The present study aimed to compare the clinical efficacy and safety profile of Ziferon and Betaferon. Objectives: In total, 41 consecutive patients with relapsing forms of Multiple Sclerosis (MS) were selected from the MS outpatient clinic affiliated to Tehran University of Medical Sciences. The patients were randomly assigned into two groups. Methods: Each group either received Ziferon 250 mcg Subcutaneously (SC) in alternate days or Betaferon 250 mcg SC on alternate days. Clinical and para-clinical outcomes, such as mean relapse rate/year score, mean Expanded Disability Status Scale (EDSS)/year score, the cumulative number, and the volume of gadolinium-enhancing lesions, in addition to the cumulative number of new T2 lesions and safety profile were evaluated for each group during the years of treatment. Results: There were no significant differences in Magnetic Resonance Imaging (MRI) outcomes (change in total lesion volume, new lesion per T2-weighted scan, and gadoliniumenhancing lesions per T1-weighted scan from baseline; P=0.236, P=0.56, & P=0.496, respectively was observed). There was no significant difference in the relapse rate between Ziferon and Betaferon treated groups (P=0.56). There were no unexpected safety events. The number of patients who discontinued the study due to adverse events occurrence was similar between the two groups. Conclusion: Evidence demonstrates the non-inferiority and bio-similarity of Ziferon (interferon beta-1b) to Betaferon in terms of efficacy and safety profile.

scholarly journals Changes in Cerebrospinal Fluid Balance of TNF and TNF Receptors in Naïve Multiple Sclerosis Patients: Early Involvement in Compartmentalised Intrathecal Inflammation

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1712
Author(s):  
Roberta Magliozzi ◽  
Francesco Pezzini ◽  
Mairi Pucci ◽  
Stefania Rossi ◽  
Francesco Facchiano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Protein Pattern ◽  
Fold Change ◽  
Cortical Lesion ◽  
Control Group ◽  
Lesion Volume ◽  
Mri Features ◽  
Csf Levels ◽  
Multiple Sclerosis Patients

An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome.

Serum amyloid A level correlates with T2 lesion volume and cortical volume in patients with multiple sclerosis

2021 ◽  
Vol 351 ◽  
pp. 577466
Author(s):  
Hiroaki Yokote ◽  
Shuta Toru ◽  
Yoichiro Nishida ◽  
Takaaki Hattori ◽  
Nobuo Sanjo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Lesion Volume ◽  
Cortical Volume ◽  
Amyloid A

scholarly journals Structure-function relationships in the visual system in multiple sclerosis: an MEG and OCT study

2017 ◽  
Vol 4 (9) ◽  
pp. 614-621 ◽  
Author(s):  
Prejaas Tewarie ◽  
Lisanne J. Balk ◽  
Arjan Hillebrand ◽  
Martijn D. Steenwijk ◽  
Bernard M. J. Uitdehaag ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual System ◽  
Structure Function

T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation

1998 ◽  
Vol 4 (5) ◽  
pp. 408-412 ◽  
Author(s):  
J I O'Riordan ◽  
M Gawne Cain ◽  
A Coles ◽  
L Wang ◽  
D AS Compston ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Strong Correlation ◽  
Measurement Techniques ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Mri Findings ◽  
Lesion Load ◽  
Post Contrast ◽  
Secondary Progressive

Magnetic resonance imaging (MRI) is increasingly being used as a monitoring tool for disease activity in therapeutic trials in multiple sclerosis. There is, however, only a limited relationship between MRI findings and clinical outcome measurements. It has been suggested that hypointense lesion load on T1 weighted imaging has a better correlation with disability than the more conventional T2 hyper intense lesion load. This study was undertaken to (i) evaluate different measurement techniques used to quantify T1 hypointense lesion load, and (ii) to compare lesion load as measured using different parameters and disability. Twenty-five patients with secondary progressive multiple sclerosis, mean age of 40 years (23-57), mean EDSS 5.7 (4-7) were analysed. T2 lesion load on FSE correlated well with both the hypointense lesion load on T1 pre-gadolinium (r=0.8, P50.0001) and T1 post-gadolinium (r=0.8, P50.0001) but less so with the enhancing lesion load (r=0.4, P50.05). There was a very strong correlation with T1 hypo-intense lesion volume pre and post gadolinium (r=0.96, P50.001). However, the EDSS was not correlated with the T2 lesion load (r=70.27, P=0.2), T1 pre-gadolinium load (r=70.3, P=0.1), T1 post gadolinium load (r=70.4, P=0.7) and enhancing lesion load (r=70.28, P=0.2), or with the degree of hypointensity of T1 weighted images determined using the threshold technique. There is a strong correlation between T1 hypointense lesion volume both pre and post gadolinium and also between T1 and T2 lesion volumes.

scholarly journals Learning ability correlates with brain atrophy and disability progression in RRMS

2018 ◽  
Vol 90 (1) ◽  
pp. 38-43 ◽  
Author(s):  
Maria Pia Sormani ◽  
Nicola De Stefano ◽  
Gavin Giovannoni ◽  
Dawn Langdon ◽  
Daniela Piani-Meier ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Volume ◽  
Practice Effect ◽  
Wilcoxon Test ◽  
Learning Ability ◽  
Lesion Volume ◽  
Volume Loss ◽  
Disability Progression ◽  
Brain Volume Loss ◽  
Quartile Group

ObjectiveTo assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis.MethodsWe compared screening (day −14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years.ResultsThe mean PASAT score at screening was 45.38, increasing on average by 3.18 from day −14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates.ConclusionsShort-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

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