Lateral ventricular volume as a proxy for brain volume loss in the assessment of no evidence of disease activity: results from a longitudinal, multicentre, real-world study

2017 ◽  
Author(s):  
Robert Zivadinov
Keyword(s):  
Disease Activity ◽  
Real World ◽  
Brain Volume ◽  
Ventricular Volume ◽  
Volume Loss ◽  
Brain Volume Loss

060 Association of brain volume loss and neda outcomes in patients with relapsing multiple sclerosis in the opera i and opera ii studies (ENCORE)

2018 ◽  
Vol 89 (6) ◽  
pp. A25.1-A25
Author(s):  
Anthony Traboulsee ◽  
Douglas Arnold ◽  
Eric C Klawiter ◽  
Eva Havrdova ◽  
Damian Fiore ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Tissue ◽  
Repeated Measures ◽  
Brain Volume ◽  
Brain Mri ◽  
Treatment Goal ◽  
Volume Loss ◽  
T2 Lesions ◽  
Brain Volume Loss

IntroductionBrain volume loss (BVL) occurs in multiple sclerosis (MS) patients, reflecting irreversible tissue damage. No evidence of disease activity (NEDA), a composite measure assessing absence of clinical and magnetic resonance imaging (MRI) disease activity has emerged as important treatment goal in MS and may be associated with preservation of brain tissue and BVL prevention.MethodsPatients in OPERA-I/II (NCT01247324/NCT01412333) received 600 mg ocrelizumab (intravenous) very 24 weeks or 44 µg subcutaneous interferon beta-1a (IFNβ-1a) 3x-weekly for 96 weeks. Brain MRI assessments were completed at baseline and 24/48/96 Weeks. Brain volume normalised for head size was measured using SIENAX software. Percent change in whole brain volume (WBV) was determined using SIENA software, changes in cortical grey (GMV) and white (WMV) matter volumes were measured using validated, locally developed Jacobian integrator atrophy software. NEDA was defined as absence of relapses, 12-week confirmed disability progression, T1 Gd–enhancing lesions and new and/or enlarging T2-lesions. Changes from baseline in brain volume were examined in NEDA patients and those with evidence of disease activity (EDA), using the mixed-effects model for repeated measures method.ResultsThe analysis included 1520 patients (ocrelizumab-761; IFNβ-1a-759). Over 96 weeks, 569 (37%) patients [ocrelizumab-363 (48%); IFNβ-1a-206(27%); p<0.001] had NEDA. Compared with EDA patients, NEDA patients had significantly less WBV loss from baseline (30%-reduction; p<0.001). In the NEDA group, ocrelizumab patients had significantly less WBV loss (32%-reduction; p<0.001), WMV loss (34%-reduction; p=0.044) and GMV loss (30%-reduction; p<0.001) from baseline than IFNβ-1a patients. In the EDA group, ocrelizumab patients had significantly less WBV loss (11%-reduction; p=0.047) and GMV loss (21%-reduction; p<0.001) but not WMV loss (1.03%-increase; p=0.90) from baseline than IFNβ-1a patients.ConclusionThese findings highlight the importance of NEDA as treatment goal with respect to brain tissue preservation regardless of treatment choice. Ocrelizumab may confer additional benefits in NEDA patients NEDA beyond what is observed with IFNβ-1a.

scholarly journals Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing–remitting multiple sclerosis

2016 ◽  
Vol 22 (10) ◽  
pp. 1297-1305 ◽  
Author(s):  
Ludwig Kappos ◽  
Nicola De Stefano ◽  
Mark S Freedman ◽  
Bruce AC Cree ◽  
Ernst-Wilhelm Radue ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Volume ◽  
Objective Measure ◽  
Volume Loss ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Background: ‘No evidence of disease activity’ (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression (‘NEDA-3’), is used as a comprehensive measure of treatment response in relapsing multiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression. Objective: To assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 (‘NEDA-4’) Methods: We analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%–1.2%). Results: At 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01–4.41; p < 0.0001). Conclusion: NEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies.

Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

2021 ◽  
pp. 135245852110479
Author(s):  
Tomas Uher ◽  
Eva Kubala Havrdova ◽  
Pascal Benkert ◽  
Niels Bergsland ◽  
Jan Krasensky ◽  
...  
Keyword(s):  
Disease Activity ◽  
Brain Volume ◽  
Added Value ◽  
Volume Loss ◽  
Prognostic Information ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss ◽  
Relapsing Remitting ◽  
Risk Of Disease

Background: The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective: To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Methods: We analyzed 369 blood samples from 155 early relapsing-remitting MS patients on interferon beta-1a. We compared disease activity, including the rate of brain volume loss in subgroups defined by NEDA-3 status and high or low sNfL (> 90th or < 90th percentile). Results: In patients with disease activity (EDA-3), those with higher sNFL had higher odds of EDA-3 in the following year than those with low sNFL (86.5% vs 57.9%; OR = 4.25, 95% CI: [2.02, 8.95]; p = 0.0001) and greater whole brain volume loss during the following year (β = −0.36%; 95% CI = [−0.60, −0.13]; p = 0.002). Accordingly, NEDA-3 patients with high sNfL showed numerically higher disease activity (EDA-3) in the following year compared with those with low sNfL (57.1% vs 31.1%). Conclusion: sNfL improves the ability to identify patients at higher risk of future disease activity, beyond their NEDA-3 status. Measurement of sNfL may assist clinicians in decision-making by providing more sensitive prognostic information.

Serum neurofilament light chain reflects inflammation-driven neurodegeneration and predicts delayed brain volume loss in early stage of multiple sclerosis

2020 ◽  
Vol 27 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Barbora Srpova ◽  
Tomas Uher ◽  
Tereza Hrnciarova ◽  
Christian Barro ◽  
Michaela Andelova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Light Chain ◽  
Repeated Measures ◽  
Brain Volume ◽  
Lesion Volume ◽  
Volume Loss ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Brain Volume Loss

Background: Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury. There is a lack of studies investigating the dynamics of relationships between sNfL levels and radiological disease activity over long-term follow-up in multiple sclerosis (MS). Objectives: To investigate the relationship among repeated measures of sNfL, lesion burden accumulation, brain volume loss and clinical measures. Methods: We investigated 172 patients in the early stages of MS (McDonald 2017 criteria). Clinical exams were performed every 3 months and brain magnetic resonance imaging (MRI) scans were collected annually over 48 months. sNfL levels were measured in serum by Simoa assay at the time of treatment initiation and then annually over 36 months. Results: In repeated-measures analysis, considering all time points, we found a strong relationship between percentage changes of sNfL and lesion burden accumulation assessed by T1 lesion volume ( p < 0.001) and T2 lesion number ( p < 0.001). There was no relationship between percentage changes of sNfL and brain volume loss over 36 months ( p > 0.1). Early sNfL levels were associated with delayed brain volume loss after 48 months ( p < 0.001). Patients with No Evidence of Disease Activity (NEDA-3) status showed lower sNfL levels compared with active MS patients. Conclusions: sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS.

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