scholarly journals Effects of ibudilast on MRI measures in the phase 2 SPRINT-MS study

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011314
Author(s):  
Robert T Naismith ◽  
Robert A Bermel ◽  
Christopher S Coffey ◽  
Andrew D Goodman ◽  
Janel Fedler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Secondary Analysis ◽  
Progressive Multiple Sclerosis ◽  
Whole Brain ◽  
T2 Lesions ◽  
Gray Matter Atrophy ◽  
Inflammatory Processes

OBJECTIVE:For progressive forms of multiple sclerosis, determine whether ibudilast has an effect on brain volume and new lesions.METHODS:A randomized, placebo controlled, blinded study evaluated ibudilast at a dose of up to 100 mg over 96 weeks in primary and secondary progressive multiple sclerosis. In this secondary analysis of a previously reported trial, secondary and tertiary endpoints included gray matter atrophy, new or enlarging T2 lesions as measured every 24 weeks, and new T1 hypointensities at 96 weeks. Whole brain atrophy measured by SIENA was a sensitivity analysis.RESULTS:129 participants were assigned to ibudilast and 126 to placebo. New or enlarging T2 lesions were observed in 37.2% on ibudilast and 29.0% on placebo (p=0.82). New T1 hypointense lesions at 96 weeks were observed in 33.3% on ibudilast and 23.5% on placebo (p=0.11). Gray matter atrophy was reduced by 35% for those on ibudilast vs. placebo (p=0.038). Progression of whole brain atrophy by SIENA was slowed by 20% in the ibudilast group compared with placebo (p=0.08).CONCLUSIONS:Ibudilast treatment was associated with a reduction in gray matter atrophy. Ibudilast treatment was not associated with a reduction in new or enlarging T2 lesions, or new T1 lesions. An effect on brain volume contributes to prior data that ibudilast appears to impact markers associated with neurodegenerative processes, but not inflammatory processes.Classification of Evidence:This study provides Class II evidence that for people with MS, ibudilast does not significantly reduce new or enlarging T2 lesions, or new T1 lesions.

Brain atrophy evolution and lesion load accrual in multiple sclerosis: a 2-year follow-up study

2008 ◽  
Vol 15 (2) ◽  
pp. 204-211 ◽  
Author(s):  
G Tedeschi ◽  
D Dinacci ◽  
M Comerci ◽  
L Lavorgna ◽  
G Savettieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Disease Progression ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Disease Duration ◽  
Lesion Load ◽  
Whole Brain ◽  
Gray Matter Atrophy

Background To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression. Methods Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points. Results The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression. Conclusions In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.

scholarly journals Whole brain and deep gray matter atrophy detection over 5 years with 3T MRI in multiple sclerosis using a variety of automated segmentation pipelines

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206939 ◽  
Author(s):  
Renxin Chu ◽  
Gloria Kim ◽  
Shahamat Tauhid ◽  
Fariha Khalid ◽  
Brian C. Healy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Automated Segmentation ◽  
Whole Brain ◽  
3T Mri ◽  
Gray Matter Atrophy ◽  
Deep Gray Matter

scholarly journals Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

2016 ◽  
Vol 74 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Juan Ignacio Rojas ◽  
Liliana Patrucco ◽  
Jimena Miguez ◽  
Edgardo Cristiano
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Inflammatory Disease ◽  
Brain Atrophy ◽  
Clinical Impact ◽  
Cognitive Disability ◽  
Permanent Damage ◽  
Gray Matter Atrophy

ABSTRACT Multiple sclerosis (MS) was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

scholarly journals Longitudinal optical coherence tomography study of optic atrophy in secondary progressive multiple sclerosis: Results from a clinical trial cohort

2017 ◽  
Vol 25 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Kimberly M Winges ◽  
Charles F Murchison ◽  
Dennis N Bourdette ◽  
Rebecca I Spain
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Optical Coherence Tomography ◽  
Brain Atrophy ◽  
Disease Duration ◽  
Progressive Multiple Sclerosis ◽  
Optical Coherence ◽  
Whole Brain ◽  
Secondary Progressive ◽  
Sd Oct

Background: Limited prospective information exists regarding spectral-domain optical coherence tomography (SD-OCT) in secondary progressive multiple sclerosis (SPMS). Objective: Document cross-sectional and longitudinal retinal nerve fiber layer (RNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) features of an SPMS clinical trial cohort. Methods: Prospective, observational study using a 2-year randomized placebo-controlled SPMS trial cohort with yearly SD-OCT testing. Post hoc analysis determined influences of optic neuritis (ON), disease duration, and baseline SD-OCT on annualized atrophy rates and on correlations between OCT and brain atrophy. Results: Mean RNFL and GCIPL values of patients ( n = 47, mean age = 59 years, mean disease duration = 30 years) were significantly lower among eyes with prior ON than those without (no history of ON (NON)). Annualized RNFL (−0.31 µm/year) and GCIPL (−0.29 µm/year) atrophy rates did not differ between ON and NON eyes. Baseline RNFL thickness >75 µm was associated with greater annualized RNFL atrophy (−0.85 µm/year). Neither RNFL nor GCIPL atrophy correlated with whole-brain atrophy. Conclusion: This study suggests that eyes with and without ON history may be pooled for atrophy analysis in SPMS clinical trials using SD-OCT. Low baseline RNFL, small retinal atrophy rates, and lack of correlation with whole-brain atrophy in this population are important trial design considerations.

Regional Gray Matter Atrophy in Early Primary Progressive Multiple Sclerosis

2006 ◽  
Vol 63 (8) ◽  
pp. 1175 ◽  
Author(s):  
Jorge Sepulcre ◽  
Jaume Sastre-Garriga ◽  
Mara Cercignani ◽  
Gordon T. Ingle ◽  
David H. Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Gray Matter Atrophy ◽  
Early Primary

MRI brain volume loss, lesion burden, and clinical outcome in secondary progressive multiple sclerosis

2021 ◽  
pp. 135245852110318
Author(s):  
Marcus W Koch ◽  
Jop Mostert ◽  
Pavle Repovic ◽  
James D Bowen ◽  
Eva Strijbis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Volume ◽  
Controlled Trial ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Cognitive Disability ◽  
Volume Loss ◽  
Secondary Progressive ◽  
T2 Lesions ◽  
Brain Volume Loss

Background: Magnetic resonance imaging (MRI) of brain volume measures are widely used outcomes in secondary progressive multiple sclerosis (SPMS), but it is unclear whether they are associated with physical and cognitive disability. Objective: To investigate the association between MRI outcomes and physical and cognitive disability worsening in people with SPMS. Methods: We used data from ASCEND, a large randomized controlled trial ( n = 889). We investigated the association of change in whole brain and gray matter volume, contrast enhancing lesions, and T2 lesions with significant worsening on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (NHPT), and Symbol Digit Modalities Test (SDMT) with logistic regression models. Results: We found no association between MRI measures and EDSS or SDMT worsening. T25FW worsening at 48 and 96 weeks, and NHPT worsening at 96 weeks were associated with cumulative new or newly enlarging T2 lesions at 96 weeks. NHPT worsening at 48 and 96 weeks was associated with normalized brain volume loss at 48 weeks, but not with other MRI outcomes. Conclusion: The association of standard MRI outcomes and disability was noticeably weak and inconsistent over 2 years of follow-up. These MRI outcomes may not be useful surrogates of disability measures in SPMS.

Central Slab versus Whole Brain to Measure Brain Atrophy in Multiple Sclerosis

2018 ◽  
Vol 80 (3-4) ◽  
pp. 207-214 ◽  
Author(s):  
Esther Ruberte ◽  
Tim Sinnecker ◽  
Michael Amann ◽  
Laura Gaetano ◽  
Yvonne Naegelin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sample Size ◽  
Clinical Outcomes ◽  
Volume Change ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Whole Brain ◽  
Sample Size Calculations ◽  
Statistical Dispersion

Background: Structural Image Evaluation using Normalization of Atrophy (SIENA) is used to measure brain atrophy in multiple sclerosis (MS). However, brain extraction is prone to artefacts in the upper and lower parts of the brain. To overcome these shortcomings, some pivotal MS trials used a central slab instead of the whole brain as input for SIENA. The aim of this study was to compare the internal consistency and statistical dispersion of atrophy measures, associations with clinical outcomes and required sample sizes in clinical trials between these two approaches. Methods: Brain volume change was assessed using SIENA in 119 MS patients with 5-years follow-up on 3D T1-weighted Magnetization Prepared Rapid Gradient Echo datasets using the whole brain or a central slab ranging from –10 to +60 mm Montreal Neurological Institute atlas coordinates. The statistical analysis included the quartile coefficient of dispersion, partial correlations with clinical outcomes and sample size calculations. Clinical outcome measures comprised the Expanded Disability Status Scale, MS Functional Composite and Symbol Digit Modalities Test. Results: Annualized brain atrophy rates were higher using central slab than whole brain as input for SIENA (–0.51 ± 0.49 vs. –0.37 ± 0.39% per year, p < 0.001). Central and whole brain volume change showed comparable statistical dispersion and similarly correlated with clinical outcomes at 5-years follow-up. Sample size calculations estimated 14% fewer patients required to detect a given treatment effect when using the central slab instead of the whole brain option in SIENA. Conclusion: Central slab and whole brain SIENA produced comparable statistical dispersion with similar associations to clinical outcomes.

Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue

2002 ◽  
Vol 8 (5) ◽  
pp. 410-414 ◽  
Author(s):  
N F Kalkers ◽  
H Vrenken ◽  
B MJ Uitdehaag ◽  
C H Polman ◽  
F Barkhof
Keyword(s):  
Multiple Sclerosis ◽  
Brain Tissue ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Peak Height ◽  
Tissue Loss ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Intracranial Volume ◽  
Whole Brain

Introduction: In multiple sclerosis (MS), brain atrophy measurement on magnetic resonance imaging (MRI) reflects overall tissue loss, especially demyelination and axonal loss. We studied which factor contributes most to the development of brain atrophy: extent and severity of lesions or damage of whole brain tissue (WBT). Methods: Eighty-six patients with MS [32 primary progressive (PP), 32 secondary progressive (SP)] and 22 relapsing-remitting (RR) were studied. MRI included T1- and T2-weighted imaging to obtain hypointense T1 lesion volume (T1LV) and two brain volume measurements: 1) the parenchymal fraction (PF; whole brain parenchymal volume/intracranial volume) as a marker of overall brain volume, and 2) the ventricular fraction (VF; ventricular volume/intracranial volume) as a marker of central atrophy. From magnetization transfer ratio (MTR) histograms, the relative peak height (rHp) was derived as an index of damage of WBT (a lower peak height reflects damage of WBT). Results: Multiple linear regression analysis revealed that damage of WBT explains most of the variance of PF (standardized coefficient b=0.59, p <0.001 for WBT and b= −0.19, p <0.05 for T1LV). These findings are independent of disease phase; even in RR patients, damage of WBT plays a dominant role in explaining the variance in overall brain volume. By contrast, the variance in VF is explained by both T1LV and damage of WBT (standardized coefficient b =0.43, p<0.001 for T1LV and b = −0.38, p <0.001 for WBT). Conclusion: This study shows that overall brain volume (PF) is best explained by damage of WBT, supporting the significance of nonfocal pathology in MS in producing tissue loss. Central atrophy (VF) is determined by both lesion volume and damage of WBT. Our results underline the importance of nonfocal pathology even in the early (RR) phase of the disease.

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