New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate

Cadavid, Diego; Cheriyan, Jojy; Skurnick, Joan; Lincoln, John A.; Wolansky, Leo; Cook, Stuart D.

doi:10.1136/jnnp.2008.171090

Cited by 43 publications

(40 citation statements)

References 26 publications

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“…A similar benefit was reported with interferon beta-1a SQ [65]. The BECOME study provided a head-to-head comparison of treatment effects on T1 black hole accumulation over 2 years and found a trend towards a lower conversion rate of acute black holes (ABH) to chronic black holes (CBH) with interferon beta-1b compared to copolymer-1 [66]. Notably, while the majority of the newly enhancing lesions were associated with ABH (62.7% overall), only a small proportion of Gd + lesions (12%) became CBH when assessed over at least a 1-year period.…”

Section: Treatment Effectssupporting

confidence: 55%

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

Sicotte

2011

Neurotherapeutics

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Summary: Imaging techniques, in particular magnetic resonance imaging (MRI), play an important role in the diagnosis and management of multiple sclerosis (MS) and related demyelinating diseases. Findings on MRI studies of the brain and spinal cord are critical for MS diagnosis, are used to monitor treatment response and may aid in predicting disease progression in individual patients. In addition, results of imaging studies serve as essential biomarkers in clinical trials of putative MS therapies and have led to important insights into disease pathophysiology. Although they are useful tools and provide in vivo measures of disease-related activity, there are some important limitations of MRI findings in MS, including the non-specific nature of detectable white matter changes, the poor correlation with clinical disability, the limited sensitivity and ability of standard measures of gadolinium enhancing lesions and T2 lesions to predict future clinical course, and the lack of validated biomarkers of long term outcomes. Advancements that hold promise for the future include new techniques that are sensitive to diffuse changes, the increased use of higher field scanners, measures that capture disease related changes in gray matter, and the use of combined structural and functional imaging approaches to assess the complex and evolving disease process that occurs during the course of MS.

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Section: Treatment Effectssupporting

confidence: 55%

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

Sicotte

2011

Neurotherapeutics

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“…10,11 all new T2 lesions (95-100%) as well as acute, transient, and chronic black holes (those lasting for more than 12 months) occur coincidentally with or evolve from Gd+ T1-weighted lesions. 37,49 However, Gd+ lesions evolve into chronic black holes less commonly than they do into T2 lesions or transient black holes. 37 This indicates that unequivocally (not related to technique, positioning, quality of scan, or questionable reader interpetation) new T2 lesions or black holes in RRMS patients had a prior inflammatory phase with alteration of the BBB of a degree sufficient to be detected, even though this may not always be documentable with less frequent or sensitive MRI.…”

Section: Background Historical Evolution Of Ms Diagnostic Criteriamentioning

confidence: 99%

“…37,49 However, Gd+ lesions evolve into chronic black holes less commonly than they do into T2 lesions or transient black holes. 37 This indicates that unequivocally (not related to technique, positioning, quality of scan, or questionable reader interpetation) new T2 lesions or black holes in RRMS patients had a prior inflammatory phase with alteration of the BBB of a degree sufficient to be detected, even though this may not always be documentable with less frequent or sensitive MRI. 37 It has been shown that T2 lesions have heterogeneous pathology, with varying degrees of abnormality ranging from edema and inflammation with phagocytosis of myelin, to demyelination, gliosis, and axonal loss, which can be mild to severe.…”

Section: Background Historical Evolution Of Ms Diagnostic Criteriamentioning

confidence: 99%

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Cook¹,

Dhib‐Jalbut²,

Dowling³

et al. 2012

International Journal of MS Care

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It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS. Int J MS Care. 2012;14:105-114. It was recently suggested by Lincoln et al. 1 that the Lublin-Reingold clinical classification of multiple sclerosis (MS) 2 for the assessment of MS phenotypes and patient evolution over time be modified to include magnetic resonance imaging (MRI). It was recommended that the classification incorporate the "conventional," generally available MRI techniques of gadolinium (Gd) T1-weighted sequences and dual-echo and fluid-attenuated inversion recovery (T2-weighted and FLAIR) images ( course over time and, in turn, more informed clinical trials and a better understanding of appropriate therapies.Prior to the meeting, a survey of members of the CMSC was conducted on the need to modify the Lublin-Reingold classification. Over a 1-week period, 141 responses were received, representing 16% of the CMSC members polled. The results were as follows: A total of 70% of respondents indicated that the LublinReingold classification did not sufficiently distinguish the different forms of MS; 87% felt that the LublinReingold classification did not sufficiently distinguish MS disease activity even within a given category of the disease; and 84% indicated that it would be useful to include certain subclinical indices of disease activity in the clinical classification, such as MRI gadoliniumother MRI modalities that are not currently widely available and other validated biomarkers might be added to the classification in the future.In response to the publication of Lincoln et al., 1 the Consortium of Multiple Sclerosis Centers (CMSC) sponsored an international consensus conference, which was held in Short Hills, New Jersey, from March 5 to 7, 2010. Participating in the conference were 28 invited MS experts from North and South America and Europe who were well versed in clinical trials, the management of MS, biostatistics, neuropathology, neuroimaging, and neuroimmunology. The goal of the meeting was to review the available...

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“…Therefore, monitoring the conversion of new active lesions into permanent T1H black holes has been used for more than a decade as a complementary approach for evaluating the clinical efficacy of disease‐modifying therapies 3, 6, 7. The assessment of new active lesions converting into permanent T1H black holes allows for detection of more advanced brain tissue deterioration in subjects with MS 8.…”

Section: Introductionmentioning

confidence: 99%

“…The assessment of new active lesions converting into permanent T1H black holes allows for detection of more advanced brain tissue deterioration in subjects with MS 8. Placebo‐controlled studies have shown that, over a 6‐12 month period, approximately 25‐40% of active MS lesions will evolve into T1H lesions 6, 79, 10, 11, 12 …”

Section: Introductionmentioning

confidence: 99%

The Effect of Three Times a Week Glatiramer Acetate on Cerebral T1 Hypointense Lesions in Relapsing‐Remitting Multiple Sclerosis

Zivadinov

Dwyer

Ramasamy

et al. 2015

Journal of Neuroimaging

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BACKGROUND AND PURPOSETwo definitions of T1 hypointense (T1H) lesions can be derived from pre‐contrast images: those that may or may not have a corresponding gadolinium‐enhancing correlate on post‐contrast images (T1H total), and those that are simultaneously non‐gadolinium‐enhancing on post‐contrast scans (T1H non‐enhancing). To determine the differences in lesion evolution between these two T1H definitions, we examined the effect of glatiramer acetate 40 mg/mL three times weekly subcutaneous injection (GA40) on the number of new or enlarging T1H total and T1H non‐enhancing lesions in patients with relapsing‐remitting multiple sclerosis (RRMS).METHODSThe Phase III GALA study randomized 1404 RRMS subjects 2:1 to receive GA40 or placebo for 12 months. MRI scans were obtained at baseline and at months 6 and 12. Cumulative numbers of T1H total and of T1H non‐enhancing lesions were analyzed using an adjusted negative binomial regression model. A total of 1,357 patients had MRI data collected at either the month 6 or month 12 visit.RESULTSAmong the 1,357 patients with MRI scans performed at either the month 6 or month 12 visit, 883 treated with GA40 developed an adjusted cumulative mean of 1.72 T1H total lesions versus 2.62 in 440 placebo controls (risk ratio, .66; 95% CI, .54‐.80; P < .0001). On T1H non‐enhanced scans, GA40‐treated patients developed an adjusted cumulative mean of 1.35 T1H non‐enhancing lesions versus 1.91 in placebo controls (risk ratio, .71; CI, .58‐.87; P = .0009).CONCLUSIONSGA40 significantly reduced the number of new or enlarging T1H total lesions and T1H non‐enhancing lesions compared with placebo. Although the treatment effect magnitude was comparable with both definitions, the use of T1H non‐enhancing lesions may be more relevant for more uniform standardization in future clinical trials.

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New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate

Abstract: Only a minority of new brain lesions in patients with MS treated with GA or IFNbeta1b convert to CBH.

Cited by 43 publications

References 26 publications

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

The Effect of Three Times a Week Glatiramer Acetate on Cerebral T1 Hypointense Lesions in Relapsing‐Remitting Multiple Sclerosis

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