Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis

Kappos, Ludwig; Moeri, David; Radüe, Ernst Wilhelm; Schoetzau, Andreas; Schweikert, Kati; Barkhof, Frederik; Miller, David H.; Guttmann, Charles R.G.; Weiner, Howard L.; Gasperini, Claudio; Filippi, Massimo

doi:10.1016/s0140-6736(98)03053-0

Cited by 446 publications

(272 citation statements)

References 32 publications

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“…New lesion activity is transient and not equally apparent at all times, and not all focal activity reaches the threshold of MRI sensitivity. Such a view is supported by the finding that the variance of enhancing lesion counts over 6 months proved to be a better predictor for relapse rate than the actual baseline lesion number 20 -indicative not only of the temporal variability of disease activity, but also of the narrow time window for capturing contrast enhancement.…”

Section: Mri Variablesmentioning

confidence: 93%

“…Translated into a crosssectional scenario, this would match exactly the observation that the variability of new lesion appearance was a stronger predictor of disease activity than was the overall number of lesions. 20 Note that the level and dynamic activity of a single new lesion in this paradigm is not to be mistaken for the overall level of disease activity, which is most commonly assessed as the total number of new lesions observed.…”

Section: Fig 10mentioning

confidence: 99%

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Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

Meier

Weiner

2007

Neurotherapeutics

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Summary:This article discusses and reviews advanced forms of serial morphometry in the context of a disease progression model in multiple sclerosis (MS). This model of disease activity distinguishes between overall disease activity and the proportion thereof that becomes permanent damage. This translates into a progression model that features a repair potential, which, when exhausted, marks the conversion or progression from relapsing to progressive disease. The level of repair capacity at a given time determines the rate of progression. Both clinical and MRI variables appear to be in support of such a model. We examine possible MRI markers for this repair capacity, particularly the short-term behavior of new MRI lesions, quantified by methods of time-series analysis-that is, capturing lesion dynamics in the form of MRI intensity change directly, rather than shape or volume change. Lower rates of individual lesion recovery may represent lower repair and greater proximity to a progressive stage. Individuals with low transient lesion turnover appear to undergo more rapid progression and atrophy. Because disease-modifying therapies aim to alter the pathophysiological chain of inflammation, demyelination, and axonal loss, a therapeutic effect may therefore be more readily apparent as a change in lesion dynamics and recovery rate and level, rather than a change in total lesion burden or enhancing lesion number. Key Words: Multiple sclerosis, disease modeling, serial MRI, morphometry, lesion evolution, repair. THE REPAIR POTENTIAL HYPOTHESISMore than 80% of newly diagnosed cases of clinically definite multiple sclerosis (MS) fall into the relapsingremitting (RRMS) category. A large proportion of RRMS patients eventually convert to a secondary progressive stage (SPMS) within 6 -10 years. 1,2 The hallmark of this stage is a progressive worsening of disability in the absence of relapses, and a shift from inflammatory to degenerative activity, apparent on MRI as fewer contrast-enhancing lesions and accelerated brain parenchymal atrophy (FIG. 1). The etiology of this progression is not known, but a premise commonly offered is that of a threshold effect and the exhaustion of structural and functional redundancy, leading from inflammatory and relapsing to more diffuse and accelerated accrual of damage.Here we review and discuss this progression model, focusing on the concept of a hypothesized repair potential as a marker for progression. Of particular interest is the possibility of obtaining early MRI markers of this repair potential from advanced forms of serial quantitativ MRI. As new therapies with alternative mechanisms (other than broad or targeted immune suppression) become available to MS patients, specific markers that reliably predict long-term progression early in the disease are becoming increasingly critical.A growing body of evidence is congruent with a repair potential model: histopathological analyses have revealed a shift from focal inflammatory activity in RRMS to diffuse damage in SPMS 3 and overall reduced...

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Section: Mri Variablesmentioning

confidence: 93%

Section: Fig 10mentioning

confidence: 99%

Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

Meier

Weiner

2007

Neurotherapeutics

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“…Conventional magnetic resonance imaging (MRI) of the brain shows typical white matter (WM) lesions on proton density (PD)-weighted and T2-weighted images. Predicting prognosis and making treatment decisions for individual patients based on these images is challenging, as correlations between brain lesion burden visualized on MRI, and disability progression measured by expanded disability status scale (EDSS, possible range: 0 -10, with a higher score indicating a higher degree of disability (1)), are only moderate (2)(3)(4)(5)(6)(7)(8)(9). This may be caused by several mechanisms: the presence of symptomatic spinal cord lesions in combination with relatively few brain lesions, pathology in normal-appearing WM (NAWM) and normal-appearing gray matter that is not visualized on conventional MRI, pathological heterogeneity (edema, demyelination, axonal loss, or gliosis) of lesions visualized on PD-weighted and T2-weighted images, and the fact that a proportion of the lesions visualized on MRI may be clinically silent (2)(3)(4)(5)(6)(7)(8)(9).…”

Section: Multiple Sclerosis (Ms) Is a Multifocal Inflammatory Demyelimentioning

confidence: 99%

Clinical correlations of brain lesion distribution in multiple sclerosis

Vellinga¹,

Geurts²,

Rostrup

et al. 2009

Magnetic Resonance Imaging

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Purpose: To explore relations between spatial distribution of multiple sclerosis (MS) lesions, and disability. In MS, the presence of asymptomatic brain lesions challenges the prediction of disability based on conventional brain MRI. Hypothesizing that symptomatology may partly be determined by lesion location, this retrospective study explored relations between lesion location and disability using voxelwise analyses in standard space. Materials and Methods:Using nonparametric permutation-based statistics, voxelwise lesion probability on T2 lesion masks was related to expanded disability status scale (EDSS) and MS functional composite (MSFC) subdomain scores and demographic characteristics of 325 MS patients. To identify statistically significant locations, a cluster-forming threshold of 3.1 was used. Results:In clusters in the periventricular region, lesion probability correlated significantly (P Ͻ 0.001) with disability and disease duration, and was higher in progressive than in relapsing disease. When controlled for lesion load (LL), no significant clusters survived. Presence and number of spinal cord lesions did not correlate with lesion probability in any location, and did not influence correlations with disability when included in its analyses.Conclusion: Periventricular lesions were related to disability. LL influenced relations between disability and lesion probability throughout the brain, suggesting interplay between lesional burden and its location in determining disability in MS.

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“…A number of studies have demonstrated that Gd enhancement is correlated with the occurrence of clinical relapses in MS (1)(2)(3). The number or volume of Gd-enhancing lesions is useful for evaluating biologically relevant treatment effects (4,5).…”

mentioning

confidence: 99%

Segmentation of gadolinium‐enhanced lesions on MRI in multiple sclerosis

Datta

Sajja

et al. 2007

Magnetic Resonance Imaging

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Purpose: To develop and implement a method for identification and quantification of gadolinium (Gd) enhancements with minimal human intervention. Materials and Methods:Dual fast spin echo (FSE), fluid attenuation inversion recovery (FLAIR), and pre-and postcontrast T1-weighted spin echo were acquired on 22 subjects. The enhancements were identified on the postcontrast T1-weighted images based on morphological operations. A single threshold based on the ratio of the difference of postcontrast and precontrast T1 images with that of precontrast T1 images is applied to the reconstructed images to reduce the false classifications. False classification of enhancements arising from enhancing vasculature and structures such as the choroid plexus that lack a blood-brain barrier were reduced by assuming that the true enhancements are always associated with hyperintense lesions on T2-weighted images (T2 lesions). The enhanced lesions were further delineated based on fuzzy connectivity. Results:The segmented Gd enhancements were evaluated quantitatively with manually identified enhancements based on similarity measures. The average similarity index (SI) of 0.76 suggests excellent performance of the proposed methodology. The Bland-Altman plot shows a close agreement between the results obtained manually and those based on the proposed methodology. Conclusion:The proposed algorithm identifies and quantifies Gd enhancements accurately with minimal human intervention.

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Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis

Cited by 446 publications

References 32 publications

Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

Time-Series Modeling of Multiple Sclerosis Disease Activity: A Promising Window on Disease Progression and Repair Potential?

Clinical correlations of brain lesion distribution in multiple sclerosis

Segmentation of gadolinium‐enhanced lesions on MRI in multiple sclerosis

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