Correlations between monthly enhanced MRI Lesion rate and changes in T2 Lesion volume in multiple sclerosis

Molyneux, Paul; Filippi, Massimo; Barkhof, Frederik; Gasperini, Claudio; Yousry, Tarek; Truyen, Luc; Lai, H. M.; Rocca, Maria A.; Moseley, I. F.; Miller, David H.

doi:10.1002/ana.410430311

Cited by 145 publications

(75 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…47 In addition, patients with RRMS frequently show a higher frequency of enhancement than patients with progressive forms of MS. Nevertheless, their presence increases the risk of continuous disease activity 48 and the short-term appearance of clinical relapses. 46,48,49 All of the disease-modifying agents that are approved by the FDA for the treatment of MS show a significant effect on limiting Gd enhancement as recently reviewed.…”

Section: Blood-brain Barrier Compromisementioning

confidence: 99%

“…Nevertheless, their presence increases the risk of continuous disease activity 48 and the short-term appearance of clinical relapses. 46,48,49 All of the disease-modifying agents that are approved by the FDA for the treatment of MS show a significant effect on limiting Gd enhancement as recently reviewed. 1 Furthermore, a drug that exacerbates MS may be detected early by observing worsening Gd enhancement.…”

Section: Blood-brain Barrier Compromisementioning

confidence: 99%

See 1 more Smart Citation

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

et al. 2007

View full text Add to dashboard Cite

Summary: Magnetic resonance imaging (MRI) has played a central role in the diagnosis and management of multiple sclerosis (MS). In addition, MRI metrics have become key supportive outcome measures to explore drug efficacy in clinical trials. Conventional MRI measures have contributed to the understanding of MS pathophysiology at the macroscopic level yet have failed to provide a complete picture of underlying MS pathology. They also show relatively weak relationships to clinical status such as predictive strength for clinical progression. Advanced quantitative MRI measures such as magnetization transfer, spectroscopy, diffusion imaging, and relaxometry techniques are somewhat more specific and sensitive for underlying pathology. These measures are particularly useful in revealing diffuse damage in cerebral white and gray matter and therefore may help resolve the dissociation between clinical and conventional MRI findings. In this article, we provide an overview of the array of tools available with brain and spinal cord MRI technology as it is applied to MS. We review the most recent data regarding the role of conventional and advanced MRI techniques in the assessment of MS. We focus on the most relevant pathologic and clinical correlation studies relevant to these measures.

show abstract

Section: Blood-brain Barrier Compromisementioning

confidence: 99%

Section: Blood-brain Barrier Compromisementioning

confidence: 99%

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

et al. 2007

View full text Add to dashboard Cite

show abstract

“…29 Large-scale clinical trials and cross-sectional studies generally use global T 2 lesion volume as surrogate for disease severity and long-term trends thereof as indicators of disease activity and therapeutic effect. 30 -34 However, a pronounced short-term variability of T 2 lesion appearance, on the order of weeks and months, is known to be a substantial confounder of such global lesion burden assessment.…”

Section: Global Lesion Burdenmentioning

confidence: 99%

“…In its current form, consequently, global T 2 lesion burden appears to be more specific as a diagnostic indicator 38 than as a measure of disease severity. 29 …”

Section: Global Lesion Burdenmentioning

confidence: 99%

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

Meier

Weiner

2007

Neurotherapeutics

View full text Add to dashboard Cite

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...

show abstract

“…The lesions detected on T2-weighted and gadolinium (Gd)-contrast-enhanced T1-weighted MRI reflect the pathological hallmark of the disease: the T2 lesion burden seems to be correlated with the number of preceding relapses 5 and the use of Gd enables visualisation of blood-brain barrier disruption and therefore inflammatory disease activity. 6 Thus, MRI has become a relevant surrogate outcome marker in MS clinical trials.…”

Section: Magnetic Resonance Imaging As a Prognostic Markermentioning

confidence: 99%

Biological Markers of Prognostic Value in Multiple Sclerosis

Pauli¹,

Reindl²,

Berger³

2008

European Neurological Review

View full text Add to dashboard Cite

Multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system (CNS), is the most common neurological disease among young adults, and carries the potential risk of permanent disability. The pathological hallmarks of the disease are multifocal white (and, most recently, also grey) matter lesions, which are characterised by variable extents of inflammation, demyelination, axonal loss, gliosis and atrophy. 1 MS has variable clinical presentations and highly heterogeneous disease courses, ranging from rare acute fulminate forms to benign MS without substantial disability. Eighty-five per cent of patients initially present with a clinically isolated syndrome (CIS); most of these patients go on to develop relapsing-remitting (RR) MS, with acute relapses alternating with periods of clinical remission or stability. 2 Ultimately, more than half of (untreated) RRMS patients convert to secondary chronic progressive (SP) MS, which is characterised by accumulating neurological disability with or without superimposed relapses. 3 The clinical outcome of MS is largely unpredictable for individual patients. The great variability of this complex disease highlights the need for reliable biological markers with high sensitivity and specificity that are able to predict the future disease course and treatment response. Furthermore, stratification of MS patients with regard to their dominating pathological processes would allow individualised differential therapeutic concepts. In this review, we discuss the prognostic value of biological markers that are currently under debate, including magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) parameters and antibodies. Markers to Predict Disease Progression Magnetic Resonance Imaging as a Prognostic MarkerMRI is a well established tool for the diagnosis 4 and management of MS that allows disease activity and progression to be monitored. The lesions detected on T2-weighted and gadolinium (Gd)-contrast-enhanced T1-weighted MRI reflect the pathological hallmark of the disease: the T2 lesion burden seems to be correlated with the number of preceding relapses 5 and the use of Gd enables visualisation of blood-brain barrier disruption and therefore inflammatory disease activity. 6 Thus, MRI has become a relevant surrogate outcome marker in MS clinical trials. Doubtless, MRI has its greatest relevance in patients with a CIS: evidence of dissemination of MS lesions in space and time and the extent of MRI activity are robust predictors of a first relapse. 7,8 However, since commonly used MRI techniques show only a weak association with future disability, 9 their prognostic value is limited and they are not useful for predicting clinical outcome in individual patients. 10 Poor clinicoradiological correlations may be due to either insensitive clinical rating scales or methodological difficulties in the detection of pathological alterations, especially axonal damage, within the normal-appearing white (NAWM) and grey matter (NAGM). 10,11 Neuropathology demonstrates t...

show abstract

Correlations between monthly enhanced MRI Lesion rate and changes in T2 Lesion volume in multiple sclerosis

Cited by 145 publications

References 35 publications

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

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

Biological Markers of Prognostic Value in Multiple Sclerosis

Contact Info

Product

Resources

About