Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H

Paolillo, Andrea; Coles, Alasdair; Molyneux, Pd; Gawne-Cain, M. L.; MacManus, Deirdre; Barker, Gareth J.; Compston, D. A. S.; Miller, D. H.

doi:10.1212/wnl.53.4.751

Cited by 210 publications

(109 citation statements)

References 29 publications

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“…4 An altered role of inflammation in SPMS is documented also from multiple treatment trials in which inflammation was effectively suppressed but accrual of atrophy remained unaltered. [5][6][7] Both clinical characteristics and MRI findings point to a similar picture of slow but accelerated accrual of damage that eventually dissociates from baseline predictors, such as the load of gadolinium-enhancing lesions. Some of the most salient findings are discussed here.…”

Section: The Repair Potential Hypothesismentioning

confidence: 97%

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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: The Repair Potential Hypothesismentioning

confidence: 97%

Section: The Repair Potential Hypothesismentioning

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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“…This confirms other studies by showing a link between increasing atrophy and disability. 68,69 In a 2-year placebo-controlled trial of ␤-interferon in relapsing remitting MS, atrophy was measured from yearly scans using brain parenchymal fraction (BPF). The mean BPF decrease was similar in both arms in year 1, but was smaller in the ␤-interferon arm in year 2.…”

Section: Atrophy Measuresmentioning

confidence: 99%

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Miller¹

2004

Neurotherapeutics

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Summary:Multiple sclerosis (MS) is a chronic disease of the CNS that most commonly affects young adults. It is usually characterized in the early years by acute relapses followed by partial or complete remission; in later years progressive and irreversible disability develops. Because of the protracted and unpredictable clinical course, biological surrogate markers are much needed to make clinical trials of potential disease-modifying treatments more efficient. Magnetic resonance (MR) outcome measures are now widely used to monitor treatment outcome in MS trials. Areas of multifocal inflammation are detected with a high sensitivity as new areas of gadolinium enhancement and T2 abnormality, and these may be considered as surrogate markers for clinical relapses. However, progressive disability is not clearly related to inflammatory lesions but rather to a progressive and diffuse process with increasing neuroaxonal loss. MR surrogate measures for neuroaxonal loss include atrophy (tissue loss in brain and spinal cord), N-acetyl aspartate, and T1 hypointense lesions. Diffuse abnormality in normal appearing brain tissue may also be monitored using magnetization transfer ratio and other quantitative MR measures. For treatment trials of new agents aimed at preventing disability, measures of neuroaxonal damage should be acquired, especially atrophy, which occurs at all stages of MS and which can be quantified in a sensitive and reproducible manner. Because the MR surrogates for neuroaxonal loss are not yet validated as predicting future disability, definitive trials should continue to monitor an appropriate disability endpoint.

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“…Было отмечено достоверное снижение активности забо-левания в виде уменьшения появления новых очагов по данным МРТ головного мозга (р < 0,001) [12][13][14]. У боль-ных с ВПРС в течение 18 месяцев после проведенного курса терапии было отмечено достоверное замедление увеличения объема Т2-гиперинтенсивных очагов.…”

Section: алемтузумаб (лемтрада)unclassified

Monoclonal Antibody for Multiple Sclerosis Treatment

Попова¹

2017

Med. sov.

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Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H

Cited by 210 publications

References 29 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?

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Monoclonal Antibody for Multiple Sclerosis Treatment

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