The effect of IFNβ-1b on the evolution of enhancing lesions in secondary progressive MS

Brex, Peter; Molyneux, Pd; Smiddy, Pauline; Barkhof, Frederik; Filippi, Massimo; Yousry, Tarek; Hahn, Dietbert; Rolland, Yan; Salonen, Oili; Pozzilli, Carlo; Polman, C.; Thompson, Alan J.; Kappos, Ludwig; Miller, David H.

doi:10.1212/wnl.57.12.2185

Cited by 63 publications

(47 citation statements)

References 26 publications

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“…Because a previous study showed that large Gd enhancing lesions were more likely than smaller ones to become T1 hypointense [3], we divided lesions as large or small for additional analysis. This was done on the electronic images according to their largest area on a single slice.…”

Section: ■ Mri Analysismentioning

confidence: 99%

“…Follow up MRI shows that most enhancing lesions result in an area of permanent high signal on T2-weighted scans indicating that chronic structural changes have occurred [4]. Whereas most lesions display hypointensity on T1-weighted images during the acute enhancing phase, a minority (about 14-41 %) become T1 hypointense with follow up [3,4,7,23]. Such chronically hypointense lesions are associated with more extensive axonal loss than the larger proportion of T2 lesions which become T1-isointense [1,22,24].…”

Section: Introductionmentioning

confidence: 99%

“…Such chronically hypointense lesions are associated with more extensive axonal loss than the larger proportion of T2 lesions which become T1-isointense [1,22,24]. Axonal loss is likely to be an important substrate of irreversible disability in MS, and there has been interest in following the accumulation of T1 hypointense lesions in studies of natural history and therapeutic intervention [2,3,7,20] The evidence that BBB breakdown is a consistent feature of new lesions suggests that migration of immunologically active white cells from the blood into the brain might be an important event in leading to foci of demyelination and ultimately axonal damage or loss [15]. A question arising is whether therapy that specifically interrupts such cell migration might prevent the formation of new lesions [26].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis

Dalton¹,

Miszkiel²,

Barker³

et al. 2004

J Neurol

121

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Section: ■ Mri Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis

Dalton¹,

Miszkiel²,

Barker³

et al. 2004

J Neurol

121

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show abstract

“…Such a treatment effect has been demonstrated for glatiramer acetate 96 and natalizumab 97 but not ␤-interferon. 98 …”

Section: T1 Hypointense Lesionsmentioning

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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“…Both IFN-β-1a and IFN-β-1b prevented the occurrence of smaller CELs more often than larger CELs during therapy. [13,14]. Such observations indicate that the ability of IFN-β to prevent CELs is non-homogeneous with respect to CEL size.…”

Section: Introductionmentioning

confidence: 99%

The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with multiple sclerosis

Gaindh¹,

Jeffries²,

Ohayon³

et al. 2008

Expert Opinion on Biological Therapy

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Background Contrast enhancing lesions (CELs) in MRI represent inflammatory events in multiple sclerosis (MS). IFN-β-1b decreases the formation of CELs. However, the ability of IFN-β-1b to reduce the size of CELs arising during therapy has not been extensively investigated. Methods Thirty patients with relapsing-remitting (RR) MS were followed for a 3-month pre-therapy phase then for a 6-month therapy phase during which treatment with IFN-β-1b at a dosage of 250 μg subcutaneously injected every other day was employed. Each patient underwent monthly clinical and MRI examinations. For all patients, CELs were identified on postcontrast T1-weighted MRIs. CEL number, size, and volume were computed using Medx software. Results The average number and total lesion volume of CELs visible during the therapy phase were significantly lower than the number and total lesion volume of CELs observed in the pre-therapy phase. However, there was no significant reduction between pre-therapy and therapy phases in the mean size of individual lesions arising during the respective phases. Conclusions Since size of CELs has been related to severity of tissue damage, the lack of size decrease during therapy suggested a limited therapeutic effect of IFN-β-1b if a blood–brain barrier breakdown has occurred.

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The effect of IFNβ-1b on the evolution of enhancing lesions in secondary progressive MS

Abstract: IFNbeta-1b reduced the number of new enhancing lesions, with a greater effect on small lesions. However, when a new enhancing lesion did become established, treatment with IFNbeta-1b did not alter its subsequent course.

Cited by 63 publications

References 26 publications

Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis

Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis

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

The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with multiple sclerosis

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