Clinical–MRI correlations in a European trial of interferon beta-1b in secondary progressive MS

Molyneux, Pd; Barker, Gareth J.; Barkhof, Frederik; Beckmann, Karola; Dahlke, Frank; Filippi, Massimo; Ghazi, Mahdiyeh Khabbaz Koche; Hahn, Dietbert; MacManus, Deirdre; Polman, Chris H.; Pozzilli, Carlo; Kappos, Ludwig; Thompson, Alan J.; Wagner, K.; Yousry, Tarek; Miller, D. H.

doi:10.1212/wnl.57.12.2191

Cited by 57 publications

(53 citation statements)

References 26 publications

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“…IL-23 is a heterodimer of the IL-12p40 and a p19 subunit and is produced in the CNS by glia cells acting mainly on T memory cells (11)(12)(13)(14). However, to our knowledge a similar dichotomy between IL-12 and IL- 23 has not yet been demonstrated in MS.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 88%

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Suppression of Ongoing Disease in a Nonhuman Primate Model of Multiple Sclerosis by a Human-Anti-Human IL-12p40 Antibody

Hart

Brok

Remarque

et al. 2005

The Journal of Immunology

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IL-12p40 is a shared subunit of two cytokines with overlapping activities in the induction of autoreactive Th1 cells and therefore a potential target of therapy in Th1-mediated diseases. We have examined whether ongoing disease in a nonhuman primate model of multiple sclerosis (MS) can be suppressed with a new human IgG1κ Ab against human IL-12p40. Lesions developing in the brain white matter were visualized and characterized with standard magnetic resonance imaging techniques. To reflect the treatment of MS patients, treatment with the Ab was initiated after active brain white matter lesions were detected in T2-weighted images. In placebo-treated control monkeys we observed the expected progressive increase in the total T2 lesion volume and markedly increased T2 relaxation times, a magnetic resonance imaging marker of inflammation. In contrast, in monkeys treated with anti-IL-12p40 Ab, changes in the total T2 lesion volume and T2 relaxation times were significantly suppressed. Moreover, the time interval to serious neurological deficit was delayed from 31 ± 10 to 64 ± 20 days (odds ratio, 0.312). These results, in a disease model with high similarity to MS, are important for ongoing and planned trials of therapies that target IL-12 and/or IL-23.

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Section: Ultiple Sclerosis (Ms)mentioning

confidence: 88%

“…Similar to the situation in MS, clinical signs in the marmoset EAE model does not always reflect the pathological changes within the CNS, the so-called clinicopathological paradox (21,22). Hence, as in MS trials, we have used MRI as an outcome measure for the current study (23,24).…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Suppression of Ongoing Disease in a Nonhuman Primate Model of Multiple Sclerosis by a Human-Anti-Human IL-12p40 Antibody

Hart

Brok

Remarque

et al. 2005

The Journal of Immunology

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“…Concentric ring enhancing lesions with central contrast pallor appear in areas of heightened local inflammation (Rovira et al, 1999). Results of serial MRI studies demonstrate that enhancement usually precedes or accompanies the appearance of most new lesions on T2-WI in all disease subtypes, even in primary-progressive MS (Molyneux et al, 2001). However, Gd-enhancement is more commonly seen in patients with relapsing-remitting (RRMS) than in patients with primary or secondary progressive MS (Thompson et al, 2000) and is considered sensitive to disease activity and predictive of future clinical relapses.…”

Section: Postcontrast T1-weighted Imagingmentioning

confidence: 96%

Neuroimaging - Clinical Applications

Bright¹

2012

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“…This relates to the discrepancy between lesion site and locomotor function, which is most commonly assessed by EDSS. Clinical MRI correlations were demonstrated between relapse rate and number of lesions seen on T2W images, suggesting a role for MRI in monitoring disease progression, and between lesion number and volume and the presence or absence of treatment 58 .…”

Section: Conventional Mri and Disabilitymentioning

confidence: 91%

“…However, in established MS, the correlation between total volume of T2 abnormalities and disability is modest or worse 58,59 . This relates to the discrepancy between lesion site and locomotor function, which is most commonly assessed by EDSS.…”

Section: Conventional Mri and Disabilitymentioning

confidence: 99%

Comparison of magnetization transfer methods for assessing macromolecular bound water in the brain and cervical spinal cord

Dopico

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Magnetization transfer (MT) imaging is a magnetic resonance imaging technique that generates contrast dependent upon the phenomenon of magnetization exchange between semi-solid macromolecular protons and water protons. This technique has the ability to indirectly image semi-solids, such as protein matrices and cell membranes, whose magnetization dies away too quickly to be imaged directly based on relaxation properties of water interacting with the semisolid lipid protons. Preliminary results suggest that MT quantification may allow improved characterization of the pathologically heterogeneous lesions of multiple sclerosis by providing a measure of demyelination through a sensitivity to myelin proteins. However, MT imaging, as currently most commonly applied, is only a semi-quantitative technique that reflects mixed tissue and experimental parameters in addition to MT. iii In this thesis a novel quantitative MT ResumenLa imagen por transferencia de magnetización (MT) es una técnica de imagen por resonancia magnética nuclear que genera contraste teniendo como base el fenómeno del intercambio de magnetización entre protones de macromoléculas de semisólidos y agua. Esta técnica tiene la propiedad de poder generar imágenes de semisólidos indirectamente, como pueden ser las matrices de proteínas y las membranas celulares, cuya magnetización cae demasiado rápido como para producir imágenes directamente basándose en las propiedades de relajación de los protones del agua interaccionando con los de lípidos. Resultados preliminares sugieren que la cuantificación de MT podría permitir una mejora en la caracterización de las lesiones patológicamente heterogéneas en esclerosis múltiple ofreciendo una medida de la desmielinizacion a través de las proteínas de la mielina. Sin embargo, la imagen MT, en su más amplio rango de aplicación, es solamente una técnica semicuantitativa que refleja una mezcla de tejido y parámetros experimentales junto con MT.En esta tesis, una nueva técnica cuantitativa de imagen (MTsat) se aplica en el cerebro y la espina dorsal cervical con el fin de evaluar si el control de esta limitación puede mejorar la discriminación neuropatológica en sujetos con esclerosis múltiple (MS). Se encontró que MTsat puede discriminar la patología en el cerebro y la espina dorsal cervical que está asociada con los diferentes grados de incapacidad de los pacientes.Además, la señal de regiones del cerebro en donde las técnicas de imagen convencionales no muestran daño de tejido arroja una correlación significativa con las escalas de incapacidad.

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Clinical–MRI correlations in a European trial of interferon beta-1b in secondary progressive MS

Cited by 57 publications

References 26 publications

Suppression of Ongoing Disease in a Nonhuman Primate Model of Multiple Sclerosis by a Human-Anti-Human IL-12p40 Antibody

Suppression of Ongoing Disease in a Nonhuman Primate Model of Multiple Sclerosis by a Human-Anti-Human IL-12p40 Antibody

Neuroimaging - Clinical Applications

Comparison of magnetization transfer methods for assessing macromolecular bound water in the brain and cervical spinal cord

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