ISNVD Abstract Book

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WEDNESDAY – FEBRUARY 22, 2012 8:50am-9:10am MRI outcomes in MS (Robert Zivadinov, USA) Multiple sclerosis (MS) is considered an inflammatory neurologic disease with suspected autoimmune origin that is characterized by pathologic changes, including the presence of multifocal, demyelinated plaques associated with inflammatory reaction and glial scar formation. It is characterized by myelin destruction and repair as well as axonal loss, which cause intermittent and accumulating neurological dysfunction along immunopathogenic mechanisms which are still unknown. MR imaging has become a routine clinical examination in MS and is used to help the diagnosis and monitoring of the natural course of the disease. Characteristic MS abnormalities, commonly seen as areas of high signal throughout the central nervous system (CNS), are best demonstrated by proton-density or T2-weighted images (T2-WI); T1-weighted images (T1-WI) reveal hypointense abnormalities that, if permanent, are proven to correlate with axonal loss and severe matrix destruction. Gadolinium (Gd)-enhanced MRI is 5-10 times more sensitive than clinical data in the assessment of disease activity, and reveals leakage through the blood-brain barrier (BBB), which is thought to be the earliest detectable change in the development of new lesions. Not only is MRI of great value in supporting a diagnosis of MS, but also several of its metrics are valid surrogate marker for monitoring disease evolution both in natural history and in experimental trials. Currently the number of new and enlarged lesions on serial T2- weighted imaging (WI) and the number and the volume of total or new enhancing lesions on serial postcontrast T1-WI are the main MRI endpoint measures used in MS clinical trials. However, neither of the conventional MRI metrics provide sufficient information about the extent and severity of the inflammatory and neurodegenerative phases of the disease. Non-conventional MRI techniques appear to be better surrogate markers for monitoring the destructive pathological processes related to disease activity and clinical progression. They are able to reveal the underlying substrate of intrinsic pathology within lesions and normal appearing brain tissue (NABT) that include edema, inflammation, demyelination, axonal loss, and neurodegeneration. They contribute to the increasing evidence for gray matter (GM) pathology in patients with MS, revealing plaques in the periventricular and deep white matter (WM) of the hemispheres, extensive demyelination in the cerebral cortex, and severe atrophy of both WM and GM. Hypointense lesions on T1-WI (black holes), the use of new cell-specific contrast agents, magnetization transfer imaging (MTI), myelin water fraction (MWF), diffusion-weighted and tensor imaging (DWI and DTI), proton MRI spectroscopy (MRS), susceptibility-weighted imaging (SWI), functional MRI (fMRI) and high field MRI are emerging as promising tools for improving our understanding of the pathophysiology of MS. Due to their ability to detect the neurodegenerative aspects of MS, including recent evidence for cortical demyelination, these techniques are receiving increased attention as clinically relevant markers of disease progression. Financial Disclosure: Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme, Bracco, Questcor, Greatbatch
WEDNESDAY – FEBRUARY 22, 2012 9:10am-9:30am Cognitive outcomes in MS (Ralph Benedict, USA) Multiple sclerosis (MS) is associated with cognitive deficits that include problems in auditory/verbal memory, visual/spatial memory, cognitive processing speed/working memory, and executive control/function. Given that an extensive battery to assess these varied domains is not feasible in most clinical trials, brief cognitive assessments have been proposed that are psychometrically sound regarding sensitivity, reliability, and validity. In this presentation, the speaker will summarize the results from two task forces on this topic: [a] the NINDS Common Data Elements Work Group, and [b] the Brief International Cognitive Assessment for MS (BICAMS). Both programs have recommended the Symbol Digit Modalities Test, a measure of cognitive processing speed, for MS clinical trials. In addition, memory and executive function outcomes have been suggested for circumstances that permit a more comprehensive assessment. Future work is planned to further validate these outcomes with respect to clinically meaningful change. Financial Disclosure: Biogen Idec, Bayer, EMD Serono, Genzyme, Accorda Shire
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Page 55 and 56: POSTER ABSTRACTS Monday, February 2
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