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Even in early stages of multiple sclerosis (MS), cognitive dysfunction is a leading cause of disability. It can have profound social and economic consequences for patients and their families. Cognitive impairment is affecting up to 65% of MS patients (Seiler 2003). Initial studies have demonstrated successful therapeutic interventions for cognitive decline in MS (Krupp et al. 2004), which underline the necessity to detect these patients in the early disease process. Moreover, preliminary studies suggest an essential role of disease modifying therapies (DMT) in inhibition of cognitive deterioration in patients with MS (Barak 2002, Flechter 2007).

Previous MRI and histopathological studies have consistently revealed the corpus callosum (CC) as one of the sites most commonly affected by demyelination and axonal loss in MS (Martola 2007). The corpus callosum index (CCI) is an easy to use MRI marker for estimating brain atrophy in patients with MS. In addition, CCI correlates with cognitive impairment (Filippi, 1996) and disability progression (Yaldizli et al 2010) in relapsing remitting MS (RRMS) patients.

This study is a cross sectional study of patients diagnosed with clinically isolated syndrome (CIS) and RRMS, who will undergo a series of tests to assess cognitive impairment, fatigue severity and depressive symptoms. Cognitive impairment will be assessed with Multiple Sclerosis Inventory Cognition (MUSIC) and symbol digit modalities test (SDMT), fatigue severity will be measured with the Fatigue Scale for Motor and Cognitive Functions (FSMC) and depressive symptoms with the Beck Depression Inventory (BDI). All tests mentioned above are validated for MS patients. In the second step we will use our large longitudinal database of serial MRI examinations from which a linear measurement of CCI will be retrospectively calculated.

Interferons may increase fatigue symptoms as a side-effect in MS patients. As the individual interferon formulations are injected in different time intervals (Betaferon® every two days, Rebif® 3 times a week and Avonex® once every week), they differ in their effect on fatigue symptoms (Melanson 2010). Fatigue is one of the main factors influencing cognitive performance tests (Andreasen 2010 and Bol 2010). In order to have a more homogenous group, we decided to include in this study only patients with one interferon therapy (Betaferon®).

We hypothesize that annual CCI decrease is higher in CIS and RRMS patients with cognitive impairment. Second we assume that CIS patients, who display low CCI at diagnosis and/or high annual CCI decrease in follow up, are more likely to develop early on clinically definite MS (CDMS). We assume that patients with higher duration of interferon-beta 1b treatment in relation to disease duration (duration of treatment/duration of disease) will have less cognitive impairment and less annual CCI decrease.