Dynamics and heterogeneity of brain damage in multiple sclerosis

by Ekaterina Kotelnikova, Narsis A. Kiani, Elena Abad, Elena H. Martinez-Lapiscina, Magi Andorra, Irati Zubizarreta, Irene Pulido-Valdeolivas, Inna Pertsovskaya, Leonidas G. Alexopoulos, Tomas Olsson, Roland Martin, Friedemann Paul, Jesper Tegn ér, Jordi Garcia-Ojalvo, Pablo Villoslada Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothes is whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less seve rely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a lon g-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an ...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research