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One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1<jats:sup>*<\/jats:sup>15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these \u201cMS subtypes\u201d should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research.<\/jats:p>","DOI":"10.4061\/2011\/932351","type":"journal-article","created":{"date-parts":[[2010,12,9]],"date-time":"2010-12-09T12:35:45Z","timestamp":1291898145000},"page":"1-12","source":"Crossref","is-referenced-by-count":31,"title":["Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease"],"prefix":"10.4061","volume":"2011","author":[{"given":"Giulio","family":"Disanto","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK"},{"name":"Department of Clinical Neurology, University of Oxford, The West Wing, John Radcliffe Hospital, Oxford, OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio J.","family":"Berlanga","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for 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