Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

Abstract

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. 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*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 “MS subtypes” 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.

[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model

“…These results indicated that [ 11 C] DAC-PET could be used to noninvasively diagnose neuroinflammation and to monitor therapeutic effectiveness in EAE. The diagnostic criteria of MS have evolved from being solely clinical symptom-based to integrating evoked potentials, spinal fluid analysis and magnetic resonance imaging assessments (Fox and Cohen 2001;Kalkers et al 2002); however, MS is still very difficult to diagnose and evaluate because of its profound heterogeneity in pathomorphology, clinical course and therapeutic response (McFarland and Martin 2007;Disanto et al 2010). Abundant evidence strongly supports that neuroinflammation lesions occur early during the disease course and that they are prominent from the onset of MS (McFarland and Martin 2007;Glass et al 2010).…”

“…The lesions at early phase are characterized by the presence of infiltrated inflammatory cells around venules and small veins. MS remains difficult to diagnose because of its profound heterogeneity in pathomorphology, clinical course and therapeutic response (Martin et al 2001;Disanto et al 2010). Trials have shown that an early diagnosis can make a marked difference to the efficacy of MS drug treatments (Hartung 2005;Heesen et al 2010).…”

High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis

“…The pathogenesis of multiple sclerosis (MS) involves inflammatory demyelination, thought to involve the activation of autoreactive T cells that in turn activate microglia and recruit macrophages, which cause demyelination and subsequent neurological damage (Disanto et al, 2010;Nylander and Hafler, 2012). In addition, meningeal ectopic B cell follicles and plasmablasts in the CSF have been reported; these cells are also likely to contribute to the pathology of MS (Aloisi et al, 2010;Meinl et al, 2006).…”

Emerging oral immunomodulating agents – focus on teriflunomide for the treatment of multiple sclerosis

“…10 In SPMS, relapses are not followed by periods of full neurological recovery and deficits accumulate as the MS progresses. 11 The accumulated deficits must persist for 6 or more months to meet the criteria for SPMS. 12 The remaining estimated 15% of CDMS patients experience a primary progressive clinical course.…”