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Multiple sclerosis (MS) is a genetically complex disease caused by the interplay of genetic and environmental factors. While it shows substantial familial accumulation, there is no evidence for typical Mendelian transmission within families. Instead, MS risk is likely governed by dozens to hundreds of genetic variants, which can also be present in the general population. The strongest genetic risk factor for MS was identified 40 years ago and lies within the HLA locus. It increases the risk of developing MS by two- to threefold. Within the last few years, genome-wide association studies (GWAS) have led to the identification of nearly 60 additional genetic risk loci. Each of these loci yields a modest to moderate risk increase (odds ratios of 1.1-1.3). Even in combination, however, the currently known risk variants merely account for a small fraction of the disease's heritability. It is likely that a major fraction of genetic MS risk that cannot be explained by GWAS, sometimes termed the 'dark matter' of GWAS, is caused by other factors, such as structural variations of the genome, rare sequence variants, or inherited epigenetic modifications. [ABSTRACT FROM AUTHOR]

Atrophy, the wasting or shrinkage of tissue, of the nervous system is the main feature of neurodegeneration, i.e. the umbrella term for the progressive loss of structure or function of neurons. Loss of neurons due to cell death and axonal degeneration characterize neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease or amyotrophic lateral sclerosis. In these illnesses, it still has to be elucidated to which extent inflammation is part of the pathology. Conversely, in chronic inflammation of the central nervous system (CNS), atrophy has previously also been described and neurodegeneration is discussed as a pathologic feature. The most frequent chronic inflammatory disease of the CNS is multiple sclerosis (MS), which leads to devastating relapsing-remitting symptoms and disability during the relapses, increasingly during the course of disease in patients. Meanwhile it became clear that axons already reveal pathology early in the disease and neurons are affected in the cortex and the spinal cord, albeit to a different extent. The broadening of understanding neurodegenerative aspects of MS pathology demands and creates new therapeutic strategies. Current medication used in MS treatment as well as medications about to be approved are primarily anti-inflammatory therapies. By modulating the immune system and thereby blocking key steps of the pathology, the immunomodulation therapies in MS have a slight impact on disability progression. There is, however, clinical and experimental data concerning the potential neuroprotective properties of novel therapies. Combining anti-inflammatory and direct neuroprotective or even neuroregenerative therapy strategies would be a step forward in the treatment of multiple sclerosis. [ABSTRACT FROM AUTHOR]

JC virus (JCV)-associated progressive multifocal leukoencephalopathy (PML) represents a rare but serious side effect of natalizumab (Tysabri®) in the treatment of patients with relapsing forms of multiple sclerosis (MS). Two factors that may increase the risk of PML have been identified: treatment duration beyond 24 months and prior immunosuppressive therapy. Recently determination of anti-JCV antibodies mirroring JCV infection has allowed a third factor to be added to this list, and a positive serological test has been included as a risk factor on the label of natalizumab. Clearly, JCV serology represents a tool for PML risk stratification in MS patients treated with natalizumab. However, current data as well as the experimental development of the underlying assay have not been validated by an independent laboratory. The present article discusses possibilities and challenges of this assay and, based on our present knowledge, provides recommendations for the clinical implementation in daily practice. [ABSTRACT FROM AUTHOR]

In 2010, the second revision of the McDonald criteria for diagnosis of multiple sclerosis was proposed. Based on new evidence, the imaging criteria for demonstration of dissemination of central nervous system lesions in space and time have been simplified, which will allow broader application in a more uniform manner. In some circumstances, dissemination in space and time can be demonstrated in a single scan. The revision simplifies the criteria and allows accelerated diagnostic procedures while preserving their sensitivity and specificity. Additionally, the applicability across populations and in children is addressed. [ABSTRACT FROM AUTHOR]