Genetic and Biochemical Factors Related to the Risk and Disability Progression in Multiple Sclerosis

Sclerosis multiplex (multiple sclerosis, MS) is a chronic autoimmune inflammatory disease of the central nervous system. The immune regulatory defects lead to the process of inflammation and neurodegenerationthat results in the deterioration of neurological functions. It is still unclear as to why MS is so devastating and rapidly progressive in one patient and less so in another. It is known that the etiopathogenesis of MS is very complex, and many factors can be involved in the risk and character of the disease and its progression. In this chapter, we discuss the general molecular and cellular mechanisms of action of genetic and biochemical factors that are related to immune system regulation and thus can be connected to the individually varying risk and disability progression of MS. We found that gene variants of the gene polymorphism rs6897932 in interleukin 7 receptor α chain gene rs10735810 in vitamin D receptor gene and HLA-DR and HLA-DQ genes as well as the serum level of vitamin D are associated with MS risk or disability progression in Central European Slovak population

The Role of Over-Nutrition and Obesity in Multiple Sclerosis

In countries with high standard of living, lowered risk of infectious diseases is parallel to increased incidence of autoimmune diseases. One of the autoimmune disorders, multiple sclerosis, affects genetically susceptible individuals. Genetic susceptibility is supposed to interact with lifestyle and environmental factors in developing autoimmunity in MS. From this point of view, epigenetics provides the bridge between the external environment and the internal genetic system. In MS, environmental burden can modulate gene expression by epigenetic modification of chromatin components, microRNAs or by subtle changes in DNA methylation. Our paper focuses on describing the epigenetic mechanisms linking environmental factors with pathogenesis of multiple sclerosis. We summarise current knowledge about the role of over-nutrition and obesity as epigenetic factors in multiple sclerosis

The role of vaspin as a predictor of coronary angiography result in SCAD (stable coronary artery disease) patients

Abstract Background The role of vaspin in the pathogenesis of stable coronary artery disease (SCAD) have been repeatedly addressed in clinical studies. However, from the point of view of clinical practice, the results of earlier studies are still inconclusive. Methods The data of 106 SCAD patients who received coronary angiography and 85 coronary artery disease-free controls were collected and analysed. The patients were divided into subgroups according to their pre-test probability (PTP) and according to the result of coronary angiography. Fasting vaspin concentrations were compared between subgroups of SCAD patients and between target group and controls. The effect of age and smoking on the result of coronary angiography was compared to the effect of vaspin using the binomial regression. Results We did not find significant difference in vaspin level between target group and controls. Unless the pre-test probability was taken into account, we did not find vaspin difference in the target group, when dividing patients on the basis of presence/absence of significant coronary stenosis. In the subgroup of SCAD patients with PTP between 15% – 65%, those with significant coronary stenoses had higher mean vaspin concentration (0,579 ± 0,898 ng/ml) than patients without significant stenoses. (0,379 ± 0,732 ng/ml) (t = −2595; p = 0,012; d = 0,658; 1-β = 0,850). Age, smoking status and vaspin significantly contributed to the HSCS prediction in binomial regression model in patients with low PTP (OR: 1.1, 4.9, 8.7, respectively). Conclusion According to our results, vaspin cannot be used as an independent marker for the presence of CAD in general population. However, our results indicate that measuring vaspin in SCAD patients might be clinically useful in patients with PTP below 66%

Current Methods of Magnetic Resonance for Noninvasive Assessment of Molecular Aspects of Pathoetiology in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease with expanding axonal and neuronal degeneration in the central nervous system leading to motoric dysfunctions, psychical disability, and cognitive impairment during MS progression. The exact cascade of pathological processes (inflammation, demyelination, excitotoxicity, diffuse neuro-axonal degeneration, oxidative and metabolic stress, etc.) causing MS onset is still not fully understood, although several accompanying biomarkers are particularly suitable for the detection of early subclinical changes. Magnetic resonance (MR) methods are generally considered to be the most sensitive diagnostic tools. Their advantages include their noninvasive nature and their ability to image tissue in vivo. In particular, MR spectroscopy (proton 1H and phosphorus 31P MRS) is a powerful analytical tool for the detection and analysis of biomedically relevant metabolites, amino acids, and bioelements, and thus for providing information about neuro-axonal degradation, demyelination, reactive gliosis, mitochondrial and neurotransmitter failure, cellular energetic and membrane alternation, and the imbalance of magnesium homeostasis in specific tissues. Furthermore, the MR relaxometry-based detection of accumulated biogenic iron in the brain tissue is useful in disease evaluation. The early description and understanding of the developing pathological process might be critical for establishing clinically effective MS-modifying therapies

The Intricate Network of Adipokines and Stroke

Cerebrovascular disorders, particularly ischemic stroke, are one of the most common neurological disorders. High rates of overweight and obesity support an interest in the role of adipose tissue and adipose tissue releasing cytokines in inducing associated comorbidities. Adipokines can serve as a key messenger to central energy homeostasis and metabolic homeostasis. They can contribute to the crosstalk between adipose tissue and brain. However recent research has offered ambiguous data on the network of adipose tissue, adipokines, and vascular disorders. In our paper we provide a critical insight into the role of adipokines in evolution of ischemic stroke

Anaplastic astrocytoma mimicking progressive multifocal leucoencephalopathy: a case report and review of the overlapping syndromes

Abstract Background Co-occurrence of multiple sclerosis (MS) and glial tumours (GT) is uncommon although occasionally reported in medical literature. Interpreting the overlapping radiologic and clinical characteristics of glial tumours, MS lesions, and progressive multifocal leukoencephalopathy (PML) can be a significant diagnostic challenge. Case presentation We report a case of anaplastic astrocytoma mimicking PML in a 27-year-old patient with a 15-year history of MS. She was treated with interferon, natalizumab and finally fingolimod due to active MS. Follow-up MRI, blood and cerebrospinal fluid examinations, and biopsy were conducted, but only the latter was able to reveal the cause of progressive worsening of patient’s disease. Conclusions Anaplastic astrocytoma misdiagnosed as PML has not yet been described. We suppose that the astrocytoma could have evolved from a low grade glioma to anaplastic astrocytoma over time, as the tumour developed adjacent to typical MS plaques. The role of the immunomodulatory treatment as well as other immunological factors in the malignant transformation can only be hypothesised. We discuss clinical, laboratory and diagnostic aspects of a malignant GT, MS lesions and PML. The diagnosis of malignant GT must be kept in mind when an atypical lesion develops in a patient with MS