Structural and ultrastructural alterations in human olfactory pathways and possible associations with herpesvirus 6 infection

Publisher Copyright: © 2017 Skuja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.publishersversionPeer reviewe

Gender hormones: Role in the pathogenesis of central nervous system disease and demyelination

Gender hormones are associated with the evolution of Multiple Sclerosis (MS) like changes in experimental models of MS. Several clinical studies have attempted to elucidate the role of gender hormones in the evolution of the clinical spectrum of the disease. We attempt to describe the currently known data regarding such associations emphasizing the potential clinical applications in different MS scenarios i.e. pregnancy, menstruation, use of oral contraceptives and hormonal replacement therapy. Moreover we discuss relevant effects of gender hormones on immunological parameters relating to MS pathogenesis. Beneficial neuroprotective effects were noted for elevated levels of estrogens, progesterone and elevated dosages of androgens. Some of these changes may be explained by a favorable immunological shift from a Th1 to Th2 response. Further elucidation of the clinical implications of such associations is necessary. © 2008 Bentham Science Publishers Ltd

Effect of seasonal fluctuation of ambient temperature on fatigue in multiple sclerosis patients living in Attica, Greece

Fatigue limits daily functioning of patients with multiple sclerosis (MS) and has a severe impact on their quality of life. Fatigue is considered a result of biological, psychological and environmental factors. This study investigated the effect of the ambient temperature on the levels of fatigue during each season of the year in MS patients and a healthy population. Forty-five MS patients and 42 healthy people matched for age and sex participated in the study. Measurement of fatigue was based on the Fatigue Severity Scale. Patients were asked which season they felt the worst fatigue. The measurements were conducted every 3 months in November, February, May and August on the last day of the month. MS patients (mean = 4.20, standard error [SE] = 0.22) exhibited a higher mean fatigue severity than the control group (mean = 2.68, SE = 0.22). MS patients did not present any significant differentiation in fatigue between seasons. However, the control group exhibited a tendency for fatigue severity to significantly increase in August, and actually experienced fatigue levels higher than the MS group during the last week of August. Significant fluctuation of fatigue was not observed in patients with MS. Patients may avoid worsening fatigue caused by climatic conditions with appropriate organization of their life routine. © 2013 Elsevier Ltd. All rights reserved

Rituximab and multiple sclerosis

Blymphocytes seem to have a fundamental role in multiple sclerosis, acting as sensors, coordinators, and regulators of the immune response. Furthermore, they are important in activating T cells and they can mediate tissue injury through diverse mechanisms. Such findings have important therapeutic implications in autoimmune central nervous system diseases in a fashion similar to other autoimmune processes. The best known monoclonal antibody targeting B cells that has been used as a novel therapy for various autoimmune conditions, as well as multiple sclerosis, is rituximab. This review summarizes the available data on the role of B cell in multiple sclerosis and further reports on current knowledge on the B-cell-depleting monoclonal antibody rituximab, its mechanism of action, and its efficacy on multiple sclerosis. Data presented were categorized in 3 groups based on the nature of data presented (radiological, clinical, and immunological data). Both case-control studies and case reports were included, while table classification was in chronological order. © 2012 by Lippincott Williams & Wilkins

Craniofacial and Neurological Phenotype in a Patient with De Novo 18q Microdeletion and 18p Microduplication

Introduction: Chromosome 18q deletion syndrome (18q-) is a rare chromosomal disorder with phenotypic variability, including mental deficiency, short stature, hypotonia, cleft palate, and hearing impairment. We present a case with features of 18q- syndrome who had combined 18q partial monosomy and 18p partial trisomy. Material and Methods: A 50-year-old female patient was examined during the genetic counseling of her brother. She had a history of congenital cleft palate and developmental deficiency with hypotonia, hearing loss, and epilepsy until adulthood. Her family history was free of related cases. Karyotype analysis and comparative genomic hybridization array (aCGH) were performed in patient’s blood samples. Results: Clinical examination showed features of 18q- syndrome including hypotonia and tremor. Neuropsychological deficiency of moderate cognitive disorder was noticed. The patient’s karyotype was normal. The aCGH analysis revealed 8 Mb deletion (del18q22.3q23) and 7.2 Mb duplication (dup18p11.32p11.23). Conclusion: Almost all patients’ clinical features were associated with 18q- syndrome. There are very few reported cases with similar genotype possibly caused by a de novo unequal recombination mechanism. © Springer Nature Switzerland AG 2020

TGF-β/BMPs: Crucial crossroad in neural autoimmune disorders

Transforming growth factor beta (TGF-β) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-β and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-β and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role in the pathophysiology of this disorder by using references from embryonic experimental research. Available literature in the TGF/BMP signalling cascade, mostly during embryonic development of the nervous system is being reviewed. An attempt is made to further elucidate a potential role of TGF/BMP signalling in the pathophysiology of MS. During demyelination, BMP signaling, through various molecular mechanisms, directs the development of the adult neural stem cell in the astrocyte rather than the oligodendrocyte direction, therefore inhibiting the repair process. Further understanding of the above relationships could lead to the development of potentially efficient therapies for MS in the future. © 2011 Elsevier B.V. All rights reserved

Validity and reliability of the FSS in Greek MS patients

Objectives: The study provided validity and reliability evidence of the Fatigue Severity Scale (FSS) in Greek patients with multiple sclerosis (MS). Materials and Methods: The FSS was administered to 72 MS patients, without co morbid fatigue and 75 matched paired controls with respect to gender and age. Both groups responded to the FSS, SF-36v2, BDI-II and a demographic questionnaire on two time points separated by a 1-week interval. Exploratory and confirmatory factor analysis was performed to test construct validity, concurrent and divergent validity, internal and test-retest reliability were also examined. Results: Exploratory and confirmatory factor analysis, intercorrelations with BDI-II (r = 0.552, p < 0.01) and SF-36v2 vitality (r = -0.715, p < 0.01) and physical functioning (r = -0.673, p < 0.01) subscales, and differences between patients and non patients (t(145) = 6.007, p < 0.001), revealed sufficient construct, concurrent and divergent validity evidence. The factor analysis demonstrated a unidimensional structure Cronbach alpha (0.953) and ICC (0.889) was high, indicating that the responses of our sample were internally consistent and stable across time. Conclusion: The Greek version of FSS is valid and reliable and may be used by clinicians and researchers to assess fatigue of Greek MS patients. © 2013 Bakalidou et al.; licensee Springer

Validity and reliability of the Greek version of the Modified Fatigue Impact Scale in multiple sclerosis patients

Fatigue in multiple sclerosis (MS) may be attributed to a variety of biological and psychological factors. Scales addressing the multidimensionality of fatigue are used in MS evaluation, although adequacy of data on their reliability and validity is questionable. The aim of the present study was to provide evidence for the validity and reliability of the Greek version of the Modified Fatigue Impact Scale (MFIS). The MFIS was translated into Greek and administered to 99 MS patients and 75 controls. Exploratory factor analysis was carried out and reliability measures were calculated. Discriminant validity was also assessed. The mean MFIS score was 33.8 (SD 17.8). Two factors (physical and cognitive) were extracted through factor analysis; a psychosocial factor was not identified. Reliability measures (intraclass correlation coefficient, Cronbach's α, Pearson's correlation) yielded high values. Patients and nonpatients differed statistically significantly in the MFIS scores; no statistically significant differences in MFIS score according to the type of MS were observed. It can be concluded that the Greek version of MFIS is valid and reliable, although questions about the scale dimensions remain. Further modifications and cultural adaptation of the scale may help create a useful tool for screening and assessment of fatigue in MS patients. © 2014 Wolters Kluwer Health