Multiple Sclerosis Patients In Relation Research Articles

Disability status among multiple sclerosis patients in relation to clinical features and switched drugs

Disability status among multiple sclerosis patients in relation to clinical features and switched drugs

Oral Colonization by Candida Species in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease that affects the central nervous system. Since immune system plays a key role in this disease, patients with MS can present higher risk of infections. This study aimed to investigate the prevalence of Candida spp. in the oral cavity of MS patients in relation to a control group METHODS: In total, 100 individuals were selected: 55 diagnosed with MS and 45 healthy individuals (control group). Saliva samples were collected and seeded in culture media selecting for Candida. Following an incubation period of 48h, colony-forming units (CFU mL-1) were counted and colonies were isolated for Candida species identification by multiplex PCR. The results were analysed by chi-squared and Mann-Whitney U statistical tests considering a significance level of 5%. Candida spp. were confirmed in the oral cavity of 50.09% patients in the MS group and 35.55% individuals in the control group. In individuals positive for the growth of Candida spp., the median values of Candida colonies were 220CFUmL-1 for the MS group and 120CFUmL-1 for the control group. However, no statistically significant differences were observed between groups for both prevalence and CFU mL-1 count. Of the Candida species identified, 73.91% were C. albicans, 21.73% C. glabrata, 2.17% C. tropicalis, and 2.17% C. krusei. The colonization of Candida spp. in the oral cavity of individuals with multiple sclerosis was higher than in the control group; however these findings were not proven to be statistically significant.

Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking

Background: Despite compelling evidence that cigarette smoking impacts the risk of developing multiple sclerosis (MS), little is known about smoking-associated changes in the primary exposed lung cells of patients. Objectives: We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HCs). Methods: We profiled DNA methylation in BAL cells from female MS (n = 17) and HC (n = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers. Results: The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle (not reaching adjusted P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. Conclusions: Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.

Bladder and urodynamic changes in multiple sclerosis

BackgroundUrinary dysfunction is a common symptom during the course of multiple sclerosis (MS). Long-term follow-up of the natural history of bladder dysfunction in MS has been seldom addressed.ObjectiveTo identify the type and the course of voiding dysfunction in MS patients in relation to the urodynamic changes of the lower urinary tract (LUT)Subjects and methodsAn observational prospective study including 120 MS patients with urinary dysfunction rated by the American Urological Association (AUA) symptoms questionnaire and assessed by urodynamic studies and followed for 1 year.ResultsIrritative symptoms were the most frequently encountered symptoms (90%), whereas overactive bladder was recorded by urodynamic studies in 35% of subjects. Urinary symptoms severity score was higher in patients with initial urodynamic abnormalities by the end of the 1-year follow-up period (P < 0.001). A statistically significant relationship was found between urinary symptoms severity score and each of expanded disability status scale (EDSS) and urodynamic pattern of abnormalities (P < 0.01).ConclusionIrritative symptoms and overactive bladder seem to be the most frequent urinary dysfunction in MS patients. Urinary symptoms are related to the degree of disability. The initial urodynamic abnormalities are associated with worse urinary dysfunction outcome after 1 year.

Early Cognitive Impairment in Multiple Sclerosis Patients In Relation To Brain Atrophy, Egyptian Sample

Abstract Background Approximately half of all patients with multiple sclerosis (MS) experience cognitive impairment, most commonly with regard to new learning and memory. Cognitive dysfunction is a leading cause of disability in MS and it can have profound social and economic consequences for patients and their families. Objective This study was conducted to discover the early cognitive domains affected in multiple sclerosis patients concomitant with the postulated brain atrophy in an Egyptian sample of multiple sclerosis patients. Patients and Methods A cross-sectional observational case-control study conducted on seventy (60) patients who came for follow-up in Ain Shams University hospitals. 40 patients were taken as cases that followed up in MS unit in Ain-Shams university hospitals. 20 participants were taken as controls taken from the general medicine clinics age and sex matched to our patient group. An informed written consent was taken from parents of each person included in the study. Results There was a statistically significant difference between the two groups in brain volumetric changes and in the parameters of cognitive assessment Conclusion Early detection and examination of cognitive functions is important for patient evaluation, follow up and treatment regimen used.

Hospitalization following influenza infection and pandemic vaccination in multiple sclerosis patients: a nationwide population-based registry study from Norway.

Patients with multiple sclerosis (MS) are at increased risk of infections and related worsening of neurological function. Influenza infection has been associated with increased risk of various neurological complications. We conducted a population-based registry study to investigate the risk of acute hospitalization of MS patients in relation to influenza infection or pandemic vaccination in Norway. The entire Norwegian population in the years 2008–2014 was defined as our study population (N = 5,219,296). Information on MS diagnosis, influenza infection and vaccination were provided by Norwegian national registries. The self-controlled case series method was used to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CI) in defined risk periods. 6755 MS patients were identified during the study period. Average age at first registration of an MS diagnosis was 51.8 years among men and 49.9 years among females (66.9%). The IRR for emergency hospitalization among MS patients the first week after an influenza diagnosis was 3.4 (95% CI 2.4–4.8). The IRR was 5.6 (95% CI 2.7–11.3) after pandemic influenza, and 4.8 (95% CI 3.1–7.4) after seasonal influenza. Pandemic vaccination did not influence risk of hospitalization [IRR within the first week: 0.7 (95% CI 0.5–1.0)]. Among MS patients, influenza infection was associated with increased risk for acute hospitalization while no increased risk was observed after pandemic vaccination. Influenza vaccination could prevent worsening of MS-related symptoms as well as risk of hospitalization.

TNFRSF13C/BAFFR P21R and H159Y polymorphisms in multiple sclerosis

Recent studies implicate B cells in multiple sclerosis (MS) pathogenesis, and consequently, several molecules participating in B cell survival and proliferation, including B-cell activating factor (BAFF), have recently been analyzed in MS patients. BAFF mediates its function through binding to three receptors; among them, its interaction with the BAFF receptor (BAFFR) is crucial in mediating its survival function. Interestingly, two common polymorphisms of the TNFRSF13C gene, encoding BAFFR, P21R (rs77874543) and H159Y (rs61756766), have been reported to affect BAFFR assembly and signaling. In order to evaluate the possible contribution of BAFFR in MS pathogenesis and/or phenotype, we analyzed both TNFRSF13C/BAFFR polymorphisms in 486 MS patients in relation to their disease severity, their disability status and the age of disease onset and duration. As control group, we used allele frequencies extracted from the Exome Aggregation Consortium (ExAC) Browser. Interestingly, we found a higher prevalence of the H159Y polymorphism in MS patients, suggesting that enhanced BAFFR-signaling might contribute to the disease pathogenesis.

Cognitive function is a major determinant of income among multiple sclerosis patients in Sweden acting independently from physical disability

Background: In multiple sclerosis (MS), various aspects of cognitive function can be detrimentally affected, thus patients’ employment and social functioning is commonly impacted. Objective: To analyse income among MS patients in relation to cognitive function, assessed with the Symbol Digit Modalities Test (SDMT). Methods: A cross-sectional study including 2080 MS patients was conducted linking national register-based data. Descriptive statistics and a two-part model were used to estimate differences in earnings and social benefits. Results: MS patients in the highest SDMT score quartile earned more than twice annually compared to patients in the lowest quartile, whereas patients in the lowest quartile received three times more income through social benefits. The difference in earnings and benefits across the SDMT performance quartiles remained statistically significant after adjusting for various clinical and socio-demographic variables, including physical disability. The corrected prevalence ratios for MS patients in the highest quartile for having income from earnings and benefits were 1.40 (95% confidence interval (CI): 1.29–1.49) and 0.81 (95% CI: 0.71–0.90), respectively, when compared to the patients in the lowest quartile. Conclusion: Cognitive function affects the financial situation of MS patients negatively and independently of physical disability. This warrants cognitive testing as a routine measure in health care services for MS patients.

Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis

BackgroundAxonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination.MethodsWallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (WldS) mutant mice.ResultsThe highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in WldS mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration did not result in a net rescue of axons in late lesion stages of experimental autoimmune encephalomyelitis.ConclusionsOur data indicate that in multiple sclerosis, ongoing demyelination in focal lesions is associated with axonal degeneration in the perilesional white matter, supporting a role for focal pathology in diffuse white matter damage. Also, our results suggest that interfering with Wallerian degeneration in inflammatory demyelination does not suffice to prevent acute axonal damage and finally axonal loss.

Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients

Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist. Seasonal variations of 25-(OH)-D serum concentrations were modelled by sinusoidal regression and seasonal variability in the prevalence of relapse by cubic regression. The mean 25-(OH)-D serum concentration was 24.8ng/ml (range 8.3–140ng/ml) with peak levels of 32.2ng/ml in July/August and nadir in January/February (17.2ng/ml). The lowest modelled prevalence of relapse was in September/October (28%) and the highest modelled prevalence in March/April (47%). The nadir of 25-(OH)-D serum concentrations preceded the peak in prevalence of relapses by two months. In summary, seasonal variation of 25-(OH)-D serum levels were inversely associated with clinical disease activity in MS patients. Future studies should investigate whether vitamin D supplementation in MS patients may decrease the seasonal risk for MS relapses.

Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients

The presence of cerebrospinal fluid oligoclonal bands (CSF-OCB) in Caucasian patients with multiple sclerosis (MS) is supportive of diagnosis, though the relation with patients' clinical and specifically cognitive features has never been established or thoroughly examined. Thus, we investigated the clinical and for the first time the cognitive profile of MS patients in relation to CSF-OCB. We studied 108 patients with and without OCB and recorded demographic characteristics and detailed clinical data. A comprehensive neuropsychological battery covering different cognitive domains (attention/processing speed, memory, perception/constructions, reasoning, executive functions) was administered to MS patients and 142 demographically related healthy controls (HC). We did not find any significant differences between patients with and without OCB on demographic and clinical parameters (p>0.05), including subtype and brain neuroimaging findings. Results revealed significantly higher cognitive scores in HC compared to both OCB subgroups, with more widespread cognitive changes in patients with OCB. Analysis between OCB subgroups showed significantly worse performance in patients with OCB on visual memory (Rey's complex figure test-recall; p=0.006). Concluding, the presence of CSF-OCB in our MS patients tends to be related to more widespread cognitive changes, specifically worse visual memory. Future longitudinal studies in different populations are warranted to better clarify the clinical and cognitive characteristics related to CSF-OCB which could serve as early biomarker in disease monitoring.

Increased thyroid autoimmunity among women with multiple sclerosis in the postpartum setting

Background: Multiple sclerosis (MS) patients are predisposed to thyroid abnormalities, but the risk for pregnancy-related thyroid pathology among MS patients has not been evaluated. Objectives: The objectives of this research are to prospectively evaluate the prevalence of thyroid autoimmunity among MS patients in relation to pregnancy, and to investigate its impact on pregnancy outcome, postpartum depression and fatigue. Methods: Forty-six pregnant MS patients underwent repeat testing for serum thyroid antibodies (Abs), clinical evaluation and thyroid hormone measurement. Results were compared to 35 age-matched healthy mothers. Results: At six months postpartum 35.3% of MS patients presented elevated levels of thyroid Abs compared to 5.7% of controls, p = 0.01. Mean thyroid Ab concentrations among MS patients were significantly reduced during pregnancy and returned to maximal levels at six months postpartum. The proportion of individuals with postpartum thyroid dysfunction did not differ significantly between MS patients and healthy controls (3.4% vs 2.9%, p = 1.00). Elevated thyroid Ab levels did not increase the risk for adverse pregnancy outcome, fatigue or postpartum depression. Conclusions: Considering the tendency of MS mothers to develop thyroid autoimmunity postpartum and in association to treatments, we recommend screening MS patients for thyroid dysfunction (TSH) during early pregnancy and after delivery.

Selective Upregulation of Scavenger Receptors in and Around Demyelinating Areas in Multiple Sclerosis

Autoantibodies and complement opsonization have been implicated in the process of demyelination in the major human CNS demyelinating disease multiple sclerosis (MS), but scavenger receptors (SRs) may also play pathogenetic roles. We characterized SR mRNA and protein expression in postmortem brain tissue from 13 MS patients in relation to active demyelination. CD68, chemokine (C-X-C motif) ligand 16 (CXCL16), class A macrophage SR (SR-AI/II), LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1), FcγRIII, and LRP-1 (low-density lipoprotein receptor-related protein 1) mRNA were upregulated in the rims of chronic active MS lesions. CD68 and CXCL16 mRNA were also upregulated around chronic active MS lesions. By immunohistochemistry, CD68, CXCL16, and SR-AI/II were expressed by foamy macrophages in the rim and by ramified microglia around chronic active MS lesions. CXCL16 and SR-AI/II were also expressed by astrocytes in MS lesions and by primary human microglia and astrocytes in vitro. These data suggest that SRs are involved in myelin uptake in MS, and that upregulation of CD68, CXCL16, and SR-AI/II is one of the initial events in microglia as they initiate myelin phagocytosis. As demyelination continues, additional upregulation of LOX-1, FcγRIII, and LRP-1 may facilitate this process.

Functional role of ipsilateral motor areas in multiple sclerosis

BackgroundIn patients with multiple sclerosis (MS), motor tasks are associated with increased activation of ipsilateral motor cortical areas. The authors examined the role of two ipsilateral motor areas during performance...

CSF hypocretin-1 concentrations correlate with the level of fatigue in multiple sclerosis patients

Considering the multiplicity of symptoms associated with multiple sclerosis (MS), there is possibility that hypocretin system function might be involved in the pathogenesis of the disease. The current study aimed to investigate the hypocretin-1 levels in cerebrospinal fluid (CSF) of MS patients in relation to different neurological deficit measures including: Ambulation Index (AI), Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS) in relapse-onset MS patients. 53 subjects were included into the study: 38 patients with a diagnosis of MS and 15 healthy controls. Among MS patients, 25 had relapsing-remitting and 13 secondary progressive MS. CSF hypocretin-1 levels did not differ between MS patients and healthy controls ( p > 0.05). A positive correlation between hypocretin-1 level and fatigue level was found in MS patients ( p < 0.05) and this effect was even stronger in the MS subgroup suffering from fatigue ( p = 0.01). Hypocretin system seems to be generally unchanged in MS but a positive correlation between hypocretin-1 level and fatigue may indicate involvement of some compensatory mechanisms stimulating the production of the neuropeptide in MS patients.

Analysis of viral and genetic factors in South African patients with multiple sclerosis

A significant association was previously demonstrated between multiple sclerosis (MS) and the functional 5'-(GT)n polymorphism in the promoter region of the SLC11A1 gene, which has been implicated in both autoimmune and infectious disease susceptibility. In the present study the role of viral infection was investigated in South African MS patients in relation to specific SLC11A1 genotypes. Serum and peripheral blood mononuclear cells (PBMC) of 49 MS patients, 33 close relatives and 39 unrelated controls previously genotyped for SLC11A1 were screened for the presence of MS-associated retrovirus (MSRV) and two herpes virus (HHV-6 and EBV) sequences. Expression of the pol gene of MSRV was detected in the serum RNA of 34/49 (69%) MS patients whilst absent in the serum of 39 unrelated healthy control individuals (p < 0.001) but was also present in 23/33 (70%) of the unaffected close relatives of the patients. HHV-6 and EBV sequences were detected in both MS patients and control individuals. The viral sequences were not confined to a specific SLC11A1 genotype. Infection with these viruses is excluded as the primary cause for MS in the South African population since no significant differences were detected between MS patients and their unaffected close family members.

Sexual dysfunction in male multiple sclerosis patients in relation to clinical findings

Seventy‐seven consecutive male patients with clinically definite or laboratory supported definite multiple sclerosis were submitted to a questionnaire and a clinical interview in order to assess the frequency, the nature of sexual dysfunction and its relationship with clinical findings. Twenty‐six patients (35%) complained of erectile dysfunction: the defect was partial and inconstant in 11 patients (14%), complete and fixed in 15 (21%). Six patients complained of premature ejaculation, in three of whom the symptom was already present before the onset of the disease. Taking the series as a whole, sexual life was poor or not satisfying at all in 34 patients. Erectile dysfunction was associated with the presence and severity of bladder dysfunction and with disability. The relationship with sensory impairment of legs was slight, no relationship was found with motor involvement of legs, type of course, age and disease duration.