Diffusion tensor imaging findings in the multiple sclerosis patients and their relationships to various aspects of disability.

BACKGROUND: The aim of the study was to assess microstructural changes within strategic brain regions in multiple sclerosis (MS) patients, using diffusion tensor imaging (DTI), with regard to various aspects of disability. MATERIAL AND METHODS: The study comprised 50 patients with relapsing-remitting MS (37 women, 13 men, mean age 36.4 yrs) and 27 age- and sex-matched controls. Using DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained within corpus callosum (CC), both thalami (TH) and middle cerebellar peduncles (MCP). Disability was assessed using Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC), Symbol Digit Modalities Test (SDMT) and Fatigue Severity Scale (FSS). DTI indices were compared between the patients and controls and in the MS group - referred to disability measures. RESULTS: Significant decrease in FA and increase in ADC within CC and both TH were found in MS patients compared to the controls. DTI indices within CC and TH correlated significantly with SDMT score, and within TH and MCP - with MSFC manual dexterity measure. CONCLUSIONS: Changes in DTI measures in normal appearing white and grey matter in the MS patients indicate subtle alterations of the tissue integrity. An occult damage to the strategic brain regions may contribute to various aspects of disability due to MS.

ALCAM and CD6--multiple sclerosis risk factors.

ALCAM and CD6 may play an important role in the pathogenesis of multiple sclerosis (MS), since they are involved in the transmigration of leukocytes across the blood-brain barrier. In this study, we confirmed our previous findings about the association of the ALCAM gene with risk, development and progression of MS. Additionally, we showed that in the case of the CD6 gene (encoding receptor of ALCAM) not only polymorphisms but also mRNA expression level are associated with MS. Our analysis revealed that the risk of the disease for AA individuals in rs12360861 was almost 3.0-fold lower in comparison to GG individuals (OR=0.34; CI95%=0.12; 0.81). Moreover, we observed lower expression of CD6 mRNA in patients than in healthy individuals (T(2)2,74=6.678; p=0.002).

Investigation of gene-gene interactions between CD40 and CD40L in Polish multiple sclerosis patients.

CD40-CD40L interaction is necessary for the activation of both humoral and cellular immune response and has been suggested to play a role in the pathogenesis of multiple sclerosis (MS). Therefore, we analyzed the combined influence of the CD40 and CD40L variants on MS susceptibility and progression on well-defined Polish population. Our investigation revealed that CT individuals in rs1883832 locus of CD40 possessed almost 1.5-fold higher risk for MS than CC individuals (OR = 1.44; 95%CI = 1.03-2.1; p = 0.032), while this risk for TT individuals was almost 2.5-fold higher (OR = 2.36; 95%CI = 1.19-4.78; p = 0.014). Moreover, for the first time, we observed the association of CD40 gene with MS development and progression. We observed that for the rs1883832CC individuals the age at diagnosis was on average 2 years lower than for the rs1883832CT and rs1883832TT individuals (CI95% = -3.69-(-0.29); p = 0.023). Additionally, we detected that individuals with TT and CT genotypes showed lower risk of developing secondary progressive course in comparison to those with CC genotype. For rs1883832TT individuals this risk was 4-fold lower (HR = 0.24; CI95% = 0.10-0.53; p = 0.00062). Despite the fact that CD40-CD40L pathway plays a key role in development of autoimmune diseases, we were not able to detect gene-gene interactions between CD40 and CD40L polymorphisms associated with multiple sclerosis.

In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging.

Twenty-two neuropsychiatric (NPSLE) and 13 systemic lupus erythematosus (SLE) patients with a normal appearing brain on plain magnetic resonance (MR) as well as 20 age-matched healthy controls underwent MR spectroscopy (MRS), perfusion-weighted (PWI) and diffusion-tensor imaging (DTI). In MRS NAA/Cr, Cho/Cr and mI/Cr ratios were calculated from the posterior cingulate cortex and left parietal white matter. In PWI, values of cerebral blood volume (CBV) were assessed from 14 regions, including gray and white matter. In DTI fractional anisotropy (FA) values were obtained from 14 white matter tracts including projection, commissural and association fibers. All MR measurements were correlated with clinical data. SLE and NPSLE patients showed significantly (p < 0.05) lower NAA/Cr ratios within both evaluated regions and FA values within the cingulum, as well as a tendency to cortical hypoperfusion. Compared to SLE, NPSLE subjects revealed lower FA values within a wide range of association fibers and corpus callosum. Advanced MR techniques are capable of in vivo detection of complex microstructural brain damage in SLE and NPSLE subjects regarding neuronal loss, mild hypoperfusion and white matter disintegrity. MRS and DTI seem to show the highest usefulness in depicting early changes in normal appearing gray and white matter in SLE patients.

Stimulated peripheral production of interferon-gamma is related to fatigue and depression in multiple sclerosis.

OBJECTIVES: The aim of the study was to evaluate the stimulated production of interferon-gamma (IFNγ) by peripheral CD3+CD4+ T lymphocytes in patients with multiple sclerosis (MS) with regard to the degree of fatigue, and to investigate relationships between immunological parameters, level of depression and clinical variables. METHODS: Forty MS patients (30 women, 10 men, aged 22-60 years): 20 fatigued and 20 non-fatigued were involved in the study. Fatigue was evaluated using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS), depression level - using Beck Depression Inventory (BDI). Production of IFNγ by stimulated peripheral blood CD3+CD4+ T lymphocytes, assessed using flow cytometry, was compared between MS patients with different levels of fatigue and controls. Correlations were searched out between immunological findings and BDI, age, duration and course of MS, relapse rate, disability (assessed in Expanded Disability Status Scale - EDSS) and its progression. RESULTS: Stimulated production of IFNγ by CD3+CD4+ T lymphocytes was higher in severely fatigued patients in comparison with non-fatigued ones and controls, tended to correlate with FSS and MFIS, and correlated with BDI. No relationships were found between immunological findings and disease-related variables. CONCLUSION: Stimulated production of IFNγ by peripheral CD3+CD4+ T lymphocytes is related to fatigue and depression in MS patients.

Antinuclear and antiphospholipid antibodies in patients with multiple sclerosis.

The prevalence of autoantibodies in multiple sclerosis (MS) patients and their clinical associations differ between various studies. This study investigated antiphospholipid and antinuclear antibodies in 85 patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) with regard to their association with demographic features, MS specific clinical features and symptoms of connective tissue diseases. Autoantibodies tested included antinuclear antibodies (ANA) with their specificities and anticardiolipin (aCL) and anti-beta-2-glycoprotein I (anti-ß2GPI) antibodies. Antinuclear antibodies were more prevalent in MS patients than in controls (63.5% vs. 3.3%; p < 0.01) and in 19% of patients specific antinuclear antibodies were detected. Anti-ß2GPI IgM antibodies were more frequent in MS patients than in the control group (20% vs. 3.3%; p < 0.05). The frequency of anticardiolipin antibodies did not differ between MS patients and controls. MS patients seropositive for ANA and extractable nuclear antigens (ENA) had significantly shorter disease duration than seronegative patients (p < 0.05) and a lower disability score (Expanded Disability Status Score; EDSS) (p < 0.05). Anti-ß2GPI antibodies were more frequent in patients with secondary progressive MS (SP-MS) and specific ANA antibodies were more frequent in patients with clinically isolated syndrome (CIS) (p < 0.05). The presence of autoantibodies was not associated with the predominant site of neurological involvement or the clinical features of connective tissue diseases.

Association of the HLA-G gene polymorphism with multiple sclerosis in a Polish population.

Summary In this study, three polymorphic sites in the HLA-G gene: -725C>G>T, -716T>G and 14bp(indel) were genotyped. Significant differences were found between patients and controls in the alleles and genotypes for -725C>G>T and in three-point haplotypes. We observed also a significant difference in the age of disease onset between patients positive and negative for 14bp(ins). The results suggest that single nucleotide polymorphisms in the promoter of the HLA-G gene (mainly -725C>G>T), and 14bp(indel), or some genetic marker in tight linkage disequilibrium with them are associated with multiple sclerosis.

Progression of multiple sclerosis is associated with exon 1 CTLA-4 gene polymorphism.

OBJECTIVES: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system which is widely believed to have a T-cell-mediated etiology. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) antigen molecule plays a key role in the downregulation of T-cell responses. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed an exon 1 (A49G) transition. MATERIAL AND METHODS: One hundred and fifty-two MS patients and 154 controls were examined. The A/G transition was genotyped by a polymerase chain reaction followed by labeling with a SNaPshot kit and detection using a capillary genetic analyzer. RESULTS: The genotype, allele and phenotype frequencies did not differ significantly between MS patients and controls. Those MS patients with AA and AG genotypes had 4.36 times greater risk of progressing from the relapsing-remitting to the secondary progressive form of the disease than those with the GG genotype. CONCLUSION: The results of our study indicate that CTLA-4 (A49G) exon 1 polymorphism is associated with MS progression.