Retinal nerve fiber layer thickness in subgroups of multiple sclerosis, measured by optical coherence tomography and scanning laser polarimetry

Optical coherence tomography (OCT) and scanning laser polarimetry (GDx ECC) are non-invasive methods used to assess retinal nerve fiber layer (RNFL) thickness, which may be a reliable tool used to monitor axonal loss in multiple sclerosis (MS). The objectives of this study are (1) to compare OCT with the GDx ECC; (2) to assess and compare the RNFL thickness in subgroups of MS. Ophthalmologic examination and RNFL assessment by OCT and GDx were performed in 65 MS patients (26 relapsing-remitting (RRMS), ten secondary-progressive (SPMS), 29 primary-progressive (PPMS)). Twenty-eight patients (43%) had a history of optic neuritis (ON). Adjustments were made for age and disease duration. RNFL thickness was reduced in eyes with previous ON (p < 0.01). No differences were found between PPMS and relapse-onset MS. OCT and GDx ECC measurements were moderately correlated (rho = 0.73, p < 0.01). Visual field-mean deviation (MD) values correlated with OCT means (r = 0.44, p < 0.01) and GDx ECC TSNIT average (r = 0.41, p < 0.01). In patients without previous ON, EDSS correlated with MD (r = -0.36, p < 0.01), visual field-pattern standard deviation (PSD) (r = 0.30, p < 0.05), OCT means (r = -0.31-0.30, p < 0.05) and macular volume (r = -0.37, p < 0.01). For MSIS-29 physical impact score, significant correlations were found with MD (r = -0.48, p < 0.01) and PSD (r = 0.48, p < 0.01). Conclusions: No differences between PPMS and relapse-onset MS subgroups were found. RNFL thickness was reduced in eyes with previous ON. Although OCT and GDx ECC findings were moderately correlated and showed significant correlations with measures of visual function in patients without previous ON, EDSS correlated significantly with visual and OCT measures, but not with GDx ECC

MODISTools - downloading and processing MODIS remotely sensed data in R

Remotely sensed data – available at medium to high resolution across global spatial and temporal scales – are a valuable resource for ecologists. In particular, products from NASA's MODerate-resolution Imaging Spectroradiometer (MODIS), providing twice-daily global coverage, have been widely used for ecological applications. We present MODISTools, an R package designed to improve the accessing, downloading, and processing of remotely sensed MODIS data. MODISTools automates the process of data downloading and processing from any number of locations, time periods, and MODIS products. This automation reduces the risk of human error, and the researcher effort required compared to manual per-location downloads. The package will be particularly useful for ecological studies that include multiple sites, such as meta-analyses, observation networks, and globally distributed experiments. We give examples of the simple, reproducible workflow that MODISTools provides and of the checks that are carried out in the process. The end product is in a format that is amenable to statistical modeling. We analyzed the relationship between species richness across multiple higher taxa observed at 526 sites in temperate forests and vegetation indices, measures of aboveground net primary productivity. We downloaded MODIS derived vegetation index time series for each location where the species richness had been sampled, and summarized the data into three measures: maximum time-series value, temporal mean, and temporal variability. On average, species richness covaried positively with our vegetation index measures. Different higher taxa show different positive relationships with vegetation indices. Models had high R2 values, suggesting higher taxon identity and a gradient of vegetation index together explain most of the variation in species richness in our data. MODISTools can be used on Windows, Mac, and Linux platforms, and is available from CRAN and GitHub (https://github.com/seantuck12/MODISTools)

Vitamin A is not associated with exacerbations in multiple sclerosis

Background Vitamin A is a multifunctional vitamin that can inhibit the formation of Th17 cells, which are probably involved in the development of relapses in MS. Furthermore, it promotes Treg formation. Therefore, vitamin A can be hypothesized to be lower in patients than in healthy controls, and to decrease relapse risk in relapsing-remitting MS (RRMS) patients. Objective To compare vitamin A levels in MS patients and controls, and to investigate whether vitamin A levels are associated with relapse risk. Methods In a case-control study all-trans-retinol levels were compared between 31 RRMS patients and 29 matched controls. In a prospective longitudinal study in 73 RRMS patients, serum samples for all-trans-retinol measurements were taken every eight weeks. Associations between all-trans-retinol concentrations and relapse rates were calculated using Poisson regression with the individual serum levels as time-dependent variable. Associations between vitamin A and vitamin D were calculated. Results Mean vitamin A levels were lower in patients (2.16 μmol/l) than in controls (2.44 μmol/l) but with borderline significance (p=0.05). In the longitudinal study, during follow-up (mean 1.7 years), 58 patients experienced a total of 139 relapses. Monthly moving averages of all-trans retinol levels were categorized into tertiles: a low (3.7 μmol/l). Relapse rates were not associated with serum all-trans retinol levels (p>0.2), in univariate nor in multivariate analysis. Serum concentrations of all-trans-retinol and 25-OH-vitamin D were positively correlated, although this correlation was weak (r=0.15). Conclusion We did not find evidence for a role for vitamin A in the disease course of RRMS. We did find an association between vitamin A and D levels in the RRMS patients, possibly explained by dietary products that contain both fat-soluble vitamins

Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation

BACKGROUND: Alkaline phosphatase (AP) is a ubiquitously expressed enzyme which can neutralize endotoxin as well as adenosine triphosphate (ATP), an endogenous danger signal released during brain injury. In this study we assessed a potential therapeutic role for AP in inhibiting neuroinflammation using three complementary approaches. METHODS: Mice were immunized to induce experimental autoimmune encephalomyelitis (EAE) and treated with AP for seven days during different phases of disease. In addition, serological assays to determine AP activity, endotoxin levels and endotoxin-reactive antibodies were performed in a cohort of multiple sclerosis (MS) patients and controls. Finally, the expression of AP and related enzymes CD39 and CD73 was investigated in brain tissue from MS patients and control subjects. RESULTS: AP administration during the priming phase, but not during later stages, of EAE significantly reduced neurological signs. This was accompanied by reduced proliferation of splenocytes to the immunogen, myelin oligodendrocyte glycoprotein peptide. In MS patients, AP activity and isoenzyme distribution were similar to controls. Although endotoxin-reactive IgM was reduced in primary-progressive MS patients, plasma endotoxin levels were not different between groups. Finally, unlike AP and CD73, CD39 was highly upregulated on microglia in white matter lesions of patients with MS. CONCLUSIONS: Our findings demonstrate that: 1) pre-symptomatic AP treatment reduces neurological signs of EAE; 2) MS patients do not have altered circulating levels of AP or endotoxin; and 3) the expression of the AP-like enzyme CD39 is increased on microglia in white matter lesions of MS patients

Serum levels of soluble forms of T cell activation antigens CD27 and CD25 in systemic lupus erythematosus in relation with lymphocytes count and disease course

Systemic lupus erythematosus (SLE) patients are characterized by a low lymphocyte count, which is considered a specific disease marker and is related to disease activity. The membrane bound molecules CD25 and CD27 are expressed and released in a soluble CD25 (sCD25) and soluble CD27 (sCD27) form by activation of predominantly T cells. In previous studies it was claimed that sCD25 as well sCD27 might be used as parameters for activation of the immune system; a correlation between the sCD25 profile with the disease course in SLE patients was also shown. To assess the relationship between lymphocyte count and these T cell activation markers, we performed a cross-sectional and a longitudinal study. In the longitudinal study three SLE patients who were known for a long time at our outpatient clinic were studied. Both T cell markers strongly correlated with each other and formed a reflection of the disease course. In all 7 periods of exacerbation, which we observed in the 3 investigated patients, both levels increased preceding this period; however, no correlation was found with the lymphocyte count. In the cross sectional study of 69 patients with SLE, sCD25 and sCD27 levels were correlated with defined disease manifestations; sCD25 was elevated in all periods of increased disease activity. The same holds true for sCD27, with the exception of patients with nephritis in which the highest levels were observed. Both profiles of sCD25 and sCD27 were strongly correlated during the whole disease course. Our data prove that in the pathogenesis of SLE an active recruitement of unprimed and primed T cells takes place

Burden of genetic risk variants in multiple sclerosis families in the Netherlands

Background: Approximately 20% of multiple sclerosis patients have a family history of multiple sclerosis. Studies of multiple sclerosis aggregation in families are inconclusive. Objective: To investigate the genetic burden based on currently discovered genetic variants for multiple sclerosis risk in patients from Dutch multiple sclerosis multiplex families versus sporadic multiple sclerosis cases, and to study its influence on clinical phenotype and disease prediction. Methods: Our study population consisted of 283 sporadic multiple sclerosis cases, 169 probands from multiplex families and 2028 controls. A weighted genetic risk score based on 102 non-human leukocyte antigen loci and HLA-DRB1*1501 was calculated. Results: The weighted genetic risk score based on all loci was significantly higher in familial than in sporadic cases. The HLA-DRB1*1501 contributed significantly to the difference in genetic burden between the groups. A high weighted genetic risk score was significantly associated with a low age of disease onset in all multiple sclerosis patients, but not in the familial cases separately. The genetic risk score was significantly but modestly better in discriminating familial versus sporadic multiple sclerosis from controls. Conclusion: Familial multiple sclerosis patients are more loaded with the common genetic variants than sporadic cases. The difference is mainly driven by HLA-DRB1*1501. The predictive capacity of genetic loci is poor and unlikely to be useful in clinical settings.</p