Sympathetic skin response in multiple sclerosis : a meta-analysis of case-control studies

The usefulness of sympathetic skin responses (SSR) in multiple sclerosis (MS) has been advocated by several studies in the last 20\ua0years; however, due to a great heterogeneity of findings, a comprehensive meta-analysis of case-control studies is in order to pinpoint consistencies and investigate the causes of discrepancies. We searched MEDLINE, EMBASE and Cochrane databases for case-control studies comparing SSR absence frequency and latency between patients with MS and healthy controls. Thirteen eligible studies including 415 MS patients and 331 healthy controls were identified. The pooled analysis showed that SSR can be always obtained in healthy controls while 34% of patients had absent SSRs in at least one limb (95% CI 22\u201347%; p\ua0<\ua00.0001) but with considerable heterogeneity across studies (I2\ua0=\ua090.3%). Patients\u2019 age explained 22% of the overall variability and positive correlations were found with Expanded Disability Status Scale and disease duration. The pooled mean difference of SSR latency showed a significant increase in patients on both upper (193\ua0ms; 95% CI 120\u2013270\ua0ms) and lower (350\ua0ms; 95% CI 190\u2013510\ua0ms) extremities. We tested the discriminatory value of SSR latency thresholds defined as the 95% confidence interval (CI) upper bound of the healthy controls, and validated the results on a new dataset. The lower limb threshold of 1.964\ua0s produces the best results in terms of sensitivity 0.86, specificity 0.67, positive predicted value 0.75 and negative predicted value 0.80. Despite a considerable heterogeneity of findings, there is evidence that SSR is a useful tool in MS

Oxidative stress is differentially present in multiple sclerosis courses, early evident, and unrelated to treatment

BACKGROUND: Oxidative stress is well documented in multiple sclerosis (MS) lesions, but its correspondence at peripheral level is still controversial. Objective. To evaluate peripheral oxidative stress markers in MS patients. METHODS: We studied total blood levels of Coenzyme Q10 (CoQ10), oxidized and reduced forms of glutathione, malondialdehyde, reactive oxygen species (ROS), anti-oxidized-low-density lipoproteins (anti-oxLDL) antibodies, and antioxidant power (PAO) in 87 patients with different MS clinical phenotypes and in 77 controls. RESULTS: CoQ10 was lower whereas anti-oxLDL antibodies titer was higher in MS patients than in controls. The benign variant of MS displayed both higher CoQ10 and higher anti-oxLDL than other MS clinical variants. Female patients had lower CoQ10 and PAO and higher ROS than male patients. Differences were greater in younger patients with shorter disease duration. Surprisingly, there was no difference for these markers between treated and untreated patients. CONCLUSION: We found lower antioxidant agents and higher anti-oxLDL antibodies in MS, and the highest antibody titers occurred in the benign form. We suggest that natural anti-oxLDL antibodies can be protective against MS, saving blood brain barrier integrity. Our findings also suggest that milder MS is associated with a distinct oxidative stress pattern, which may provide a useful biomarker of disease prognosis

Immunological and clinical effect of diet modulation of the gut microbiome in multiple sclerosis patients: A pilot study

Pathogenesis of autoimmune disorders, including multiple sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10) or a "Western Diet" (WD group; N = 10) for at least 12 months. Gut microbiota composition, analyzed by 16 S V4 rRNA gene sequencing and immunological profiles, was examined after a minimum of 12 months of diet. Results showed that, in the HV/LP diet group compared to the WD group: (1) Lachnospiraceae family was significantly more abundant; (2) IL-17-producing T CD4+ lymphocytes (p = 0.04) and PD-1 expressing T CD4+ lymphocytes (p = 0.0004) were significantly decreased; and (3) PD-L1 expressing monocytes (p = 0.009) were significantly increased. In the HV/LP diet group, positive correlations between Lachnospiraceae and both CD14+/IL-10+ and CD14+/TGF\uce\ub2+monocytes (RSp= 0.707, p = 0.05, and RSp= 0.73, p = 0.04, respectively), as well as between Lachnospiraceae and CD4+/CD25+/FoxP3+ T lymphocytes (RSp= 0.68, p = 0.02) were observed. Evaluation of clinical parameters showed that in the HV/LP diet group alone the relapse rate during the 12 months follow-up period and the Expanded Disability Status Scale score at the end of the study period were significantly reduced. Diet modulates dysbiosis and improves clinical parameters in MS patients by increasing anti-inflammatory circuits. Because Lachnospiraceae favor Treg differentiation as well as TGF\uce\ub2 and IL-10 production this effect could be associated with an increase of these bacteria in the microbiota

The EP-score to assess treatment efficacy in RRMS patients : a preliminary study

Aim of the study: The aim of this retrospective study was to preliminarily assess whether the EP-score, a summary score derived from multimodal evoked potentials tests, might be used as a measure of treatment efficacy in multiple sclerosis (MS). Materials and methods: A sample of 56 relapsing remitting MS (RRMS) patients who at diagnosis started treatment with interferon \u3b2 (INF\u3b2, n = 19), glatiramer acetate (GA, n = 15) or refused any chronic treatment were assessed at baseline (before treatment) and at a median of 1.7 and 3.6 years thereafter. Outcome variables were Expanded Disability Status Scale (EDSS), EP-Score, visual evoked potentials (VEP) and somatosensory evoked potentials (SEP) scores measured as differences between baseline and follow-ups. Statistical differences between groups and follow-ups were assessed using non-parametric analyses. Results: Treatment effects were not significant for EDSS both at the first and at the second follow-up, while a trend toward significance was observed in the EP-score only in the first follow-up (p = 0.07). Post-hoc analysis showed a greater decrease in median VEP-score for the IFN\u3b2 group compared to the GA and DF groups at both the first and second follow-ups. Conclusions: We found no evidence that either INF\u3b2 or GA significantly improved disability in RRMS patients. Using the EP-score as an outcome measure, we found that it was improved at both follow-ups in the INF\u3b2 group mainly due to a decrease in the VEP-score. This finding supports the proposal to include the EP-score as an additional outcome variable in future studies of treatment efficacy in MS

Sensory evoked potentials to predict short-term progression of disability in multiple sclerosis

To devise a multivariate parametric model for short-term prediction of disability using the Expanded Disability Status Scale (EDSS) and multimodal sensory EP (mEP). A total of 221 multiple sclerosis (MS) patients who underwent repeated mEP and EDSS assessments at variable time intervals over a 20-year period were retrospectively analyzed. Published criteria were used to compute a cumulative score (mEPS) of abnormalities for each of 908 individual tests. Data of a statistically balanced sample of 58 patients were fed to a parametrical regression analysis using time-lagged EDSS and mEPS along with other clinical variables to estimate future EDSS scores at 1 year. Whole sample cross-sectional mEPS were moderately correlated with EDSS, whereas longitudinal mEPS were not. Using the regression model, lagged mEPS and lagged EDSS along with clinical variables provided better future EDSS estimates. The R2 measure of fit was significant and 72% of EDSS estimates showed an error value of ±0.5. A parametrical regression model combining EDSS and mEPS accurately predicts short-term disability in MS patients and could be used to optimize decisions concerning treatment.</p

DEVELOPMENTS OF COLLABORATIVE RESEARCH ON VR APPLICATIONS FOR MENTAL HEALTH. FOCUS ON CYBERSICKNESS AND MEMORY TESTING.

International audienceThe collaboration between our two scientificinstitutions is significant contributing to VR research intoseveral fields of clinical application. Concerning theimportant issue of side-effects, future studies will clarifywhether the encouraging results obtained in the recent past,that demonstrate few side-effects, in patients withneurological diseases can be confirmed, and whetherspecific recommendations for the use of immersive VR inselected clinical populations can be made. Recentcollaborative studies on the application of non-immersiveVR to improve clinical testing of spatial memory providedevidence of good replicability of results in both healthy andneurologically affected groups. The development ofretraining applications for spatial memory impairments andfuture studies aimed at assessing the impact of ambulatorydisability on spatial cognitive abilities will be based onthese findings. Finally, a newly approved transnationalproject will lead our groups into the field of the assistivetechnology to improve working skills and opportunities foremployment of people with mental disabilities who seekemployment