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

The study was supported by a grant of the Italian Ministry of Health, Ricerca Corrente funding program 2014–2015 [RC2014].The usefulness of sympathetic skin responses (SSR) in multiple sclerosis (MS) has been advocated by several studies in the last 20 years; 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 22-47%; p < 0.0001) but with considerable heterogeneity across studies (I2 = 90.3%). Patients' 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 ms; 95% CI 120-270 ms) and lower (350 ms; 95% CI 190-510 ms) 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 s 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.Publisher PDFPeer reviewe

Exploring the predictive value of the evoked potentials score in MS within an appropriate patient population : a hint for an early identification of benign MS?

This study was supported by the Italian Ministry of Health, Ricerca Corrente funding plan to the institutional research activity of the Scientific Institute S. Maria Nascente of the Don C. Gnocchi Foundation.Background: The prognostic value of evoked potentials (EPs) in multiple sclerosis (MS) has not been fully established. The correlations between the Expanded Disability Status Scale (EDSS) at First Neurological Evaluation (FNE) and the duration of the disease, as well as between EDSS and EPs, have influenced the outcome of most previous studies. To overcome this confounding relations, we propose to test the prognostic value of EPs within an appropriate patient population which should be based on patients with low EDSS at FNE and short disease duration. Methods: We retrospectively selected a sample of 143 early relapsing remitting MS (RRMS) patients with an EDSS < 3.5 from a larger database spanning 20 years. By means of bivariate logistic regressions, the best predictors of worsening were selected among several demographic and clinical variables. The best multivariate logistic model was statistically validated and prospectively applied to 50 patients examined during 2009-2011. Results: The Evoked Potentials score (EP score) and the Time to EDSS 2.0 (TT2) were the best predictors of worsening in our sample (Odds Ratio 1.10 and 0.82 respectively, p=0.001). Low EP score (below 15-20 points), short TT2 (lower than 3-5 years) and their interaction resulted to be the most useful for the identification of worsening patterns. Moreover, in patients with an EP score at FNE below 6 points and a TT2 greater than 3 years the probability of worsening was 10% after 4-5 years and rapidly decreased thereafter. Conclusions: In an appropriate population of early RRMS patients, the EP score at FNE is a good predictor of disability at low values as well as in combination with a rapid buildup of disability. Interestingly, an EP score at FNE under the median together with a clinical stability lasting more than 3 years turned out to be a protective pattern. This finding may contribute to an early identification of benign patients, well before the term required to diagnose Benign MS (BMS).Publisher PDFPeer reviewe

Chronic cerebro-spinal insufficiency in multiple sclerosis and meniere disease: same background, different patterns?

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by demyelinating lesions with acute phases and progressive loss of sensori-motor functions. M\ue8ni\ue9re disease (MD) is a disorder of the inner ear characterized by acute spells of vertigo and hearing loss and progressive loss of cochleo-vestibular function. Both the diseases have a multifactorial pathogenesis and quite the same chronic cerebro-spinal insufficiency (CCSVI) frequency. However, as far as Author\u2019s knowledge concerns, no patients affected with both diseases are described so far. The aim of this paper is to investigate whether MS and MD present different CCSVI patterns. Three groups of patients were enrolled: 60 definite MS - 27 definite unilateral MD (MEN) - 41 with other no-M\ue8ni\ue9re, audio-vestibular disorders (OVD). All subjects underwent magnetic resonance venography (MRV) and venous Duplex (ECD) and only patients that satisfied both MRV and ECD CCSVI diagnostic criteria were considered. J1 was normal in 57% of MS, 88% of MEN and 95% of OVD. Stenosis (ST) were detected, respectively, in 30% of MS and 2% in MEN and OVD. J2 was normal in 78% of MS, 64% of MEN and 95% of OVD. At this level alterations of the trunk (AT) were detected in 17% in MS and 26% in MEN; J3 was normal in 74% of MS, 64% of MEN and 86% of OVD. AT were found in 15% of MS, 26% of MEN and 8% of OVD. Hyperplasia of the Vertebral Veins was observed in 35% of MS, 40% of MEN and in 15% of OVD. Other compensatory collaterals were detected in 25% in MS and only in 5% in MEN and OVD. Our results indicate that the MS pattern is characterized by J1 stenosis, J2 trunk alterations, a prevalence of J1-J2 medial-distal alterations, compensatory collaterals besides vertebral venous system. MD pattern is characterized by trunk alteration in J3, a prevalence of J3-J2 medial-proximal alterations and vertebral veins hyperplasia without other detectable collaterals. Although the group of patients with venous alterations is very small, OVD patients show a CCSVI pattern that is more similar to MD than MS pattern. The difference between MS and MD patterns indicates that CCSVI is not a unique entity and it could be an explanation of the fact that subjects affected with both the diseases are not reported

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

Longitudinal associations between mindfulness and well-being in people with multiple sclerosis

Background/Objective: Depression, anxiety, fatigue, and sleep problems are typical conditions reported in people with multiple sclerosis (MS), often resulting in a reduction of their quality of life (QOL) and well-being. Mindfulness is a multifaceted and complex construct that has been increasingly explored for its correlated to well-being. Despite preliminary evidence, longitudinal data about the impact of mindfulness on QOL in MS remain limited. In addition, Langerian mindfulness, one of the prominent approaches to mindfulness, is yet unexplored in this field. The study aims to examine the longitudinal relationships between two forms of mindfulness (Langerian and contemplative) and QOL, anxiety, depression, fatigue, and sleep. Method: Within a larger randomized controlled trial of an online mindfulness-based stress reduction intervention, a cohort of 156 people with MS was recruited and assessed for both mindfulness constructs, QOL, anxiety, depression, fatigue, and sleep problems. Assessments were repeated after 2 and after another 6 months. Results: Both mindfulness constructs were highly correlated with all investigated outcomes. Both Langerian and contemplative mindfulness predicted higher QOL, lower anxiety, depression, fatigue, and sleep, over time. Conclusions: In both approaches dispositional mindfulness is a protective factor against depression, anxiety, fatigue, and sleep in people with MS

Changing lifestyle of persons with multiple sclerosis : development, feasibility and preliminary results of a novel high-impact collaborative intervention in leisure environments

Objective: Only a limited percentage of persons with MS (pwMS) participate to multidisciplinary rehabilitation (MDR) because of poor support, knowledge and motivation. We reasoned that pwMS should be more effectively prepared to increase their adherence. We implemented an innovative collaborative approach, called “brief highimpact preparatory experience” (b-HIPE), inspired by an overarching model based on the interplay between competence, motivation and opportunity to increase in a short time awareness and motivation of pwMS. Methods: B-HIPE integrates physiotherapy, mindfulness, sailing, healthy diet, and cultural activities to be experienced in a convivial form at a beautiful seaside location in Sardinia. Sixteen pwMS participated to 3 successive one-week editions of the b-HIPE, co-sponsored by the Rotary Club of Milan and supported by researchers of our Institute and of partner associations. The feasibility was assessed with structured questionnaires and free reports concerning accommodation, logistics, coordination, social climate and the specific activities proposed. For this pilot study we used a single-group design with repeated measurements at baseline and post-intervention. The SF-36 QoL scale was the main outcome measure, the Fatigue Severity Scale (FSS), the Berg Balance scale (BBS) and the 9 hole peg test (9HPT) were the secondary outcomes. Results: The approach was feasible. Scores on several FS-36 scales and secondary outcomes were significantly improved. Participants’ satisfaction with all aspects of the experience was above expectations. PwMS became more motivated and aware of physical and mental resources, all learned to sail adapted monohulls, strategies to master stress and to modify their diet according to specific recommendations. Conclusion: B-HIPE is safe and feasible. The interplay of multiple factors produced in a very short time the expected changes in participants’ attitude toward a healthier lifestyle. A monitoring program is ongoing to assess long-term effects including adherence to hospital-based MDR.Publisher PDFPeer reviewe

Influence of a high‐impact multidimensional rehabilitation program on the gut microbiota of patients with multiple sclerosis

Multiple sclerosis (MS) is a neurodegenerative inflammatory condition mediated by autoreactive immune processes. Due to its potential to influence host immunity and gut‐brain communication, the gut microbiota has been suggested to be involved in the onset and progression of MS. To date, there is no definitive cure for MS, and rehabilitation programs are of the utmost importance, especially in the later stages. However, only a few people generally participate due to poor support, knowledge, and motivation, and no information is available on gut microbiota changes. Herein we evaluated the potential of a brief high‐impact multidimensional rehabilitation program (B‐HIPE) in a leisure environment to affect the gut microbiota, mitigate MS symptoms and improve quality of life. B‐HIPE resulted in modulation of the MS‐typical dysbiosis, with reduced levels of pathobionts and the replenishment of beneficial short‐chain fatty acid producers. This partial recovery of a eubiotic profile could help counteract the inflammatory tone typically observed in MS, as supported by reduced circulating lipopolysaccharide levels and decreased populations of pro‐inflammatory lymphocytes. Improved physical performance and fatigue relief were also found. Our findings pave the way for integrating clinical practice with holistic approaches to mitigate MS symptoms and improve patients’ quality of life

B Lymphocytes in Multiple Sclerosis : Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity

B lymphocytes contribute to the pathogenesis of Multiple Sclerosis (MS) by secreting antibodies and producing cytokines. This latter function was analyzed in myelin olygodendrocyte protein (MOG)-stimulated CD19+B lymphocytes of 71 MS patients with different disease phenotypes and 40 age- and sex-matched healthy controls (HC). Results showed that: 1) CD19+/TNF alpha+, CD19+/IL-12+ and CD19+/IFN gamma+ lymphocytes are significantly increased in primary progressive (PP) compared to secondary progressive (SP), relapsing-remitting (RR), benign (BE) MS and HC; 2) CD19+/IL-6+ lymphocytes are significantly increased in PP, SP and RR compared to BEMS and HC; and 3) CD19+/IL-13+, CD19+/IL-10+, and CD19+/IL-10+/TGF beta+ (Bregs) B lymphocytes are reduced overall in MS patients compared to HC. B cells expressing BTLA, a receptor whose binding to HVEM inhibits TcR-initiated cytokine production, as well as CD19+/ BTLA+/IL-10+ cells were also significantly overall reduced in MS patients compared to HC. Analyses performed in RRMS showed that fingolimod-induced disease remission is associated with a significant increase in Bregs, CD19+/BTLA+, and CD19+/BTLA+/IL-10+ B lymphocytes. B lymphocytes participate to the pathogenesis of MS via the secretion of functionally-diverse cytokines that might play a role in determining disease phenotypes. The impairment of Bregs and CD19+/BTLA+ cells, in particular, could play an important pathogenic role in MS

Bridging the gap between chronic cerebrospinal venous insufficiency and M&#233;ni&#232;re disease

M\ue9ni\ue8re disease (MD) is a chronic illness of the inner ear that affects a substantial number of patients every year worldwide. Because of a dearth of well-controlled studies, the medical and surgical management of MD remains quite empirical. The main reason is that it is very difficult to investigate patients affected with \u201cCertain MD\u201d due to the post-mortem criterion necessary for this diagnostic grade. The aim of this paper is an attempt to approach MD into the context of the more recent findings about the global brain waste clearance system, to which inner ear is anatomically and functionally connected, in order to build a reasonable model of MD pathogenesis. it seems nowadays reasonable to state that CCSVI may be the anatomical background to develop endolymphatic hydrops in MD, the worldwide accepted pathogenetic mechanism of the disease. The mechanism leading from CCSVI to MD is still debated. Since MD has been correlated mostly to a wide and different diseases and treatments, CCSVI may be considered more than a cause of MD per se, rather the anatomical predisposition to develop the disease. CCSVI may lead to endolymphatic hydrops through a pure \u201chydraulic\u201d mechanism but in the model proposed in this paper CCSVI interplays with the Glymphatic (GS) and Brain Lymphatic System (LS) and MD development is due to a failure of the congenital venous abnormalities: MD develops when vascular and/or glymphatic and/or lymphatic compensation fails