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

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

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

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

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

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

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon