心血管领域-心律失常方向

METHODS::The discriminative value of CSF total protein (CSF-TP) in subtypes of Guillain-Barré syndrome has not been well documented in North-American patients. We reviewed 173 cases from a single institution, comprising the following clinical categories of neuropathy: 134 Sensorimotor (SM) GBS, 13 Motor (M) GBS, 8 Localized (L) GBS, and 18 Miller Fisher syndrome (MFS). We grouped the electrophysiological interpretation in primarily demyelinating, primarily axonal and normal / equivocal categories. Mean CSF-TP were substantially higher for SM and L-GBS, as well as cases classified as Acute-onset chronic inflammatory demyelinating polyneuropathy. They were lower for M-GBS and L-GBS. The most statistically significant correlation was found for elevated CSF-TP in GBS cases showing an electrophysiologic pattern classified as demyelinating (1.56 g/L) compared with axonal (0.68 g/L) or normal/ equivocal patterns (0.65 g/L). There was a correlation between CSF-TP and time interval between symptom onset and lumbar puncture. There was a weak correlation between CSF-TP and maximal overall-clinical severity grade, which was likely mostly determined by the electorphysiological pattern. Though CSF-TP is a sensitive test for GBS in the second week after onset, it may not be a reliable predictor of clinical severity. There is a robust association of CSF-TP elevation and a demyelinative electrophysiologic pattern and a suggestion that lower mean CSF-TP values can be expected in GBS-spectrum disorders thought to represent nodo-paranodopathies.

METHODS:PURPOSE:To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI). MATERIALS AND METHODS:The Brave Dreams trial ( ClinicalTrials.gov identifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a secondary assessment, venograms of patients who underwent venous angioplasty were graded as "favorable" (n=38) or "unfavorable" (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared. RESULTS:Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005). CONCLUSION:Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Secondary analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.

METHODS:BACKGROUND:Atrophied T2-lesion volume (LV) is a novel MRI marker representing brain-lesion loss due to atrophy, able to predict long-term disability progression and conversion to secondary-progressive multiple sclerosis (MS). OBJECTIVE:To better characterize atrophied T2-LV via comparison with other multidisciplinary markers of MS progression. METHODS:We studied 127 MS patients (85 relapsing-remitting, RRMS and 42 progressive, PMS) and 20 clinically isolated syndrome (CIS) utilizing MRI, optical coherence tomography, and serum neurofilament light chain (sNfL) at baseline and at 5-year follow-up. Symbol Digit Modalities Test (SDMT) was obtained at follow-up. Atrophied T2-LV was calculated by combining baseline lesion masks with follow-up CSF partial-volume maps. Measures were compared between MS patients who developed or not disease progression (DP). Partial correlations between atrophied T2-LV and other biomarkers were performed, and corrected for multiple comparisons. RESULTS:Atrophied T2-LV was the only biomarker that significantly differentiated DP from non-DP patients over the follow-up (p = 0.007). In both DP and non-DP groups, atrophied T2-LV was associated with baseline T2-LV and T1-LV (both p = 0.003), absolute change of T1-LV (DP p = 0.038; non-DP p = 0.003) and percentage of brain volume change (both p = 0.003). Furthermore, in the DP group, atrophied T2-LV was related to baseline brain parenchymal (p = 0.017) and thalamic (p = 0.003) volumes, thalamic volume change and follow-up SDMT (both p = 0.003). In non-DP patients, atrophied T2-LV was significantly related to baseline sNfL (p = 0.008), contrast-enhancing LV (p = 0.02) and percentage ventricular volume change (p = 0.003). CONCLUSION:Atrophied T2-LV is associated with disability accrual in MS, and to several multimodal markers of disease evolution.

METHODS::Introduction: Multiple sclerosis (MS) is an immune-mediated disorder. Long noncoding RNAs (lncRNAs, LncR, Linc RNA) have role in many autoimmune and inflammatory disorders, including MS. LincR-Gng2-5 AS locus in T helper 1 cell (TH1) and LincR-Epas1-3AS in T helper 2 cell (TH2) cell were located in a genomic region rich in genes code for proteins with immune regulatory function. Our aim was to evaluate the LincR-Gng2-5' and LincR-Epas1-3'AS fold change in blood of MS patients versus healthy controls and correlate it with disease severity, assessed based on Expanded Disability Status Scale (EDSS).Material and Methods: Sixty MS patients 42 relapsing remitting (RR, RRMS), 18 Secondary progressive (SP, SPMS) and sixty controls (age-matched and sex-matched) were studied. Blood of patients and control group undergone the investigation of LincR-Gng2-5' and LincR-Epas1-3'AS fold change by real-time PCR. Fold change >2 and p < .05 represent significant result.Results: LincR-Gng2-5' was significantly upregulated in MS patients with mean fold change (2.559) and (p = .03). Meanwhile, LincR-Epas1-3'AS levels were significantly downregulated with mean fold change (0.5964) and (p < .004). Patients with SP showed a significantly higher level of LincR-Gng2-5-fold change (3.71 ± 0.7) than that of RR (1.33 ± 0.3). LincR-Epas1-3'AS was markedly reduced among SP (0.43 ± 0.2) than that of RR (0.66 ± 0.1) but with no significant difference. As regards disease severity (EDSS); there was a significant positive correlation with LincR-Gng2-5 and negative correlation with LincR-Epas1-3'AS. LincR- Gng2-5and LincR-Epas1-3'AS, both are dysregulated in MS patient suggesting a role in disease pathogenesis.Conclusion: LincR-Gng2-5 AS and LincR-Epas1-3'AS fold change are correlated to MS severity (EDSS).

METHODS::Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination and axonal damage and resulting in a range of physical, mental or even psychiatric symptoms. Key role of oxidative stress (OS) in the pathogenesis of MS has been suggested, as indicated by the biochemical analysis of cerebrospinal fluid and blood samples, tissue homogenates, and animal models of multiple sclerosis. OS causes demyelination and neurodegeneration directly, by oxidation of lipids, proteins and DNA but also indirectly, by inducing a dysregulation of the immunity and favoring the state of pro-inflammatory response. In this review, we discuss the interrelated mechanisms of the impaired redox signaling, of which the most important are inflammation-induced production of free radicals by activated immune cells and growth factors, release of iron from myelin sheath during demyelination and mitochondrial dysfunction and consequent energy failure and impaired oxidative phosphorylation. Review also provides an overview of the interplay between inflammation, immunity and OS in MS. Finally, this review also points out new potential targets in MS regarding attenuation of OS and inflammatory response in MS.

METHODS::A recent study of autologous hematopoietic stem cell transplantation (AHSCT) for active relapsing-remitting multiple sclerosis (RRMS) showed efficacy in preventing disease worsening. However, the immunologic basis for efficacy remains poorly defined. Multiple sclerosis pathology is known to be driven by inflammatory T cells that infiltrate the CNS. Therefore, we hypothesized that the preexisting T cell repertoire in the intrathecal compartment of active RRMS participants was ablated and replaced with new clones following AHSCT. T cell repertoires were assessed using high-throughput TCRβ chain sequencing in paired cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T cells from participants that underwent AHSCT, before and up to 4 years following transplantation. More than 90% of the preexisting CSF repertoire in participants with active RRMS was removed following AHSCT and replaced with clonotypes predominantly generated from engrafted autologous stem cells. Of the preexisting clones in CSF, approximately 60% were also detected in blood before therapy, and concordant treatment effects were observed for clonotypes in both compartments following AHSCT. These results indicate that replacement of the preexisting TCR repertoire in active RRMS is a mechanism for AHSCT efficacy and suggest that peripheral blood could serve as a surrogate for CSF to define mechanisms associated with efficacy in future studies of AHSCT.

METHODS::Removal of chondroitin sulfate proteoglycans (CSPGs) with chondroitinase ABC I (ChABC) facilitates axonal plasticity, axonal regeneration and remyelination, following injury to the central nervous system (CNS). However, the ChABC rapidly undergoes thermal inactivity and needs to be injected repeatedly. Here this limitation was overcame by immobilizing the ChABC on porous silicon (PSi) nanoparticles (ChABC@PSi). The efficacy of immobilized ChABC on CSPGs level and the demyelination insult was assessed in mice corpora callosa demyelinated by 6 weeks cuprizone (CPZ) feeding. ChABC@PSi was able to reduce the amount of CSPGs two weeks after animals treatment. CSPGs digestion by ChABC@PSi reduced the extent of demyelinated area as well as the astrogliosis. Furthermore, ChABC@PSi treatment increased the number of newly generated oligodendrocyte lineage cells which imply for enhanced myelin repair. Our results showed that effective CSPGs digestion by ChABC@PSi enhanced remyelination in CPZ model. Accordingly, ChABC@PSi may have a great potential to be used for treatment of diseases like multiple sclerosis and spinal cord injury by promoting the regeneration of damaged nerves.

METHODS:BACKGROUND:Multiple sclerosis (MS) is an unpredictable, chronic neurological disease accompanied with high rates of depression and anxiety, particularly in the early stages of diagnosis. There is evidence to suggest that cognitive behavioural therapy (CBT) is effective for the treatment of depression amongst individuals with MS; however, there is a paucity of tailored CBT interventions designed to be offered in the newly diagnosed period. This trial is the first to assess the effectiveness and cost-effectiveness of a tailored CBT intervention compared to a supportive listening (SL) intervention amongst individuals with MS who are depressed. METHODS:ACTION-MS is a two-arm parallel group, assessor-blinded, active comparator, randomised controlled trial which will test whether a tailored CBT-based intervention compared to an SL intervention can reduce depression and related factors such as anxiety, fatigue, pain and sleep problems in those newly diagnosed with MS. Sixty participants who are within 5 years of having received a diagnosis of MS and scored within the mild to moderate range of depression on the Beck Depression Inventory (BDI-II) will be recruited from MS clinics located across three hospital sites in Melbourne, Australia. The primary outcome is depression severity using the BDI-II at post-assessment. Intervention satisfaction and acceptability will be assessed. A cost-effectiveness analysis will also be conducted. Data will be analysed on an intention-to-treat basis. DISCUSSION:There is a scarcity of psychological interventions for depression targeting the newly diagnosed period. However, interventions during this time point have the potential to have a major impact on the mental and physical wellbeing of those newly diagnosed with MS. The current trial will provide data on the effectiveness of a tailored CBT intervention for the treatment of depression in those newly diagnosed with MS. Findings will also provide effect size estimates that can be used to power a later-stage multi-centre trial of treatment efficacy, and will provide information on the mechanisms underlying any treatment effects and cost-effectiveness data for delivering this intervention in outpatient MS clinics. TRIAL REGISTRATION:ISRCTN trials registry, ISRCTN63987586. Current controlled trials. Retrospectively registered on 20 October 2017.

METHODS:BACKGROUND:Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. METHODS:A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). RESULTS:State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. CONCLUSIONS:EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.

METHODS::AMiCUS is a human-robot interface that enables tetraplegics to control an assistive roboticarm in real-time using only head motion, allowing them to perform simple manipulation tasksindependently. The interface may be used as a standalone system or to provide direct control aspart of a semi-autonomous system. Within this work, we present our new gesture-free prototypeAMiCUS 2.0, which has been designed with special attention to accessibility and ergonomics. As such,AMiCUS 2.0 addresses the needs of tetraplegics with additional impairments that may come alongwith multiple sclerosis. In an experimental setup, both AMiCUS 1.0 and 2.0 are compared with eachother, showing higher accessibility and usability for AMiCUS 2.0. Moreover, in an activity of dailyliving, a proof-of-concept is provided that an individual with progressed multiple sclerosis is able tooperate the robotic arm in a temporal and functional scope, as would be necessary to perform directcontrol tasks for use in a commercial semi-autonomous system. The results indicate that AMiCUS 2.0makes an important step towards closing the gaps of assistive technology, being accessible to thosewho rely on such technology the most.