心血管领域-心律失常方向

METHODS::Calcium ions are vital for maintaining the physiological and biochemical processes inside cells. The central nervous system (CNS) is particularly dependent on calcium homeostasis and its dysregulation has been associated with several neurodegenerative disorders including Parkinson's disease (PD), Alzheimer's disease (AD) and Huntington's disease (HD), as well as with multiple sclerosis (MS). Hence, the modulation of calcium influx into the cells and the targeting of calcium-mediated signaling pathways may present a promising therapeutic approach for these diseases. This review provides an overview on calcium channels in neurons and glial cells. Special emphasis is put on MS, a chronic autoimmune disease of the CNS. While the initial relapsing-remitting stage of MS can be treated effectively with immune modulatory and immunosuppressive drugs, the subsequent progressive stage has remained largely untreatable. Here we summarize several approaches that have been and are currently being tested for their neuroprotective capacities in MS and we discuss which role calcium could play in this regard.

METHODS:PURPOSE OF REVIEW:The purpose of this review is to provide an update on advances in the understanding of pediatric demyelinating optic neuritis. RECENT FINDINGS:In the past decade, the disease phenotypes for demyelinating syndromes in children have been more clearly defined. Pediatric optic neuritis may present as a clinically isolated syndrome or in the setting of underlying neurologic disease. In addition to optic neuritis associated with multiple sclerosis or neuromyelitis optica, recent work has identified antibodies to the myelin oligodendrocyte glycoprotein (MOG IgG) as a unique demyelinating cause with distinct features regarding treatment and prognosis. The disease phenotypes for demyelinating pediatric optic neuritis have expanded. Treatment strategies vary and are not universally effective for each cause of demyelinating disease. Accurately distinguishing among these unique clinical syndromes is therefore critical for initiation of appropriate treatment to prevent disability, to maximize visual outcomes, and to provide insight into long-term prognosis.

METHODS:BACKGROUND:Cervical spinal cord atrophy (CSCA), which partly reflects the axonal loss in the spinal cord, is increasingly recognized as a valuable predictor of disease outcome. However, inconsistent results have been reported regarding the correlation of CSCA and clinical disability in multiple sclerosis (MS). The aim of this meta-analysis was to synthesize the available data obtained from 3.0-Tesla (3T) MRI scanners and to explore the relationship between CSCA and scores on the Expanded Disability Status Scale (EDSS). METHODS:We searched PubMed, Embase, and Web of Science for articles published from the database inception to February 1, 2019. The quality of the articles was assessed according to a quality evaluation checklist which was created based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. We conducted a meta-analysis of the correlation between EDSS scores and CSCA at 3T MRI in MS. RESULTS:Twenty-two eligible studies involving 1933 participants were incorporated into our meta-analysis. Our results demonstrated that CSCA was negatively and moderately correlated with EDSS scores (rs = -0.42, 95% CI: -0.51 to -0.32; p < 0.0001). Subgroup analyses revealed a weaker correlation in the group of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) (rs = -0.19, 95% CI: -0.31 to -0.07; p = 0.0029). CONCLUSIONS:The correlation between CSCA and EDSS scores was significant but moderate. We encourage more studies using reliable and consistent methods to explore whether CSCA is suitable as a predictor for MS progression.

METHODS::Neuromyelitis optica (NMO) is a disease characterised by severe relapses of optic neuritis and longitudinally extensive transverse myelitis and it has a strong female predilection. Pain is one of the most typical symptom in NMO. However, few studies have been conducted to examine the neuropathic pain mechanism of NMO patients or gender-specific effects using magnetic resonance imaging technique. A total of 38 female patients with NMO, 28 with pain (NMOWP) and 10 without pain (NMOWoP), were classified using the Brief Pain Inventory (BPI); 22 healthy females were also recruited. We used the FSL Image Registration and Segmentation Toolbox (FIRST) for subcortical region volumes quantifications, and voxel-based morphometry analysis for cortical gray matter (GM) volume, to examine the brain morphology in NMOWP patients. In addition, correlation test between structural measurements of NMO patients and clinical indexes was also performed. The results showed: 1) no significant differences in cortical GM density between the NMOWP and NMOWoP groups; 2) significantly smaller hippocampus and pallidum volumes in the NMOWP group compared with the NMOWoP group; 3) significant negative correlation between the average BPI and volumes of the accumbens nucleus and thalamus in NMO patients. These results revealed that structural abnormality exists in NMO female patients who have pain, with significant implications for our understanding of the brain morphology in NMO patients with pain.

METHODS:BACKGROUND:Impairments in long-term and working memory are widespread in Multiple Sclerosis (MS), setting on in early disease stages. These memory impairments may limit patients' ability to take informed and competent medical decisions, too. In healthy populations, memory abilities predict decision quality across a wide range of tasks. These studies suggest that higher working memory capacity supports decisions in cognitively taxing tasks, whereas better semantic memory facilitates decisions in tasks requiring knowledge retrieval. In individuals with MS, previous studies have linked less accurate decisions to memory deficits and reduced executive functioning, too. However, these studies focussed on decisions under risk and did not broadly assess decision making skills. We aimed to fill this gap in a cross-sectional study. METHODS:Hundred thirty-seven participants with MS were recruited during their stay in an MS specialized rehabilitation centre. In a first test session, participants completed a standardized test battery for working memory and semantic memory, the inventory for memory diagnostics. In a second test session, participants filled out the Adult Decision Making Competence battery (A-DMC). This version of the A-DMC measured decision making competence on five subscales: Resistance to Framing Effects, Under/Overconfidence, Applying Decision Rules, Consistency in Risk Perception, and Resistance to Sunk Cost Effects. In addition, participants were screened for depression and cognitive fatigue. RESULTS:Working memory was impaired in most participants, whereas semantic memory was not impaired. To understand which memory abilities underlie distinct components of decision making in people with MS, we used structural equation modelling. Replicating previous findings in a healthy sample, working memory capacity was associated with the ability to recall semantic knowledge. Participants with lower working memory capacity were less resistant to framing effects and adhered to decision rules less. In contrast, participants with worse semantic memory assessed their own knowledge less accurately, perceived risks less consistently, and made more errors in applying decision rules. Cognitive fatigue and depression unlikely explain these relationships. CONCLUSIONS:Taken together, our study suggests that the memory problems, frequently reported in MS patients, may reach out to higher-order cognitive functions, such as decision making skills. Supporting shared decision-making and patient autonomy within MS thus requires to take memory impairments into account and to match the information provided to the patient's memory abilities.

METHODS::Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients may still face progressive disability because of failure of myelin regeneration and loss of neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which a disease allele exerts a pathogenic effect. Applying this approach to MS risk loci, we pinpoint likely pathogenic cell types for 70%. In addition to T cell loci, we unexpectedly identified myeloid- and CNS-specific risk loci, including two sites that dysregulate transcriptional pause release in oligodendrocytes. Functional studies demonstrated inhibition of transcriptional elongation is a dominant pathway blocking oligodendrocyte maturation. Furthermore, pause release factors are frequently dysregulated in MS brain tissue. These data implicate cell-intrinsic aberrations outside of the immune system and suggest new avenues for therapeutic development. VIDEO ABSTRACT.

METHODS:BACKGROUND:Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. The MS patients may display biochemical changes in their cerebrospinal fluid, peripheral blood and saliva. Since the salivary profile plays a critical role in maintaining oral health and function, the analysis of saliva in the MS patients would be beneficial to prevent oral diseases, such as dental caries. OBJECTIVES:The aim of this study was to evaluate the dental status and salivary profile of the MS patients. MATERIAL AND METHODS:The study involved 25 MS patients and 25 healthy controls who were examined with regard to the calcium and phosphorus level, pH and flow rate of saliva as well as the decayed, missing and filled teeth (DMFT) index for permanent first molars. Student's t-test, the χ2 test and the Mann-Whitney test were utilized to compare the study groups. RESULTS:Significantly lower salivary flow rates were observed in the MS patients as compared to the controls. The salivary calcium and phosphorus levels were significantly higher in the case group during the first 6 years of the disease and 6-11 years after the onset of the disease, respectively, in comparison with the controls; however, there was no significant difference between the groups in terms of pH. The DMFT index for permanent first molars was higher in the MS patients than in the healthy controls, but not significantly. The number of carious and missing permanent first molars was significantly higher in the MS patients. CONCLUSIONS:Multiple sclerosis appears to significantly change the salivary profile and dental status of the patients.

METHODS::Conventional MR imaging techniques are sensitive to pathologic changes of the brain and spinal cord seen in MS, but they lack specificity for underlying axonal and myelin integrity. By isolating the signal contribution from different tissue compartments, newly developed advanced multicompartment diffusion MR imaging models have the potential to detect specific tissue subtypes and associated injuries with increased pathologic specificity. These models include neurite orientation dispersion and density imaging, diffusion basis spectrum imaging, multicompartment microscopic diffusion MR imaging with the spherical mean technique, and models enabled through high-gradient diffusion MR imaging. In this review, we provide an appraisal of the current literature on the physics principles, histopathologic validation, and clinical applications of each of these techniques in both brains and spinal cords of patients with MS. We discuss limitations of each of the methods and directions that future research could take to provide additional validation of their roles as biomarkers of axonal and myelin injury in MS.

METHODS:BACKGROUND:Multiple sclerosis (MS) is a chronic disease that is associated with a variety of MS-specific symptoms. Many of these symptoms have a negative impact on health-related quality of life (HRQoL). Until now it is unclear which MS-specific symptoms have the highest impact on the HRQoL. METHODOLOGY:The study is based on the data of a member survey of the German MS Society (DMSG) in 2015 (n = 424). Considering socio-demographic variables and general medical variables, the influence of MS-specific symptoms on HRQoL was examined. The HRQoL was collected using the Multiple Sclerosis Quality of Life-54 (MSQOL-54) instrument. In a pretest, all influencing variables were tested for a significant mean difference (p = 0.05), or a mean correlation (Pearson's r ≥ 0.3). Subsequently, the influence of the variables identified in the pretest on the HRQoL was investigated by multiple linear regression analysis. RESULTS:We calculated a mean physical health composite score (PHCS) of 48.3 (sd = 17.7) and a mean mental health composite score (MHCS) of 56.0 (sd = 20.1). The most fundamental factors influencing HRQoL were the MS-specific symptoms of depression, pain and cognitive impairment. MS-related symptoms with a mobility context showed declining PHCS. Speech disorder and dizziness were associated with a decreasing MHCS. Employment status was the only socio-economic factor that significantly affected HRQoL in multiple regression. The general medical factors showed no significant influence on HRQoL. CONCLUSION:MS-specific symptoms have a major impact on the HRQoL of people with MS. Our study show that especially the so-called 'hidden symptoms' such as the symptoms of depression, pain and cognitive impairment have a significant influence on the HRQoL. Greater attention should be paid to these in the care of people with MS. HINTERGRUND:Multiple Sklerose (MS) ist eine chronisch progredient verlaufende Erkrankung, welche mit einer Vielzahl von MS-spezifischen Symptomen einhergeht. Viele dieser Symptome wirken sich negativ auf die gesundheitsbezogene Lebensqualität (Health Related Quality of Life, HRQoL) der Betroffenen aus. Bisher ungeklärt ist, welche MS-spezifischen Symptome einen besonders großen Einfluss auf die HRQoL haben. METHODIK:Die durchgeführte Untersuchung basiert auf den Daten einer Mitgliederbefragung der Deutschen MS Gesellschaft (DMSG) im Jahr 2015 (n = 424). Unter Berücksichtigung von soziodemographischen Variablen und allgemeinen medizinischen Variablen wurde der Einfluss der MS-spezifischen Symptome auf die HRQoL untersucht. Die HRQoL wurde mit dem Multiple Sclerosis Quality of Life-54-Instrument (MSQOL-54-Instrument) erhoben. In einem Vortest wurden alle Einflussfaktoren auf einen signifikanten Mittelwertunterschied (p = 0,05) bzw. eine mittlere Korrelation (Pearson’s r ≥ 0,3) getestet. Anschließend wurde der Einfluss der im Vortest identifizierten Variablen auf die HRQoL mithilfe der multiplen linearen Regressionsanalyse untersucht. ERGEBNISSE:Für die Befragten konnte ein durchschnittlicher Physical Health Composite Score (PHCS) von 48,3 (sd = 17,7) und ein durchschnittlicher Mental Health Composite Score von 56,0 (sd = 20,1) errechnet werden. Als wichtigste Einflussfaktoren auf die HRQoL ergeben sich die MS-spezifischen Symptome Depression, Schmerz und kognitive Einschränkungen. MS-bedingte Symptome mit einem Mobilitätskontext zeigen negativen Zusammenhang mit dem PHCS. Sprechstörung und Schwindel sind mit einem abnehmenden MHCS verbunden. Der Beschäftigungsstatus ist der einzige sozioökonomische Faktor, der sich in der multiplen Regression signifikant auf die HRQoL auswirkt. Die allgemeinen medizinischen Faktoren zeigen keinen signifikanten Einfluss auf die HRQoL. SCHLUSSFOLGERUNG:MS-spezifische Symptome haben einen großen Einfluss auf die HRQoL von Menschen mit MS. In der Untersuchung konnte gezeigt werden, dass besonders die sogenannten „versteckten Symptome“ einen wesentlichen Einfluss auf die HRQoL haben. Hier sind beispielsweise die Symptome Depression, Schmerz und kognitive Einschränkungen zu nennen. Diese sollten stärker in der Versorgung von Menschen mit MS berücksichtigt werden.

METHODS:INTRODUCTION:Fatigue is one of the most common disabling symptoms in patients with multiple sclerosis (MS) which is present in 75% of these patients and is usually associated with functional disabilities. According to the literature, there is no general agreement on the effectiveness of the existing treatments for fatigue in patients with MS. As transcranial direct current stimulation (tDCS) is a relatively new method in the treatment of fatigue symptoms in patients with MS, the purpose of this study was to systematically review published evidence conducted to assess the effects of tDCS on fatigue in patients with MS. MATERIAL & METHODS:A thorough literature search of published articles was conducted from 1996 to 2019 in different databases including PubMed, Science Direct, OVID, Google Scholar, Cochrane Library, Scopus, Embase, ProQuest and web of science with keywords of "tDCS", "multiple Sclerosis" and "Fatigue". Results yielded 1017 studies, which after excluding articles based on duplication and title and abstract, 8 of them were selected for review in this study. RESULTS:The results from the literature revealed that six studies indicated positive effects of tDCS stimulation on fatigue reduction. In four studies stimulation was over the right dorsolateral prefrontal cortex (DLPFC); in three studies stimulation placed over the whole body's primary somatosensory cortex (S1); and in one study stimulation applied over the posterior parietal cortex. In most studies, no serious side effects were reported. CONCLUSION:Most studies revealed that tDCS can reduce the adverse effects of MS-related fatigue in particular cognitive type. As follow-ups were either absent or short period, as well as the application of treatment protocols and measurement instruments were different, it was very difficult to draw strong conclusion on the effects of tDCS in patients with MS. However, further large scale studies with long term follow-up are still recommended.