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Galvanic vestibular stimulation (GVS) has increasingly been used to stimulate the vestibular system in health and disease. While perceptible supra-threshold GVS destabilizes postural control in healthy control (HC) subjects, imperceptible 'noisy' GVS (nGVS) is reported to improve postural control in patients with bilateral vestibulopathy (BV) and therapeutic devices using nGVS are currently under development. We questioned (1) whether perceptible GVS destabilizes postural control of BV patients, expecting any effect to be smaller than in healthy subjects due to the patients' vestibulopathy, and (2) whether imperceptible nGVS improves postural control in comparison to an active sham stimulus in context-dependent conditions, hypothesizing that it fades off once postural control becomes more challenging with respect to its sensory (standing on foam) or cognitive (dual task) complexity. We tested postural responses of 30 BV patients to bimastoidal perceptible (lowGVS, highGVS) or imperceptible (nGVS, sham, noGVS)bulo-perceptional and vestibulo-spinal thresholds should be taken into account. Finally, our data suggest that individual motion perception thresholds for GVS could potentially serve as a predictor of postural control safety and falling risk in BV.Neuroimaging underpinnings of state (in the moment, transient) mental fatigue in multiple sclerosis (MS) are not well understood. The current pilot study examined the effect of state mental fatigue on brain activation (measured using functional magnetic resonance imaging [fMRI]) during conditions of varying cognitive loads of rapid information processing in persons with MS relative to healthy controls. Nineteen persons with MS and 17 healthy controls underwent fMRI scanning while performing a modified version of the Symbol Digit Modalities Test, which consisted of high and low cognitive load conditions with comparable visual stimulation. State mental fatigue was assessed using the Visual Analog Scale of Fatigue before and after each run of the behavioral task. Results indicated that the healthy control group recruited significantly more anterior brain regions (superior and middle frontal gyri, insula, and superior temporal gyrus) to meet increased task demands during the high cognitive load condition as fatigue level increased (p  less then  0.05), which was accompanied by shorter response time. In contrast, the MS group did not recruit anterior areas to the same extent as the healthy control group as task demands and fatigue increased. Indeed, the MS group continued to activate more posterior brain regions (precuneus, lingual gyrus, and middle occipital gyrus) for the high cognitive load condition (p  less then  0.05) with no improvement in speed. In conclusion, persons with MS may allocate neural resources less efficiently than healthy controls when faced with increased task demands, which may result in increased mental fatigue. Results of the current pilot investigation warrant replication with a larger sample size.BACKGROUND Dimethyl fumarate (DMF) tolerability and safety in multiple sclerosis (MS) has been analyzed in randomized clinical trials. Real-life studies are needed to assess possible harms of this therapy in a wider MS population. OBJECTIVE To evaluate DMF tolerability, safety and persistence in MS in a real-world setting. METHODS We conducted a multicenter prospective study of patients who started DMF, attended in 16 public hospitals of Spain. A specific database was elaborated to collect data on most frequent adverse events (AE). Regression models were used to analyze the effect of demographic and clinical characteristics on risk of AEs and DMF discontinuation. RESULTS We collected data of 886 patients (2681 patients/years-exposition) with median 39.5 (IQR 23, 51.5) months on DMF exposure; 25.3% were treatment naïve and 74.7% switched to DMF from other disease-modifying therapies. DMF was discontinued in 29.9% of patients, in 13.2% due to AEs and in 13.5% to inefficacy. AEs were experienced by 71.2%, being flushing the most frequent (44.1%), 5.4% developed grade III lymphopenia, without cases of grade IV. Females showed a higher risk of flushing and gastroenteric symptoms (OR 1.49, p = 0.011; OR 1.69, p = 0.001, respectively); lymphopenia was associated with older age (OR 1.04, p  less then  0.001), and a higher EDSS with lymphopenia (OR 1.10, p = 0.035) and DMF withdrawal (HR 1.43, p = 0.012). No safety problems were reported. CONCLUSIONS Our findings confirm good tolerability and safety of DMF in real-world setting and suggest that women have an increased risk of AEs and higher baseline disability involves greater risk of drug discontinuation.PURPOSE Combined use of contact endoscopy (CE) and Narrow Band Imaging (NBI, Olympus®) is suggested for the visualization of specific vascular changes indicative of glottic neoplasia. We investigated the interrater reliability and agreement in 3 recognized classification systems of vascular changes applied to images from CE + NBI in patients suspected for glottic neoplasia. METHODS Six experienced head and neck surgeons familiar with NBI rated 120 images obtained by CE + NBI by 3 classification systems of vascular changes as suggested by Ni et al. (N-C), Puxeddu et al. (P-C), and the European Laryngological Society (ELS-C). Three raters were experienced in CE, and three raters had only limited experience with CE. Crude agreement and Fleiss' kappa with 95% confidence interval were estimated for all 6 raters, and for the 2 levels of expertise for each original classification system and for dichotomized versions of the N-C and the P-C based on suggested neoplastic potential. RESULTS The interrater crude agreement and the corresponding kappa values for the ELS-C were good and significantly higher than those for the N-C and P-C for all raters, irrespective of the level of experience with CE (p  less then  0.0001). There were no significant differences between the N-C and the P-C (p = 0.16). SC-43 cell line Kappa was considerably improved for both the N-C and the P-C to a level not different from the ELS-C (p = 0.21-0.71) when their 5 original categories were pooled into dichotomized classifications. CONCLUSION Difficulties in reliably classifying vascular changes in CE + NBI are evident. Two-tier classification systems are the most reliable.
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