SummaryFatigue is a frequent and distressing symptom in patients with multiple sclerosis (MS). In contrast, sleepiness, characterized by difficulties to stay awake and alert during the day, seems to be less prevalent in MS; however exact studies are lacking. In addition, there is a semantic confusion of the concepts of "fatigue" and "sleepiness", which are often used interchangeably. We conducted a systematic review of studies using the Epworth sleepiness scale (ESS) for the assessment of daytime sleepiness in patients with MS. The summarized results of 48 studies demonstrate that sleepiness, as indicated by elevated ESS scores, is less prevalent and less severe than fatigue but is present in a significant proportion of patients with MS. In most cross-sectional and longitudinal studies, there was a moderate association between ESS scores and various fatigue rating scales. Longitudinal studies on the effect of wakefulness-promoting agents failed to show a consistent improvement of sleepiness or fatigue as compared to placebo. It has also been shown that daytime sleepiness is frequently associated with comorbid sleep disorders that are often underrecognized and undertreated in MS. Sleepiness and potential sleep disorders may also precipitate and perpetuate fatigue in patients with MS and should be part of the differential diagnostic assessment. To support an appropriate decision-making process, we propose an algorithm for the evaluation of sleepiness as compared to fatigue in patients with MS.
Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Muscle-specific kinase-antibodies (MuSK-ABs) are detected in ~ 6% of MG, but data on outcome of MuSK-MCs are still lacking. We made a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody positive MG (AchR-MG) or MuSK-MG between 2006 and 2015 in a retrospective German multicenter study. We identified 19 MuSK-AB associated MCs in 15 patients and 161 MCs in 144 patients with AchR-ABs only. In contrast to patients with AchR-AB, MuSK-AB patients were more often female (p = 0.05, OR = 2.74) and classified as Myasthenia Gravis Foundation of America-class IV before crisis (p = 0.04, OR = 3.25). MuSK-AB patients suffer more often from multiple chronic disease (p = 0.016, OR = 4.87) and were treated more invasively in terms of plasma exchanging therapies (not significant). The number of days of mechanical ventilation (MV) (43.0 ± 53.1 vs. 17.4 ± 18; p < 0.0001), days on an intensive care unit (ICU) (45.3 ± 49.5 vs. 21.2 ± 19.7; p < 0.0001), and hospital-length of stay (LOS) (55.9 ± 47.6 vs. 28.8 ± 20.9 days; p < 0.0001) were significantly increased in MuSK-MC. Remarkable is that these changes were mainly due to patients with MusK-ABs only, whereas patients’ outcome with both antibodies was similar to AchR-MCs. Furthermore, our data showed a shortened duration of MV after treatment with plasma exchanging therapies compared to treatment with intravenous immunoglobulin in MuSK-MCs. We conclude that MuSK-AB-status is associated with a longer need of MV, ICU-LOS, and hospital-LOS in MC, and therefore recommend early initiation of a disease-specific therapy.
Methanogenic archaea are widespread anaerobic microorganisms responsible for the production of biogenic methane. Several new species of psychrotolerant methanogenic archaea were recently isolated from a permafrost-affected soil in the Lena Delta (Siberia, Russia), showing an exceptional resistance against desiccation, osmotic stress, low temperatures, starvation, UV and ionizing radiation when compared to methanogens from non-permafrost environments. To gain a deeper insight into the differences observed in their resistance, we described the chemical composition of methanogenic strains from permafrost and non-permafrost environments using confocal Raman microspectroscopy (CRM). CRM is a powerful tool for microbial identification and provides fingerprint-like information about the chemical composition of the cells. Our results show that the chemical composition of methanogens from permafrost-affected soils presents a high homology and is remarkably different from strains inhabiting non-permafrost environments. In addition, we performed a phylogenetic reconstruction of the studied strains based on the functional gene mcrA to prove the different evolutionary relationship of the permafrost strains. We conclude that the permafrost methanogenic strains show a convergent chemical composition regardless of their genotype. This fact is likely to be the consequence of a complex adaptive process to the Siberian permafrost environment and might be the reason underlying their resistant nature.
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