Searching for a marker of REM sleep behavior disorder: submentalis muscle EMG amplitude analysis during sleep in patients with narcolepsy/cataplexy

STUDY OBJECTIVES: To evaluate the amplitude of submentalis muscle EMG activity during sleep in patients with narcolepsy/cataplexy with or without REM sleep behavior disorder (RBD). DESIGN: Observational study with consecutive recruitment. SETTINGS: Sleep laboratory. PATIENTS: Thirty-four patients with narcolepsy/cataplexy and 35 age-matched normal controls. MEASUREMENTS AND RESULTS: Half the patients (17 subjects) had a clinical and video polysomnographic diagnosis of RBD. The average amplitude of the rectified submentalis muscle EMG signal was used to assess muscle atonia, and the new REM sleep Atonia Index was computed. Chin muscle activations were detected and their duration and interval analyzed. REM sleep Atonia Index was lower in both patient groups (with narcolepsy patients with RBD showing the lowest values) with respect to controls, and it did not correlate with age as it did in controls. The total number of chin EMG activations was significantly higher in both patient groups than controls. No significant differences were found between the two groups of patients, although more chin EMG activations were noted in narcolepsy patients with RBD than those without. CONCLUSIONS: Elevated muscle activity during REM sleep is the only polysomnographic marker of RBD. This study shows that polysomnographically evident RBD is present in many patients with narcolepsy/ cataplexy. This condition might be specific to narcolepsy/cataplexy, reflecting a peculiar form of REM sleep related motor dyscontrol (i.e., status dissociatus), paving the way to enacting dream behaviors, and correlated with the specific neurochemical and neuropathological substrate of narcolepsy/cataplexy.     

The European Narcolepsy Network (EU‐NN) database

Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease‐specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web‐based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post‐marketing medication side‐effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.     

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes

OBJECTIVE: To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS: Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS: A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Delta-factors-that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Delta-cardiopulmonary (4.0), Delta-skin (3.0), Delta-vascular (2.0), and Delta-articular/muscular (1.0) for patients with dSSc; (b) Delta-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Delta-cardiopulmonary (1.5), Delta-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Delta-cardiopulmonary (2.0), Delta-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Delta-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients. CONCLUSIONS: Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.     

Vitamin E affects cell death in adult rat dentate gyrus

We have previously reported the presence of dying cells in the granule cell layer (GCL) of adult rat dentate gyrus (DG), where neurogenesis occurs. In particular, we found that cell death in the GCL increased in vitamin E deficiency and decreased in vitamin E supplementation. These findings were regarded as related to changes in neurogenesis rate, which in turn was influenced by vitamin E availability; a neuroprotective effect of vitamin E on cell death was also proposed. In order to verify this latter hypothesis, we have studied cell death in all layers of DG in vitamin E-deficient and vitamin E-supplemented rats and in control rats at different ages, using TUNEL and nick translation techniques. The phenotype of TUNEL-positive cells was characterized and the existence of dying BrdU-positive cells was investigated. Dying cells with neuronal phenotype were observed throughout the DG in all experimental groups. The number of TUNEL-positive cells decreased from juvenile to adult age. A higher number of TUNEL-positive cells in vitamin E-deficient rats and a lower number in vitamin E-supplemented rats, with respect to age-matched controls, were found; moreover, in these groups, TUNEL-positive cells had a different percentage distribution in the different layers of the DG. Our results confirm the occurrence of cell death in DG, demonstrate that cell death affects neuronal cells and support the hypothesis that the effect of vitamin E on cell death is not related to neurogenesis.     

Gender Differences in Epidemiology,Pathophysiology, and Treatment of Hypertension

Purpose of Review

This review aims to examine gender differences in both the epidemiology and pathophysiology of hypertension and to explore gender peculiarities on the effects of antihypertensive agents in decreasing BP and CV events.

Recent Findings

Men and women differ in prevalence, awareness, and control rate of hypertension in an age-dependent manner. Studies suggest that sex hormones changes play a pivotal role in the pathophysiology of hypertension in postmenopausal women. Estrogens influence the vascular system inducing vasodilatation, inhibiting vascular remodeling processes, and modulating the renin-angiotensin aldosterone system and the sympathetic system. This leads to a protective effect on arterial stiffness during reproductive age that is dramatically reversed after menopause.

Summary

Data on the efficacy of antihypertensive therapy between genders are conflicting, and the underrepresentation of aged women in large clinical trials could influence the results. Therefore, further clinical research is needed to uncover potential gender differences in hypertension to promote the development of a gender-oriented approach to antihypertensive treatment.

     

Is proliferative colonic disease presentation changing?

AIM: To compare the site, age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome, Italy, during two periods.METHODS: CRC data were collected from surgery/pathology registers, and polyp data from colonoscopy reports. Patients who met the criteria for familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study. Overlap of patients between the two groups (cancers and polyps) was carefully avoided. The χ² statistical test and a regression analysis were performed.RESULTS: Data from a total of 768 patients (352 and 416 patients, respectively, in periods A and B) who underwent surgery for cancer were collected. During the same time periods, a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B). A proximal shift in cancer occurred during the latter years for both sexes, but particularly in males. Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31, 95%CI: 2.00-5.47; P < 0.0001). A similar proximal shift was observed for polyps, particularly in males (OR 1.87, 95%CI: 1.23-2.87; P < 0.0038), but also in females (OR 1.62, 95%CI: 0.96-2.73; P < 0.07).CONCLUSION: The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade, particularly in males.