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    • It is evident that RBD is

    2018-11-13

    It is evident that RBD is situated at a strategic and busy crossroad of clinical (sleep) medicine and the neurosciences. RBD offers great breadth and depth of research opportunities, including extensive inter-disciplinary and multi-national research opportunities [20]. To this end, the International RBD Study Group (IRBD-SG) was founded and legally incorporated in Marburg, Germany. The IRBD-SG comprises a network of leading basic science and clinical RBD researchers, with the purpose of promoting international scientific research and education on RBD and its related fields, and optimizing medical care for afflicted patients by improving diagnostic and therapeutic measures. The IRBD-SG has so far held eight research symposia, in Marburg (2007, 2008, 2011), Montreal (2010), Otsu City, Japan (2011), and Paris (2012), Valencia (2013) and Helsinki (2015). Given the relatively low number of patients with RBD identified at individual RBD research centers, a major focus of the IRBD-SG is to facilitate multicenter studies. To date, six IRBD-SG studies have been published in peer-reviewed journals [28–33], the notable findings of which will now be summarized, together with a seventh collaborative group study that involved many members of the IRBD-SG [34]. In an environmental risk factor study [28], patients with iRBD who were free of dementia and parkinsonism were recruited from 13 centers. Controls were matched according to age and sex. Potential environmental and lifestyle risk factors were assessed via standardized questionnaire. A total of 694 participants (347 patients, 347 controls) were recruited. Compared to controls, RBD patients were significantly more likely to have been smokers, and to have had head injury, pesticide exposure, and worked as farmers, and so it Caspase-3 Colorimetric Assay Kit was concluded that these comprised risk factors for iRBD. A second study tested a single screening question for RBD [29]. 242 RBD iRBD patients and 242 controls were given a screening question about dream-enactment, with a yes/no response option. All patients and controls had undergone vPSG studies that confirmed the RBD diagnosis or excluded a RBD diagnosis (in the controls). There was a 93.8% sensitivity and 87.2% specificity to this single question, which compared favorably to reports on longer RBD screening questionnaires. A third study devised controlled active treatment studies for symptomatic and neuroprotective therapies, which also represented a consensus statement by the IRBD-SG [30]. This publication serves to anticipate the arrival of promising neuroprotective, or disease-modifying, therapies to be tested in double-blind fashion in newly-diagnosed iRBD patients. However, it is currently not known when such promising agents will be identified for testing. This remains the most pressing and challenging issue in the convergent fields of RBD and PD. A fourth study investigated the frequency of proxy-reported RBD (viz. dream-enactment) among relatives of patients with vPSG-confirmed iRBD [31]. A total of 316 patients and 316 controls were recruited from 12 IRBD-SG centers. A positive family history of dream enactment was reported in 13.8% of iRBD cases compared to 4.8% of controls (odds ratio [OR]=3.9, 95% confidence interval [CI] 2.0–7.7). ORs were increased for both siblings and parents. These findings suggest a possible genetic contribution to RBD. However, a limitation of this study was the lack of vPSG studies (to confirm or exclude RBD) in the first-degree relatives. A fifth study addressed the topic of comorbidity and medication use in iRBD patients, in a multi-center case-control study [32]. Patients with iRBD were significantly more likely to report depression and concomitant antidepressant use (predominantly SSRIs). Patients with iRBD also reported significantly more ischemic heart disease, after adjusting for cardiovascular risk factors. A sixth study addressed autonomic symptoms in iRBD [33]. The study was encouraged by knowledge that patients with iRBD are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Patients with vPSG-confirmed iRBD (318 cases) and 318 controls were recruited from 13 neurological centers in 10 countries. A validated scale to study the disorders of the autonomic nervous system in Parkinson׳s disease (PD) patients, the SCOPA-AUT, was administered to all the patients and controls. Patients with iRBD experienced significantly more problems with gastrointestinal, urinary, and cardiovascular functioning. The most prominent differences in severity of autonomic symptoms between our iRBD patients and controls emerged in the gastrointestinal domain. Interestingly, it has been reported that an altered gastrointestinal motility, with clinical complaints of constipation, can predate the motor phase of PD. These findings underscore the importance of collecting data on autonomic symptoms in iRBD patients.