1,721,066 research outputs found
Pain, opioids, and sleep: implications for restless legs syndrome treatment
No full textOpioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described. By targeting pain and its consequences, opioids are the first-line treatment in many diseases and conditions with both acute and chronic pain and have thus been used in both acute and chronic pain conditions over the last 40 years. Addiction, dependence, and tolerability of opioids show a wide variability interindividually, as the response to opioids is influenced by a complex combination of genetic, molecular, and phenotypic factors. Although several trials have now addressed opioid treatment in RLS, hyperalgesia as a complication of long-term opioid treatment, or opioid opioid interaction have not received much attention so far. Therapeutic opioids may act not only on opioid receptors but also via histamine or N-methyl-D-aspartate (NMDA) receptors. In patients with RLS, one of the few studies investigating opioid bindings found that possible brain regions involved in the severity of RLS symptoms are similar to those known to be involved in chronic pain, such as the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex, and orbitofrontal cortex). The results of this diprenorphine positron emission tomography study suggested that the more severe the RLS, the greater the release of endogenous opioids. Since 1993, when the first small controlled study was performed with oxycodone in RLS, opioids have been considered an efficacious off-label therapy in patients with severe RLS. A recent trial has proved the efficacy of a combination of prolonged release oxycodone/naloxone in patients with severe RLS as second-line therapy, with a mean dosage of 10/5 mg twice daily (mean difference of International Restless Legs Syndrome Study Group Rating Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been licensed as the first opioid therapy in Europe. The current results from both short- and long-term trials and studies with opioids encourage optimism in alleviating RLS symptoms in patients with severe RLS, or possibly during or after augmentation. (C) 2016 Elsevier B.V. All rights reserved
Rethinking clinical trials in restless legs syndrome: A roadmap.
No full textThe number of large clinical trials of restless legs syndrome (RLS) have decreased in recent years, this coincides with reduced interest in developing and testing novel pharmaceuticals. Therefore, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force of global experts to examine the causes of these trends and make recommendations to facilitate new clinical trials. In our article, we delve into potential complications linked to the diagnostic definition of RLS, identify subpopulations necessitating more attention, and highlight issues pertaining to endpoints and study frameworks. In particular, we recommend developing alternative scoring methods for more accurate RLS diagnosis, thereby improving clinical trial specificity. Furthermore, enhancing the precision of endpoints will increase study effect sizes and mitigate study costs. Suggestions to achieve this include developing online, real-time sleep diaries with high-frequency sampling of nightly sleep latency and the use of PLMs as surrogate markers. Furthermore, to reduce the placebo response, strategies should be adopted that include placebo run-in periods. As RLS is frequently a chronic condition, priority should be given to long-term studies, using a randomized, placebo-controlled, withdrawal design. Lastly, new populations should be investigated to develop targeted treatments such as mild RLS, pregnancy, hemodialysis, or iron-deficient anemia
Part 2. Identification of problems in functioning of persons with sleep disorders from the health professional perspective using the International Classification of Functioning, Disability and Health (ICF) as a reference: a worldwide expert survey
No full textObjectives. The objective of this study is to identify relevant aspects of functioning as well as related environmental factors from the perspective of health professionals worldwide experienced in treating persons with any kind of (primary) sleep disorder.Methods. A structured email survey was sent to 174 selected international experts. Using six open-ended questions, physicians, nurses, therapists, technicians, biologists and psychologists were asked to indicate the problems in functioning experienced by individuals with (primary) sleep disorders including contextual factors like environmental and personal factors which influence functioning. The International Classification of Functioning, Disability and Health (ICF) was used as a frame of reference to analyse the data. All answers were translated ("linked") to the ICF based on established coding rules. Absolute and relative frequencies of the linked ICF categories were reported.Results. One hundred and twenty-three experts (70.7%) from six World Health Organization (WHO) regions (54 countries) mentioned 5200 themes which were linked to 7256 ICF categories. The majority of these linkings (33.3%) were attributed to 58 different ICF categories of the ICF component body functions, followed by 21.8% of linkings to 52 categories of environmental factors, 16.1% of linkings to 49 different categories in activities and participation, and 9.7% of linkings to 29 categories of body structures.Conclusion. Health professionals addressed a large variety of functional problems reflecting the complexity of sleep disorders. The ICF provided a comprehensive framework in order to integrate answers from different professional backgrounds and different world regions
Comorbidities, treatment, and pathophysiology in restless legs syndrome.
No full textRestless legs syndrome, also known as Willis-Ekbom disease, is a common neurological condition whose manifestation is affected by complex environmental and genetic interactions. Restless legs syndrome can occur on its own, mostly at a young age, or with comorbidities such as cardiovascular disease, diabetes, and arterial hypertension, making it a difficult condition to properly diagnose. However, the concept of restless legs syndrome as being two entities, primary or secondary to another condition, has been challenged with genetic data providing further insight into the pathophysiology of the condition. Although dopaminergic treatment was formerly the first-line therapy, prolonged use can result in a serious worsening of symptoms known as augmentation. Clinical studies on pregabalin, gabapentin enacarbil, oxycodone-naloxone, and iron preparations have provided new treatment options, but most patients still report inadequate long-term management of symptoms. Studies of the hypoxic pathway activation and iron deficiency have provided valuable information about the pathophysiology of restless legs syndrome that should now be translated into new, more effective treatments for restless legs syndrome
Sleep-related motor and behavioral disorders: Recent advances and new entities
No full textABSTRACT Patients with sleep‐related motor and behavioral disorders present to a variety of subspecialty clinics (neurology, sleep medicine, respiratory medicine, psychiatry). Diagnosing these disorders can be difficult, and sometimes they have a significant impact on quality of life. Alongside a number of common and well‐recognized conditions, several new disease entities have been described in recent years that present with abnormal nocturnal motor phenomena (such as ADCY5‐associated disease and anti‐IgLON5 disease). Our understanding of the neural basis and prognostic significance of other sleep‐related disorders has also grown, particularly rapid eye movement sleep behavior disorder. This review (along with a collection of previously unpublished videos) is intended to aid in the recognition and treatment of these patients. The recent change in terminology from nocturnal frontal lobe epilepsy to sleep‐related hypermotor epilepsy is also discussed. © 2018 International Parkinson and Movement Disorder Societ
Brain imaging in RBD.
No full textNeuroimaging studies can provide in vivo insights to the early structural and functional brain changes in patients with idiopathic RBD (iRBD) and may help give a prognosis of disease course. This chapter summarizes the major findings of neuroimaging studies in iRBD, a specific prodromal stage of Parkinson’s disease (PD) and other α-synucleinopathies. Molecular imaging techniques, magnetic resonance imaging (MRI), and transcranial sonography (TCS) are all discussed
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