Sleep disturbances in patients with amyotrophic lateral sclerosis: current perspectives

Nature and Science of Sleep Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Nature and Science of Sleep downloaded from https://www.dovepress.com/ by 88.198.20.149 on 24-Oct-2019 For personal use only. Sleep disturbances in patients with amyotrophic lateral sclerosis: current perspectives This article was published in the following Dove Press journal: Nature and Science of Sleep Matthias Boentert Department of Neurology, University Hospital Muenster, Muenster, Germany Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease inevitably leading to generalized muscle weakness and premature death. Sleep disturbances are extremely common in patients with ALS and substantially add to the burden of disease for both patients and caregivers. Disruption of sleep can be caused by physical symptoms, such as muscle cramps, pain, reduced mobility, spasticity, mucus retention, and restless legs syndrome. In addition, depression and anxiety may lead to significant insomnia. In a small subset of patients, rapid eye movement (REM) sleep behavioral disorder may be present, reflecting neurodegeneration of central nervous system pathways which are involved in REM sleep regulation. With regard to overall prognosis, sleep-disordered breathing (SDB) and nocturnal hypoventilation (NH) are of utmost importance, particularly because NH precedes respiratory failure. Timely mechanical ventilation is one of the most significant therapeutic measures to prolong life span in ALS, and transcutaneous capnometry is superior to pulse oxymetry to detect NH early. In addition, it has been shown that in patients on home ventilatory support, survival time depends on whether normocapnia, normoxia, and elimination of apneic events during sleep can be reliably achieved. Several studies have investigated sleep patterns and clinical determinants of sleep disruption in ALS, but exact prevalence numbers are unknown. Thus, constant awareness for sleep-related symptoms is appropriate. Since no curative treatment can be offered to affected patients, sleep complaints should be thoroughly investigated in order to identify any treatable etiology and improve or stabilize quality of life as much as possible. The use of hypnotics should be confined to palliation during the terminal phase and refractory insomnia in earlier stages of the disease, taking into account that most compounds potentially aggravate SDB. Keywords: amyotrophic lateral sclerosis, sleep disorders, sleep-disordered breathing, noninvasive ventilation, health-related quality of life Plain language summary Correspondence: Matthias Boentert Department of Neurology, University Hospital Muenster, Albert-SchweitzerCampus 1, Building A1 48149, Münster, Germany Tel +49 251 834 4458 Fax +49 251 834 5059 Email 97 submit your manuscript | www.dovepress.com Nature and Science of Sleep 2019:11 97–111 DovePress © 2019 Boentert. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://doi.org/10.2147/NSS.S183504 Powered by TCPDF (www.tcpdf.org) Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease which causes advancing weakness of all muscles. Depending on the muscle involved, patients may suffer from reduced mobility, swallowing difficulties, impaired speech, and finally, respiratory muscle weakness. In patients with ALS, many different problems may cause sleep disturbances. For example, patients cannot turn around in bed any more, or they get pain from being severely immobilized. Many patients have difficulties to fall or stay asleep because of muscle cramps and restless legs. Respiratory muscle weakness is the most important condition which may disturb sleep because it leads to shallow breathing during the night and accumulation of carbon dioxide in the blood. If this is present, life span of ALS patients can be improved by starting non-invasive ventilation (NIV) using a facial mask. This can be even better achieved when NIV is started as early as it becomes necessary. In addition, regular follow-up appointments in a sleep lab help to ensure Dovepress Nature and Science of Sleep downloaded from https://www.dovepress.com/ by 88.198.20.149 on 24-Oct-2019 For personal use only. Boentert optimal home ventilation. Sleep disturbances are very common in patients with ALS, and constant awareness for sleep-related complaints is appropriate. Since there is no cure for ALS, it is even more important to systematically look for treatable problems and symptoms in order to improve or maintain quality of life as much as possible. The use of sleep medications should be confined to the last phase of the disease prior to death or to intractable insomnia in earlier stages. Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the central and peripheral nervous system. The term ALS covers a broad clinical spectrum of different disease manifestations (or rather entities) which share the degeneration of both upper and lower motor neurons.1,2 Upper motor neuron involvement leads to increased muscle tone, spastic paresis and, if the corticobulbar tract is affected, to pseudobulbar palsy. Degeneration of lower motor neurons causes fasciculations, atrophy, and weakness of involved muscles. Virtually all skeletal muscles may be affected, including the extraocular and sphincter externi muscles in later stages of the disease.3,4 In a subset of patients, degeneration of the motor system is accompanied by either mild to moderate cognitive and behavioral abnormalities or overt frontotemporal dementia.5 The prevalence of ALS has been reported to be 5–8/100.000 in industrialized countries, with a peak of disease manifestation between 50 and 70 years of age.6–9 The lifetime risk for ALS may be as high as 1:300 for men and 1:400 for women.10,11 Although vast evidence has been collected on different pathomechanisms leading to motor neuron degeneration,12 no causative treatment is available to date. Only two compounds have been approved for the treatment of ALS, which include riluzole (possibly protecting motor neurons from glutamate excitotoxicity)13–15 and edaravone which has been postulated to scavenge free oxygen radicals.16,17 However, both medications can only be considered as disease-modifying but do not actually halt its progression. Thus, depending on the individual course of t (...truncated)