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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 3  |  Page : 664-665

High time we focus on sleep in amyotrophic lateral sclerosis!

Department of Neurology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication15-May-2018

Correspondence Address:
Dr. Garima Shukla
Room #2, 6th Floor, Neurosciences Center, All India Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.232309

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How to cite this article:
Shukla G, Gupta A. High time we focus on sleep in amyotrophic lateral sclerosis!. Neurol India 2018;66:664-5

How to cite this URL:
Shukla G, Gupta A. High time we focus on sleep in amyotrophic lateral sclerosis!. Neurol India [serial online] 2018 [cited 2022 Jul 3];66:664-5. Available from: https://www.neurologyindia.com/text.asp?2018/66/3/664/232309

While amyotrophic lateral sclerosis (ALS) remains a serious illness with early and high mortality rates, one of the factors which has consistently been identified as the cause of death is acute respiratory failure. As respiration gets initially affected during sleep, it is not at all surprising that sleep disordered breathing (SDB) is highly prevalent (40%–45%) among patients with ALS.[1] Nocturnal hypoventilation has also been found with a similar high prevalence in these patients.[1] At a deeper level, sleep-related (nocturnal) rise in PaCO2 commonly found in ALS can largely be attributed to rapid eye movement (REM)-related loss of tone in the diaphragm, which is most resilient to the physiological atonia of REM sleep. Chemosensitivity that regulates ventilatory responses to hypoxia and hypercapnia is reduced during sleep, much more so during REM sleep; and among patients with ALS, this physiological phenomenon is grossly exaggerated and results in CO2 retention frequently observed in ALS.[2] Importantly, because there is a lot of variability in blood gases during a single sleep episode, it is mandated that at least one baseline evaluation of respiration and a simultaneous noninvasive evaluation of oxygen saturation and CO2 levels is carried out for all patients with ALS, especially in those with neck weakness and bulbar involvement, and certainly in those with respiratory involvement.

A Cochrane review concludes that mechanical ventilation, to a considerable extent, prolongs survival among patients with ALS and improves or maintains their quality of life significantly. While with the use of early mechanical ventilation, survival is not prolonged among patients with ALS with poor bulbar function, even in this subpopulation, significant improvement is seen in the mean symptom domain of the sleep apnea quality-of-life index.[3]

Evaluation and appropriate treatment of problems during sleep, especially respiratory, in patients with ALS is, therefore, the need of the hour. Systematic categorization of patients who would benefit from early noninvasive ventilation would certainly help to some extent in providing best possible quality of life to patients suffering from this serious ailment.

Apart from SDB, other primary sleep disorders may also contribute to poor sleep quality and the resultant overall health-related quality of life in ALS. A few studies have demonstrated a high (18%–25%) prevalence of restless legs syndrome (RLS) in ALS,[4],[5] and at least one study has shown a very high periodic limb movement (PLM) index in ALS (53%) compared with normal controls (11%), with early mortality being more common among those with a PLM index greater than five.[6] Timely recognition and treatment of RLS could certainly contribute towards improving the quality of life in ALS.

Studying occurrence of REM sleep behavior disorder in association with ALS (especially familial) might provide insights into the diverse pathogenic processes of this illness. The observation of loss of normally preserved tone in respiratory muscles (diaphragm and accessory muscles such as sternomastoid and genioglossus) is an important indicator of respiratory failure. Better characterization of diaphragm function and tone of various muscles of respiration during sleep could lead to identification of patients who should be selected for early mechanical ventilation.

The study by Panda et al., appearing in this issue, is an important contribution to literature on sleep problems reported by patients suffering from ALS.[7] The recognition of a high prevalence of perceived sleep problems is the first step toward better confirmation and classification of various primary sleep disorders and sleep-related symptoms among these patients. There are certain limitations acknowledged by the authors, mainly a small sample size and lack of polysomnographic assessment; nevertheless, the study does provide an overview of sleep problems reported by patients with ALS. The only predictor of sleep disorders or disturbed sleep reported in this study is excessive daytime sleepiness. While this is similar to the observation made by Lo Coco et al.,[8] our view is that this is scientifically not a very appropriate predictor to be studied in a regression model, as it is a natural co-symptom of disturbed sleep. Similarly, tabulation of a number of patients classified to be having various sleep disorders as “good” and “poor' sleepers is possibly self-explanatory and is not required. The other points which can be discussed are the very high prevalence of insomnia and depression–anxiety and the low prevalence of RLS. The former could be a consequence of a small sample size. For the latter, it is more possible that patients may not have readily recognized their symptoms to match the questions derived from the RLS rating scale alone, and a more extensive tool for this ethnic population may help to identify more patients with RLS.[9]

An important relationship which could have been studied is between the presence of sleep-related symptoms, as well as depression and anxiety, with the use of riluzole and/or anti-depressants, before embarking upon the current evaluation. While most of the latter medications are known to reduce REM sleep percentage, riluzole has been shown to increase the same [10] and has also been shown to have an antidepressant effect on its own.[11]

Making a serious note of the paucity of large well-designed studies on sleep, especially on SDB in ALS, it is important that such studies [7] incorporate a detailed clinical evaluation and special protocol polysomnography be carried out, as that will help to guide important therapeutic decisions for these patients.

  References Top

Boentert M, Glatz C, Helmle C, Okegwo A, Young P. Prevalence of sleep apnoea and capnographic detection of nocturnal hypoventilation in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2018;89:418-24.  Back to cited text no. 1
Aboussouan LS, Mireles-Cabodevila E. Sleep-disordered breathing in neuromuscular disease: Diagnostic and therapeutic challenges. Chest 2017;152:880-92.  Back to cited text no. 2
Radunovic A, Annane D, Rafiq MK, Mustfa N. Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 2013;(3):CD004427.  Back to cited text no. 3
Lo Coco D, Piccoli F, La Bella V. Restless legs syndrome in patients with amyotrophic lateral sclerosis. Mov Disord 2010;25:2658-61.  Back to cited text no. 4
Limousin N, Blasco H, Corcia P, Arnulf I, Praline J. The high frequency of restless legs syndrome in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2011;12:303-6.  Back to cited text no. 5
Moszczynski AJ, Tandon A, Coelho FM, Zinman L, Murray B. Mortality associated with periodic limb movements during sleep in amyotrophic lateral sclerosis patients. Einstein (Sao Paulo) 2012;10:428-32.  Back to cited text no. 6
Panda S, Gourie-Devi M, Sharma A. Sleep disorders in amyotrophic lateral sclerosis: A questionnaire-based study from India. Neurol India 2018;66:700-8.  Back to cited text no. 7
  [Full text]  
Lo Coco D, Mattaliano P, Spataro R, Mattaliano A, La Bella V. Sleep wake disturbances in patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2011;82:839-42.  Back to cited text no. 8
Shukla G, Bajpai G, Gupta A, Katoch J, Mohammed A, Pandey RM. Evaluation of the diagnostic yield of ARQIP – A new restless legs syndrome diagnostic questionnaire and validation of its Hindi translation. Neurol India 2018 (in press).  Back to cited text no. 9
Stutzmann JM, Lucas M, Blanchard JC, Laduron PM. Riluzole, a glutamate antagonist, enhances slow wave and REM sleep in rats. Neurosci Lett 1988;88:195-200.  Back to cited text no. 10
Sanacora G, Kendell SF, Fenton L, Coric V, Krystal JH. Riluzole augmentation for treatment-resistant depression. Am J Psychiatr 2004;161:2132.  Back to cited text no. 11


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