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• Sleep apnoea and nocturnal hypoventilation in patients with amyotrophic lateral sclerosis
  Tomoyuki Kawada
  Published on: 11 July 2018
• Classification of respiratory events in amyotrophic lateral sclerosis: diagnostic and therapeutic challenges
  Grazia Crescimanno, Francesca Greco, Alessandra Sorano and Oreste Marrone
  Published on: 15 March 2018

• Published on: 11 July 2018

  Sleep apnoea and nocturnal hypoventilation in patients with amyotrophic lateral sclerosis

  • Tomoyuki Kawada, Professor Nippon Medical School

  Boentert et al. investigated the prevalence of sleep apnoea and nocturnal hypoventilation (NH) in 250 patients with non-ventilated amyotrophic lateral sclerosis (ALS) by considering gender and severity of bulbar dysfunction (1). Prevalence of NH and apnoea-hypopnoea index (AHI) >5/hour was 40.0% and 45.6%, respectively, and 22.3% of patients had both NH and sleep apnoea. Sleep apnoea was significantly more common in male patients and negatively associated with bulbar function. I have some concerns with this study.

  First, the authors did not conduct stratified analysis by gender. As the prevalence of sleep apnoea differs by gender, the association between sleep apnoea, NH and severity of bulbar dysfunction should be analyzed by stratification with gender.

  Second, the authors conducted univariate analyses, and adjustment of independent variables cannot be made. Although the number of patients is limited, recommendation for the use of transcutaneous capnography should be based by appropriate adjustments of confounders.

  Finally, Park et al. evaluated the relationship between nocturnal hypoxia and cognitive dysfunction in patients with ALS, and patients with nocturnal hypoxia showed poor memory retention and retrieval efficiency. They speculated that patients with ALS might be exposed to repeated episodes of deoxygenation-reoxygenation during sleep, because of the weakness of the respiratory muscles. In order to evaluate the effect of desaturation on ALS...

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  Boentert et al. investigated the prevalence of sleep apnoea and nocturnal hypoventilation (NH) in 250 patients with non-ventilated amyotrophic lateral sclerosis (ALS) by considering gender and severity of bulbar dysfunction (1). Prevalence of NH and apnoea-hypopnoea index (AHI) >5/hour was 40.0% and 45.6%, respectively, and 22.3% of patients had both NH and sleep apnoea. Sleep apnoea was significantly more common in male patients and negatively associated with bulbar function. I have some concerns with this study.

  First, the authors did not conduct stratified analysis by gender. As the prevalence of sleep apnoea differs by gender, the association between sleep apnoea, NH and severity of bulbar dysfunction should be analyzed by stratification with gender.

  Second, the authors conducted univariate analyses, and adjustment of independent variables cannot be made. Although the number of patients is limited, recommendation for the use of transcutaneous capnography should be based by appropriate adjustments of confounders.

  Finally, Park et al. evaluated the relationship between nocturnal hypoxia and cognitive dysfunction in patients with ALS, and patients with nocturnal hypoxia showed poor memory retention and retrieval efficiency. They speculated that patients with ALS might be exposed to repeated episodes of deoxygenation-reoxygenation during sleep, because of the weakness of the respiratory muscles. In order to evaluate the effect of desaturation on ALS prognosis, cognitive function should also be included for the analysis.

  Reference

  1. Boentert M, Glatz C, Helmle C, et al. Prevalence of sleep apnoea and capnographic detection of nocturnal hypoventilation in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2018;89(4):418-424.

  2. Park SY, Kim SM, Sung JJ, et al. Nocturnal hypoxia in ALS is related to cognitive dysfunction and can occur as clusters of desaturations. PLoS One 2013;8(9):e75324.

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  Conflict of Interest:
  None declared.

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• Published on: 15 March 2018

  Classification of respiratory events in amyotrophic lateral sclerosis: diagnostic and therapeutic challenges

  • Grazia Crescimanno, Pneumologist 1 Italian National Research Council, Institute of Biomedicine and Molecular Immunology, Palermo.
  • Other Contributors:
    • Francesca Greco, Sleep technologist
    • Alessandra Sorano, MD
    • Oreste Marrone, Pneumologist

  Dear Editor,
  We read with great interest the article of Boentert et al.1 recently published on this journal. In their paper, the authors describe polysomnographic findings in a large series of non-ventilated patients with amyotrophic lateral sclerosis (ALS). One of the points the authors underscore is that in their patients most respiratory events during sleep were of the obstructive, and not of the central type. This finding is in agreement with what described by Kimura,2 but not by several other authors who found that most respiratory events were of the central type.3 Furthermore, the authors of this paper did not find that obstructive apneas were preferentially associated with bulbar ALS, similarly to David et al.4 but unlike what described by Santos et al.5 However, the tables in the article show that most of the respiratory events were hypopneas, whose type was not specified.
  Criteria for scoring sleep disordered breathing events have changed over time, especially as regards hypopneas. Only recently a general rule for type of hypopnea, central or obstructive has been proposed. Obstructive hypopneas are those where at least one of three criteria is met during the event: presence of snoring, flow limitation demonstrated by a flattening of the nasal pressure derived flow signal, opposing thoracic and abdominal movements. Absence of all these criteria characterizes central hypopneas.6 However, standard criteria for apneas and hypopneas fit well to patients wi...

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  Dear Editor,
  We read with great interest the article of Boentert et al.1 recently published on this journal. In their paper, the authors describe polysomnographic findings in a large series of non-ventilated patients with amyotrophic lateral sclerosis (ALS). One of the points the authors underscore is that in their patients most respiratory events during sleep were of the obstructive, and not of the central type. This finding is in agreement with what described by Kimura,2 but not by several other authors who found that most respiratory events were of the central type.3 Furthermore, the authors of this paper did not find that obstructive apneas were preferentially associated with bulbar ALS, similarly to David et al.4 but unlike what described by Santos et al.5 However, the tables in the article show that most of the respiratory events were hypopneas, whose type was not specified.
  Criteria for scoring sleep disordered breathing events have changed over time, especially as regards hypopneas. Only recently a general rule for type of hypopnea, central or obstructive has been proposed. Obstructive hypopneas are those where at least one of three criteria is met during the event: presence of snoring, flow limitation demonstrated by a flattening of the nasal pressure derived flow signal, opposing thoracic and abdominal movements. Absence of all these criteria characterizes central hypopneas.6 However, standard criteria for apneas and hypopneas fit well to patients with sleep apnea syndromes, but may be difficult to use in patients with other disorders, and in particular in those with neuromuscular diseases.
  The separate occurrence of central and obstructive hypopneas was reported in some ALS studies, although standard criteria were not applied. However, a sharp separation of obstructive and central hypopneas in patients with ALS may be difficult, either using standard criteria or not, and often factitious. A clear flattening of the flow signal may not be clearly identified with a weak flow signal. Paradoxical thoraco-abdominal movements may be the effect not only of upper airway narrowing but also of respiratory muscle weakness. Finally, perhaps most importantly, presence of obstruction during a hypopnea does not exclude a simultaneous reduction of respiratory drive, thus a concomitant central genesis of the event.
  Even when dealing with apneas, the precise nature of an event in neuromuscular patients is often dubious based on its polygraphic appearance. In the International Classification of Sleep Disorders, central apneas are indicated as the result of a failure of ventilatory control centers to initiate ventilatory effort.7 However, in common practice central apneas are identified by the absence of respiratory movements on polygraphic recordings, although it may not be always easy to precisely identify the pathogenesis of an event based on its polygraphic expression. In neuromuscular patients, many apneas are associated with very small movements. That may lead different scorers to classify them as either central or obstructive. Some authors suggested to introduce the new category of “pseudocentral apneas” to indicate events occurring when the contraction of respiratory muscles is too weak to maintain breathing, which may be more often seen in phasic REM sleep.8 During these events, deflections in the traces of the respiratory movements are very small. Despite their polygraphic aspect resembles apneas more often of the central type, their pathogenesis depends more on peripheral that on central causes. This category of events is not taken in consideration by most authors studying neuromuscular patients. Probably, a non-uniform way to score respiratory events in ALS is one reason for some discrepancies among studies.
  We are aware that a correct identification of central and obstructive events is important, because they require different ventilatory approaches that may have a strong influence on sleep quality, therapy acceptance and, in the long-term, disease evolution and survival. Use of positive expiratory pressure, which is mandatory when obstructive events are present, is not only useless, but also questionable in case of absence of upper airway obstruction, as it enhances patient-ventilator asynchronies and sympathetic nervous system tone during sleep.9
  Possibly, criteria for scoring sleep disordered breathing events in non-ventilated patients with neuromuscular diseases should be better standardized. They could be useful to have a better agreement among physicians who evaluate polysomnographic recordings, and to better guide in the choice of an appropriate therapeutic strategy.

  REFERENCES

  1 Boentert M, Glatz C, Helmle C, et al. Prevalence of sleep apnoea and capnographic detection of nocturnal hypoventilation in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2017 doi: 10.1136/jnnp-2017-316515.
  2 Kimura K, Tachibana N, Kimura J, et al. Sleep-disordered breathing at an early stage of amyotrophic lateral sclerosis. J Neurol Sci 1999;164:37-43.
  3 Aboussouan LS, Mireles-Cabodevila E. Sleep-Disordered Breathing in Neuromuscular Disease: Diagnostic and Therapeutic Challenges. Chest 2017;152:880-892.
  4 David WS, Bundlie SR, Mahdavi Z. Polysomnographic studies in amyotrophic lateral sclerosis. J Neurol Sci 1997;152:29-35
  5 Santos C, Braghiroli A, Mazzini L, et al. Sleep-related breathing disorders in amyotrophic lateral sclerosis. Monaldi Arch Chest Dis 2003;59:160-5.
  6 Berry RB, Budhiraja R, Gottlieb DJ, et al. American Academy of Sleep Medicine. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med 2012;8:597-619
  7 American Academy of Sleep Medicine . International Classification of Sleep Disorders . 3rd ed. Darien, IL : American Academy of Sleep Medicine; 2014.
  8 Gould GA, Gugger M, Molloy J, et al. Breathing pattern and eye movement density during REM sleep in humans. Am Rev Respir Dis 1988;138:874-7
  9 Crescimanno G, Greco F, Arrisicato S, et al. Effects of positive end expiratory pressure administration during non-invasive ventilation inpatients affected by amyotrophic lateral sclerosis: A randomized crossover study. Respirology 2016;21:1307-13

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  Conflict of Interest:
  None declared.

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