Commentary on “Transient intracranial pressure elevations (B waves) associated with sleep apnea”: the neglected role of cyclic alternating pattern

IF 5.9 1区 医学 Q1 NEUROSCIENCES Fluids and Barriers of the CNS Pub Date : 2024-09-17 DOI:10.1186/s12987-024-00569-x
Carlotta Mutti, Clara Rapina, Francesco Rausa, Giulia Balella, Dario Bottignole, Marcello Giuseppe Maggio, Liborio Parrino
{"title":"Commentary on “Transient intracranial pressure elevations (B waves) associated with sleep apnea”: the neglected role of cyclic alternating pattern","authors":"Carlotta Mutti, Clara Rapina, Francesco Rausa, Giulia Balella, Dario Bottignole, Marcello Giuseppe Maggio, Liborio Parrino","doi":"10.1186/s12987-024-00569-x","DOIUrl":null,"url":null,"abstract":"<p>Riedel et al. recently published an interesting paper on the association between intracranial pressure (ICP) elevation, measured through the Lundberg B waves, and sleep apnea in a group of patients with idiopathic intracranial hypertension (IIH) and hydrocephalus [1].</p><p>ICP B waves are defined as short, repetitive elevation of intracranial pressure of up to 50 mmHg with a frequency of 0.5-2 waves/min, which are typically observed in patients with IIH, but can also be measured in subjects with normal intracranial pressure [2].</p><p>Obstructive sleep apnea (OSA) is a multi-systemic syndrome characterized by phasic interruptions of airflow during sleep, leading to severe sleep fragmentation and cardiovascular consequences, presenting a typical 20-40 s periodicity (Panel A, Fig. 1).</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12987-024-00569-x/MediaObjects/12987_2024_569_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"383\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12987-024-00569-x/MediaObjects/12987_2024_569_Fig1_HTML.png\" width=\"685\"/></picture><p><b>A</b> Vertical integration between CAP fluctuations during NREM sleep, respiratory events, oxygen desaturation and pulse rate dynamic in a patient affected by OSA. <b>B</b> figure published in Riedel et al., 2023 showing the vertical integration between ICP oscillations, obstructive apnea events and sleep fragmentation. <b>C</b> example of physiological CAP fluctuations during NREM sleep in a healthy subject. <b>D</b> example of stable NREM with no CAP intrusion</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>According to Riedel et al. [1], there is an interesting association between ICP B waves and sleep apnea. The overlap of B waves with repetitive respiratory events induces a further increase in the ICP elevation (See Panel B in Fig. 1). The synusoidal pattern becomes particularly relevant during obstructive respiratory events (compared to central-type events), whereas the introduction of CPAP leads to overall reduction of phasic ICP elevations.</p><p>Riedel et al. [1] show the temporal coupling between ICP fluctuations, nasal airflow flattening, thorax and abdomen activity changes, SatO2% oscillations and sleep stage dynamics.</p><p>In Panel B (Fig. 1) severe sleep fragmentation characterized by numerous brief awakening lasting &lt; 2 min is recognizable in a patient with idiopathic normal pressure hydrocephalus and OSA during stage N2 of NREM sleep.</p><p>It is known that OSA is closely associated cyclic alternating pattern (CAP) oscillations, including not only fast but also slow-wave arousals [3], tightly linked to the severity of the ongoing sleep-disordered breathing [4]. CAP is the electrophysiological biomarker of sleep instability, periodically interrupting the EEG background during NREM sleep (Panel C). It is interesting to notice that CAP shares exactly the same time domain of Lundberg B waves, ranging from 2 to 60 s, and overcomes the rigid boundaries of 30 s for sleep scoring. The remaining stationary EEG activity during NREM sleep is described as non-CAP sleep (Panel D, Fig. 1).</p><p>Instead of speaking of brief awakenings or arousals, we suggest that the association between Lundberg B waves and the OSA-dependent sleep-fragmentation is more adequately mirrored by CAP metrics. The relationship between CAP and ICP B waves was already anticipated in a previous study on sleep in a comatose patient [5].</p><p>Riedel et al. [1] demonstrated that Lundberg B waves are significantly modified by CPAP in the explored OSA cohort. CAP undergoes the same evolution, reducing its fluctuations under non-invasive ventilation [6].</p><p>These findings may explain the partial loss of a clear-cut oscillatory pattern of ICP fluctuations during REM sleep, as it is know that CAP physiologically occurs only in NREM sleep [7].</p><p>Regardless of the sleep stage, NREM sleep can been described as a bimodal brain state with the alternation of stable (non-CAP) and unstable (CAP) regimens (respectively see Panel C and Panel D in Fig. 1). A “vertically integrated” approach, inclusive of extra-encephalographic features (e.g. cardiopulmonary coupling, behavioural changes and perhaps, also the intracranial B waves), is probably the most adequate methodology to investigate all the oscillations during NREM sleep [8]</p><p>To the best of our knowledge, studies exploring the link between ICP elevations and CAP had never been performed. We foster the exploration of the potentially entangled relationship between these two periodic events with further investigations.</p><p>No datasets were generated or analysed during the current study.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Riedel CS, Martinez-Tejada I, Andresen M, Wilhjelm JE, Jennum P, Juhler M. Transient intracranial pressure elevations (B waves) are associated with sleep apnea. Fluids Barriers CNS. 2023;20(1):69. https://doi.org/10.1186/s12987-023-00469-6.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\"2.\"><p>Riedel CS, Martinez-Tejada I, Norager NH, Kempfner L, Jennum P, Juhler M. B-waves are present in patients without intracranial pressure disturbances. J Sleep Res. 2021;30(4): e13214. https://doi.org/10.1111/jsr.13214.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"3.\"><p>Milioli G, Bosi M, Grassi A, et al. Can sleep microstructure improve diagnosis of OSAS? integrative information from CAP parameters. Arch Ital Biol. 2015;153(2–3):194–203. https://doi.org/10.12871/0003982920152344.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"4.\"><p>Gnoni V, Drakatos P, Higgins S, et al. Cyclic alternating pattern in obstructive sleep apnea: a preliminary study. J Sleep Res. 2021;30(6): e13350. https://doi.org/10.1111/jsr.13350.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"5.\"><p>Terzano MG, Gatti PL, Manzoni GC, Formentini E, Mancia D. Is the EEG cyclic alternating pattern a true autonomous entity? analytic study in a case of post-traumatic coma with good prognosis. Eur Neurol. 1982;21(5):324–34. https://doi.org/10.1159/000115499.</p><p>Article CAS PubMed Google Scholar </p></li><li data-counter=\"6.\"><p>Parrino L, Thomas RJ, Smerieri A, Spaggiari MC, Del Felice A, Terzano MG. Reorganization of sleep patterns in severe OSAS under prolonged CPAP treatment. Clin Neurophysiol. 2005;116(9):2228–39. https://doi.org/10.1016/j.clinph.2005.05.005.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"7.\"><p>Terzano MG, Parrino L, Boselli M, Spaggiari MC, Di Giovanni G. Polysomnographic analysis of arousal responses in obstructive sleep apnea syndrome by means of the cyclic alternating pattern. J Clin Neurophysiol. 1996;13(2):145–55. https://doi.org/10.1097/00004691-199603000-00005.</p><p>Article CAS PubMed Google Scholar </p></li><li data-counter=\"8.\"><p>Parrino L, Halasz P, Szucs A, et al. Sleep medicine: Practice, challenges and new frontiers. Front Neurol. 2022;13:966659. https://doi.org/10.3389/fneur.2022.966659.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Sleep Disorders Center, Department of Medicine and Surgery, Parma University Hospital, Parma, Italy</p><p>Carlotta Mutti, Clara Rapina, Francesco Rausa, Giulia Balella, Dario Bottignole &amp; Liborio Parrino</p></li><li><p>Interdepartmental Centre for Sleep Medicine, University of Parma, Parma, Italy</p><p>Carlotta Mutti, Francesco Rausa, Marcello Giuseppe Maggio &amp; Liborio Parrino</p></li><li><p>Geriatric Clinic Unit, Geriatric-Rehabilitation Department, University Hospital, 43126, Parma, Italy</p><p>Marcello Giuseppe Maggio</p></li></ol><span>Authors</span><ol><li><span>Carlotta Mutti</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Clara Rapina</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Francesco Rausa</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Giulia Balella</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Dario Bottignole</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Marcello Giuseppe Maggio</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Liborio Parrino</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Contributions</h3><p>C.M. and L.P. wrote the main manuscript text and prepared figures. All authors reviewed and approved the manuscript in its final form.</p><h3>Corresponding author</h3><p>Correspondence to Liborio Parrino.</p><h3>Competing interests</h3>\n<p>The authors declare no competing interests.</p><h3>Publisher's Note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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“Transient intracranial pressure elevations (B waves) associated with sleep apnea”: the neglected role of cyclic alternating pattern. <i>Fluids Barriers CNS</i> <b>21</b>, 75 (2024). https://doi.org/10.1186/s12987-024-00569-x</p><p>Download citation<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><ul data-test=\"publication-history\"><li><p>Received<span>: </span><span><time datetime=\"2024-06-04\">04 June 2024</time></span></p></li><li><p>Accepted<span>: </span><span><time datetime=\"2024-08-18\">18 August 2024</time></span></p></li><li><p>Published<span>: </span><span><time datetime=\"2024-09-17\">17 September 2024</time></span></p></li><li><p>DOI</abbr><span>: </span><span>https://doi.org/10.1186/s12987-024-00569-x</span></p></li></ul><h3>Share this article</h3><p>Anyone you share the following link with will be able to read this 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Abstract

Riedel et al. recently published an interesting paper on the association between intracranial pressure (ICP) elevation, measured through the Lundberg B waves, and sleep apnea in a group of patients with idiopathic intracranial hypertension (IIH) and hydrocephalus [1].

ICP B waves are defined as short, repetitive elevation of intracranial pressure of up to 50 mmHg with a frequency of 0.5-2 waves/min, which are typically observed in patients with IIH, but can also be measured in subjects with normal intracranial pressure [2].

Obstructive sleep apnea (OSA) is a multi-systemic syndrome characterized by phasic interruptions of airflow during sleep, leading to severe sleep fragmentation and cardiovascular consequences, presenting a typical 20-40 s periodicity (Panel A, Fig. 1).

Fig. 1
Abstract Image

A Vertical integration between CAP fluctuations during NREM sleep, respiratory events, oxygen desaturation and pulse rate dynamic in a patient affected by OSA. B figure published in Riedel et al., 2023 showing the vertical integration between ICP oscillations, obstructive apnea events and sleep fragmentation. C example of physiological CAP fluctuations during NREM sleep in a healthy subject. D example of stable NREM with no CAP intrusion

Full size image

According to Riedel et al. [1], there is an interesting association between ICP B waves and sleep apnea. The overlap of B waves with repetitive respiratory events induces a further increase in the ICP elevation (See Panel B in Fig. 1). The synusoidal pattern becomes particularly relevant during obstructive respiratory events (compared to central-type events), whereas the introduction of CPAP leads to overall reduction of phasic ICP elevations.

Riedel et al. [1] show the temporal coupling between ICP fluctuations, nasal airflow flattening, thorax and abdomen activity changes, SatO2% oscillations and sleep stage dynamics.

In Panel B (Fig. 1) severe sleep fragmentation characterized by numerous brief awakening lasting < 2 min is recognizable in a patient with idiopathic normal pressure hydrocephalus and OSA during stage N2 of NREM sleep.

It is known that OSA is closely associated cyclic alternating pattern (CAP) oscillations, including not only fast but also slow-wave arousals [3], tightly linked to the severity of the ongoing sleep-disordered breathing [4]. CAP is the electrophysiological biomarker of sleep instability, periodically interrupting the EEG background during NREM sleep (Panel C). It is interesting to notice that CAP shares exactly the same time domain of Lundberg B waves, ranging from 2 to 60 s, and overcomes the rigid boundaries of 30 s for sleep scoring. The remaining stationary EEG activity during NREM sleep is described as non-CAP sleep (Panel D, Fig. 1).

Instead of speaking of brief awakenings or arousals, we suggest that the association between Lundberg B waves and the OSA-dependent sleep-fragmentation is more adequately mirrored by CAP metrics. The relationship between CAP and ICP B waves was already anticipated in a previous study on sleep in a comatose patient [5].

Riedel et al. [1] demonstrated that Lundberg B waves are significantly modified by CPAP in the explored OSA cohort. CAP undergoes the same evolution, reducing its fluctuations under non-invasive ventilation [6].

These findings may explain the partial loss of a clear-cut oscillatory pattern of ICP fluctuations during REM sleep, as it is know that CAP physiologically occurs only in NREM sleep [7].

Regardless of the sleep stage, NREM sleep can been described as a bimodal brain state with the alternation of stable (non-CAP) and unstable (CAP) regimens (respectively see Panel C and Panel D in Fig. 1). A “vertically integrated” approach, inclusive of extra-encephalographic features (e.g. cardiopulmonary coupling, behavioural changes and perhaps, also the intracranial B waves), is probably the most adequate methodology to investigate all the oscillations during NREM sleep [8]

To the best of our knowledge, studies exploring the link between ICP elevations and CAP had never been performed. We foster the exploration of the potentially entangled relationship between these two periodic events with further investigations.

No datasets were generated or analysed during the current study.

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Authors and Affiliations

  1. Sleep Disorders Center, Department of Medicine and Surgery, Parma University Hospital, Parma, Italy

    Carlotta Mutti, Clara Rapina, Francesco Rausa, Giulia Balella, Dario Bottignole & Liborio Parrino

  2. Interdepartmental Centre for Sleep Medicine, University of Parma, Parma, Italy

    Carlotta Mutti, Francesco Rausa, Marcello Giuseppe Maggio & Liborio Parrino

  3. Geriatric Clinic Unit, Geriatric-Rehabilitation Department, University Hospital, 43126, Parma, Italy

    Marcello Giuseppe Maggio

Authors
  1. Carlotta MuttiView author publications

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  2. Clara RapinaView author publications

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Contributions

C.M. and L.P. wrote the main manuscript text and prepared figures. All authors reviewed and approved the manuscript in its final form.

Corresponding author

Correspondence to Liborio Parrino.

Competing interests

The authors declare no competing interests.

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Mutti, C., Rapina, C., Rausa, F. et al. Commentary on “Transient intracranial pressure elevations (B waves) associated with sleep apnea”: the neglected role of cyclic alternating pattern. Fluids Barriers CNS 21, 75 (2024). https://doi.org/10.1186/s12987-024-00569-x

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关于 "与睡眠呼吸暂停相关的一过性颅内压升高(B 波)"的评论:被忽视的周期性交替模式的作用
Riedel 等人最近发表了一篇有趣的论文,研究了一组特发性颅内高压(IIH)和脑积水患者的颅内压(ICP)升高(通过伦德伯格 B 波测量)与睡眠呼吸暂停之间的关系[1]。ICP B 波是指颅内压短时、重复性升高,最高可达 50 mmHg,频率为 0.5-2 波/分钟,通常在 IIH 患者中观察到,但也可在颅内压正常的受试者中测量到[2]。阻塞性睡眠呼吸暂停(OSA)是一种多系统综合征,其特点是睡眠期间气流的阶段性中断,导致严重的睡眠破碎和心血管后果,呈现典型的 20-40 秒周期性(图 1,A 组)。B 图发表于 Riedel 等人,2023 年,显示了 ICP 振荡、阻塞性呼吸暂停事件和睡眠片段之间的垂直整合。C 健康人 NREM 睡眠期间 CAP 生理波动示例。根据 Riedel 等人的研究[1],ICP B 波与睡眠呼吸暂停之间存在有趣的联系。B 波与重复呼吸事件重叠会导致 ICP 进一步升高(见图 1 中的 B 小组)。Riedel 等人[1] 显示了 ICP 波动、鼻气流平缓、胸腹活动变化、SatO2% 振荡和睡眠阶段动态之间的时间耦合。众所周知,OSA 与周期性交替模式(CAP)振荡密切相关,不仅包括快波唤醒,还包括慢波唤醒[3],与正在发生的睡眠呼吸紊乱的严重程度密切相关[4]。CAP 是睡眠不稳定性的电生理生物标记,在 NREM 睡眠期间周期性地干扰脑电图背景(C 小组)。值得注意的是,CAP 与伦德伯格 B 波的时域完全相同,从 2 秒到 60 秒不等,突破了睡眠评分 30 秒的硬性界限。NREM 睡眠期间剩余的静止脑电图活动被描述为非 CAP 睡眠(图 1,D 小组)。我们认为,CAP 指标更能反映 Lundberg B 波与 OSA 依赖性睡眠支离破碎之间的关联,而不是简短的觉醒或唤醒。Riedel 等人[1]的研究表明,在研究的 OSA 患者群中,CPAP 会显著改变 Lundberg B 波。这些发现可能解释了为什么在快速眼动睡眠中 ICP 波动会部分丧失清晰的振荡模式,因为众所周知,CAP 生理上只发生在快速眼动睡眠中[7].无论处于哪个睡眠阶段,快速眼动睡眠都可以被描述为稳定(非 CAP)和不稳定(CAP)交替的双峰大脑状态(分别见图 1 中的面板 C 和面板 D)。垂直整合 "方法包括脑电图以外的特征(如心肺耦合、行为变化,或许还包括颅内 B 波),可能是研究 NREM 睡眠期间所有振荡的最适当方法[8]。据我们所知,探索 ICP 升高与 CAP 之间联系的研究从未进行过。Riedel CS, Martinez-Tejada I, Andresen M, Wilhjelm JE, Jennum P, Juhler M. Transient intracranial pressure elevations (B waves) are associated with sleep apnea.Fluids Barriers CNS.2023;20(1):69. https://doi.org/10.1186/s12987-023-00469-6.Article PubMed PubMed Central Google Scholar Riedel CS, Martinez-Tejada I, Norager NH, Kempfner L, Jennum P, Juhler M. B波存在于无颅内压紊乱的患者中。J Sleep Res. 2021;30(4): e13214. https://doi.org/10.1111/jsr.13214.Article PubMed Google Scholar Milioli G, Bosi M, Grassi A, et al. Can sleep microstructure improve diagnosis of OSAS? integrative information from CAP parameters.2015;153(2-3):194-203. https://doi.org/10.12871/0003982920152344.
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来源期刊
Fluids and Barriers of the CNS
Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience
CiteScore
10.70
自引率
8.20%
发文量
94
审稿时长
14 weeks
期刊介绍: "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).
期刊最新文献
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