Compromised Dynamic Cerebral Autoregulation in Patients With Central Disorders of Hypersomnolence

Fang Deng, Yanan Zhang, Ran Zhang, Qi Tang, Zhenni Guo, Yudan Lv, Zan Wang, Yi Yang, Fang Deng, Yanan Zhang, Ran Zhang, Qi Tang, Zhenni Guo, Yudan Lv, Zan Wang, Yi Yang

Abstract

Objective: We aimed to investigate the dynamic cerebral autoregulation (dCA) in patients with central disorders of hypersomnolence during wakefulness. Methods: Thirty-six patients with central disorders of hypersomnolence were divided into three groups according to polysomnography and multiple sleep latency test results: the idiopathic hypersomnia group (IH), narcolepsy type 1 without rapid-eye-movement sleep behavior disorder group (NT1-RBD), and narcolepsy type 1 with rapid-eye-movement sleep behavior disorder group (NT1 + RBD), with 12 patients in each group. Twelve sex- and age-matched healthy controls were recruited. We assessed the Epworth sleepiness scale (ESS) and dCA of all subjects. dCA was assessed by analyzing the phase difference (PD) using transfer function analysis. The ESS and dCA were analyzed before and after standardized treatment in 24 patients with narcolepsy type 1. Results: The overall PD of the IH, NT1-RBD, and NT1 + RBD groups were lower than that of the control group (P < 0.001). There were no significant differences between the overall PD of the NT1-RBD and NT1 + RBD group (P > 0.05). The ESS scores decreased and the overall PD increased after treatment in 24 patients with narcolepsy type 1 (P < 0.001). Multivariable analysis showed that mean sleep latency in multiple sleep latency test was independently associated with impaired overall PD (P < 0.05). Conclusions: The dCA is impaired in patients with central disorders of hypersomnolence. The impairment of dCA occurs irrespective of NT1-RBD/+RBD. The ESS score and dCA improved in patients with narcolepsy type 1 after medication treatment. The mean sleep latency in multiple sleep latency test was independently associated with impaired dCA. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02752139.

Keywords: central disorders of hypersomnolence; dynamic cerebral autoregulation; idiopathic hypersomnia; narcolepsy type 1; rapid-eye-movement sleep behavior disorder.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Deng, Zhang, Zhang, Tang, Guo, Lv, Wang and Yang.

Figures

Figure 1
Figure 1
ESS scores in the patients with IH, NT1-RBD, NT1 + RBD, and controls. *Different from controls (P < 0.05). ESS, Epworth sleepiness scale.
Figure 2
Figure 2
The autoregulatory parameter and statistical distributions in the patients with IH, NT1-RBD, NT1 + RBD, and controls. Statistical distributions of overall phase difference (A) and its transfer function (B) in each group. *Difference of overall phase difference in patients with IH, NT1-RBD, NT1 + RBD, and controls (P < 0.05).
Figure 3
Figure 3
Comparison of ESS in narcolepsy type 1 group before and after treatment. *Represents statistical difference (P < 0.05).
Figure 4
Figure 4
The autoregulatory parameter and statistical distributions in narcolepsy type 1 group before and after treatment. Statistical distributions of phase difference (A) and its transfer function (B) in narcolepsy type 1 group before and after treatment. *Represents statistical difference (P < 0.05).

References

    1. Khan Z, Trotti LM. Central disorders of hypersomnolence: focus on the narcolepsies and idiopathic hypersomnia. Chest. (2015) 148:262–73. 10.1378/chest.14-1304
    1. Wada M, Mimura M, Noda Y, Takasu S, Plitman E, Honda M, et al. . Neuroimaging correlates of narcolepsy with cataplexy: a systematic review. Neurosci Res. (2019) 142:16–29. 10.1016/j.neures.2018.03.005
    1. Boucetta S, Montplaisir J, Zadra A, Lachapelle F, Soucy JP, Gravel P, et al. . Altered regional cerebral blood flow in idiopathic hypersomnia. Sleep. (2017) 40:zsx140. 10.1093/sleep/zsx140
    1. Claassen JA, Meel-van den Abeelen AS, Simpson DM, Panerai RB. International Cerebral Autoregulation Research Network (CARNet). Transfer function analysis of dynamic cerebral autoregulation: a white paper from the International Cerebral Autoregulation Research Network. J Cereb Blood Flow Metab. (2016) 36:665–80. 10.1177/0271678X15626425
    1. Donnelly J, Aries MJ, Czosnyka M. Further understanding of cerebral autoregulation at the bedside: possible implications for future therapy. Expert Rev Neurother. (2015) 15:169–85. 10.1586/14737175.2015.996552
    1. Claassen JA, Zhang R. Cerebral autoregulation in Alzheimer's disease. J Cereb Blood Flow Metab. (2011) 31:1572–7. 10.1038/jcbfm.2011.69
    1. Hamel E. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol. (2006) 100:1059–64. 10.1152/japplphysiol.00954.2005
    1. Baruzzi A, Cirignotta F, Coccagna G, Calderini G, Lugaresi E. Cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid in hypersomnia with periodic apneas or idiopathic hypersomnia: preliminary results. Sleep. (1980) 3:247–9. 10.1093/sleep/3.3-4.247
    1. Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, Holmes S. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci USA. (1999) 96:10911–6. 10.1073/pnas.96.19.10911
    1. Armstead WM, Riley J, Vavilala MS. Norepinephrine protects cerebral autoregulation and reduces hippocampal necrosis after traumatic brain injury via blockade of ERK MAPK and IL-6 in juvenile pigs. J Neurotrauma. (2016) 33:1761–7. 10.1089/neu.2015.4290
    1. Geday J, Hermansen F, Rosenberg R, Smith DF. Serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans. Synapse. (2005) 55:224–9. 10.1002/syn.20112
    1. Antelmi E, Pizza F, Franceschini C, Ferri R, Plazzi G. REM sleep behavior disorder in narcolepsy: a secondary form or an intrinsic feature? Sleep Med Rev. (2020) 50:101254. 10.1016/j.smrv.2019.101254
    1. Vendette M, Gagnon JF, Soucy JP, Gosselin N, Postuma RB, Tuineag M, et al. . Brain perfusion and markers of neurodegeneration in rapid eye movement sleep behavior disorder. Mov Disord. (2011) 26:1717–24. 10.1002/mds.23721
    1. Lv S, Wang Z, Sun X, Jin H, Liu J, Deng F, et al. . Compromised dynamic cerebral autoregulation in patients with idiopathic rapid eye movement behavior disorder: a case-control study using transcranial doppler. Front Psychiatry. (2020) 11:51. 10.3389/fpsyt.2020.00051
    1. Lv S, Guo ZN, Jin H, Sun X, Jia M, Ma H, et al. . Compromised dynamic cerebral autoregulation in patients with epilepsy. Biomed Res Int. (2018) 2018:6958476. 10.1155/2018/6958476
    1. Luo MY, Guo ZN, Qu Y, Zhang P, Wang Z, Jin H, et al. . Compromised dynamic cerebral autoregulation in patients with depression. Front Psychiatry. (2019) 10:373. 10.3389/fpsyt.2019.00373
    1. van Beek AH, Claassen JA, Rikkert MG, Jansen RW. Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly. J Cereb Blood Flow Metab. (2008) 28:1071–85. 10.1038/jcbfm.2008.13
    1. Kuo TB, Chern CM, Sheng WY, Wong WJ, Hu HH. Frequency domain analysis of cerebral blood flow velocity and its correlation with arterial blood pressure. J Cereb Blood Flow Metab. (1998) 18:311–8. 10.1097/00004647-199803000-00010
    1. Joo EY, Hong SB, Tae WS, Kim JH, Han SJ, Cho YW. Cerebral perfusion abnormality in narcolepsy with cataplexy. Neuroimage. (2005) 28:410–6. 10.1016/j.neuroimage.2005.06.019
    1. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M. Reduced number of hypocretin neurons in human narcolepsy. Neuron. (2000) 27:469–74. 10.1016/S0896-6273(00)00058-1
    1. Black SW, Yamanzka A, Kilduff TS. Challenges in the development of therapeutics for narcolepsy. Progress in Neurobiology (2017) 152:89–113. 10.1016/j.pneurobio.2015.12.002
    1. Jones BE. Arousal systems. Front Biosci. (2003) 8:s438–51. 10.2741/1074
    1. Chiara B, Alessandro S. The link between narcolepsy and autonomic cardio- vascular dysfunction: a translational perspective. Clin Auton Res. (2018) 28:545–55. 10.1007/s10286-017-0473-z
    1. Knudsen S, Gammeltoft S, Jennum PJ. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency. Brain. (2010) 133:568–79. 10.1093/brain/awp320
    1. Antelmi E, Pizza F, Vandi S, Neccia G, Ferri R, Bruni O, et al. . The spectrum of REM sleep-related episodes in children with type 1 narcolepsy. Brain. (2017) 140:1669–79. 10.1093/brain/awx096
    1. Dauvilliers Y, Baumann CR, Carlander B, Bischof M, Blatter T, Lecendreux M, et al. . CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions. J Neurol Neurosurg Psychiatry. (2003) 74:1667–73. 10.1136/jnnp.74.12.1667
    1. Vernet C, Leu-Semenescu S, Buzare MA, Arnulf I. Subjective symptoms in idiopathic hypersomnia: beyond excessive sleepiness. J Sleep Res. (2010) 19:525–34. 10.1111/j.1365-2869.2010.00824.x
    1. Yang CM, Huang YS, Song YC. Clinical utility of the Chinese version of the pediatric daytime sleepiness scale in children with obstructive sleep apnea syndrome and narcolepsy. Psychiatry Clin Neurosci. (2010) 64:134–40. 10.1111/j.1440-1819.2009.02054.x
    1. Guo ZN, Sun X, Zhao Y, Yan X, Zhang R, Wang Z, et al. . Temporal course of cerebral autoregulation in patients with narcolepsy Type 1: two case reports. Front Neurol. (2019) 9:1155. 10.3389/fneur.2018.01155
    1. Arand DL, Bonnet MH. The multiple sleep latency test. Handb Clin Neurol. (2019) 160:393–403. 10.1016/B978-0-444-64032-1.00026-6

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다