Abstract
Background
Sleep disorders in patients with autoimmune encephalitis (AE) are increasingly reported. Early recognition and treatment have significant importance regarding the potential of sleep disorders’ effect on morbidity and even mortality. There are a limited number of studies related to polysomnography (PSG) in these patients. Here, we report the clinical and PSG data of patients with AE and sleep disorders, with a particular interest in sleep-related breathing disorders (SRBD).
Methods
Seventeen patients with diagnosed AE and acute or subacute onset sleep complaints who underwent video-electroencephalography-PSG recordings in our tertiary center were investigated.
Results
The mean age was 50, with eight females and nine males. The detected antibodies were against leucine-rich glioma-inactivated 1(LGI-1) in 6, anti-contactin-associated protein-2(CASPR2) in 3, voltage-gated potassium channel complex antigens(VGKC) in 1, anti-glycine in 1, dipeptidyl-peptidase-like protein-6(DPPX) in 1, anti-Hu in 1, and anti-amphiphysin in 1. All commercially available and known autoimmune encephalitis-related antibodies were negative in 3 of the patients. Final diagnosis after PSG was circadian rhythm sleep disorder (n = 3), periodic limb movement disorder (n = 3), insomnia (n = 5), central apnea with or without Cheyne–Stokes breathing (CSB) (n = 4), obstructive sleep apnea (OSA) (n = 4), non-rapid eye movement (NREM) and REM parasomnia (n = 8), faciobrachial dystonic seizures (n = 2), and subclinical seizures (n = 1). Sleep microstructure was disrupted in 9, REM periods without atonia occurred in 4, and brief sleep fragments consisting of theta activity interspersed with faster rhythms existed in 7 patients. Nearly half of our patients (47%) had SRBD, and the mean apnea–hypopnea index (AHI) was 14.
Conclusions
Sleep disorders are frequent and essential components of AEs. Systematic clinical questionnaires and routine PSG assessments would significantly impact the correct diagnosis and proper treatment of SRBD and the overall prognosis of AE.
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Abbreviations
- AASM:
-
American Academy of Sleep Medicine
- AE:
-
Autoimmune encephalitis
- AHI:
-
Apnea–hypopnea index
- ANNA-2:
-
Anti-neuronal nuclear antibody 2
- CASPR2:
-
Contactin-associated protein-2
- CRMP-5:
-
Collapsin-response mediator protein 5
- CSA:
-
Central sleep apnea
- CSB:
-
Cheyne–Stokes breathing
- CSF:
-
Cerebrospinal fluid
- DNER:
-
Delta/notch-like epidermal growth factor-related receptor
- DPPX:
-
Dipeptidyl-peptidase-like protein- 6
- EDS:
-
Excessive daytime sleepiness
- EEG:
-
Electroencephalography
- GAD 65:
-
Glutamic acid decarboxylase 65
- IQR:
-
Interquartile range
- IVIG:
-
Intravenous immunoglobulin
- LGI1:
-
Leucine-rich glioma-inactivated 1
- MRI:
-
Magnetic resonance imaging
- NMDAR:
-
N-methyl-d-aspartate receptor
- NREM:
-
Non-rapid eye movement
- OSA:
-
Obstructive sleep apnea
- PCA-1:
-
Purkinje cell antibody 1
- PLM:
-
Periodic limb movements
- PSG:
-
Polysomnography
- REM:
-
Rapid eye movement
- SE:
-
Sleep efficiency
- SOX-1:
-
Sry-like high mobility group box 1
- SPSS:
-
Statistical Package for the Social Sciences
- SRBD:
-
Sleep-related breathing disorder
- TST:
-
Total sleep time
- VGKC:
-
Voltage-gated potassium channel complex
- Zic4:
-
Zinc finger protein 4
References
Graus F et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15(4):391–404. https://doi.org/10.1016/s1474-4422(15)00401-9
Liguori R et al (2001) Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 124(Pt 12):2417–2426. https://doi.org/10.1093/brain/124.12.2417
Barone DA, Krieger AC (2016) Sleep disturbances in voltage-gated potassium channel antibody syndrome. Sleep Med 21:171–173. https://doi.org/10.1016/j.sleep.2015.11.012
Cornelius JR et al (2011) Sleep manifestations of voltage-gated potassium channel complex autoimmunity. Arch Neurol 68(6):733–738. https://doi.org/10.1001/archneurol.2011.106
Iranzo A et al (2006) Rapid eye movement sleep behavior disorder and potassium channel antibody-associated limbic encephalitis. Ann Neurol 59(1):178–181. https://doi.org/10.1002/ana.20693
Kawamura N et al (2005) A patient with paraneoplastic limbic encephalitis induced by breast cancer presenting with hypersomnia. Rinsho Shinkeigaku 45(8):575–578
Tobin WO et al (2014) DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology 83(20):1797–1803. https://doi.org/10.1212/wnl.0000000000000991
Gaig C et al (2017) Clinical manifestations of the anti-IgLON5 disease. Neurology 88(18):1736–1743. https://doi.org/10.1212/wnl.0000000000003887
Pradhan S et al (2019) Antibody negative autoimmune encephalitis- does it differ from definite one? Ann Indian Acad Neurol 22(4):401–408. https://doi.org/10.4103/aian.AIAN_206_19
Serdaroğlu E, Tezer F, Saygi S (2018) Autoimmune epilepsy and/or limbic encephalitis can lead to changes in sleep spindles. Noro Psikiyatr Ars 55(4):320–324. https://doi.org/10.5152/npa.2017.19442
Blattner MS, Day GS (2020) Sleep disturbances in patients with autoimmune encephalitis. Curr Neurol Neurosci Rep 20(7):28. https://doi.org/10.1007/s11910-020-01048-0
Josephs KA et al (2004) Neurophysiologic studies in Morvan syndrome. J Clin Neurophysiol 21(6):440–445. https://doi.org/10.1097/00004691-200411000-00008
Blattner MS et al (2019) Sleep disturbances are common in patients with autoimmune encephalitis. J Neurol 266(4):1007–1015. https://doi.org/10.1007/s00415-019-09230-2
Sabater L et al (2014) A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study. Lancet Neurol 13(6):575–586. https://doi.org/10.1016/s1474-4422(14)70051-1
Landolfi JC, Nadkarni M (2003) Paraneoplastic limbic encephalitis and possible narcolepsy in a patient with testicular cancer: case study. Neuro Oncol 5(3):214–216. https://doi.org/10.1215/s1152851702000467
Dauvilliers Y et al (2013) Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy. JAMA Neurol 70(10):1305–1310. https://doi.org/10.1001/jamaneurol.2013.2831
Purcell SM et al (2017) Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource. Nat Commun 8:15930. https://doi.org/10.1038/ncomms15930
Ariño H et al (2020) Sleep disorders in anti-NMDAR encephalitis. Neurology 95(6):e671–e684. https://doi.org/10.1212/wnl.0000000000009987
Punjabi NM et al (2009) Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 6(8):e1000132. https://doi.org/10.1371/journal.pmed.1000132
Silber MH (2016) Autoimmune sleep disorders. Handb Clin Neurol 133:317–326. https://doi.org/10.1016/b978-0-444-63432-0.00018-9
Lin N et al (2020) Sleep disorders in leucine-rich glioma-inactivated protein 1 and contactin protein-like 2 antibody-associated diseases. Front Neurol 11:696. https://doi.org/10.3389/fneur.2020.00696
Honorat JA et al (2017) IgLON5 antibody: neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm 4(5):e385. https://doi.org/10.1212/nxi.0000000000000385
Dalmau J et al (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7(12):1091–1098. https://doi.org/10.1016/s1474-4422(08)70224-2
Dalmau J et al (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10(1):63–74. https://doi.org/10.1016/s1474-4422(10)70253-2
Dalmau J et al (2007) Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61(1):25–36. https://doi.org/10.1002/ana.21050
Gaig C et al (2018) The sleep disorder in anti-lgLON5 disease. Curr Neurol Neurosci Rep 18(7):41. https://doi.org/10.1007/s11910-018-0848-0
Gable MS et al (2012) The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 54(7):899–904. https://doi.org/10.1093/cid/cir1038
Boulos MI et al (2019) Normal polysomnography parameters in healthy adults: a systematic review and meta-analysis. Lancet Respir Med 7(6):533–543. https://doi.org/10.1016/s2213-2600(19)30057-8
Muñoz-Lopetegi A et al (2020) Sleep disorders in autoimmune encephalitis. Lancet Neurol 19(12):1010–1022. https://doi.org/10.1016/s1474-4422(20)30341-0
Donovan LM, Kapur VK (2016) Prevalence and characteristics of central compared to obstructive sleep apnea: analyses from the sleep heart health study cohort. Sleep 39(7):1353–1359. https://doi.org/10.5665/sleep.5962
Senaratna CV et al (2017) Prevalence of obstructive sleep apnea in the general population: a systematic review. Sleep Med Rev 34:70–81. https://doi.org/10.1016/j.smrv.2016.07.002
Nissen MS, Blaabjerg M (2019) Anti-IgLON5 disease: a case with 11-year clinical course and review of the literature. Front Neurol 10:1056. https://doi.org/10.3389/fneur.2019.01056
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by IE and FIT. The first draft of the manuscript was written by IE and FIT, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Conceptualization, IE and FIT; methodology, IE and FIT; formal analysis and investigation, IE and FIT; writing — original draft preparation, IE and FIT; writing — review and editing, IE, BE, ES, SS, and FIT; funding acquisition, none; resources, IE, BE, ES, SS, and FIT; and supervision, BE, ES, SS, and FIT.
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Erkent, I., Elibol, B., Saka, E. et al. Sleep disorders and polysomnography findings in patients with autoimmune encephalitis. Neurol Sci 44, 1351–1360 (2023). https://doi.org/10.1007/s10072-022-06513-x
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DOI: https://doi.org/10.1007/s10072-022-06513-x