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The Sleep Disorder in Anti-lgLON5 Disease

Current Neurology and Neuroscience Reports volume 18, Article number: 41 (2018) Cite this article

Abstract

Purpose of Review

To review the clinical and polysomnographic features of the sleep disorder occurring in the recently described anti-IgLON5 disease. The hallmark of the disease is the presence of antibodies against IgLON5, a neural cell adhesion molecule of unknown function. The disease presents a robust HLA association, and the neuropathological examination shows a novel neuronal tauopathy with predominant hypothalamic and brainstem involvement.

Recent Findings

Most patients (> 80%) present sleep-related vocalizations with movements and behaviors and sleep-disordered breathing. Polysomnographic studies show (1) a complex NREM sleep parasomnia at sleep initiation characterized by undifferentiated NREM or poorly structured N2 sleep with sleep-talking or mumbling, and simple or finalistic movements followed by normal periods of N3 or N2 NREM sleep, (2) REM sleep behavior disorder (RBD), and (3) obstructive sleep apnea with stridor. The last two features appear mainly in periods where NREM sleep normalizes.

Summary

Identification of the anti-IgLON5 sleep disorder is important to suspect the disease. The combination of abnormal NREM sleep initiation, followed by normal periods of NREM sleep and RBD, represents a novel parasomnia.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. •• Sabater L, Gaig C, Gelpi E, et al. 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. 2014;13:575–86. In this paper the disease is identified and described for first time.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. •• Gaig C, Graus F, Compta Y, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology. 2017;88:1736–43. The clinical presentation of the disease is described in detail in a series of 22 patients.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. •• Gelpi E, Höftberger R, Graus F, et al. Neuropathological criteria of anti-IgLON5-related tauopathy. Acta Neuropathol. 2016;132:531–43. The neuropathological features of the disease are described in detail and neuropathological criteria for anti-IgLON5 disease are defined.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. van Sonderen A, Ariño H, Petit-Pedrol M, Leypoldt F, Körtvélyessy P, Wandinger KP, et al. The clinical spectrum of Caspr2 antibody-associated disease. Neurology. 2016;87:521–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Movement disorder society-endorsed PSP study group. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. 2017;32:853–64.

    Article  PubMed  PubMed Central  Google Scholar 

  6. • Högl B, Heidbreder A, Santamaria J, Graus F, Poewe W. IgLON5 autoimmunity and abnormal behaviours during sleep. Lancet. 2015;385:1590. Report of the first patient after the initial description of the disease.

    Article  PubMed  Google Scholar 

  7. Bahtz R, Teegen B, Borowski K, Probst C, Blöcker IM, Fechner K, et al. Autonatibodies against IgLON5: two new cases. J Neuroimmunol. 2014;275:8.

    Article  Google Scholar 

  8. Schröder JB, Melzer N, Ruck T, et al. Isolated dysphagia as initial sign of anti-IgLON5 syndrome. Neurol Neuroimmunol Neuroinflamm. 2016;4(1):e302.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Haitao R, Yingmai Y, Yan H, Fei H, Xia L, Honglin H, et al. Chorea and parkinsonism associated with autoantibodies to IgLON5 and responsive to immunotherapy. J Neuroimmunol. 2016;300:9–10.

    Article  PubMed  CAS  Google Scholar 

  10. Bonello M, Jacob A, Ellul MA, Barker E, Parker R, Jefferson S, et al. IgLON5 disease responsive to immunotherapy. Neurol Neuroimmunol Neuroinflamm. 2017;4(5):e383.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Haitao R, Huiqin L, Tao Q, Xunzhe Y, Xiaoqiu S, Wei L, et al. Autoimmune encephalitis associated with vitiligo? J Neuroimmunol. 2017;310:14–6.

    Article  PubMed  CAS  Google Scholar 

  12. Wenninger S. Expanding the clinical Spectrum of IgLON5-syndrome. J Neuromuscul Dis. 2017;4:337–9.

    Article  PubMed  Google Scholar 

  13. • Honorat JA, Lomorowski L, Josephs KA, et al. IgLON5 antibody. Neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm. 2017;4(5):e385. Description of another series of 20 patients with antibodies against IgLON5.

    Article  PubMed  PubMed Central  Google Scholar 

  14. • Simabukuro MM, Sabater L, Adoni T, et al. Sleep disorder, chorea, and dementia associated with IgLON5 antibodies. Neurol Neuroimmunol Neuroinflamm. 2015;2:e136. Additional description of a patient with anti-IgLON5 antibodies and progressive disease course.

    Article  PubMed  PubMed Central  Google Scholar 

  15. • Brüggemann N, Wandinger KP, Gaig C, Sprenger A, Junghanns K, Helmchen C, et al. Dystonia, lower limb stiffness, and upward gaze palsy in a patient with IgLON5 antibodies. Mov Disord. 2016;31:762–4. Description of a patient with atypical clinical features.

    Article  PubMed  Google Scholar 

  16. Montojo MT, Piren V, Benkhadra F, et al. Mimicking progressive supranuclear palsy and causing Tako-Tsubo syndrome: a case report on IgLON5 encephalopathy [abstract]. Mov Disord. 2015;30(Suppl 1):710.

    Google Scholar 

  17. Iranzo A, Santamaría J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep. 2005;28:203–6.

    Article  PubMed  Google Scholar 

  18. Zucconi M, Ferri R, Allen R, Baier PC, Bruni O, Chokroverty S, et al. The official World Association of Sleep Medicine (WASM) standards for recording and scoring periodic leg movements in sleep (PLMS) and wakefulness (PLMW) developed in collaboration with a task force from the International Restless Legs Syndrome Study Group (IRLSSG). Sleep Med. 2006;7:175–83.

    Article  PubMed  Google Scholar 

  19. Mahowald MW, Schenck CH. Status dissociatus: a perspective on states of being. Sleep. 1991;14:69–79.

    Article  PubMed  CAS  Google Scholar 

  20. Montagna P, Lugaresi E. Agrypnia Excitata: a generalized overactivity syndrome and a useful concept in the neurophysiopathology of sleep. Clin Neurophysiol. 2002;113:552–60.

    Article  PubMed  CAS  Google Scholar 

  21. Gaig C, Iranzo A, Santamarí J, Dalmau J, Graus F. Sleep disorder associated with antibodies to IgLON5: parasomnia or agrypnia?—Authors’ reply. Lancet Neurol. 2014;13:864–5.

    Article  PubMed  Google Scholar 

  22. Baiardi S, Provini F, Avoni P, Pasquinelli M, Liguori R. Immunotherapy of oneiric stupor in Morvan syndrome: efficacy documented by actigraphy. Neurology. 2015;84:2457–9.

    Article  PubMed  Google Scholar 

  23. Dumitrascu O, Schenck CH, Applebee G, Attarian H. Parasomnia overlap disorder: a distinct pathophysiologic entity or a variant of rapid eye movement sleep behavior disorder? A case series. Sleep Med. 2013;14:1217–20.

    Article  PubMed  Google Scholar 

  24. Cagnin A, Mariotto S, Fiorini M, Gaule M, Bonetto N, Tagliapietra M, et al. Microglial and neuronal TDP-43 pathology in anti-IgLON5-related taupathy. J Clin Alzheimer’s Dis. 2017;59:13–20.

    Article  CAS  Google Scholar 

  25. Sabater L, Planagumà J, Dalmau J, Graus F. Cellular investigations with human antibodies associated with the anti-IgLON5 syndrome. J Neuroinflammation. 2016;13(1):226.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Ellen Gelpi, Institute of Neurology, Medical University of Vienna, for her help in the design of Fig. 2.

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Affiliations

  1. Neurology Service, Hospital Clínic of Barcelona, C/Villarroel 170, 08036, Barcelona, Spain

    Carles Gaig, Alex Iranzo, Joan Santamaria & Francesc Graus

  2. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Carles Gaig, Alex Iranzo, Joan Santamaria & Francesc Graus

  3. Multidisciplinary Sleep Unit, Hospital Clínic of Barcelona, Barcelona, Spain

    Carles Gaig, Alex Iranzo & Joan Santamaria

  4. Centro de Investigación Biomedica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

    Carles Gaig, Alex Iranzo & Joan Santamaria

Authors
  1. Carles Gaig
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  2. Alex Iranzo
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  3. Joan Santamaria
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  4. Francesc Graus
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Corresponding author

Correspondence to Francesc Graus.

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Conflict of Interest

Carles Gaig, Alex Iranzo, and Joan Santamaria each declare no potential conflicts of interest. Francesc Graus received a licensing fee from Euroimmun for the use of IgLON5 as an autoantibody test.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Sleep

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Gaig, C., Iranzo, A., Santamaria, J. et al. The Sleep Disorder in Anti-lgLON5 Disease. Curr Neurol Neurosci Rep 18, 41 (2018). https://doi.org/10.1007/s11910-018-0848-0

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  • DOI: https://doi.org/10.1007/s11910-018-0848-0

Keywords

  • Anti-IgLON5 disease
  • NREM onset parasomnia
  • REM sleep behavior disorder
  • Stridor
  • Sleep-breathing disorder
  • Tauopathy