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Sleep disturbances in essential tremor: an investigation of associated brain microstructural changes using diffusion tensor imaging

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Abstract

Essential tremor (ET) is a complex, neurodegenerative disorder that includes motor and non-motor symptoms. There is growing interest in its non-motor features, including sleep disturbances (SD). There are no studies evaluating the brain structural correlates of SD in ET. We aimed to identify brain microstructural changes related to SD in ET. SD was evaluated using the Pittsburg sleep quality index (PSQI). Diffusion tensor imaging (DTI), with reported measures being fractional anisotropy (FA) and apparent diffusion coefficient (ADC), was used to evaluate microstructural brain changes. DTI data were compared in ET patients with vs. without SD. The mean age of 40 ET patients was 49.20 ± 21.06 years. The mean PSQI score was 6.13 ± 3.99, and 18 (45.0%) patients had SD. The mean PSQI score of patients with vs. without SD was 9.78 ± 2.98 vs. 3.14 ± 1.28 (p < 0.001). Patients with vs. without SD differed significantly with respect to several DTI findings: right (R) superior cerebellar peduncle ADC (p = 0.04), left (L) dorsolateral prefrontal cortex FA (p < 0.01), L frontooccipital fasciculus FA (p = 0.02), R posterior corona radiata (RPCR) FA (p = 0.01), L posterior corona radiata FA (p = 0.04), R posterior thalamic radiation (RPTR) FA (p = 0.02), and fornix FA (p = 0.03) Significant correlations between PSQI scores and RPCR FA (r = − 0.50, p = 0.02) and RPTR FA (r = − 0.67, p = 0.001) were also observed. Our findings suggest that certain brain changes may be associated with the clinical expression of SD in ET. These changes are discussed in terms of their possible neuroanatomical and physiological significance.

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Abbreviations

ET:

Essential tremor

CI:

Cognitive impairment

DTI:

Diffusion tensor imaging

FA:

Fractional anisotropy

ADC:

Apparent diffusion coefficient

BDI-II:

Beck depression inventory-II

BAS:

Beck anxiety scale

SD:

Sleep disturbances

PSQI:

Pittsburg sleep quality index

EDS:

Excessive daytime sleepiness

ESS:

Epworth sleepiness scale

LRA:

Linear regression analysis

References

  1. Clark LN, Louis ED. Essential tremor. In: Handbook of clinical neurology, vol. 147. Elsevier; 2018. p. 229–39.

    Google Scholar 

  2. Louis ED, Ottman R, Hauser WA. How common is the most common adult movement disorder? Estimates of the prevalence of essential tremor throughout the world. Mov Disord. 1998;13:5–10.

    Article  CAS  PubMed  Google Scholar 

  3. Dogu O, Sevim S, Camdeviren H, Sasmaz T, Bugdayci R, Aral M, Kaleagasi H, Un S, Louis ED. Prevalence of essential tremor: door-to-door neurological exams in Mersin Province, Turkey. Neurology. 2003;61:1804–7.

    Article  CAS  PubMed  Google Scholar 

  4. Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, Raethjen J, Stamelou M, Testa CM, Deuschl G. Consensus Statement on the classification of tremors from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018;33(1):75–87.

    Article  PubMed  Google Scholar 

  5. Benito-Leon J, Louis ED. Essential tremor: emerging views of a common disorder. Nat Clin Pract Neurol. 2006;2(12):666–78.

    Article  PubMed  Google Scholar 

  6. Louis ED. The evolving definition of essential tremor: what are we dealing with? Parkinsonism Relat Disord. 2018;1(46):S87-91.

    Article  Google Scholar 

  7. Louis ED. Essential tremor: a nuanced approach to the clinical features. Pract Neurol. 2019;19(5):389–98.

    Article  PubMed  Google Scholar 

  8. Chunling W, Zheng X. Review on clinical update of essential tremor. Neurol Sci. 2016;37(4):495–502.

    Article  PubMed  Google Scholar 

  9. Bermejo-Pareja F, Puertas-Martín V. Cognitive features of essential tremor: a review of the clinical aspects and possible mechanistic underpinnings. Tremor Other Hyperkinetic Mov. 2012;2:2.

    Article  Google Scholar 

  10. Louis ED. Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry. Lancet Neurol. 2010;2010(9):613–22. https://doi.org/10.1016/S1474-4422(10)70090-9.

    Article  Google Scholar 

  11. Louis ED, Lenka A. The olivary hypothesis of essential tremor: time to lay this model to rest? Tremor Other Hyperkinetic Mov. 2017;7:473.

    Article  Google Scholar 

  12. Benito-Leo’n J. Essential tremor: from a monosymptomatic disorder to a more complex entity. Neuroepidemiology. 2008;31:191–2. https://doi.org/10.1159/000154933.

    Article  Google Scholar 

  13. Bhalsing KS, Saini J, Pal PK. Understanding the pathophysiology of essential tremor through advanced neuroimaging: a review. J Neurol Sci. 2013;335(1–2):9–13. https://doi.org/10.1016/j.jns.2013.09.003 (Epub 2013 Sep 10).

    Article  PubMed  Google Scholar 

  14. Klaming R, Annese J. Functional anatomy of essential tremor: lessons from neuroimaging. AJNR Am J Neuroradiol. 2014;35(8):1450–7. https://doi.org/10.3174/ajnr.A3586 (Epub 2013 Apr 25).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sharifi S, Nederveen AJ, Booij J, van Rootselaar AF. Neuroimaging essentials in essential tremor: a systematic review. Neuroimage Clin. 2014;5:217–31. https://doi.org/10.1016/j.nicl.2014.05.003 (eCollection).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Louis ED, Faust PL. Essential tremor pathology: neurodegeneration and reorganization of neuronal connections. Nat Rev Neurol. 2020;20:1–5.

    Google Scholar 

  17. Tantik Pak A, Şengül Y, Otcu Temur H, Alkan A. Impaired integrity of commissural and association fibers in essential tremor patients: evidence from a diffusion tensor imaging study. Turk J Med Sci. 2021;51(1):328–34. https://doi.org/10.3906/sag-2004-305 (PMID: 33021759).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yousaf T, Pagano G, Wilson H, Politis M. Neuroimaging of sleep disturbances in movement disorders. Front Neurol. 2018;11(9):767.

    Article  Google Scholar 

  19. Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JA. Sleep disorders in essential tremor: systematic review and meta-analysis. Sleep. 2020. https://doi.org/10.1093/sleep/zsaa039.

    Article  PubMed  Google Scholar 

  20. Sengul Y, Sengul H. Is it true that essential tremor affects sleep? A comparison between young essential tremor patients and normal controls. Sleep Biol Rhythms. 2015;13(4):309–14.

    Article  Google Scholar 

  21. Sengul Y, Sengul HS, Yucekaya SK, Yucel S, Bakim B, Pazarcı NK, Özdemir G. Cognitive functions, fatigue, depression, anxiety, and sleep disturbances: assessment of nonmotor features in young patients with essential tremor. Acta Neurol Belg. 2015;115(3):281–7.

    Article  PubMed  Google Scholar 

  22. Gerbin M, Viner AS, Louis ED. Sleep in essential tremor: a comparison with normal controls and Parkinson’s disease patients. Parkinsonism Relat Disord. 2012;18(3):279–84.

    Article  PubMed  Google Scholar 

  23. Louis ED. Non-motor symptoms in essential tremor: a review of the current data and state of the field. Parkinsonism Relat Disord. 2016;22(Suppl 1):S115–8. https://doi.org/10.1016/j.parkreldis.2015.08.034.

    Article  PubMed  Google Scholar 

  24. Benito-León J, Louis ED, Bermejo-Pareja F. Short sleep duration heralds essential tremor: a prospective, population-based study. Mov Disord. 2013;28:1700–7. https://doi.org/10.1002/mds.25590.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G. Diffusion tensor MR imaging of the human brain. Radiology. 1996;201(3):637–48.

    Article  CAS  PubMed  Google Scholar 

  26. Nestrasil I, Svatkova A, Rudser KD, Chityala R, Wakumoto A, Mueller BA, Bednařík P, Tuite P, Wu X, Bushara K. White matter measures correlate with essential tremor severity-A pilot diffusion tensor imaging study. Brain and behavior. 2018;8(8):e01039. https://doi.org/10.1002/brb3.1039.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Shin DH, Han BS, Kim HS, Lee PH. Diffusion tensor imaging in patients with essential tremor. Am J Neuroradiol. 2008;29(1):151–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jia L, Jia-lin S, Qin D, Qing L, Yan Z. A diffusion tensor imaging study in essential tremor. J Neuroimaging. 2010;21(4):370–4. https://doi.org/10.1111/j.1552-6569.2010.00535.x.

    Article  PubMed  Google Scholar 

  29. Klein JC, Lorenz B, Kang J-S, Baudrexel S, Seifried C, van de Loo S, Hilker R. Diffusion tensor imaging of white matter involvement in essential tremor. Hum Brain Mapp. 2010;32(6):896–904. https://doi.org/10.1002/hbm.21077.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Saini J, Bagepally BS, Bhatt MD, Chandran V, Bharath RD, Prasad C, Pal PK. Diffusion tensor imaging: tract based spatial statistics study in essential tremor. Parkinsonism Relat Disord. 2012;18(5):477–82. https://doi.org/10.1016/j.parkreldis.2012.01.006.

    Article  PubMed  Google Scholar 

  31. Bhalsing KS, Kumar KJ, Saini J, Yadav R, Gupta AK, Pal PK. White matter correlates of cognitive impairment in essential tremor. AJNR Am J Neuroradiol. 2015;36(3):448–53. https://doi.org/10.3174/ajnr.A4138 (Epub 2014 Oct 22).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sengul Y, Otcu H, Ustun I, Sengul HS, Cersonsky T, Alkan A, Louis ED. Neuroimaging depression and anxiety in essential tremor: a diffusion tensor imaging study. Clin Imaging. 2019;1(58):96–104.

    Article  Google Scholar 

  33. Tantik Pak A, Otcu H, Sengul HS, Corakci Z, Sengul Y, Alkan A. Cognitive and brain micro-structural correlates of alexithymia in essential tremor patients. Appl Neuropsychol Adult. 2020;11:1–10. https://doi.org/10.1080/23279095.2020.1786693 (Epub ahead of print. PMID: 32657147).

    Article  Google Scholar 

  34. Schneider LD. Anatomy and physiology of normal sleep. In: Miglis MG, editor. Sleep and neurologic disease. Elsevier; 2017. p. 1–28.

    Google Scholar 

  35. Morris J. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43:2412–4.

    Article  CAS  PubMed  Google Scholar 

  36. Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J. TRS study group: Assessment of interrater and intrarater reliability of the Fahn–Tolosa–Marin Tremor Rating Scale in essentialtremor. Mov Disord. 2007;30:833–8.

    Article  Google Scholar 

  37. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry res. 1989;28(2):193–213.

    Article  CAS  PubMed  Google Scholar 

  38. Izci B, Ardic S, Firat H, Sahin A, Altinors M, Karacan I. Reliability and validity studies of the Turkish version of the Epworth Sleepiness Scale. Sleep Breath. 2008;12:161–8.

    Article  PubMed  Google Scholar 

  39. Wang YP, Gorenstein C. Psychometric properties of the beck depression inventory-II: a comprehensive review. Rev Bras Psiquiatr. 2013;35(4):416–31.

    Article  PubMed  Google Scholar 

  40. Piotrowski C. The status of the beck anxiety inventory in contemporary research. Psychol Rep. 1999;85:261–2.

    Article  CAS  PubMed  Google Scholar 

  41. http://www.asnr2.org/neurographics/7/1/26/White%20Matter%20Tract%20Anatomy/DTI%20tutorial%201.html. Accessed 30 July 2018.

  42. Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4(3):316–29.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Raggi A, Ferri R. Sleep disorders in neurodegenerative diseases. Eur J Neurol. 2010;17:1326–38.

    Article  CAS  PubMed  Google Scholar 

  44. Rohl B, Collins K, Morgan S, Cosentino S, Huey ED, Louis ED. Daytime sleepiness and nighttime sleep quality across the full spectrum of cognitive presentations in essential tremor. J Neurol Sci. 2016;15(371):24–31.

    Article  Google Scholar 

  45. Taber KH, Hurley RA. Functional neuroanatomy of sleep and sleep deprivation. J Neuropsychiatry Clin Neurosci. 2006;18(1):1–5.

    Article  PubMed  Google Scholar 

  46. Kocevska D, Tiemeier H, Lysen TS, de Groot M, Muetzel RL, Van Someren EJ, Ikram MA, Vernooij MW, Luik AI. The prospective association of objectively measured sleep and cerebral white matter microstructure in middle-aged and older persons. Sleep. 2019;42(10):zsz140.

    Article  PubMed  Google Scholar 

  47. Kanda A, Matsui T, Ebihara S, Arai H, Sasaki H. Periventricular white matter lesions and sleep alteration in older people. J Am Geriatr Soc. 2003;51(3):432–3.

    Article  PubMed  Google Scholar 

  48. Sexton CE, Zsoldos E, Filippini N, Griffanti L, Winkler A, Mahmood A, Allan CL, Topiwala A, Kyle SD, Spiegelhalder K, Singh-Manoux A. Associations between self-reported sleep quality and white matter in community-dwelling older adults: a prospective cohort study. Hum Brain Mapp. 2017;38(11):5465–73.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Li S, Tian J, Bauer A, Huang R, Wen H, Li M, Wang T, Xia L, Jiang G. Reduced integrity of right lateralized white matter in patients with primary insomnia: a diffusion-tensor imaging study. Radiology. 2016;280(2):520–8.

    Article  PubMed  Google Scholar 

  50. Chung SJ, Choi Y-H, Kwon H, Park Y-H, Yun HJ, Yoo HS, Lee PH. Sleep disturbance may alter white matter and resting state functional connectivities in Parkinson’s disease. Sleep. 2017. https://doi.org/10.1093/sleep/zsx009.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Baars B, Gage NM. Fundamentals of cognitive neuroscience: a beginner’s guide. Academic Press; 2013.

    Google Scholar 

  52. Yang Y, Zhu DM, Zhang C, Zhang Y, Wang C, Zhang B, Zhao W, Zhu J, Yu Y. Brain structural and functional alterations specific to low sleep efficiency in major depressive disorder. Front Neurosci. 2020;31(14):50.

    Article  Google Scholar 

  53. Khalsa S, Hale JR, Goldstone A, Wilson RS, Mayhew SD, Bagary M, Bagshaw AP. Habitual sleep durations and subjective sleep quality predict white matter differences in the human brain. Neurobiol Sleep Circadian Rhythms. 2017;1(3):17–25.

    Article  Google Scholar 

  54. Mander BA, Zhu AH, Lindquist JR, Villeneuve S, Rao V, Lu B, Saletin JM, Ancoli-Israel S, Jagust WJ, Walker MP. White matter structure in older adults moderates the benefit of sleep spindles on motor memory consolidation. J Neurosci. 2017;37(48):11675–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gent TC, Bandarabadi M, Herrera CG, Adamantidis AR. Thalamic dual control of sleep and wakefulness. Nat Neurosci. 2018;21(7):974–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. DelRosso LM, Hoque R. The cerebellum and sleep. Neurol Clin. 2014;32(4):893–900.

    Article  PubMed  Google Scholar 

  57. Canto CB, Onuki Y, Bruinsma B, van der Werf YD, De Zeeuw CI. The sleeping cerebellum. Trends Neurosci. 2017;40(5):309–23.

    Article  CAS  PubMed  Google Scholar 

  58. Zhou F, Huang M, Gu L, Hong S, Jiang J, Zeng X, Gong H. Regional cerebral hypoperfusion after acute sleep deprivation: a STROBE-compliant study of arterial spin labeling fMRI. Medicine. 2019;98(2):e14008.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Borragán G, Guerrero-Mosquera C, Guillaume C, Slama H, Peigneux P. Decreased prefrontal connectivity parallels cognitive fatigue-related performance decline after sleep deprivation. An optical imaging study. Biol Psychol. 2019;1(144):115–24.

    Article  Google Scholar 

  60. Yang L, Lei Y, Wang L, Chen P, Cheng S, Chen S, Sun J, Li Y, Wang Y, Hu W, Yang Z. Abnormal functional connectivity density in sleep-deprived subjects. Brain Imaging Behav. 2018;12(6):1650–7.

    Article  PubMed  Google Scholar 

  61. Vetrivelan R, Qiu MH, Chang C, Lu J. Role of basal ganglia in sleep–wake regulation: neural circuitry and clinical significance. Front Neuroanat. 2010;23(4):145.

    Google Scholar 

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Acknowledgements

Corresponding author (Yildizhan Sengul) thanks Turkish Neurological Society for their unquestioning support.

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Authors and Affiliations

  1. Department of Neurology, Bezmialem Foundation University School of Medicine, Bezmialem Foundation University, Iskender Paşa Mh., Adnan Menderes Bulvarı, Vatan Cad, 34093, Fatih, İstanbul, Turkey

    Yildizhan Sengul

  2. Department of Radiology, Bezmialem Foundation University School of Medicine, Bezmialem Foundation University, Fatih, Istanbul, Turkey

    Hafize Otcu Temur, Ismet Ustun & Alpay Alkan

  3. Department of Psychology, Gaziosmanpasa Research and Training Hospital, Ministry of Health University, Gaziosmanpasa, Istanbul, Turkey

    Hakan S. Sengul

  4. Department of Neurology and Neurotherapeutics, University of Texas Southwestern, Dallas, TX, USA

    Keith Radler & Elan D. Louis

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  1. Yildizhan Sengul
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  3. Hakan S. Sengul
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  4. Ismet Ustun
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Contributions

YS collaborated in: 1) the conception, 2) organization of the research project, 3) data analysis and 4) the writing of the manuscript first draft. HOT collaborated in: 1) organization of the research project; 2) data analysis. HS collaborated in: 1) the conception, 2) organization of the research project; 3) data analysis. IU collaborated in: 1) organization of the research project. KR collaborated in: 1) the writing of the manuscript first draft and AA collaborated in: 1) organization of the research project. EDL collaborated in: 1) the conception, 2) organization of the research project, 3) data analysis and 4) the review and critique of the manuscript.

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Correspondence to Yildizhan Sengul.

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Sengul, Y., Otcu Temur, H., Sengul, H.S. et al. Sleep disturbances in essential tremor: an investigation of associated brain microstructural changes using diffusion tensor imaging. Sleep Biol. Rhythms 19, 383–391 (2021). https://doi.org/10.1007/s41105-021-00328-7

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