Evidence of central involvement in essential tremor: a detailed study of auditory pathway physiology

Abstract

Essential tremor (ET) is a common tremor disorder that is likely neurodegenerative. The pathophysiology of ET involves the cerebellum and its connections in the brainstem and thalamus. Hearing dysfunction has been shown to be a non-motor finding in ET patients. A limited number of studies have suggested that cochlear pathology is the cause, but studies have not evaluated the integrity of the primary auditory pathway in ET. The main aim of this study is to investigate the integrity of the auditory pathway via auditory brainstem response (ABR) and auditory middle latency response (AMLR), thereby allowing us to evaluate the auditory pathway from the 8th cranial nerve to the cerebral cortex. Sixteen ET patients and sixteen age- and gender-matched controls (64 ears) were evaluated. In the ABR study, we detected prolongation of wave V peak latencies (ms) in ET (p = 0.02). In the AMLR study, P0 (p = 0.03), Pa (p = 0.008), Na (p = 0.03), and Nb (p = 0.01) waves differed between the two groups. Eleven ET patients and four control subjects had abnormal electrophysiological findings (ABR or AMLR or both) (68.8% vs. 25%, p = 0.01). Tremor duration was greater in ET patients with abnormal electrophysiological findings (p = 0.01). Finally, we observed prolongation of latencies after the ABR III wave, indicating that abnormalities exist within the superior olivary complex. For the first time, our research provides evidence that ET-related pathology is present at the subcortical and cortical levels of the auditory pathway.

This is a preview of subscription content, log in to check access.

Abbreviations

ABR:

Auditory brainstem response

AMLR:

Auditory middle latency response

ET:

Essential tremor

References

  1. Aitkin LM, Boyd J (1978) Acoustic input to the lateral pontine nuclei. Hear Res 1:67–77

    CAS  Article  Google Scholar 

  2. Akshoomoff NA, Courchesne E, Townsend J (1997) Attention coordination and anticipatory control. Int Rev Neurobiol 41:575–598

    CAS  Article  Google Scholar 

  3. Azumi T, Nakashima K, Takahashi K (1993) Auditory middle latency responses in patients with epilepsy. Electromyogr Clin Neurophysiol 34:185–191

    Google Scholar 

  4. Balaban H, Altuntaş EE, Uysal IO, Sentürk IA, Topaktaş S (2012) Audio-vestibular evaluation in patients with essential tremor. Eur Arch Otorhinolaryngol 269:1577–1581. https://doi.org/10.1007/s00405-011-1801-x

    Article  PubMed  Google Scholar 

  5. Benito-León J, Labiano-Fontcuberta A (2016) Linking essential tremor to the cerebellum: clinical evidence. Cerebellum 15:253–262. https://doi.org/10.1007/s12311-015-0741-1

    Article  PubMed  Google Scholar 

  6. Benito-León J, Louis ED, Bermejo-Pareja F (2007) Neurological disorders in central spain (NEDICES) study group reported hearing impairment in essential tremor: a population-based case-control study. Neuroepidemiology 29:213–217

    Article  Google Scholar 

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

    Article  Google Scholar 

  8. Celebisoy N, Aydo I, Ekmekci O, Akyurekli O (1996) Middle latency auditory evoked potentials (MLAEPs) in (MS). Acta Neurol Scand 93:318–321

    CAS  Article  Google Scholar 

  9. Cerasa A, Quattrone A (2016) Linking essential tremor to the cerebellum-neuroimaging evidence. Cerebellum 3:263–275. https://doi.org/10.1007/s12311-015-0739-8

    CAS  Article  Google Scholar 

  10. Desmond JE, Fiez JA (1998) Neuroimaging studies of the cerebellum: language, learning and memory. Trends Cogn Sci 2:355–362

    CAS  Article  Google Scholar 

  11. Filip P, Lungu OV, Manto MU, Bareš M (2016) Linking essential tremor to the cerebellum: physiological evidence. Cerebellum 15:774–780 (Review)

    Article  Google Scholar 

  12. Green JB, Burba A, Freed DM, Elder WW, Xu W (1997) The P1 component of the middle latency auditory potential may differentiate a brainstem subgroup of Alzheimer disease. Alzheimer Dis Assoc Disord 11(3):153–157

    CAS  Article  Google Scholar 

  13. Grimes AM, Grady CL, Pikus A (1987) Auditory evoked potentials in patients with dementia of the Alzheimer type. Ear Hear 8:157–161

    CAS  Article  Google Scholar 

  14. Hallett M, Grafman J (1997) Executive function and motor skill learning. Int Rev Neurobiol 41:297–323

    CAS  Article  Google Scholar 

  15. Handforth A (2016) Linking essential tremor to the cerebellum-animal model evidence. Cerebellum 15:285–298. https://doi.org/10.1007/s12311-015-0750-0

    Article  PubMed  Google Scholar 

  16. Huffman RF, Henson OW Jr (1990) The descending auditory pathway and acousticomotor systems: connections with the inferior colliculus. Brain Res Rev 15:295–323

    CAS  Article  Google Scholar 

  17. Japaridze G, Shakarishvili R, Kevanishvili Z (2002) Auditory brainstem, middle latency, and slow cortical responses in multiple sclerosis. Acta Neurol Scand 106:47

    CAS  Article  Google Scholar 

  18. Kodama Y, Ieda T, Hirayama M, Koike Y, Ito H, Sobue G (1999) Auditory brainstem responses in patients with autonomic failure with Parkinson’s disease and multiple system atrophy. J Auton Nerv Syst 24(77):184–189

    Article  Google Scholar 

  19. Kratochwil CF, Maheshwari U, Rijli FM (2017) The long journey of pontine nuclei neurons: from rhombic lip to cortico-ponto-cerebellar circuitry. Front Neural Circuits 17(11):33. https://doi.org/10.3389/fncir.2017.00033

    CAS  Article  Google Scholar 

  20. Kraus N, McGee T (1990) Clinical applications of the middle latency response. J Am Acad Audiol 1(3):130–133

    CAS  PubMed  Google Scholar 

  21. Kraus N, Ozdamar O, Hier D, Stein L (1982) Auditory middle latency responses (MLRs) in patients with cortical lesions. Electroencephalogr Clin Neurophysiol 54:275–287

    CAS  Article  Google Scholar 

  22. Louis ED (2016a) Non-motor symptoms in essential tremor: a review of the current data and state of the field. Parkinsonism Relat Disord 22:115–118. https://doi.org/10.1016/j.parkreldis.2015.08.034

    Article  Google Scholar 

  23. Louis ED (2016b) Linking essential tremor to the cerebellum: neuropathological evidence. Cerebellum 153:235–242. https://doi.org/10.1007/s12311-015-0692-6(Review)

    Article  Google Scholar 

  24. Louis ED (2016c) De sedibus et causis morborum: is essential tremor a primary disease of the cerebellum? Cerebellum 15:233–234. https://doi.org/10.1007/s12311-015-0689-1

    Article  PubMed  Google Scholar 

  25. Louis ED (2018) Essential tremor and the cerebellum. Handb Clin Neurol 155:245–258. https://doi.org/10.1016/B978-0-444-64189-2.00016-0

    Article  PubMed  Google Scholar 

  26. Louis ED, Okun MS (2011) It is time to remove the ‘benign’ from the essential tremor label. Parkinsonism Relat Disord 17:516–520. https://doi.org/10.1016/j.parkreldis.2011.03.012

    Article  PubMed  PubMed Central  Google Scholar 

  27. Louis ED, Joyce JL, Cosentino S (2019) Mind the gaps: what we don’t know about cognitive impairment in essential tremor. Parkinsonism Relat Disord. https://doi.org/10.1016/j.parkreldis.2019.02.038([Epub ahead of print] Review)

    Article  PubMed  PubMed Central  Google Scholar 

  28. Marin-Lahoz J, Gironell A (2016) Linking essential tremor to the cerebellum: neurochemical evidence. Cerebellum 15:243–252. https://doi.org/10.1007/s12311-015-0735-z

    CAS  Article  PubMed  Google Scholar 

  29. Martini A, Comacchio F, Magnavita V (1991) Auditory brainstem and middle latency evoked responses in the clinical evaluation of diabetes. Diabet Med 8:74–77

    Article  Google Scholar 

  30. McGee T, Kraus N, Comperatore C, Nicol T (1991) Subcortical and cortical components of the MLR generating system. Brain Res 29(544):211–220

    Article  Google Scholar 

  31. Molinari M, Leggio MG, Solida A, Ciorra R, Misciagna S, Silveri MC, Petrosini L (1997) Cerebellum and procedural learning: evidence from focal cerebellar lesions. Brain 120:1753–1762

    Article  Google Scholar 

  32. Musiek F, Nagle S (2018) The middle latency response: a review of findings in various central nervous system lesions. J Am Acad Audiol 29:855–867. https://doi.org/10.3766/jaaa.16141

    Article  PubMed  Google Scholar 

  33. Neves IF, Gonçalves IC, Leite AR, Magliaro ACL, Matas CG (2007) Middle latency response study of auditory evoked potentials’ amplitudes and lantencies audiologically normal individuals. Rev Bras Otorrinolaringol 73:75–80. https://doi.org/10.1590/S0034-72992007000100012

    Article  Google Scholar 

  34. Nojszewska M, Pilczuk B, Zakrzewska-Pniewska B, Rowińska-Marcińska K (2007) The auditory system involvement in Parkinson disease: electrophysiological and neuropsychological correlations. J Clin Neurophysiol 26(6):430–437. https://doi.org/10.1097/WNP.0b013e3181c2bcc8

    Article  Google Scholar 

  35. O'Mahony D, Rowan M, Feely J, Walsh JB, Coakley D (1994) Primary auditory pathway and reticular activating system dysfunction in Alzheimer’s disease. Neurology 44:2089–2094

    CAS  Article  Google Scholar 

  36. Ondo WG, Sutton L, Dat Vuong K, Lai D, Jankovic J (2003) Hearing impairment in essential tremor. Neurology 28(61):1093–1097

    Article  Google Scholar 

  37. Petacchi A, Laird AR, Fox PT, Bower JM (2005) Cerebellum and auditory function: an ALE meta-analysis of functional neuroimaging studies. Hum Brain Mapp 25:118–128

    Article  Google Scholar 

  38. Phillips NA, Connolly J, Charles Mate-Kole C, Gray J (1997) Individual differences in auditory middle latency responses in elderly adults and patients with Alzheimer’s disease. Int J Psychophys 27:125–136

    CAS  Article  Google Scholar 

  39. Pickles JO (2015) Auditory pathways: anatomy and physiology. Handb Clin Neurol 129:3–25. https://doi.org/10.1016/B978-0-444-62630-1.00001-9

    Article  PubMed  Google Scholar 

  40. Profant O, Roth J, Bureš Z, Balogová Z, Lišková I, Betka J, Syka J (2017) Auditory dysfunction in patients with Huntington’s disease. Clin Neurophysiol 128(10):1946–1953. https://doi.org/10.1016/j.clinph.2017.07.403

    Article  PubMed  Google Scholar 

  41. Purdy SC, Kelly AS, Davies MG (2002) Auditory brainstem response, middle latency response, and late cortical evoked potentials in children with learning disabilities. J Am Acad Audiol 13:367–382

    PubMed  Google Scholar 

  42. Rapoport M, Van Reekum R, Mayberg H (2000) The role of the cerebellum in cognition and behavior: a selective review. J Neuropsychiatry Clin Neurosci 12:193–198

    CAS  Article  Google Scholar 

  43. Robinson K, Rudge P (1977) Abnormalities of the auditory evoked potentials in patients with multiple sclerosis. Brain: J Neurol 100:19–40

    Article  Google Scholar 

  44. Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121:561–579

    Article  Google Scholar 

  45. Shim HJ, An YH, Kim DH, Yoon JE, Yoon JH (2017) Comparisons of auditory brainstem response and sound level tolerance in tinnitus ears and non-tinnitus ears in unilateral tinnitus patients with normal audiograms. PLoS ONE 18(12):e0189157. https://doi.org/10.1371/journal.pone.0189157(eCollection 2017)

    CAS  Article  Google Scholar 

  46. Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J, TRS study group (2007) Assessment of interrater and interrater reliability of the Fahn–Tolosa–Marin tremor rating scale in essential tremor. Mov Disord 30:833–883

    Article  Google Scholar 

  47. Starr A, Achor J (1975) Auditory brain stem responses in neurological disease. Arch Neurol 32:761–768

    CAS  Article  Google Scholar 

  48. Ten Donkelaar HJ (2011) Clinical neuroanatomy, ©Springer-Verlag, Berlin, Heidelberg, 305. 10.1007/978-3-642-19134–3_7

  49. Yilmaz NH, Akbostanci MC, Yılmaz N (2015) Sensorineural hearing loss in non-depressed essential tremor cases and controls: a clinical and audiometric study. Tremor Other Hyperkinet Mov (N Y) 29(5):281. https://doi.org/10.7916/D8XW4HKQ

    Article  Google Scholar 

Download references

Acknowledgements

We thank the study participants and control subjects for their contributions to this study and Tess Cersonsky and Keith Radler for their valuable contribution. Corresponding author thanks Turkish Neurological Society and Dr. Rumeyza Kazancıoglu for their support.

Funding

There is no funding source in this study.

Author information

Affiliations

Authors

Contributions

YS participated in the conception and design of the study, the acquisition of data, the analysis and interpretation of data, and drafting the manuscript or revising it critically for important intellectual content. NB participated in the conception and design of the study, the acquisition of data, the analysis and interpretation of data, and drafting the manuscript or revising it critically for important intellectual content. EL participated in the conception and design of the study, the analysis and interpretation of data, and drafting the manuscript or revising it critically for important intellectual content.

Corresponding author

Correspondence to Yildizhan Sengul.

Ethics declarations

Conflict of interest

There is no conflict of interest between authors.

Ethical approval

The study protocol was conducted in accordance with ethical principles stated in the ‘Declaration of Helsinki’ and approved by the Ethical Committee of Bezmialem Foundation University Hospital.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1337 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sengul, Y., Bal, N. & Louis, E.D. Evidence of central involvement in essential tremor: a detailed study of auditory pathway physiology. J Neural Transm 127, 1153–1159 (2020). https://doi.org/10.1007/s00702-020-02215-w

Download citation

Keywords

  • Essential tremor
  • Auditory brainstem response
  • Middle latency response
  • Auditory pathway
  • Neurodegenerative
  • Pathology