Essential Tremor –  Is There a New Nosological Concept?

Authors: P. Hollý;  E. Růžička
Authors‘ workplace: Neurologická klinika a Centrum klinických neurověd 1. LF UK a VFN v Praze
Published in: Cesk Slov Neurol N 2017; 80/113(5): 527-533
Category: Review Article


Essential tremor (ET), the most common form of pathological tremor, affects up to 4% of the population. Accord­ing to the traditional concept, ET is a monosymptomatic benign clinical entity where tremor is associated with longevity and positive family history. Despite the high prevalence and suspected genetic component, research failed so far to find a causative gene mutation for ET. The main reason is probably related to an imperfectly bounded nosological concept. There are still uncertainties around clinical definition of ET, which does not include isolated head tremor, voice tremor or task-specific tremors that often overlap with dystonic tremor. Moreover, numerous studies have shown the incidence of parkinsonism, cerebellar signs and cognitive disorders in ET. Age of onset turns out as a key factor, characterized by two peaks in the adolescence and in the old age. The classical concept of ET corresponds to early onset disease characterized by a positive family history, more benign progression, and relief after alcohol. Conversely, so called aging-related tremor is usually characterized by late-onset, sporadic occurrence, rapid progression, and also by cognitive dysfunction and other symptoms and signs suggestive of neurodegenerative disorder. Thus, rather than a monosymptomatic nosological entity, ET appears as a group of diseases featuring action tremor. Besides unclear etiology, the possible contribution of neurodegenerative processes remains an open question in the pathogenesis of ET. Thereafter, a thorough description of the individual phenotype along with the methods of genome-wide association studies can contribute to finding causal gene polymorphisms in ET and to elucidate the pathogenesis of various forms of the disease.

Key words:
essential tremor – dystonic tremor – aging-related tremor – genetics – cerebellum

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


1. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad HocScientific Committee. Mov Disord 1998;13 (Suppl 3):2– 23.

2. Edwards MJ, Deuschl G. Tremor syndromes. Con­tinuum (Minneap Minn) 2013;19:1213– 4.

3. Jankovic J. Parkinson‘s dis­ease: clinical features and diag­­nosis. J Neurol Neurosurg Psychiatry 2008;79:368– 76.

4. Bain PG. Tremor. Parkinsonism & related disorders 2007;13 (Suppl 3):S369– 74.

5. Critchley M. Observations on essential (heredofamial) tremor. Brain: a journal of neurology 1949;72:113– 139.

6. Pelnář J. Das Zittern. Berlin: Springer 1913.

7. Minor LS. Neue Beobachtungen über das erbliche Zittern. Russk Klin 1929;12:713– 725.

8. Elble RJ. Dia­gnostic criteria for essential tremor and dif­ferential dia­gnosis. Neurology 2000;54:S2– 6.

9. 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.

10. Louis ED, Ferreira JJ. How common is the most com­mon adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord 2010;25:534– 41.

11. Louis ED, Thawani SP, Andrews HF. Prevalence of essential tremor in a multiethnic, community-based study in northern Manhattan, New York, N.Y. Neuroepidemiology 2009;32:208– 14.

12. Gutierrez J, Park J, Badejo O, Louis ED. Worse and Worse and Worse: Essential Tremor Patients‘ Longitudinal Perspectives on Their Condition. Front Neurol 2016;7:175.

13. Louis ED, Clark L, Ottman R. Familial Aggregation and Co-Aggregation of Essential Tremor and Parkinson‘s Dis­ease. Neuroepidemiology 2016;46:31– 6.

14. Bain PG, Findley LJ, Thompson PD, et al. A study of hereditary essential tremor. Brain 1994;117(Pt 4):805– 24.

15. Louis ED, Ford B, Frucht S, et al. Risk of tremor and impairment from tremor in relatives of patients with essential tremor: a community-based family study. Ann Neurol 2001;49:761– 69.

16. Louis ED, Dogu O. Does age of onset in essential trem­or have a bimodal distribution? Data from a tertiary referral sett­ing and a population-based study. Neuroepidemiology 2007;29:208– 12.

17. Hopfner F, Ahlf A, Lorenz D, et al. Early- and late-onset essential tremor patients represent clinically distinct subgroups. Mov Disord 2016;31:1560– 66.

18. Erro R, Rubio­-Agusti I, Saifee TA, et al. Rest and other types of tremor in adult-onset primary dystonia. J Neurol Neurosurg Psychiatry 2014;85:965– 68.

19. Jedynak CP, Bonnet AM, Agid Y. Tremor and idiopathic dystonia. Mov Disord 1991;6:230–6.

20. Albanese A, Sorbo FD. Dystonia and Tremor: The Clinical Syndromes with Isolated Tremor. Tremor Other Hyperkinet Mov (N Y) 2016;6:319. doi: 10.7916/ D8X34XBM.

21. Defazio G, Conte A, Gigante AF, et al. Is tremor in dystonia a phenotypic feature of dystonia? Neurology 2015;84:1053– 59. doi: 10.1212/ WNL.0000000000001341.

22. Elble RJ. Defin­ing dystonic tremor. Curr Neuropharmacol 2013;11:48– 52. doi: 10.2174/ 157015913804999478.

23. Rivest J, Marsden CD. Trunk and head tremor as isolat­ed manifestations of dystonia. Mov Disord 1990;5:60– 65.

24. Pal PK, Samii A, Schulzer M, et al. Head tremor in cervical dystonia. Can J Neurol Sci 2000;27:137– 42.

25. Munchau A, Schrag A, Chuang C, et al. Arm tremor in cervical dystonia differs from essential tremor and can be classified by onset age and spread of symp­toms. Brain: a journal of neurology 2001;124:1765– 76.

26. Lalli S, Albanese A. The dia­gnostic challenge of primary dystonia: evidence from misdia­gnosis. Mov Disord 2010;25:1619– 26.

27. Louis ED. When do essential tremor patients develop head tremor? Influences of age and duration and evidence of a bio­logical clock. Neuroepidemiology 2013;41:110– 15.

28. Agnew A, Frucht SJ, Louis ED. Supine head tremor: a clinical comparison of essential tremor and spasmodic torticollis patients. Journal of neurology, neurosurgery, and psychiatry 2012;83:179– 81.

29. Masuhr F, Wissel J, Muller J, et al. Quantification of sensory trick impact on tremor amplitude and frequency in 60 patients with head tremor. Mov Disord 2000;15:960– 4.

30. Louis ED, Ford B, Barnes LF. Clinical subtypes of essential tremor. Arch Neurol 2000;57:1194– 8.

31. Jankovic J. Essential tremor: clinical characteristics. Neurology 2000;54:S21– 25.

32. Sulica L, Louis ED. Clinical characteristics of essential voice tremor: a study of 34 cases. Laryngoscope 2010;120:516– 28.

33. Bain PG. Task-specific tremor. Handb Clin Neurol 2011;100:711– 8.

34. Sheehy MP, Marsden CD. Writers‘ cramp-a focal dystonia. Brain 1982;105 (Pt 3):461– 80.

35. Sheehy MP, Rothwell JC, Marsden CD. Writer‘s cramp. Adv Neurol 1988;50:457– 72.

36. Waddy HM, Fletcher NA, Hard­ing AE, et al. A genetic study of idiopathic focal dystonias. Ann Neurol 1991;29:320– 4.

37. Bain PG, Findley LJ, Britton TC, et al. Primary writ­ing tremor. Brain 1995;118 (Pt 6):1461– 72.

38. Soland VL, Bhatia KP, Volonte MA, et al. Focal task-specific tremors. Mov Disord 1996;11:665– 70.

39. Deuschl G, Petersen I, Lorenz D, et al. Tremor in the elderly: Essential and aging-related tremor. Mov Disord 2015;30:1327-1334.

40. Jankovic J, Beach J, Schwartz K, et al. Tremor and longevity in relatives of patients with Parkinson‘s dis­ease, essential tremor, and control subjects. Neurology 1995;45:645– 8.

41. Louis ED, Benito-Leon J, Ottman R et al. Neurological Disorders in Central Spain Study G. A population-based study of mortality in essential tremor. Neurology 2007;69:1982– 9.

42. Jasinska-Myga B, Wider C. Genetics of essential tremor. Parkinsonism Relat Disord 2012;18 (Suppl 1):S138– 9. doi: 10.1016/ S1353-8020(11)70043-8.

43. Jimenez-Jimenez FJ, Garcia-Martin E, Lorenzo-Betancor O, et al. LINGO1 and risk for essential tremor: results of a meta-analysis of rs9652490 and rs11856808. J Neurol Sci 2012;317:52– 7. doi: 10.1016/ j.jns.2012.02.030.

44. Thier S, Lorenz D, Nothnagel M, et al. Polymorphisms in the glial glutamate transporter SLC1A2 are associated with essential tremor. Neurology 2012;79:243– 8.

45. Muller SH, Girard SL, Hopfner F, et al. Genome-wide association study in essential tremor identifies three new loci. Brain 2016;139:3163– 9. doi: 10.1093/ brain/ aww242.

46. 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.

47. Louis ED, Galecki M, Rao AK. Four Essential Tremor Cases with Moderately Impaired Gait: How Impaired can Gait be in this Dis­ease? Tremor Other Hyperkinet Mov (N Y). 2013;4;3. doi: 10.7916/ D8QV3K7G.

48. Louis ED, Rao AK, Gerbin M. Functional correlates of gait and balance difficulty in essential tremor: bal­ance confidence, near misses and falls. Gait Posture 2012;35:43– 7. doi: 10.1016/ j.gaitpost.2011.08.002.

49. Louis ED, Rios E, Rao AK. Tandem gait performance in essential tremor: clinical correlates and association with midline tremors. Mov Disord 2010;25:1633– 8. doi: 10.1002/ mds.23144.

50. Hoskovcova M, Ulmanova O, Sprdlik O, et al. Disorders of balance and gait in essential tremor are associated with midline tremor and age. Cerebellum 2013;12:27– 34. doi: 10.1007/ s12311-012-0384-4.

51. Bares M, Husarova I, Lungu OV. Essential tremor, the cerebellum, and motor timing: towards integrat­ing them into one complex entity. Tremor Other Hyperkinet Mov (N Y). 2012;2. doi: 10.7916/ D8CN72N0.

52. Bares M, Lungu OV, Husarova I, et al. Predictive motor tim­ing performance dissociates between early dis­eases of the cerebellum and Parkinson‘s dis­ease. Cerebellum 2010;9:124– 35. doi:10.1007/ s12311-009-0133-5.

53. Lombardi WJ, Woolston DJ, Roberts JW, et al. Cognitive deficits in patients with essential tremor. Neurology 2001;57:785– 90.

54. Louis ED, Benito-Leon J, Vega-Quiroga S, et al. Neurological Disorders in Central Spain Study G. Faster rate of cognitive decline in essential tremor cases than controls: a prospective study. European journal of neurology : the official journal of the European Federation of Neurological Societies 2010;17:1291– 7.

55. Janicki SC, Cosentino S, Louis ED. The cognitive side of essential tremor: what are the therapeutic implications? Ther Adv Neurol Disord 2013;6:353– 68. doi: 10.1177/ 1756285613489591.

56. Lou JS, Jankovic J. Essential tremor: clinical correlates in 350 patients. Neurology 1991;41:234– 8.

57. Benito-Leon J, Louis ED, Bermejo-Pareja F. Risk of incident Parkinson‘s dis­ease and parkinsonism in essential tremor: a population based study. J Neurol Neurosurg Psychiatry. 2009;80(4):423– 5. doi: 10.1136/ jnnp.2008.147223.

58. Vilarino-Guell C, Ross OA, Wider C, et al. LINGO1 rs9652490 is associated with essential tremor and Parkinson dis­ease. Parkinsonism Relat Disord 2010;16:109– 11.

59. Deuschl G, Wenzelburger R, Loffler K, et al. Essential tremor and cerebellar dysfunction clinical and kinematic analysis of intention tremor. Brain 2000;123(Pt 8):1568– 80.

60. Cerasa A, Quattrone A. Link­ing Essential Tremor to the Cerebellum-Neuroimag­ing Evidence. Cerebellum 2016;15:263– 75. doi: 10.1007/ s12311-015-0739-8.

61. Filip P, Lungu OV, Manto MU, et al. Link­ing Essential Tremor to the Cerebellum: Physiological Evidence. Cerebellum 2016;15:774– 80.

62. Benito-Leon J, Louis ED, Sanchez-Ferro A, et al. Rate of cognitive decline dur­ing the premotor phase of essential tremor: a prospective study. Neurology 2013;81:60– 6. doi: 10.1212/ WNL.0b013e318297ef2b.

63. Sengul Y, Sengul HS, Yucekaya SK, et al. Cognitive functions, fatigue, depression, anxiety, and sleep disturbances: assessment of nonmotor features in young patients with essential tremor. Acta Neurol Belg 2015;115:281– 7. doi: 10.1007/ s13760-014-0396-6.

64. Quattrone A, Cerasa A, Messina D, et al. Essential head tremor is associated with cerebellar vermis atrophy: a volumetric and voxel-based morphometry MR imag­ing study. AJNR Am J Neuroradiol 2008;29:1692– 7. doi: 10.3174/ ajnr.A1190.

65. Bagepally BS, Bhatt MD, Chandran V, et al. Decrease in cerebral and cerebellar gray matter in essential tremor: a voxel-based morphometric analysis under 3T MRI. J Neuroimag­ing 2012;22:275– 8. doi: 10.1111/ j.15526569.2011.00598.x.

66. Benito-Leon J, Alvarez-Linera J, Hernandez-Tamames JA, et al. Brain structural changes in essential tremor: voxel-based morphometry at 3-Tesla. J Neurol Sci 2009;287:138– 42. doi: 10.1016/ j.jns.2009.08.037.

67. Lin CH, Chen CM, Lu MK, et al. VBM Reveals Brain Vol­-ume Differences between Parkinson‘s Dis­ease and Essential Tremor Patients. Front Hum Neurosci 2013;7:247. doi: 10.3389/ fnhum.2013.00247.

68. Daniels C, Peller M, Wolff S, et al. Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor. Neurology 2006;67:1452– 6.

69. Louis ED, Shungu DC, Chan S, et al. Metabolic abnormality in the cerebellum in patients with essential tremor: a proton magnetic resonance spectroscopic imag­ing study. Neurosci Lett 2002;333:17– 20.

70. Pagan FL, Butman JA, Dambrosia JM, et al. Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy. Neurology 2003;60:1344– 7.

71. Nicoletti G, Manners D, Novellino F, et al. Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor. Neurology 2010;74:988– 94. doi: 10.1212/ WNL.0b013e3181d5a460.

72. Shin DH, Han BS, Kim HS, et al. Diffusion tensor imag­ing in patients with essential tremor. AJNR Am J Neuroradiol 2008;29:151– 3. doi: 10.3174/ ajnr.A0744.

73. Martinelli P, Rizzo G, Manners D, et al. Diffusion-weight­-ed imag­ing study of patients with essential tremor. Mov Disord 2007;22:1182– 5. doi: 10.1002/ mds.21287.

74. Sharifi S, Nederveen AJ, Booij J, et al. Neuroimag­ing essentials in essential tremor: a systematic review. Neuroimage Clin 2014;5:217– 31. doi: 10.1016/ j.nicl.2014.05.003.

75. Boecker H, Weindl A, Brooks DJ, et al. GABAergic dysfunction in essential tremor: an 11C-flumazenil PET study. J Nucl Med 2010;51:1030– 5. doi: 10.2967/ jnumed.109.074120.

76. Gironell A, Figueiras FP, Pagonabarraga J, et al.Gaba and serotonin molecular neuroimag­ing in essential tremor: a clinical correlation study. Parkinsonism RelatDisord 2012;18:876– 80. doi: 10.1016/ j.parkreldis.2012.04.024.

77. Louis ED, Vonsattel JP. The emerg­ing neuropathol­ogy of essential tremor. Mov Disord 2008;23:174– 82. doi: 10.1002/ mds.21731.

78. Shill HA, Adler CH, Beach TG. Lewy bodies in essential tremor are no different than in controls. Parkinson­ism Relat Disord 2016;23:106– 7. doi: 10.1016/ j.parkreldis.2015.11.025. 79. Zesiewicz TA, Elble RJ, Louis ED, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommit­tee of the American Academy of Neurology. Neurol­ogy 2011;77:1752– 5. doi: 10.1212/ WNL.0b013e318236f0fd.

80. Koller WC, Vetere-Overfield B. Acute and chronic effects of propranolol and primidone in essential tremor. Neurology 1989;39:1587– 8.

81. Agundez JA, Jimenez-Jimenez FJ, Alonso-Navarro H,et al. The potential of LINGO-1 as a therapeutic targetfor essential tremor. Expert Opin Ther Targets 2015;19:1139– 48. doi: 10.1517/ 14728222.2015.1028360.

82. Flora ED, Perera CL, Cameron AL, et al. Deep brain stimulation for essential tremor: a systematic review. Mov Disord. 2010;25(11):1550– 9. doi: 10.1002/ mds.23195.

83. Young RF, Li F, Vermeulen S, et al. Gamma Knife thalamotomy for treatment of essential tremor: long-term results. J Neurosurg 2010;112:1311– 7.

84. Elias WJ, Lipsman N, Ondo WG, et al. A Random­ized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med 2016;375:730-739. doi: 10.3171/ 2009.10.JNS09332.

85. Mostile G, Jankovic J. Alcohol in essential tremor and other movement disorders. Mov Disord 2010;25:2274– 84. doi: 10.1002/ mds.23240.

86. Hopfner F, Erhart T, Knudsen K, et al. Test­ing for alcohol sensitivity of tremor amplitude in a large cohort with essential tremor. Parkinsonism Relat Disord 2015;21:848– 51. doi: 10.1016/ j.parkreldis.2015.05.005.

87. Manto M, Laute MA. A possible mechanism for the beneficial effect of ethanol in essential tremor. Eur J Neurol 2008;15:697– 705. doi: 10.1111/ j.1468-1331.2008.02150.x.

88. Ulmanova O, Vinopalova M, Zima T, et al. Biomarkers demonstrate increased consumption, but not abuse, of ethanol in essential tremor. J Neurol 2012;259:1177– 80. doi: 10.1007/ s00415-011-6323-3.

89. Haubenberger D, Nahab FB, Voller B, et al. Treatment of essential tremor with long-chain alcohols: still experimental or ready for prime time? Tremor Other Hyperkinet Mov (N Y). 2014;4. doi: 10.7916/ D8RX991R.

90. Axelrad JE, Louis ED, Honig LS, et al. Reduced Purkinje cell number in essential tremor: a postmortem study. Arch Neurol 2008;65:101–7. doi: 10.1001/archneurol.2007.8.

Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

Issue 5

2017 Issue 5

Most read in this issue
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account