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Table of Contents
Vol. 31, No. 3, 2008
Issue release date: October 2008
Section title: Review
Free Access
Neuroepidemiology 2008;31:139–149
(DOI:10.1159/000151523)

Environmental Epidemiology of Essential Tremor

Louis E.D.
GH Sergievsky Center, Department of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, N.Y., USA
email Corresponding Author

Dr. Elan Louis

Unit 198, Neurological Institute

710 West 168th Street

New York, NY 10032 (USA)

Tel. +1 212 305 9194, Fax +1 212 305 1304, E-Mail EDL2@columbia.edu


References

  1. Louis ED: Clinical practice: essential tremor. New Engl J Med 2001;345:887–891.
  2. Busenbark KL, Nash J, Nash S, Hubble JP, Koller WC: Is essential tremor benign? Neurology 1991;41:1982–1983.
  3. Bain PG, Findley LJ, Thompson PD, Gresty MA, Rothwell JC, Harding AE, Marsden CD: A study of hereditary essential tremor. Brain 1994;117:805–824.
  4. Louis ED, Barnes L, Albert SM, Cote L, Schneier FR, Pullman SL, Yu Q: Correlates of functional disability in essential tremor. Mov Disord 2001;16:914–920.
  5. Koller W, Biary N, Cone S: Disability in essential tremor: effect of treatment. Neurology 1986;36:1001–1004.
  6. Rautakorpi I: Essential tremor: an epidemiological, clinical and genetic study; thesis, Turku, 1978.
  7. Louis ED: Essential tremor. Lancet Neurol 2005;4:100–110.
  8. Cohen O, Pullman S, Jurewicz E, Watner D, Louis ED: Rest tremor in patients with essential tremor: prevalence, clinical correlates, and electrophysiologic characteristics. Arch Neurol 2003;60:405–410.
  9. Leegwater-Kim J, Louis ED, Pullman SL, Floyd AG, Borden S, Moskowitz CB, Honig LS: Intention tremor of the head in patients with essential tremor. Mov Disord 2006;21:2001–2005.
  10. Deuschl G, Wenzelburger R, Loffler K, Raethjen J, Stolze H: Essential tremor and cerebellar dysfunction clinical and kinematic analysis of intention tremor. Brain 2000;123:1568–1580.
  11. Singer C, Sanchez-Ramos J, Weiner WJ: Gait abnormality in essential tremor. Mov Disord 1994;9:193–196.
  12. Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G: The gait disorder of advanced essential tremor. Brain 2001;124:2278–2286.
  13. Koster B, Deuschl G, Lauk M, Timmer J, Guschlbauer B, Lucking CH: Essential tremor and cerebellar dysfunction: abnormal ballistic movements. J Neurol Neurosurg Psychiatry 2002;73:400–405.
  14. Helmchen C, Hagenow A, Miesner J, Sprenger A, Rambold H, Wenzelburger R, Heide W, Deuschl G: Eye movement abnormalities in essential tremor may indicate cerebellar dysfunction. Brain 2003;126:1319–1332.
  15. Chatterjee A, Jurewicz EC, Applegate LM, Louis ED: Personality in essential tremor: further evidence of non-motor manifestations of the disease. J Neurol Neurosurg Psychiatry 2004;75:958–961.
  16. Lorenz D, Schwieger D, Moises H, Deuschl G: Quality of life and personality in essential tremor patients. Mov Disord 2006;21:1114–1118.
  17. Tan EK, Fook-Chong S, Lum SY, Gabriel C, Koh KK, Prakash KM, Louis ED: Non-motor manifestations in essential tremor: use of a validated instrument to evaluate a wide spectrum of symptoms. Parkinsonism Relat Disord 2005;11:375–380.
  18. Miller KM, Okun MS, Fernandez HF, Jacobson CE 46th, Rodriguez RL, Bowers D: Depression symptoms in movement disorders: comparing Parkinson’s disease, dystonia, and essential tremor. Mov Disord 2007;22:666–672.
  19. Louis ED, Benito-Leon J, Bermejo-Pareja F: Self-reported depression and anti-depressant medication use in essential tremor: cross-sectional and prospective analyses in a population-based study. Eur J Neurol 2007;14:1138–1146.
  20. Dogu O, Louis ED, Sevim S, Kaleagasi H, Aral M: Clinical characteristics of essential tremor in mersin, turkey – a population-based door-to-door study. J Neurol 2005;252:570–574.
  21. Schneier FR, Barnes LF, Albert SM, Louis ED: Characteristics of social phobia among persons with essential tremor. J Clin Psychiatry 2001;62:367–372.
  22. Louis ED: Behavioral symptoms associated with essential tremor. Adv Neurol 2005;96:284–290.
    External Resources
  23. Findley LJ: Expanding clinical dimensions of essential tremor. J Neurol Neurosurg Psychiatry 2004;75:948–949.
  24. Lombardi WJ, Woolston DJ, Roberts JW, Gross RE: Cognitive deficits in patients with essential tremor. Neurology 2001;57:785–790.
  25. Lacritz LH, Dewey R Jr, Giller C, Cullum CM: Cognitive functioning in individuals with ‘benign’ essential tremor. J Int Neuropsychol Soc 2002;8:125–129.
  26. Duane DD, Vermilion KJ: Cognitive deficits in patients with essential tremor. Neurology 2002;58:1706; author reply 1706.
  27. Vermilion K, Stone A, Duane D: Cognition and affect in idiopathic essential tremor. Mov Disord 2001;16.
  28. Gasparini M, Bonifati V, Fabrizio E, Fabbrini G, Brusa L, Lenzi GL, Meco G: Frontal lobe dysfunction in essential tremor: a preliminary study. J Neurol 2001;248:399–402.
  29. Benito-Leon J, Louis ED, Bermejo-Pareja F: Population-based case-control study of cognitive function in essential tremor. Neurology 2006;66:69–74.
  30. Benito-Leon J, Louis ED, Bermejo-Pareja F: Elderly-onset essential tremor is associated with dementia. Neurology 2006;66:1500–1505.
  31. Bermejo-Pareja F, Louis ED, Benito-Leon J: Risk of incident dementia in essential tremor: a population-based study. Mov Disord 2007.
  32. Benito-Leon J, Louis ED: Essential tremor: emerging views of a common disorder. Nat Clin Pract Neurol 2006;2:666–678.
  33. 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 neurologic exams in Mersin province, Turkey. Neurology 2003;61:1804–1806.
  34. 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.
  35. Rautakorpi I, Takala J, Marttila RJ, Sievers K, Rinne UK: Essential tremor in a finnish population. Acta Neurol Scand 1982;66:58–67.
  36. Louis ED, Dure LSt, Pullman S: Essential tremor in childhood: a series of nineteen cases. Mov Disord 2001;16:921–923.
  37. Louis ED, Fernandez-Alvarez E, Dure LS 4th, Frucht S, Ford B: Association between male gender and pediatric essential tremor. Mov Disord 2005;20:904–906.
  38. Louis ED, Ottman R: Study of possible factors associated with age of onset in essential tremor. Mov Disord 2006;21:1980–1986.
  39. 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;29:208–212.
  40. Louis ED, Barnes LF, Ford B, Pullman SL, Yu Q: Ethnic differences in essential tremor. Arch Neurol 2000;57:723–727.
  41. Louis ED, Marder K, Cote L, Pullman S, Ford B, Wilder D, Tang MX, Lantigua R, Gurland B, Mayeux R: Differences in the prevalence of essential tremor among elderly African Americans, Whites, and Hispanics in Northern Manhattan, NY. Arch Neurol 1995;52:1201–1205.
  42. Louis ED, Fried LP, Fitzpatrick AL, Longstreth WT Jr, Newman AB: Regional and racial differences in the prevalence of physician-diagnosed essential tremor in the United States. Mov Disord 2003;18:1035–1040.
  43. Rajput AH, Offord KP, Beard CM, Kurland LT: Essential tremor in Rochester, Minnesota: a 45-year study. J Neurol Neurosurg Psychiatry 1984;47:466–470.
  44. Benito-Leon J, Bermejo-Pareja F, Louis ED: Incidence of essential tremor in three elderly populations of central Spain. Neurology 2005;64:1721–1725.
  45. Critchley M: Observations of essential (heredofamilial) tremor. Brain 1949;72:113–139.
  46. Louis ED, Ford B, Barnes LF: Clinical subtypes of essential tremor. Arch Neurol 2000;57:1194–1198.
  47. Louis ED, Jurewicz EC, Watner D: Community-based data on associations of disease duration and age with severity of essential tremor: implications for disease pathophysiology. Mov Disord 2003;18:90–93.
  48. Elble RJ, Higgins C, Hughes L: Longitudinal study of essential tremor. Neurology 1992;42:441–443.
  49. Putzke JD, Whaley NR, Baba Y, Wszolek ZK, Uitti RJ: Essential tremor: predictors of disease progression in a clinical cohort. J Neurol Neurosurg Psychiatry 2006;77:1235–1237.
  50. Yahr MD, Orosz D, Purohit DP: Co-occurrence of essential tremor and Parkinson’s disease: clinical study of a large kindred with autopsy findings. Parkinsonism Relat Disord 2003;9:225–231.
  51. Shahed J, Jankovic J: Exploring the relationship between essential tremor and Parkinson’s disease. Parkinsonism Relat Disord 2007;13:67–76.
  52. Louis ED, Levy G, Mejia-Santana H, Cote L, Andrews H, Harris J, Waters C, Ford B, Frucht S, Fahn S, Ottman R, Marder K: Risk of action tremor in relatives of tremor-dominant and postural instability gait disorder PD. Neurology 2003;61:931–936.
  53. Ondo WG, Lai D: Olfaction testing in patients with tremor-dominant Parkinson’s disease: Is this a distinct condition? Mov Disord 2005;20:471–475.
  54. Pahwa R, Koller WC: Is there a relationship between Parkinson’s disease and essential tremor? Clin Neuropharmacol 1993;16:30–35.
  55. Geraghty JJ, Jankovic J, Zetusky WJ: Association between essential tremor and Parkinson’s disease. Ann Neurol 1985;17:329–333.
  56. Chaudhuri KR, Buxton-Thomas M, Dhawan V, Peng R, Meilak C, Brooks DJ: Long duration asymmetrical postural tremor is likely to predict development of Parkinson’s disease and not essential tremor: clinical follow up study of 13 cases. J Neurol Neurosurg Psychiatry 2005;76:115–117.
  57. Louis ED, Frucht SJ: Prevalence of essential tremor in patients with Parkinson’s disease versus Parkinson-plus syndromes. Mov Disord 2007;22:1402–1407.
  58. Benito-Leon J, Bermejo-Pareja F: Risk of incident Parkinson’s disease and Parkinsonism in essential tremor: a population-based study. Neurology 2008;70:A191.
    External Resources
  59. Louis ED, Faust PL, Vonsattel JP, Honig LS, Rajput A, Robinson CA, Pahwa R, Lyons KE, Ross GW, Borden S, Moskowitz CB, Lawton A, Hernandez N: Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain 2007;130:3297–3307.
  60. Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, Moskowitz CB: Essential tremor associated with focal nonnigral Lewy bodies: a clinicopathologic study. Arch Neurol 2005;62:1004–1007.
  61. Ross GW, Cerosimo M, et al: Pathological investigation of essential tremor Neurology 2004;62:A537–A538.
  62. Louis ED, Benito-Leon J, Ottman R, Bermejo-Pareja F: A population-based study of mortality in essential tremor. Neurology 2007;69:1982–1989.
  63. Hardesty DE, Maraganore DM, Matsumoto JY, Louis ED: Increased risk of head tremor in women with essential tremor: longitudinal data from the Rochester Epidemiology Project. Mov Disord 2004;19:529–533.
  64. Louis ED, Ford B, Frucht S: Factors associated with increased risk of head tremor in essential tremor: a community-based study in Northern Manhattan. Mov Disord 2003;18:432–436.
  65. Hubble JP, Busenbark KL, Pahwa R, Lyons K, Koller WC: Clinical expression of essential tremor: effects of gender and age. Mov Disord 1997;12:969–972.
  66. Louis ED, Vonsattel JP: The emerging neuropathology of essential tremor. Mov Disord 2007;23:174–182.
    External Resources
  67. Louis ED, Vonsattel JP, Honig LS, Ross GW, Lyons KE, Pahwa R: Neuropathologic findings in essential tremor. Neurology 2006;66:1756–1759.
  68. Higgins JJ, Lombardi RQ, Pucilowska J, Jankovic J, Golbe LI, Verhagen L: HS1-BP3 gene variant is common in familial essential tremor. Mov Disord 2006;21:306–309.
  69. Deng H, Le W, Jankovic J: Genetics of essential tremor. Brain 2007;130:1456–1464.
  70. Higgins JJ, Pho LT, Nee LE: A gene (ETM) for essential tremor maps to chromosome 2p22-p25. Mov Disord 1997;12:859–864.
  71. Higgins JJ, Loveless JM, Jankovic J, Patel PI: Evidence that a gene for essential tremor maps to chromosome 2p in four families. Mov Disord 1998;13:972–977.
  72. Kovach MJ, Ruiz J, Kimonis K, Mueed S, Sinha S, Higgins C, Elble S, Elble R, Kimonis VE: Genetic heterogeneity in autosomal dominant essential tremor. Genet Med 2001;3:197–199.
  73. Shatunov A, Sambuughin N, Jankovic J, Elble R, Lee HS, Singleton AB, Dagvadorj A, Ji J, Zhang Y, Kimonis VE, Hardy J, Hallett M, Goldfarb LG: Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain 2006;129:2318–2331.
  74. Gulcher JR, Jonsson P, Kong A, Kristjansson K, Frigge ML, Karason A, Einarsdottir IE, Stefansson H, Einarsdottir AS, Sigurthoardottir S, Baldursson S, Bjornsdottir S, Hrafnkelsdottir SM, Jakobsson F, Benedickz J, Stefansson K: Mapping of a familial essential tremor gene, FET1, to chromosome 3q13. Nat Genet 1997;17:84–87.
  75. Marshall J: Observations on essential tremor. J Neurol Neurosurg Psychiatry 1962;25:122–125.
  76. Higgins JJ, Jankovic J, Lombardi RQ, Pucilowska J, Tan EK, Ashizawa T, Ruszczyk MU: Haplotype analysis of the ETM2 locus in familial essential tremor. Neurogenetics 2003;4:185–189.
  77. Higgins JJ, Lombardi RQ, Pucilowska J, Jankovic J, Tan EK, Rooney JP: A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology 2005;64:417–421.
  78. Higgins JJ, Lombardi RQ, Pucilowska J, Ruszczyk MU: Integrated physical map of the human essential tremor gene region (ETM2) on chromosome 2p24.3-p24.2. Am J Med Genet B Neuropsychiatr Genet 2004;127:128–130.
    External Resources
  79. Higgins JJ, Lombardi RQ, Tan EK, Jankovic J, Pucilowska J, Rooney JP: Haplotype analysis at the ETM2 locus in a Singaporean sample with familial essential tremor. Clin Genet 2004;66:353–357.
  80. Aridon P, Ragonese P, De Fusco M, Salemi G, Casari G, Savettieri G: Further evidence of genetic heterogeneity in familial essential tremor. Parkinsonism Relat Disord 2007.
  81. Ma S, Davis TL, Blair MA, Fang JY, Bradford Y, Haines JL, Hedera P: Familial essential tremor with apparent autosomal dominant inheritance: Should we also consider other inheritance modes? Mov Disord 2006;21:1368–1374.
  82. Martinez C, Garcia-Martin E, Alonso-Navarro H, Benito-Leon J, Puertas I, Rubio L, Lopez-Alburquerque T, Agundez JA, Jimenez-Jimenez FJ: Alcohol dehydrogenase 2 genotype and allelic variants are not associated with the risk for essential tremor. Clin Neuropharmacol 2007;30:196–200.
  83. Sazci A, Ergul E, Bayulkem K: Association of the c677t and a1298c polymorphisms of methylenetetrahydrofolate reductase gene in patients with essential tremor in turkey. Mov Disord 2004;19:1472–1476.
  84. Martinez C, Garcia-Martin E, Alonso-Navarro H, Benito-Leon J, Puertas I, Rubio L, Lopez-Alburquerque T, Agundez JA, Jimenez-Jimenez FJ: Glutathione-s-transferase p1 polymorphism and risk for essential tremor. Eur J Neurol 2008;15:234–238.
  85. Alonso-Navarro H, Martinez C, Garcia-Martin E, Benito-Leon J, Garcia-Ferrer I, Vazquez-Torres P, Puertas I, Lopez-Alburquerque T, Agundez JA, Jimenez-Jimenez FJ: Cyp2c19 polymorphism and risk for essential tremor. Eur Neurol 2006;56:119–123.
  86. Louis ED, Applegate L, Graziano JH, Parides M, Slavkovich V, Bhat HK: Interaction between blood lead concentration and δ-amino-levulinic acid dehydratase gene polymorphisms increases the odds of essential tremor. Mov Disord 2005;20:1170–1177.
  87. Blair MA, Ma S, Phibbs F, Fang JY, Cooper MK, Davis TL, Hedera P: Reappraisal of the role of the DRD3 gene in essential tremor. Parkinsonism Relat Disord 2008.
  88. Deng H, Xie WJ, Le WD, Huang MS, Jankovic J: Genetic analysis of the GABRA1 gene in patients with essential tremor. Neurosci Lett 2006;401:16–19.
  89. Xiao Y, Zhang BS: Association of the polymorphism in α-2 macroglobulin gene with essential tremor and Parkinson’s disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2006;23:84–85.
  90. Agundez JA, Jimenez-Jimenez FJ, Tejeda R, Ledesma MC, Orti-Pareja M, Gasalla T, Molina JA, Ruiz J, Coria F, Duarte J, Vazquez A, Ladero JM, Benitez J: CYP2D6 polymorphism is not associated with essential tremor. Eur Neurol 1997;38:99–104.
  91. Louis ED, Ottman R: How familial is familial tremor? The genetic epidemiology of essential tremor. Neurology 1996;46:1200–1205.
  92. Louis ED, Ottman R, Ford B, Pullman S, Martinez M, Fahn S, Hauser WA: The Washington Heights-Inwood genetic study of essential tremor: methodologic issues in essential-tremor research. Neuroepidemiology 1997;16:124–133.
  93. Hornabrook RW, Nagurney JT: Essential tremor in Papua, New Guinea. Brain 1976;99:659–672.
  94. Critchley E: Clinical manifestations of essential tremor. J Neurol Neurosurg Psychiatry 1972;35:365–372.
  95. Salemi G, Aridon P, Calagna G, Monte M, Savettieri G: Population-based case-control study of essential tremor. Ital J Neurol Sci 1998;19:301–305.
  96. Martinelli P, Gabellini AS, Gulli MR, Lugaresi E: Different clinical features of essential tremor: a 200-patient study. Acta Neurol Scand 1987;75:106–111.
  97. Aiyesimoju AB, Osuntokun BO, Bademosi O, Adeuja AO: Hereditary neurodegenerative disorders in Nigerian Africans. Neurology 1984;34:361–362.
  98. Tanner CM, Goldman SM, Lyons KE, Aston DA, Tetrud JW, Welsh MD, Langston JW, Koller WC: Essential tremor in twins: an assessment of genetic versus environmental determinants of etiology. Neurology 2001;57:1389–1391.
  99. Lorenz D, Frederiksen H, Moises H, Kopper F, Deuschl G, Christensen K: High concordance for essential tremor in monozygotic twins of old age. Neurology 2004;62:208–211.
  100. Larsson T, Sjogren T: Essential tremor: a clinical and genetic population study. Acta Psychiatr Scand Suppl 1960;36:1–176.
  101. Louis ED, Ford B, Frucht S, Barnes LF, X-Tang M, Ottman R: Risk of tremor and impairment from tremor in relatives of patients with essential tremor: a community-based family study. Ann Neurol 2001;49:761–769.
  102. Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ: Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson’s disease. Neurotoxicology 1999;20:239–247.
  103. Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ: Occupational exposures to metals as risk factors for Parkinson’s disease. Neurology 1997;48:650–658.
  104. Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Richardson RJ: The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998;50:1346–1350.
  105. Rybicki BA, Johnson CC, Uman J, Gorell JM: Parkinson’s disease mortality and the industrial use of heavy metals in Michigan. Mov Disord 1993;8:87–92.
  106. Racette BA, McGee-Minnich L, Moerlein SM, Mink JW, Videen TO, Perlmutter JS: Welding-related Parkinsonism: clinical features, treatment, and pathophysiology. Neurology 2001;56:8–13.
  107. Baldereschi M, Inzitari M, Vanni P, Di Carlo A, Inzitari D: Pesticide exposure might be a strong risk factor for Parkinson’s disease. Ann Neurol 2007.
  108. Dick FD: Parkinson’s disease and pesticide exposures. Br Med Bull 2006;79–80:219–231.
  109. Ritz B, Yu F: Parkinson’s disease mortality and pesticide exposure in California 1984–1994. Int J Epidemiol 2000;29:323–329.
  110. Semchuk KM, Love EJ, Lee RG: Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology 1992;42:1328–1335.
  111. Shcherbatykh I, Carpenter DO: The role of metals in the etiology of Alzheimer’s disease. J Alzheimers Dis 2007;11:191–205.
  112. Perl DP: Relationship of aluminum to Alzheimer’s disease. Environ Health Perspect 1985;63:149–153.
  113. Morahan JM, Yu B, Trent RJ, Pamphlett R: Genetic susceptibility to environmental toxicants in ALS. Am J Med Genet B Neuropsychiatr Genet 2007;144:885–890.
  114. Lambert D, Waters CH: Essential tremor. Curr Treat Options Neurol 1999;1:6–13.
  115. McKenna DJ: Plant hallucinogens: springboards for psychotherapeutic drug discovery. Behav Brain Res 1996;73:109–116.
  116. Zetler G, Singbartl G, Schlosser L: Cerebral pharmacokinetics of tremor-producing harmala and iboga alkaloids. Pharmacology 1972;7:237–248.
  117. Sakai S: Chemical studies of indole alkaloids. Yakugaku Zasshi 1995;115:351–369.
  118. De Meester C: Genotoxic potential of β-carbolines: a review. Mut Res 1995;339:139–153.
  119. Langston JW, Langston EB, Irwin I: MPTP-induced Parkinsonism in human and non-human primates – clinical and experimental aspects. Acta Neurol Scand Suppl 1984;100:49–54.
  120. Smeyne RJ, Jackson-Lewis V: The MPTP model of Parkinson’s disease. Brain Res Mol Brain Res 2005;134:57–66.
  121. Du W, Aloyo VJ, Harvey JA: Harmaline competitively inhibits [3H]MK-801 binding to the nmda receptor in rabbit brain. Brain Res 1997;770:26–29.
  122. Martin FC, Handforth A: Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor. Mov Disord 2006;21:1641–1649.
  123. Martin FC, Thu Le A, Handforth A: Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications. Mov Disord 2005;20:298–305.
  124. Krahl SE, Martin FC, Handforth A: Vagus nerve stimulation inhibits harmaline-induced tremor. Brain Res 2004;1011:135–138.
  125. Handforth A, Krahl SE: Suppression of harmaline-induced tremor in rats by vagus nerve stimulation. Mov Disord 2001;16:84–88.
  126. Sinton CM, Krosser BI, Walton KD, Llinas RR: The effectiveness of different isomers of octanol as blockers of harmaline-induced tremor. Pflugers Arch 1989;414:31–36.
  127. Milner TE, Cadoret G, Lessard L, Smith AM: EMG analysis of harmaline-induced tremor in normal and three strains of mutant mice with Purkinje cell degeneration and the role of the inferior olive. J Neurophysiol 1995;73:2568–2577.
  128. Trouvin JH, Jacqmin P, Rouch C, Lesne M, Jacquot C: Benzodiazepine receptors are involved in tabernanthine-induced tremor: in vitro and in vivo evidence. Eur J Pharmacol 1987;140:303–309.
  129. Fuentes JA, Longo VG: An investigation on the central effects of harmine, harmaline and related β-carbolines. Neuropharmacology 1971;10:15–23.
  130. Cross AJ, Misra A, Sandilands A, Taylor MJ, Green AR: Effect of chlormethiazole, dizocilpine and pentobarbital on harmaline-induced increase of cerebellar cyclic GMP and tremor. Psychopharmacology (Berl) 1993;111:96–98.
  131. Rappaport MS, Gentry RT, Schneider DR, Dole VP: Ethanol effects on harmaline-induced tremor and increase of cerebellar cyclic GMP. Life Sci 1984;34:49–56.
  132. Louis ED, Shungu DC, Chan S, Mao X, Jurewicz EC, Watner D: Metabolic abnormality in the cerebellum in patients with essential tremor: a proton magnetic resonance spectroscopic imaging study. Neurosci Lett 2002;333:17–20.
  133. Louis ED, Shungu DC, Mao X, Chan S, Jurewicz EC: Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: implications for disease pathology. Mov Disord 2004;19:672–677.
  134. Louis ED, Vonsattel JP, Honig LS, Lawton A, Moskowitz C, Ford B, Frucht S: Essential tremor associated with pathologic changes in the cerebellum. Arch Neurol 2006;63:1189–1193.
  135. Pagan FL, Butman JA, Dambrosia JM, Hallett M: Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy. Neurology 2003;60:1344–1347.
  136. Shill H, Sabbagh M, Connor D, Caviness J, Beach T: Pathological changes in prospectively-ascertained essential tremor subjects. Neurology 2007;68.
  137. Axelrad JE LE, Honig LS, Flores I, Ross GW, Pahwa R, Lyons KE, Faust PL, Vonsattel JP: Reduced Purkinje cell number in essential tremor: a postmortem study. Arch Neurol 2008;65:101–107.
  138. O’Hearn E, Long DB, Molliver ME: Ibogaine induces glial activation in parasagittal zones of the cerebellum. Neuroreport 1993;4:299–302.
  139. O’Hearn E, Molliver ME: Degeneration of purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience 1993;55:303–310.
  140. O’Hearn E, Molliver ME: The olivocerebellar projection mediates ibogaine-induced degeneration of purkinje cells: a model of indirect, trans-synaptic excitotoxicity. J Neurosci 1997;17:8828–8841.
  141. Robertson HA: Harmaline-induced tremor: the benzodiazepine receptor as a site of action. Eur J Pharmacol 1980;67:129–132.
  142. Lewin L: Untersuchungen über Banisteria caapi sp. Arch Exp Pathol Pharmacol 1928;129:133–149.
  143. Pennes HH, Hoch PH: Psychotomimetics, clinical and theoretical considerations: harmine, win-2299 and nalline. Am J Psychiatry 1957;113:887–892.
  144. Moncrieff J: Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection. J Chromatogr 1989;496:269–278.
  145. Anderson NJ, Tyacke RJ, Husbands SM, Nutt DJ, Hudson AL, Robinson ES: In vitro and ex vivo distribution of [3H]harmane, an endogenous β-carboline, in rat brain. Neuropharmacology 2006;50:269–276.
  146. Matsubara K, Collins MA, Akane A, Ikebuchi J, Neafsey EJ, Kagawa M, Shiono H: Potential bioactivated neurotoxicants, n-methylated β-carbolinium ions, are present in human brain. Brain Res 1993;610:90–96.
  147. Gearhart DA, Collins MA, Lee JM, Neafsey EJ: Increased β-carboline 9N-methyltransferase activity in the frontal cortex in Parkinson’s disease. Neurobiol Dis 2000;7:201–211.
  148. Wakabayashi K, Totsuka Y, Fukutome K, Oguri A, Ushiyama H, Sugimura T: Human exposure to mutagenic/carcinogenic heterocyclic amines and comutagenic β-carbolines. Mutat Res 1997;376:253–259.
  149. Pfau W, Skog K: Exposure to β-carbolines norharman and harman. J Chromatogr B Analyt Technol Biomed Life Sci 2004;802:115–126.
  150. Gross GA, Turesky RJ, Fay LB, Stillwell WG, Skipper PL, Tannenbaum SR: Heterocyclic aromatic amine formation in grilled bacon, beef and fish and in grill scrapings. Carcinogenesis 1993;14:2313–2318.
  151. Skog K, Solyakov A, Arvidsson P, Jagerstad M: Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectrometry. J Chromatogr A 1998;803:227–233.
  152. Skog K: Cooking procedures and food mutagens: a literature review. Food Chem Toxicol 1993;31:655–675.
  153. Layton DW, Bogen KT, Knize MG, Hatch FT, Johnson VM, Felton JS: Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research. Carcinogenesis 1995;16:39–52.
  154. Sinha R, Rothman N, Salmon CP, Knize MG, Brown ED, Swanson CA, Rhodes D, Rossi S, Felton JS, Levander OA: Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings. Food Chem Toxicol 1998;36:279–287.
  155. Sinha R, Knize MG, Salmon CP, Brown ED, Rhodes D, Felton JS, Levander OA, Rothman N: Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness. Food Chem Toxicol 1998;36:289–297.
  156. Herraiz T: Relative exposure to β-carbolines norharman and harman from foods and tobacco smoke. Food Addit Contam 2004;21:1041–1050.
  157. Louis ED, Zheng W, Jurewicz EC, Watner D, Chen J, Factor-Litvak P, Parides M: Elevation of blood β-carboline alkaloids in essential tremor. Neurology 2002;59:1940–1944.
  158. Louis ED, Jiang W, Pellegrino KM, Rios E, Factor-Litvak P, Henchcliffe C, Zheng W: Elevated blood harmane (1-methyl-9H-pyrido[3,4-B]indole) concentrations in essential tremor. Neurotoxicology 2008;29:294–300.
  159. Louis ED, Zheng W, Mao X, Shungu DC: Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study. Neurology 2007;69:515–520.
  160. Louis ED, Zheng W, Applegate L, Shi L, Factor-Litvak P: Blood harmane concentrations and dietary protein consumption in essential tremor. Neurology 2005;65:391–396.
  161. Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, Hennekens CH, Speizer FE: Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985;122:51–65.
  162. Louis ED, Keating GA, Bogen KT, Rios E, Pellegrino KM, Factor-Litvak P: Dietary epidemiology of essential tremor: meat consumption and meat cooking practices. Neuroepidemiology 2008;30:161–166.
  163. Kuhn W, Muller T, Grosse H, Rommelspacher H: Plasma harman and norharman in Parkinson’s disease. J Neural Transm Suppl 1995;46:291–295.
  164. Coulehan JL, Hirsch W, Brillman J, Sanandria J, Welty TK, Colaiaco P, Koros A, Lober A: Gasoline sniffing and lead toxicity in Navajo adolescents. Pediatrics 1983;71:113–117.
  165. Winegar DA, Levy BS, Andrews JS Jr, Landrigan PJ, Scruton WH, Krause MJ: Chronic occupational exposure to lead: an evaluation of the health of smelter workers. J Occup Med 1977;19:603–606.
  166. Booze RM, Mactutus CF, Annau Z, Tilson HA: Neonatal triethyl lead neurotoxicity in rat pups: initial behavioral observations and quantification. Neurobehav Toxicol Teratol 1983;5:367–375.
  167. Goldings AS, Stewart RM: Organic lead encephalopathy: behavioral change and movement disorder following gasoline inhalation. J Clin Psychiatry 1982;43:70–72.
  168. Seshia SS, Rjani KR, Boeckx RL, Chow PN: The neurological manifestations of chronic inhalation of leaded gasoline. Dev Med Child Neurol 1978;20:323–334.
  169. Valpey R, Sumi SM, Copass MK, Goble GJ: Acute and chronic progressive encephalopathy due to gasoline sniffing. Neurology 1978;28:507–510.
  170. Young RS, Grzyb SE, Crismon L: Recurrent cerebellar dysfunction as related to chronic gasoline sniffing in an adolescent girl: lead poisoning from ‘leaded’ gasoline as an attendent complication. Clin Pediatr (Phila) 1977;16:706–708.
  171. McConnell P, Berry M: The effects of postnatal lead exposure on purkinje cell dendritic development in the rat. Neuropathol Appl Neurobiol 1979;5:115–132.
  172. Walsh TJ, Tilson HA: Neurobehavioral toxicology of the organoleads. Neurotoxicology 1984;5:67–86.
  173. Louis ED, Jurewicz EC, Applegate L, Factor-Litvak P, Parides M, Andrews L, Slavkovich V, Graziano JH, Carroll S, Todd A: Association between essential tremor and blood lead concentration. Environ Health Perspect 2003;111:1707–1711.
  174. Dogu O, Louis ED, Tamer L, Unal O, Yilmaz A, Kaleagasi H: Elevated blood lead concentrations in essential tremor: a case-control study in Mersin, Turkey. Environ Health Perspect 2007;115:1564–1568.
  175. Taylor JR: Neurological manifestations in humans exposed to chlordecone and follow-up results. Neurotoxicology 1982;3:9–16.
  176. Taylor JR, Selhorst JB, Houff SA, Martinez AJ: Chlordecone intoxication in man. I. Clinical observations. Neurology 1978;28:626–630.
  177. Louis ED, Factor-Litvak P, Parides M, Andrews L, Santella RM, Wolff MS: Organochlorine pesticide exposure in essential tremor: a case-control study using biological and occupational exposure assessments. Neurotoxicology 2006;27:579–586.
  178. Cannon SB, Veazey JM Jr, Jackson RS, Burse VW, Hayes C, Straub WE, Landrigan PJ, Liddle JA: Epidemic kepone poisoning in chemical workers. Am J Epidemiol 1978;107:529–537.
  179. Jiménez-Jiménez FJ dT-HM, Alonso-Navarro H, Ayuso-Peralta L, Arévalo-Serrano J, Ballesteros-Barranco A, Puertas I, Jabbour-Wadih T, Barcenilla B: Environmental risk factors for essential tremor. Eur Neurol 2007;58:106–113.
  180. Prakash KM, Fook-Choong S, Yuen Y, Tan EK: Exploring the relationship between caffeine intake and essential tremor. J Neurol Sci 2006;251:98–101.
  181. Louis ED, Applegate LM, Factor-Litvak P, Parides MK, Andrews L: Essential tremor: occupational exposures to manganese and organic solvents. Neurology 2004;63:2162–2164.
  182. Fabrizio E, Vanacore N, Valente M, Rubino A, Meco G: High prevalence of extrapyramidal signs and symptoms in a group of Italian dental technicians. BMC Neurol 2007;7:24.
  183. Louis ED, Ford B, Pullman S, Baron K: How normal is ‘normal’? Mild tremor in a multiethnic cohort of normal subjects. Arch Neurol 1998;55:222–227.
  184. Ben-Shlomo Y: How far are we in understanding the cause of parkinson’s disease? J Neurol Neurosurg Psychiatry 1996;61:4–16.
  185. Rautakorpi I, Marttila RJ, Rinne UK: Alcohol consumption of patients with essential tremor. Acta Neurol Scand 1983;68:177–179.
  186. Nasrallah HA, Schroeder D, Petty F: Alcoholism secondary to essential tremor. J Clin Psychiatry 1982;43:163–164.
  187. Louis ED, Jurewicz EC, Applegate L, Luchsinger JA, Factor-Litvak P, Parides M: Semiquantitative study of current coffee, caffeine, and ethanol intake in essential tremor cases and controls. Mov Disord 2004;19:499–504.
  188. Torvik A, Torp S: The prevalence of alcoholic cerebellar atrophy: a morphometric and histological study of an autopsy material. J Neurol Sci 1986;75:43–51.
  189. Gorell JM, Rybicki BA, Johnson CC, Peterson EL: Smoking and parkinson’s disease: a dose-response relationship. Neurology 1999;52:115–119.
  190. Ritz B, Ascherio A, Checkoway H, Marder KS, Nelson LM, Rocca WA, Ross GW, Strickland D, Van Den Eeden SK, Gorell J: Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol 2007;64:990–997.
  191. Benito-Leon J, Louis ED, Permejo-Pareja F: Population-based case-control study of cigarette smoking and essential tremor. Mov Disord 2008;23:246–252.
  192. Louis ED, Benito-Leon J, Permejo-Pareja F: Population-based prospective study of cigarette smoking and risk of incident essential tremor. Neurology 2008;70:1682–1687.
  193. Mudo G, Belluardo N, Fuxe K: Nicotinic receptor agonists as neuroprotective/neurotrophic drugs: progress in molecular mechanisms. J Neural Transm 2007;114:135–147.
  194. Meissner W, Hill MP, Tison F, Gross CE, Bezard E: Neuroprotective strategies for Parkinson’s disease: conceptual limits of animal models and clinical trials. Trends Pharmacol Sci 2004;25:249–253.
  195. Zanardi A, Leo G, Biagini G, Zoli M: Nicotine and neurodegeneration in ageing. Toxicol Lett 2002;127:207–215.
  196. Jeyarasasingam G, Tompkins L, Quik M: Stimulation of non-α7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture. Neuroscience 2002;109:275–285.
  197. Maggio R, Riva M, Vaglini F, Fornai F, Molteni R, Armogida M, Racagni G, Corsini GU: Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors. J Neurochem 1998;71:2439–2446.