The Cerebellum

, Volume 13, Issue 4, pp 501–512 | Cite as

From Neurons to Neuron Neighborhoods: the Rewiring of the Cerebellar Cortex in Essential Tremor

Review

Abstract

Remarkably little has been written on the biology of essential tremor (ET), despite its high prevalence. The olivary model, first proposed in the 1970s, is the traditional disease model for ET; however, the model is problematic for a number of reasons. Recently, intensive tissue-based studies have identified a series of structural changes in the brains of most ET cases, and nearly all of the observed changes are located in the cerebellar cortex. These studies suggest that Purkinje cells are central to the pathogenesis of ET and may thus provide a focus for the development of novel therapeutic strategies. Arising from these studies, a new model of ET proposes that the population of Purkinje cells represents the site of the initial molecular/cellular events leading to ET. Furthermore, a number of secondary changes/remodeling observed in the molecular and granular layers (i.e., in the Purkinje cell “neighborhood”) are likely to be of additional mechanistic importance. On a physiological level, the presence of remodeling indicates the likely formation of aberrant synapses and the creation of new/abnormal cortical circuits in ET. Specific efforts need to be devoted to understanding the cascade of biochemical and cellular events occurring in the Purkinje cell layer in ET and its neuron neighborhood, as well as the physiological effects of secondary remodeling/rewiring that are likely to be occurring in this brain region in ET.

Keywords

Essential tremor Cerebellum Biology Pathophysiology Purkinje Neurodegeneration 

References

  1. 1.
    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(5):534–41.PubMedGoogle Scholar
  2. 2.
    Dogu O, Sevim S, Camdeviren H, et al. Prevalence of essential tremor: door-to-door neurologic exams in Mersin Province, Turkey. Neurology. 2003;61(12):1804–6.PubMedGoogle Scholar
  3. 3.
    Benito-León J, Bermejo-Pareja F, Morales JM, Vega S, Molina JA. Prevalence of essential tremor in three elderly populations of central Spain. Mov Disord. 2003;18(4):389–94.PubMedGoogle Scholar
  4. 4.
    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(6):761–9.PubMedGoogle Scholar
  5. 5.
    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(1):5–10.PubMedGoogle Scholar
  6. 6.
    Lieberman A, Imke S, Brewer M, et al. High prevalence of tremor in a retirement community. Neurology. 1994;44:A213.Google Scholar
  7. 7.
    Elble RJ. Tremor in ostensibly normal elderly people. Mov Disord. 1998;13(3):457–64.PubMedGoogle Scholar
  8. 8.
    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(3):208–14.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Louis ED. Clinical practice. Essential tremor. N Engl J Med. 2001;345(12):887–91.PubMedGoogle Scholar
  10. 10.
    Louis ED. Essential tremor. Lancet Neurol. 2005;4(2):100–10.PubMedGoogle Scholar
  11. 11.
    Brennan KC, Jurewicz EC, Ford B, Pullman SL, Louis ED. Is essential tremor predominantly a kinetic or a postural tremor? A clinical and electrophysiological study. Mov Disord. 2002;17(2):313–6.PubMedGoogle Scholar
  12. 12.
    Louis ED. The primary type of tremor in essential tremor is kinetic rather than postural: cross-sectional observation of tremor phenomenology in 369 cases. Eur J Neurol. 2013;20(4):725–7.PubMedCentralPubMedGoogle Scholar
  13. 13.
    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(3):405–10.PubMedGoogle Scholar
  14. 14.
    Louis ED, Frucht SJ, Rios E. Intention tremor in essential tremor: prevalence and association with disease duration. Mov Disord. 2009;24(4):626–7.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Leegwater-Kim J, Louis ED, Pullman SL, et al. Intention tremor of the head in patients with essential tremor. Mov Disord. 2006;21(11):2001–5.PubMedGoogle Scholar
  16. 16.
    Kronenbuerger M, Konczak J, Ziegler W, et al. Balance and motor speech impairment in essential tremor. Cerebellum. 2009;8(3):389–98.PubMedGoogle Scholar
  17. 17.
    Earhart GM, Clark BR, Tabbal SD, Perlmutter JS. Gait and balance in essential tremor: variable effects of bilateral thalamic stimulation. Mov Disord. 2009;24(3):386–91.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Parisi SL, Héroux ME, Culham EG, Norman KE. Functional mobility and postural control in essential tremor. Arch Phys Med Rehabil. 2006;87(10):1357–64.PubMedGoogle Scholar
  19. 19.
    Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. The gait disorder of advanced essential tremor. Brain. 2001;124(Pt 11):2278–86.PubMedGoogle Scholar
  20. 20.
    Hubble JP, Busenbark KL, Pahwa R, Lyons K, Koller WC. Clinical expression of essential tremor: effects of gender and age. Mov Disord. 1997;12(6):969–72.PubMedGoogle Scholar
  21. 21.
    Hoskovcová M, Ulmanová O, Sprdlík O, et al. Disorders of balance and gait in essential tremor are associated with midline tremor and age. Cerebellum. 2013;12(1):27–34.PubMedGoogle Scholar
  22. 22.
    Louis ED, Rios E, Rao AK. Tandem gait performance in essential tremor: clinical correlates and association with midline tremors. Mov Disord. 2010;25(11):1633–8.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Rao AK, Uddin J, Gillman A, Louis ED. Cognitive motor interference during dual-task gait in essential tremor. Gait Posture. 2013;38(3):403–9.PubMedGoogle Scholar
  24. 24.
    Singer C, Sanchez-Ramos J, Weiner WJ. Gait abnormality in essential tremor. Mov Disord. 1994;9(2):193–6.PubMedGoogle Scholar
  25. 25.
    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 Nov 4;3. pii: tre-03-200-4597-1.Google Scholar
  26. 26.
    Tröster AI, Woods SP, Fields JA, et al. Neuropsychological deficits in essential tremor: an expression of cerebello-thalamo-cortical pathophysiology? Eur J Neurol. 2002;9(2):143–51.PubMedGoogle Scholar
  27. 27.
    Benito-León J, Louis ED, Bermejo-Pareja F. Population-based case–control study of cognitive function in essential tremor. Neurology. 2006;66(1):69–74.PubMedGoogle Scholar
  28. 28.
    Thenganatt MA, Louis ED. Personality profile in essential tremor: a case–control study. Parkinsonism Relat Disord. 2012;18(9):1042–4.PubMedCentralPubMedGoogle Scholar
  29. 29.
    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(7):958–61.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Tan EK, Fook-Chong S, Lum SY, et al. Non-motor manifestations in essential tremor: use of a validated instrument to evaluate a wide spectrum of symptoms. Parkinsonism Relat Disord. 2005;11(6):375–80.PubMedGoogle Scholar
  31. 31.
    Louis ED, Benito-León 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(10):1138–46.PubMedGoogle Scholar
  32. 32.
    Miller KM, Okun MS, Fernandez HF, Jacobson 4th CE, Rodriguez RL, Bowers D. Depression symptoms in movement disorders: comparing Parkinson’s disease, dystonia, and essential tremor. Mov Disord. 2007;22(5):666–72.PubMedGoogle Scholar
  33. 33.
    Lorenz D, Poremba C, Papengut F, Schreiber S, Deuschl G. The psychosocial burden of essential tremor in an outpatient- and a community-based cohort. Eur J Neurol. 2011;18(7):972–9.PubMedGoogle Scholar
  34. 34.
    Benito-León J. Essential tremor: from a monosymptomatic disorder to a more complex entity. Neuroepidemiology. 2008;31(3):191–2.PubMedGoogle Scholar
  35. 35.
    Shill HA, Adler CH, Sabbagh MN, et al. Pathologic findings in prospectively ascertained essential tremor subjects. Neurology. 2008;70(16 Pt 2):1452–5.PubMedGoogle Scholar
  36. 36.
    Louis ED. Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry. Lancet Neurol. 2010;9(6):613–22.PubMedGoogle Scholar
  37. 37.
    Louis ED. Essential tremors: a family of neurodegenerative disorders? Arch Neurol. 2009;66(10):1202–8.PubMedCentralPubMedGoogle Scholar
  38. 38.
    Louis ED. “Essential tremor” or “the essential tremors”: is this one disease or a family of diseases? Neuroepidemiology. 2013;42(2):81–9.PubMedGoogle Scholar
  39. 39.
    Kaindlstorfer C, Granata R, Wenning GK. Tremor in multiple system atrophy—a review. Tremor Other Hyperkinet Mov (N Y). 2013 Sep 3;3. pii: tre-03-165-4252-1.Google Scholar
  40. 40.
    Perlman SL. Spinocerebellar degenerations. Handb Clin Neurol. 2011;100:113–40.PubMedGoogle Scholar
  41. 41.
    Gardner RJ, Knight MA, Hara K, Tsuji S, Forrest SM, Storey E. Spinocerebellar ataxia type 15. Cerebellum. 2005;4(1):47–50.PubMedGoogle Scholar
  42. 42.
    Holmes SE, O’Hearn E, Margolis RL. Why is SCA12 different from other SCAs? Cytogenet Genome Res. 2003;100(1–4):189–97.PubMedGoogle Scholar
  43. 43.
    Shaikh AG, Zee DS, Mandir AS, Lederman HM, Crawford TO. Disorders of upper limb movements in ataxia-telangiectasia. PLoS One. 2013;8(6):e67042.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Gitchel GT, Wetzel PA, Baron MS. Slowed saccades and increased square wave jerks in essential tremor. Tremor Other Hyperkinet Mov (N Y). 2013 Sep 3;3. pii: tre-03-178-4116-2.Google Scholar
  45. 45.
    Helmchen C, Hagenow A, Miesner J, et al. Eye movement abnormalities in essential tremor may indicate cerebellar dysfunction. Brain. 2003;126(Pt 6):1319–32.PubMedGoogle Scholar
  46. 46.
    Bares M, Lungu OV, Husárová I, Gescheidt T. Predictive motor timing performance dissociates between early diseases of the cerebellum and Parkinson’s disease. Cerebellum. 2010;9(1):124–35.PubMedGoogle Scholar
  47. 47.
    Trillenberg P, Führer J, Sprenger A, et al. Eye-hand coordination in essential tremor. Mov Disord. 2006;21(3):373–9.PubMedGoogle Scholar
  48. 48.
    Avanzino L, Bove M, Tacchino A, et al. Cerebellar involvement in timing accuracy of rhythmic finger movements in essential tremor. Eur J Neurosci. 2009;30(10):1971–9.PubMedGoogle Scholar
  49. 49.
    Manto M, Bower JM, Conforto AB, et al. Consensus paper: roles of the cerebellum in motor control—the diversity of ideas on cerebellar involvement in movement. Cerebellum. 2012;11(2):457–87.PubMedGoogle Scholar
  50. 50.
    Bareš M, Husárová 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. pii: tre-02-93-653-1. Epub 2012 Sep 12.Google Scholar
  51. 51.
    Dupuis MJ, Delwaide PJ, Boucquey D, Gonsette RE. Homolateral disappearance of essential tremor after cerebellar stroke. Mov Disord. 1989;4(2):183–7.PubMedGoogle Scholar
  52. 52.
    Schuurman PR, Bosch DA, Bossuyt PM, et al. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. 2000;342(17):461–8.PubMedGoogle Scholar
  53. 53.
    Bucher SF, Seelos KC, Dodel RC, Reiser M, Oertel WH. Activation mapping in essential tremor with functional magnetic resonance imaging. Ann Neurol. 1997;41(1):32–40.PubMedGoogle Scholar
  54. 54.
    Colebatch JG, Findley LJ, Frackowiak RS, Marsden CD, Brooks DJ. Preliminary report: activation of the cerebellum in essential tremor. Lancet. 1990;336(8722):1028–30.PubMedGoogle Scholar
  55. 55.
    Jenkins IH, Bain PG, Colebatch JG, et al. A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections. Ann Neurol. 1993;34(1):82–90.PubMedGoogle Scholar
  56. 56.
    Wills AJ, Jenkins IH, Thompson PD, Findley LJ, Brooks DJ. Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study. Ann Neurol. 1994;36(4):636–42.PubMedGoogle Scholar
  57. 57.
    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(1):17–20.PubMedGoogle Scholar
  58. 58.
    Pagan FL, Butman JA, Dambrosia JM, Hallett M. Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy. Neurology. 2003;6(8):1344–7.Google Scholar
  59. 59.
    Klein JC, Lorenz B, Kang JS, et al. Diffusion tensor imaging of white matter involvement in essential tremor. Hum Brain Mapp. 2011;32(6):896–904.PubMedGoogle Scholar
  60. 60.
    Nicoletti G, Manners D, Novellino F, et al. Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor. Neurology. 2010;74(12):988–94.PubMedGoogle Scholar
  61. 61.
    Shin DH, Han BS, Kim HS, Lee PH. Diffusion tensor imaging in patients with essential tremor. AJNR Am J Neuroradiol. 2008;29(1):151–3.PubMedGoogle Scholar
  62. 62.
    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(9):1692–7.PubMedGoogle Scholar
  63. 63.
    Benito-León J, Alvarez-Linera J, Hernández-Tamames JA, Alonso-Navarro H, Jiménez-Jiménez FJ, Louis ED. Brain structural changes in essential tremor: voxel-based morphometry at 3-Telsa. J Neurol Sci. 2009;287(1–2):138–42.PubMedGoogle Scholar
  64. 64.
    Cerasa A, Messina D, Nicoletti G, et al. Cerebellar atrophy in essential tremor using an automated segmentation method. AJNR Am J Neuroradiol. 2009;30(6):1240–3.PubMedGoogle Scholar
  65. 65.
    Louis ED, Murray MJ, Miller MA, Pullman SL, Vonsattel JP. Late-life action tremor in a southern sea otter (enhydris lutris nereis). Mov Disord. 2004;19(2):222–6.PubMedGoogle Scholar
  66. 66.
    Louis ED. Re-thinking the biology of essential tremor: from models to morphology. Parkinsonism Related Disord. 2013;20:S88–93.Google Scholar
  67. 67.
    Llinás R, Volkind RA. The olivo-cerebellar system: functional properties as revealed by harmaline-induced tremor. Exp Brain Res. 1973;18:69–87.PubMedGoogle Scholar
  68. 68.
    Zetler G, Singbartl G, Schlosser L. Cerebral pharmacokinetics of tremor-producing harmala and iboga alkaloids. Pharmacology. 1972;7:237–48.PubMedGoogle Scholar
  69. 69.
    Martin FC, Le Thu A, Handforth A. Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications. Mov Disord. 2005;20(3):298–305.PubMedGoogle Scholar
  70. 70.
    Robertson HA. Harmaline-induced tremor: the benzodiazepine receptor as a site of action. Eur J Pharmacol. 1980;67(1):129–32.PubMedGoogle Scholar
  71. 71.
    Handforth A, Krahl SE. Suppression of harmaline-induced tremor in rats by vagus nerve stimulation. Mov Disord. 2001;16(1):84–8.PubMedGoogle Scholar
  72. 72.
    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(22):8828–41.PubMedGoogle Scholar
  73. 73.
    O’Hearn E, Molliver ME. Administration of a non-NMDA antagonist, GYKI 52466, increases excitotoxic Purkinje cell degeneration caused by ibogaine. Neuroscience. 2004;127(2):373–83.PubMedGoogle Scholar
  74. 74.
    Elble RJ. Animal models of action tremor. Mov Disord. 1998;13 Suppl 3:35–9.PubMedGoogle Scholar
  75. 75.
    Handforth A. Harmaline tremor: underlying mechanisms in a potential animal model of essential tremor. Tremor Other Hyperkinet Mov (N Y). 2012;2. pii: 02-92-769-1.Google Scholar
  76. 76.
    de Oliveira RB, Howlett MC, Gravina FS, et al. Pacemaker currents in mouse locus coeruleus neurons. Neuroscience. 2010;170(1):166–77.PubMedGoogle Scholar
  77. 77.
    Penington NJ, Tuckwell HC. Properties of I(A) in a neuron of the dorsal raphe nucleus. Brain Res. 2012;1449:60–8.PubMedGoogle Scholar
  78. 78.
    Jahnsen H, Llinás R. Ionic basis for the electro-responsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J Physiol. 1984;349:227–47.PubMedCentralPubMedGoogle Scholar
  79. 79.
    Hansen ST, Meera P, Otis TS, Pulst SM. Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2. Hum Mol Genet. 2013;22(2):271–83.PubMedCentralPubMedGoogle Scholar
  80. 80.
    Louis ED, Babij R, Cortés E, Vonsattel JP, Faust PL. The inferior olivary nucleus: a postmortem study of essential tremor cases versus controls. Mov Disord. 2013;28(6):779–86.PubMedCentralPubMedGoogle Scholar
  81. 81.
    Louis ED, Faust PL, Vonsattel JP, et al. Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain. 2007;130(Pt 12):3297–307.PubMedGoogle Scholar
  82. 82.
    Babij R, Lee M, Cortés E, Vonsattel JP, Faust PL, Louis ED. Purkinje cell axonal anatomy: quantifying morphometric changes in essential tremor versus control brains. Brain. 2013;136(Pt 10):3051–61.PubMedGoogle Scholar
  83. 83.
    Grimaldi G, Manto M. Is essential tremor a Purkinjopathy? The role of the cerebellar cortex in its pathogenesis. Mov Disord. 2013. doi:10.1002/mds.25645.PubMedGoogle Scholar
  84. 84.
    Yu M, Ma K, Faust PL, et al. Increased number of Purkinje cell dendritic swellings in essential tremor. Eur J Neurol. 2012;19(4):625–30.PubMedCentralPubMedGoogle Scholar
  85. 85.
    Axelrad JE, Louis ED, Honig LS, et al. Reduced Purkinje cell number in essential tremor: a postmortem study. Arch Neurol. 2008;65(1):101–7.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Louis ED, Babij R, Lee M, Cortés E, Vonsattel JP. Quantification of cerebellar hemispheric purkinje cell linear density: 32 ET cases versus 16 controls. Mov Disord. 2013. doi:10.1002/mds.25629.PubMedCentralGoogle Scholar
  87. 87.
    Kuo SH, Erickson-Davis C, Gillman A, Faust PL, Vonsattel JP, Louis ED. Increased number of heterotopic Purkinje cells in essential tremor. J Neurol Neurosurg Psychiatry. 2011;82(9):1038–40.PubMedGoogle Scholar
  88. 88.
    Erickson-Davis CR, Faust PL, Vonsattel JP, Gupta S, Honig LS, Louis ED. “Hairy baskets” associated with degenerative Purkinje cell changes in essential tremor. J Neuropathol Exp Neurol. 2010;69(3):262–71.PubMedCentralPubMedGoogle Scholar
  89. 89.
    Kuo SH, Tang G, Louis ED, et al. Lingo-1 expression is increased in essential tremor cerebellum and is present in the basket cell pinceau. Acta Neuropathol. 2013;125(6):879–89.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Paris-Robidas S, Brochu E, Sintes M, et al. Defective dentate nucleus GABA receptors in essential tremor. Brain. 2012;135(Pt 1):105–16.PubMedGoogle Scholar
  91. 91.
    Rajput A, Robinson CA, Rajput AH. Essential tremor course and disability: a clinicopathologic study of 20 cases. Neurology. 2004;62(6):932–6.PubMedGoogle Scholar
  92. 92.
    Rajput AH, Robinson CA, Rajput ML, Robinson SL, Rajput A. Essential tremor is not dependent upon cerebellar Purkinje cell loss. Parkinsonism Relat Disord. 2012;18(5):626–8.PubMedGoogle Scholar
  93. 93.
    Louis ED, Faust PL, Vonsattel JP. Purkinje cell loss is a characteristic of essential tremor: towards a more mature understanding of pathogenesis. Parkinsonism Relat Disord. 2012;18(8):1003–4.PubMedGoogle Scholar
  94. 94.
    Rossi F, Jankovski A, Sotelo C. Target neuron controls the integrity of afferent axon phenotype: a study on the Purkinje cell-climbing fiber system in cerebellar mutant mice. J Neurosci. 1995;15(3 Pt 1):2040–56.PubMedGoogle Scholar
  95. 95.
    Rossi F, Jankovski A, Sotelo C. Differential regenerative response of Purkinje cell and inferior olivary axons confronted with embryonic grafts: environmental cues versus intrinsic neuronal determinants. J Comp Neurol. 1995;359(4):663–77.PubMedGoogle Scholar
  96. 96.
    Chan-Palay V. The recurrent collaterals of Purkinje cell axons: a correlated study of the rat’s cerebellar cortex with electron microscopy and the Golgi method. Z Anat Entwicklungsgesch. 1971;134(2):200–34.PubMedGoogle Scholar
  97. 97.
    Dusart I, Morel MP, Wehrlé R, Sotelo C. Late axonal sprouting of injured Purkinje cells and its temporal correlation with permissive changes in the glial scar. J Comp Neurol. 1999;408(3):399–418.PubMedGoogle Scholar
  98. 98.
    Carulli D, Buffo A, Strata P. Reparative mechanisms in the cerebellar cortex. Prog Neurobiol. 2004;72(6):373–98.PubMedGoogle Scholar
  99. 99.
    Bermejo-Pareja F. Essential tremor—a neurodegenerative disorder associated with cognitive defects? Nat Rev Neurol. 2011;7(5):273–82.PubMedGoogle Scholar
  100. 100.
    Benito-León J. Essential tremor: one of the most common neurodegenerative diseases? Neuroepidemiology. 2011;36(2):77–8.PubMedCentralPubMedGoogle Scholar
  101. 101.
    LaRoia H, Louis ED. Association between essential tremor and other neurodegenerative diseases: what is the epidemiological evidence? Neuroepidemiology. 2011;37(1):1–10.PubMedCentralPubMedGoogle Scholar
  102. 102.
    Deuschl G, Elble R. Essential tremor—neurodegenerative or nondegenerative disease towards a working definition of ET. Mov Disord. 2009;24(14):2033–41.PubMedGoogle Scholar
  103. 103.
    Bonuccelli U. Essential tremor is a neurodegenerative disease. J Neural Transm. 2012;119(11):1383–7.PubMedGoogle Scholar
  104. 104.
    Critchley M, Greenfield JC. Olivo-ponto-cerebellar atrophy. Brain. 1948;71:343–64.Google Scholar
  105. 105.
    Mckinlay Gardner RJ, Knight MA, Hara K, Tsuji S, Forrest SM, Storey E. Spinocerebellar ataxia type 15. Cerebellum. 2005;4:47–50.Google Scholar
  106. 106.
    Storey E, Knight MA, Forrest SM, Mckinlay Gardner RJ. Spinocerebellar ataxia type 20. Cerebellum. 2005;4:55–7.PubMedGoogle Scholar
  107. 107.
    Edener U, Wollner J, Hehr U, et al. Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation. Eur J Human Gen. 2010;18:965–8.Google Scholar
  108. 108.
    Louis ED. Essential tremor and other forms of kinetic tremor. In: Grimaldi G, Manto M, editors. Mechanisms and emerging therapies in tremor disorders. New York: Springer; 2013. p. 167–201.Google Scholar
  109. 109.
    Louis ED, Yi H, Erickson-Davis C, Vonsattel JP, Faust PL. Structural study of Purkinje cell axonal torpedoes in essential tremor. Neurosci Lett. 2009;450(3):287–91.PubMedCentralPubMedGoogle Scholar
  110. 110.
    Louis ED, Ma K, Babij R, et al. Neurofilament protein levels: quantitative analysis in essential tremor cerebellar cortex. Neurosci Lett. 2012;518(1):49–54.PubMedCentralPubMedGoogle Scholar
  111. 111.
    Xu Z, Cork LC, Griffin JW, Cleveland DW. Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell. 1993;73(1):23–33.PubMedGoogle Scholar
  112. 112.
    Liem RK, Leung CL. Neuronal intermediate filament overexpression and neurodegeneration in transgenic mice. Exp Neurol. 2003;184(1):3–8.PubMedGoogle Scholar
  113. 113.
    Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci. 2001;2(11):806–19.PubMedGoogle Scholar
  114. 114.
    Robertson J, Kriz J, Nguyen MD, Julien JP. Pathways to motor neuron degeneration in transgenic mouse models. Biochimie. 2002;84(11):1151–60.PubMedGoogle Scholar
  115. 115.
    Beaulieu JM, Nguyen MD, Julien JP. Late onset of motor neurons in mice overexpressing wild-type peripherin. J Cell Biol. 1999;147(3):531–44.PubMedCentralPubMedGoogle Scholar
  116. 116.
    Mentis GZ, Díaz E, Moran LB, Navarrete R. Early alterations in the electrophysiological properties of rat spinal motoneurones following neonatal axotomy. J Physiol. 2007;582(Pt 3):1141–61.PubMedCentralPubMedGoogle Scholar
  117. 117.
    Ma WY, Vacca-Galloway LL. Reduced branching and length of dendrites detected in cervical spinal cord motoneurons of Wobbler mouse, a model for inherited motoneuron disease. J Comp Neurol. 1991;311(2):210–22.PubMedGoogle Scholar
  118. 118.
    March PA, Thrall MA, Brown DE, Mitchell TW, Lowenthal AC, Walkley SU. GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C. Acta Neuropathol. 1997;94(2):164–72.PubMedGoogle Scholar
  119. 119.
    Sasaki S, Iwata M. Dendritic synapses of anterior horn neurons in amyotrophic lateral sclerosis: an ultrastructural study. Acta Neuropathol. 1996;91(3):278–83.PubMedGoogle Scholar
  120. 120.
    Rossi F, Borsello T, Strata P. Exposure to kainic acid mimics the effects of axotomy in cerebellar Purkinje cells of the adult rat. Eur J Neurosci. 1994;6(3):392–402.PubMedGoogle Scholar
  121. 121.
    Bravin M, Savio T, Strata P, Rossi F. Olivocerebellar axon regeneration and target reinnervation following dissociated Schwann cell grafts in surgically injured cerebella of adult rats. Eur J Neurosci. 1997;9(12):2634–49.PubMedGoogle Scholar
  122. 122.
    Dusart I, Sotelo C. Lack of Purkinje cell loss in adult rat cerebellum following protracted axotomy: degenerative changes and regenerative attempts of the severed axons. J Comp Neurol. 1994;347(2):211–32.PubMedGoogle Scholar
  123. 123.
    Leclerc N, Gravel C, Plioplys A, Hawkes R. Basket cell development in the normal and hypothyroid rat cerebellar cortex studied with a monoclonal anti-neurofilament antibody. Can J Biochem Cell Biol. 1985;63(6):564–76.PubMedGoogle Scholar
  124. 124.
    Buckmaster PS, Jongen-Rêlo AL. Highly specific neuron loss preserves lateral inhibitory circuits in the dentate gyrus of kainate-induced epileptic rats. J Neurosci. 1999;19(21):9519–29.PubMedGoogle Scholar
  125. 125.
    de Lanerolle NC, Kim JH, Robbins RJ, Spencer DD. Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain Res. 1989;495(2):387–95.PubMedGoogle Scholar
  126. 126.
    Arellano JI, Muñoz A, Ballesteros-Yáñez I, Sola RG, DeFelipe J. Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus. Brain. 2004;127(Pt 1):45–64.PubMedGoogle Scholar
  127. 127.
    Stefansson H, Steinberg S, Petursson H, et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat Genet. 2009;41(3):277–9.PubMedCentralPubMedGoogle Scholar
  128. 128.
    Vilariño-Güell C, Wider C, Ross OA, et al. LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease. Neurogenetics. 2010;11(4):401–8.PubMedCentralPubMedGoogle Scholar
  129. 129.
    Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet. 2010;18(7):838–43.PubMedCentralPubMedGoogle Scholar
  130. 130.
    Deng H, Gu S, Jankovic J. LINGO1 variants in essential tremor and Parkinson’s disease. Acta Neurol Scand. 2012;125(1):1–7.PubMedGoogle Scholar
  131. 131.
    Louis ED, Agnew A, Gillman A, Gerbin M, Viner AS. Estimating annual rate of decline: prospective, longitudinal data on arm tremor severity in two groups of essential tremor cases. J Neurol Neurosurg Psychiatry. 2011;82(7):761–5.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.GH Sergievsky Center, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  2. 2.Department of Neurology, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  3. 3.Department of Epidemiology, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  4. 4.Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

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