References 1. Louis ED, Ferreira JJ. How common is the most common adult move- ment disorde r? Update on the worldwide prevalence of essential tremor. Mov Disord 2010; 25 : 534 \200 \2234 1 . Arch Neurol 2009; 66 : 1202 \200\2238 . 27. Louis ED, Vonsattel JP. Th e emerging neuropathology of essential tremor. Mov Disord 2008; 23 : 174 \200\2238 2 . 28. Axelrad JE, Louis ED, Honig LS, et al. Reduced Purkinje cell number in essential tremor : a postmortem study. Arch Neurol 2008; 65 : 101 \200\2237 . 29. Louis ED, Faust PL, Vonsa ttel JP, et al. Neuropathological changes in essential tremor: 33 cases compared with 21 co ntrols. Brain 2007; 130 : 3297 \200\22330 7 . 2. Louis ED, Ford B, Wendt KJ, Cameron G. Clinical characteristics of essential tremor: dat a from a community-based study. Mov Disord 1998; 13 : 803 \200\2238 . 3. Lorenz D, Poremba C, Papengut F, Schreiber S, Deuschl G. Th e psychoso- cial burden of e ssential tremor in an outpatient- and a community-base d cohort. Eur J Neurol 2011; 18 : 97 2 \200\2239 . 30. Louis ED, Vonsattel JP, Honig LS, Ross GW, Lyons KE, Pahwa R. Neuropathologic fi ndings in essential tremor. Neurology 2006; 66 : 1756 \200\2239 . 4. Wenning GK, Kiechl S, Seppi K, et al. Prevalence of movement disor- ders in men and wome n aged 50 \200\2238 9 years (Bruneck Study cohort): a population-base d study. Lancet Neuro l 2005; 4 : 815 \200\2232 0 . 31. Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, Moskowitz CB. Essential trem or associated with focal nonnigral Lewy bodies: a clin- icopathologic study. Arch Neurol 20 05; 62 : 1004 \200\2237 . 5. 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 \200\2231 1 . 32. Shill HA, Adler CH, Sabbagh MN, et al. Pathologic fi ndings in prospec- tively ascertai ned essential tremor subjects. Neurology 2008; 70 : 1452 \200\2235 . 33. Rajput AH, Robins on CA, Rajput ML, Rajput A. Cerebellar Purkinje cell loss is not pathognomonic of essential tremor. Parkinsonism Relat Disord 2011 ; 17 : 16 \200\22321 . 6. Raethjen J, Deuschl G. Tremor. Curr Opin Neurol 2009; 22 : 400 \200\2235 . 7. Stefansso n H, Steinberg S, Petursson H, et al. Variant in the sequence of the LINGO1 gene confers ri sk of essential tremor. Nat Genet 2009; 41 : 277 \200\2239 . 34. Elble RJ. Animal models of action tremor. Mov Disord 1998; 13 (Suppl 3): 35 \200\2239 . 8. Higgins JJ, Pho LT, Nee LE. A gene (ETM) for essential tremor maps to chromosome 2p22-p2 5. Mov Disord 1997; 12 : 859 \200\2236 4 . 35. Schnitzler A, Munks C, Butz M, Timmermann L, Gross J. Synchronized brain network associ ated with essential tremor as revealed by magne- toencephalography. Mov Disord 2009; 24 : 1 629 \200\2233 5 . 9. Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain 2006; 129 : 2318 \200\2233 1 . 36. Hellwig B, Haussler S, Schelter B, et al. Tremor-correlate d cortical activ- ity in essential tremor. Lancet 2001; 357 : 519 \200\2232 3 . 10. Tan EK. LINGO1 and essential tremor: linking the shakes. Linking LINGO1 to essential tremor. Eur J Hum Genet 2010; 18 : 739 \200\2234 0 . 37. Hurtado JM, Lachaux JP, Beckley DJ, Gray CM, Sigvardt KA. Inter- and intralimb oscillat or coupling in parkinsonian tremor. Mov Disord 2000; 15 : 683 \200\2239 1 . 11. Th ier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essent ial tremor in Europeans. Mov Disord 2010; 25 : 709 \200\2231 5 . 38. Raethjen J, Lindemann M, Schmaljohann H, Wenzelburger R, Pfi ster G, Deuschl G. Multipl e oscillators are causing parkinsonian and essential tremor. Mov Disord 2000; 15 : 84 \200 \2239 4 . 12. Tan EK, Teo YY, Prakash KM, et al. LINGO1 variant increases risk of familial essential tremor. Neurology 2009; 73 : 1161 \200\2232 . 39. Deuschl G, Elble R. Essential tremor \200\224neurodegenerative or nondegen- erative dis ease. Towards a working defi nition of ET. Mov Disord 2009; 24 : 2033 \200\2234 1 . 13. Vilarino-Guell C, Wider C, Ross OA, et al. LINGO1 and LINGO2 variants are associated wi th essential tremor and Parkinson disease. Neurogenetics 2010; 11 : 401 \200\2238 . CHAPTER 16 Essential tremor and other tremors 173 66. Louis ED, Benito-Leon J, Vega-Quiroga S, Bermejo-Pareja F. Faster rate of cognitive dec line in essential tremor cases than controls: a prospective study. Eur J Neurol 2010; 17 : 1291 \200\2237 . 40. Jankovic J, Noebels JL. Genetic mouse models of essential tremor. Are they essential? J Clin Invest 2005; 115 : 584 \200\2236 . 41. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Trem or. Ad Hoc Scientifi c Committee. Mov Disord 1998; 13 (Suppl 3): 2 \200\2232 3 . 67. Benito-Le n J, Louis ED, Bermejo-Pareja F. Risk of incident Parkinson \200\231s dise ase and parkinsonism in essential tremor: a population based study. J Neurol Neurosurg Psyc hiatry 2009; 80 : 423 \200\2235 . 42. Louis ED, Ottman R, Ford B, et al. Th e Washington Heights \200\223 Inwoo d Genetic Stu dy of Essential Tremor: methodologic issues in essential-tremo r research. Neuroepidemiolog y 1997; 16 : 124 \200\2233 3 . 68. Ondo WG, Sutton L, Dat Vuong K, Lai D, Jankovic J. Hearing impair- ment in essential tremor. Neurology 2003; 61 : 1093 \200\2237 . 69. Hawkes C, Shah M, Findley L. Olfactory function in essential tremor: a defi cit unrelat ed to disease duration or severity. Neurology 2003; 61 : 871 \200\2232 . 43. Mostile G, Jankovic J. Alcohol in essential tremor and other movement disorders. Mov Disord 2010; 25 : 2274 \200\2238 4 . 44. Elble RJ. Diagnostic criteria for essential tremor and diff erential diagno- 70. Gironell A, Kulisevsky J, Pascual-Sedano B, Barbanoj M. Routine neu- rophysiologic trem or analysis as a diagnostic tool for essential tremor: a prospective study. J Clin Neurophy siol 2004; 21 : 446 \200\2235 0 . sis. Neurology 2000; 54 : S 2 \200\2236 . 45. Whaley NR, Putzke JD, Baba Y, Wszolek ZK, Uitti RJ. Essential tremor: phenotypic expres sion in a clinical cohort. Parkinsonism Relat Disord 2007; 13 : 333 \200\2239 . 71. Deuschl G, Krack P, Lauk M, Timmer J. Clinical neurophysiology of tremor. J Clin Neurophysiol 1996; 13 : 110 \200\2232 1 . 46. Deuschl G, Wenzelburger R, Loffl er K, Raethjen J, Stolze H. Essential tremor and cereb ellar dysfunction: clinical and kinematic analysis of intention tremor. Brain 2000; 123 : 1 568 \200\2238 0 . 72. Muthuraman M, Hossen A, Heute U, Deuschl G, Raethjen J. A new diag- nostic test to dist inguish tremulous Parkinson \200\231s disease from advanced essential tremor. Mov Disord 20 11; 26 : 1548 \200\22352 . 47. Cohen O, Pullman S, Jurewicz E, Watner D, Louis ED. Rest tremor in patients with essent ial tremor: prevalence, clinical correlates, and elec- trophysiologic characteristics. Arch Neurol 2003; 60 : 405 \200\2231 0 . 73. Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol 2011; 10 : 148 \200\2236 1 . 48. Lorenz D, Schwieger D, Moises H, Deuschl G. Quality of life and person- 74. Elble RJ, Pullman SL, Matsumoto JY, Raethjen J, Deuschl G, Tintner R. Tremor amplitude is logarithmically related to 4- and 5-poin t tremor rat- ing scales. Brain 2006; 129 : 266 0 \200\2236 . ality in essential tremor patients. Mov Disord 2006; 21 : 1114 \200\2231 8 . 49. Quinn NP, Schneider SA, Schwingenschuh P, Bhatia KP. Tremor \200\224some controversial aspects. Mov Disord 2011; 26 : 18 \200\2232 3 . 75. Sasso E, Perucca E, Calzetti S. Double-blin d comparison of primi- done and phenobarbit al in essential tremor. Neurology 1988; 38 : 808 \200\2231 0 . 50. Bain PG, Findley LJ, Th ompson PD, et al. A study of hereditary essential tremor. Brain 1994; 117 : 805 \200\2232 4 . 76. Findley LJ, Cleeves L, Calzetti S. Primidone in essential tremor of the hands and head: a double blind controlled clinical study. J Neurol Neurosurg Psychiatry 1985; 48 : 911 \200\2231 5 . 51. Lou JS, Jankovic J. Essential tremor: clinical correlates in 350 patients. Neurology 1991; 41 : 234 \200\2238 . 52. Tanner CM, Goldman SM, Lyons KE, et al. Essential tremor in twins: an assessment of gen etic vs environmental determinants of etiology. Neurology 2001; 57 : 1389 \200\2239 1 . 77. Brin MF, Lyons KE, Doucette J, et al. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology 2001; 56 : 1523 \200\2238 . 53. Elble RJ. Essential tremor frequency decreases with time. Neurology 78. Th ompson C, Lang A, Parkes JD, Marsden CD. A double-blin d trial of clonazepam in beni gn essential tremor. Clin Neuropharmacol 1984; 7 : 83 \200\2238 . 2000; 55 : 1547 \200\2235 1 . 54. Gironell A, Martinez-Corral M, Pagonabarraga J, Kulisevsky J. Th e Glass scale: a simpl e tool to determine severity in essential tremor. Parkinsonism Relat Disord 2010; 16 : 412 \200\2231 4 . 79. Wissel J, Masuhr F, Schelosky L, Ebersbach G, Poewe W. Quantitative assessment of botul inum toxin treatment in 43 patients with head tremor. Mov Disord 1997; 12 : 722 \200\2236 . 55. Auff E, Doppelbauer A, Fertl E. Essential tremor: functional disability vs. subjective impairment. J Neural Transm 1991; 33 : 105 \200\2231 0 . 80. Pahwa R, Busenbark K, Swanson-Hyland EF, et al. Botulinum toxin 56. Busenbark KL, Nash J, Nash S, Hubble JP, Koller WC. Is essential tremor treatment of essential head tremor. Neurology 1995; 45 : 822 \200\2234 . benign? Neurology 1991; 41 : 1982 \200\2233 . 81. Blomstedt P, Sandvik U, Tisch S. Deep brain stimulation in the posterior subthalamic ar ea in the treatment of essential tremor. Mov Disord 2010; 25 : 1350 \200\2236 . 57. Louis ED, Levy G, Cote LJ, Mejia H, Fahn S, Marder K. Clinical cor- relates of action t remor in Parkinson disease. Arch Neurol 2001; 58 : 1630 \200\2234 . 82. Hariz MI, Krack P, Alesch F, et al. Multicentre European study of tha- lamic stimulatio n for parkinsonian tremor: a 6 year follow-u p. J Neurol Neurosurg Psychiatry 2008; 79 : 69 4 \200\2239 . 58. Louis ED, Barnes L, Albert SM, et al. Correlates of functional disability in essential tremor. Mov Disord 2001; 16 : 914 \200\2232 0 . 59. Fahn S, Tolosa E, Marin C. Clinical rating scale for tremor. In: Jankovic J, Tolosa E ( eds) Parkinson \200\231s disease and movement disorders , pp. 271 \200\22380 . Baltimore, M D: Williams & Wilkins, 1993. 83. Blomstedt P, Hariz GM, Hariz MI, Koskinen LO. Th alamic deep brain stimulation in the t reatment of essential tremor: a long-ter m follow-u p. Br J Neurosurg 2007; 21 : 504 \200 \2239 . 60. Troster AI, Pahwa R, Fields JA, Tanner CM, Lyons KE. Quality of life in Essential Tremo r Questionnaire (QUEST): development and initial vali- dation. Parkinsonism Relat Disord 20 05; 11 : 367 \200\2237 3 . 84. Sydow O, Th obois S, Alesch F, Speelman JD. Multicentre European study of thalamic stim ulation in essential tremor: a six year follow up. J Neurol Neurosurg Psychiatry 2003; 74 : 1387 \200\2239 1 . 61. Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. Th e gait disorder of advanced essential tremor. Brain 2001; 124 : 2278 \200\2238 6 . 85. Lyons KE, Koller WC, Wilkinson SB, Pahwa R. Long term safety and effi cacy of unilatera l deep brain stimulation of the thalamus for parkin- sonian tremor. J Neurol Neurosurg Psyc hiatry 2001; 71 : 682 \200\2234 . 62. Helmchen C, Hagenow A, Miesner J, et al. Eye movement abnormalities in essential tremor may indicate cerebellar dysfunction. Brain 2003; 126 : 1319 \200\2233 2 . 86. Limousin P, Speelman JD, Gielen F, Janssens M. Multicentre European study of thalamic s timulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry 1999; 66 : 2 89 \200\2239 6 . 63. Klebe S, Stolze H, Grensing K, Volkmann J, Wenzelburger R, Deuschl G. Infl uence of alc ohol on gait in patients with essential tremor. Neurology 2005; 65 : 96 \200\22310 1 . 87. Koller W, Graner D, Mlcoch A. Essential voice tremor: treatment with propranolol. Neurology 1985; 35 : 106 \200\2238 . 64. Duane DD, Vermilion KJ. Cognitive defi cits in patients with essential tremor. Neurology 2002; 58 : 1706 . 88. Warrick P, Dromey C, Irish J, Durkin L. Th e treatment of essential voice tremor with b otulinum toxin A: a longitudinal case report. J Voice 2000; 14 : 410 \200\2232 1 . 65. Lombardi WJ, Woolston DJ, Roberts JW, Gross RE. Cognitive defi cits in patients with essential tremor. Neurology 2001; 57 : 785 \200\2239 0 . Oxford Textbook of Movement Disorders 174 112. Williams A, Gill S, Varma T, et al. Deep brain stimulation plus best med- ical therapy versus best medical therapy alone for advanced Parkinson \200\231s disease (PD SURG trial) : a randomized, open-labe l trial. Lancet Neurol 2010; 9 : 581 \200\2239 1 . 89. Warrick P, Dromey C, Irish JC, Durkin L, Pakiam A, Lang A. Botulinum toxin for essentia l tremor of the voice with multiple anatomical sites of tremor: a crossover design study of unilateral versus bilateral injection. Laryngoscope 2000; 110 : 1366 \200\2237 4 . 113. Jedynak CP, Bonnet AM, Agid Y. Tremor and idiopathic dystonia. Mov 90. Hassler R, Mundinger F, Riechert T. Stereotaxis in Parkinson syndrome: clinical \200 \223anatomica l contributions to its physiology, with an atlas of the basal ganglia in park insonism. Berlin: Springer Verlag, 1979. Disord 1991; 6 : 230 \200\2236 . 114. Vidailhet M, Jedynak CP, Pollak P, Agid Y. Pathology of symptomatic tremors. Mov Disord 1998; 13 (Suppl 3): 49 \200\2235 4 . 91. Voges J, Hilker R, Botzel K, et al. Th irty days complication rate follow- ing surgery performed for deep-brain-stimulatio n. Mov Disord 2007; 22 : 1486 \200\2239 . 115. Deuschl G. Dystonic tremor. Rev Neurol (Paris) 2003; 159 : 900 \200\2235 . 116. Rives t J, Marsden CD. Trunk and head tremor as isolated manifestations 92. Plaha P, Ben-Shlomo Y, Patel NK, Gill SS. Stimulation of the caudal zona incerta is sup erior to stimulation of the subthalamic nucleus in improv- ing contralateral parkinsonism. Brain 2006; 129 : 1732 \200\2234 7 . of dystonia. Mov Disord 1990; 5 : 60 \200\2235 . 117. Koda J, Ludlow CL. An evaluation of laryngeal muscle activation in patients with voice tremor. Otolaryngol Head Neck Surg 1992; 107 : 684 \200\2239 6 . 93. Raethjen J, Lemke MR, Lindemann M, Wenzelburger R, Krack P, Deuschl G. Amitriptyline en hances the central component of physi- ological tremor. J Neurol Neurosurg Psychiatry 2001; 70 : 78 \200\2238 2 . 118. Elble RJ, Moody C, Higgins C. Primary writing tremor. A form of focal dystonia? Mov Disord 1990; 5 : 118 \200\2232 6 . 94. Marsden CD, Meadows JC. Th e eff ect of adrenaline on the contraction of human muscle: one mechanism whereby adrenaline increases the amplitude of physiological tremor. J Physiol 1968; 194 : 70 \200\2231 P. 119. Bain PG, Findley LJ, Britton TC, et al. Primary writing tremor. Brain 1995; 116 : 203 \200\2239 . 120. Schneider SA, Bhatia KP. Th e entity of jaw tremor and dystonia. Mov 95. Raethjen J, Lauk M, Koster B, et al. Tremor analysis in two normal Disord 2007; 22 : 1491 \200\2235 . cohorts. Clin Neurophysiol 2004; 115 : 2151 \200\2236 . 121. Ferraz HB, De Andrade LA, Silva SM, Borges V, Rocha MS. [Postural tremor and dystonia. Clinical aspects and physiopathological consid- erations.] Arq Neuropsiquiatr 1994; 52 : 4 66 \200\2237 0 . 96. Elble RJ, Higgins C, Elble S. Electrophysiologic transition from physi- ologic tremor t o essential tremor. Mov Disord 2005; 20 : 1038 \200\2234 2 . 97. Feely J, Peden N. Use of b eta-adrenocepto r blocking drugs in hyperthy- 122. Bartolome FM, Fanjul S, Cantarero S, Hernandez J, Garcia Ruiz PJ. [Primary focal dysto nia: descriptive study of 205 patients. ] Neurologia 2003; 18 : 59 \200\2236 5 . roidism. Drugs 1984; 27 : 425 \200\2234 6 . 98. Findley LJ, Gresty MA, Halmagyi GM. Tremor, the cogwheel phenom- enon and clonus in Par kinson \200\231s disease. J Neurol Neurosurg Psychiatry 1981; 44 : 534 \200\2234 6 . 123. Masuhr F, Wissel J, Muller J, Scholz U, Poewe W. Quantifi cation of sen- sory trick im pact on tremor amplitude and frequency in 60 patients with head tremor. Mov Disord 2000; 15 : 960 \200\2234 . 99. Raethjen J, Pohle S, Govindan RB, Morsnowski A, Wenzelburger R, Deuschl G. Parkinsonian action tremor: interference with object manipulation and lacking levodopa response. Exp Ne urol 2005; 194 : 151 \200\2236 0 . 124. Schwingenschuh P, Ruge D, Edwards MJ, et al. Distinguishing SWEDDs patients with asymm etric resting tremor from Parkinson \200\231s disease: a clinical and electrophysiological study. Mov Disord 2011; 25 : 560 \200\2239 . 125. Kupsch A, Benecke R, Muller J, et al. Pa llidal deep-brai n stimulation in primary generalized or segmental dystonia. N Engl J Med 2 006; 355 : 1978 \200\2239 0 . 100. Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson \200\231s disease. N Engl J Med 2004; 351 : 2498 \200\22350 8 . 101. Navan P, Findley LJ, Undy MB, Pearce RK, Bain PG. A randomly assigned double-blin d cr oss-ove r study examining the relative anti-parkinsonia n tremor eff ects of pramipexole an d pergolide. Eur J Neurol 2005; 12 : 1 \200\2238 . 126. Elble RJ. Origins of tremor [comment]. Lancet 2000; 355 : 1113 \200\2231 4 . 127. Ljub isavljevic M, Kacar A, Milanovic S, Svetel M, Kostic VS. Changes in cortical inhibition dur ing task-specifi c contractions in primary writing tremor patients. Mov Disord 2006; 21 : 8 55 \200\2239 . 102. Pogarell O, Gasser T, van Hilten JJ, et al. Pramipexole in patients with Parkinson \200\231s disease and marked drug resistant tremor: a randomized, double blind, placebo con trolled multicentre study. J Neurol Neurosurg Psychiatry 2002; 72 : 713 \200\2232 0 . 128. Zeuner KE, Peller M, Knutzen A, Hallett M, Deuschl G, Siebner HR. Motor re-trainin g d oes not need to be task specifi c to improve writer \200\231s cramp. Mov Disord 2008; 23 : 2319 \200\2232 7 . 103. Schrag A, Keens J, Warner J. Ropinirole for the treatment of tremor in 129. Zeuner KE, Shill HA, Sohn YH, et al. Motor training as treatment in early Parkinson \200\231s disease. Eur J Neurol 2002; 9 : 253 \200\2237 . focal hand dystonia. Mov Disord 2005; 20 : 335 \200\2234 1 . 104. Perry EK, Kilford L, Lees AJ, Burn DJ, Perry RH. Increased Alzheimer pathology in Park inson \200\231s disease related to antimuscarinic drugs. Ann Neurol 2003; 54 : 235 \200 \2238 . 130. Zeuner KE, Bara-Jimenez W, Noguchi PS, Goldstein SR, Dambrosia JM, Hallett M. Sensory training for patients with focal hand dystonia. Ann Neurol 2002; 51 : 593 \200\2238 . 105. Bonuccelli U, Ceravolo R, Salvetti S, et al. Clozapine in Parkinson \200\231s disease tremor. Eff ects of acute and chronic administration. Neurology 1997; 49 : 1587 \200\2239 0 . 131. Espay AJ, Hung SW, Sanger TD, Moro E, Fox SH, Lang AE. A writing device improves writi ng in primary writing tremor. Neurology 2005; 64 : 1648 \200\2235 0 . 106. Spieker S, Eisebitt R, Breit S, et al. Tremorlytic activity of budipine in 132. Papapetropoulos S, Singer C. Treatment of primary writing tremor with botulinum toxin type a injections: report of a case series. Clin Neuropharmacol 2006; 29 : 364 \200\2237 . Parkinson \200\231s disease. Clin Neuropharmacol 1999; 22 : 115 \200\2231 9 . 107. Koller WC, Herbster G. Adjuvant therapy of parkinsonian tremor. Arch Neurol 1987; 44 : 921 \200\2233 . 133. Lungu C, Karp BI, Alter K, Zolbrod R, Hallett M. Long-ter m follow-u p of botulinum to xin therapy for focal hand dystonia: outcome at 10 years or more. Mov Disord 2011; 26 : 750 \200\2233 . 108. Rajput AH, Jamieson H, Hirsh S, Quraishi A. Relative effi cacy of alcohol and proprano lol in action tremor. Can J Neurol Sci 1975; 2 : 31 \200\2235 . 109. Deuschl G, Schade-Bri ttinger C, Krack P, et al. A randomized trial of deep-brai n stimulation for Parkinson \200 \231s disease. N Engl J Med 2006; 355 : 896 \200\22390 8 . 134. Blomstedt P, Fytagoridis A, Tisch S. Deep brain stimulation of the poste- rior subthal amic area in the treatment of tremor. Acta Neurochir (Wien) 2009; 151 : 31 \200\2236 . 135. Findley L, Capildeo R. Movement disorders: tremor . London: Macmillan, 110. Krack P, Benazzouz A, Pollak P, et al. Treatment of tremor in Parkinson \200\231s dise ase by subthalamic nucleus stimulation. Mov Disord 1998; 13 : 907 \200\2231 4 . 1984. 136. Alusi SH, Glickman S, Aziz TZ, Bain PG. Tremor in multiple sclerosis. J Neurol Neurosurg Psychiatry 1999; 66 : 131 \200\2234 . 111. Weaver FM, Follett K, Stern M, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 2009; 301 : 63 \200\2237 3 . 137. Baba Y, Uitti RJ. Fragile X-associate d tremor/ataxia syndrome and movements disorders. Curr Opin Neurol 2005; 18 : 393 \200\2238 . CHAPTER 16 Essential tremor and other tremors 175 162. Holmes G. On certain tremors in organic cerebral lesions. Brain 1904; 138. Hallett M, Berardelli A, Matheson J, Rothwell J, Marsden CD. Physiological analysis of simple rapid movements in patients with cer- ebellar defi cits. J Neurol Neurosurg Psychia try 1991; 54 : 124 \200\2233 3 . 27 : 327 \200\2237 5 . 163. Krack P, Deuschl G, Kaps M, Warnke P, Schneider S, Traupe H. Delayed onset of \200 \230rubral tremor \200\231 23 years aft er brainstem trauma. Mov Disord 1994; 9 : 240 \200 \2232 . 139. Rascol A, Clanet M, Montastruc JL, Delage W, Guiraud-Chaumeil B. L5H tryptophan in the cerebellar syndrome treatment. Biomedicine 1981; 35 : 112 \200\2231 3 . 164. Remy P, de Recondo A, Defer G, et al. Peduncular \200\230rubral \200\231 tremor and d opaminergic denervation: a PET study. Neurology 1995; 45 : 472 \200\2237 . 165. Samie MR, Selhorst JB, Koller WC. Post-traumati c midbrain tremors. 140. Trouillas P, Serratrice G, Laplane D, et al. Levorotatory form of 5-hydroxytryptopha n in Friedreich \200\231s ataxia: results of a double-blin d drug-placeb o cooperative study . Arch Neurol 1995; 52 : 456 \200\2236 0 . Neurology 1990; 40 : 62 \200\2236 . 141. Striano P, Coppola A, Vacca G, et al. Levetiracetam for cerebellar tremor in multiple sclerosis: an open-labe l pilot tolerability and effi cacy study. J Neurol 2006; 253 : 762 \200\2236 . 166. Biary N, Cleeves L, Findley L, Koller W. Post-traumati c tremor. Neurology 1989; 39 : 103 \200\2236 . 167. Ferlazzo E, Morgante F, Rizzo V, et al. Successful treatment of Holmes 142. Fox P, Bain PG, Glickman S, Carroll C, Zajicek J. Th e eff ect of canna- bis on tremor in patients with multiple sclerosis. Neurology 2004; 62 : 1105 \200\2239 . tremor by levetiracetam. Mov Disord 2008; 23 : 2101 \200\2233 . 168. Striano P, Elefante A, Coppola A, et al. Dramatic response to levetira- cetam in post- ischaemi c Holmes \200\231 tremor. J Neurol Neurosurg Psychiatry 2007; 78 : 438 \200\2239 . 143. Alusi SH, Aziz TZ, Glickman S, Jahanshahi M, Stein JF, Bain PG. Stereotactic lesional surgery for the treatment of tremor in multi- ple sclerosis: a prospective case \200\223con trolle d study. Brain 2001; 124 : 1576 \200\2238 9 . 169. Acar G, Acar F, Bir LS, Kizilay Z, Cirak B. Vim stimulation in Holmes \200\231 tremor secondary to subarachnoid hemorrhage. Neurol Res 2010; 32 : 992 \200\2234 . 144. Lozano AM. Vim thalamic stimulation for tremor. Arch Med Res 2000; 170. Deuschl G, Mischke G, Schenck E, Schulte-Monting J, Lucking CH. Symptomatic and essent ial rhythmic palatal myoclonus. Brain 1990; 113 : 1645 \200\2237 2 . 31 : 266 \200\2239 . 145. Schuurman PR, Bosch DA, Bossuyt PM, et al. A comparison of contin- uous thalamic stimu lation and thalamotomy for suppression of severe tremor. N Engl J Med 2000; 342 : 461 \200 \2238 . 171. Deuschl G, Toro C, Valls-Sole J, Zeffi ro T, Zee DS, Hallett M. Symptomatic and essent ial palatal tremor. 1: Clinical, physiological and MRI analysis. Brain 1994; 117 : 775 \200 \2238 8 . 146. Herzog J, Hamel W, Wenzelburger R, et al. Kinematic analysis of tha- lamic versus subt halamic neurostimulation in postural and intention tremor. Brain 2007; 130 : 1608 \200\2232 5 . 172. Masucci EF, Kurtzke JF, Saini N. Myorhythmia: a widespread movement disorder. Clinicop athological correlations. Brain 1984; 107 : 53 \200\2237 9 . 173. Deuschl G, Wilms H. Clini cal spectrum and physiology of palatal 147. Heilman KM. Orthostatic tremor. Arch Neurol 1984; 41 : 880 \200\2231 . 148. Th ompson PD, Rothwell JC, Day BL, et al. Th e physiology of orthostatic tremor. Mov Disord 2002; 17 (Suppl 2): S 63 \200\2236 . tremor. Arch Neurol 1986; 43 : 584 \200\2237 . 174. Samuel M, Torun N, Tuite PJ, Sharpe JA, Lang AE. Progressive ataxia and palatal tremor (PAPT): clinical and MRI assessment with review of palatal tremors. Brain 2004; 127 : 1252 \200\2236 8 . 149. Aguilar D, Sigford KE, Soontarapornchai K, et al. A quantitative assess- ment of tremo r and ataxia in FMR1 premutation carriers using CATSYS. Am J Med Genet A 2008; 146 : 629 \200\2233 5 . 175. Deuschl G, Jost S, Schumacher M. Symptomatic palatal tremor is asso- 150. Apartis E, Tison F, Arne P, Jedynak CP, Vidailhet M. Fast orthostatic tremor in Parkin son \200\231s disease mimicking primary orthostatic tremor. Mov Disord 2001; 16 : 1133 \200\2236 . ciated with signs of cerebellar dysfunction. J Neurol 1996; 243 : 553 \200\2236 . 176. Leigh RJ, Averbuch-Heller L, Tomsak RL, Remler BF, Yaniglos SS, Dell \200\231Osso LF. Treatment of abnormal eye movements that impair vision: strategies based on current concept s of physiology and pharmacology. Ann Neurol 1994; 36 : 129 \200\2234 1 . 151. McManis PG, Sharbrough FW. Orthostatic tremor: clinical and electro- physiologic characteristics. Muscle Nerve 1993; 16 : 1254 \200\2236 0 . 152. Britton TC, Th ompson PD. Primary orthostatic tremor. BMJ 1995; 310 : 177. Repka MX, Savino PJ, Reinecke RD. Treatment of acquired nystagmus with botulinum neuro toxin A. Arch Ophthalmol 1994; 112 : 1320 \200\2234 . 178. Bakheit AM, Behan PO. Palatal m yoclonus successfully treated with 143 \200\2234 . 153. Leu-Semenescu S, Roze E, Vidailhet M, et al. Myoclonus or tremor in orthostatism: an u nder-recognize d cause of unsteadiness in Parkinson \200\231s disease. Mov Disord 2007; 22 : 2063 \200\2239 . clonazepam. J Neurol Neurosurg Psychiatry 1990; 53 : 806 . 179. Erickson JC, Carrasco H, Grimes JB, Jabbari B, Cannard KR. Palatal tremor and myorhyth mia in Hashimoto \200\231s encephalopathy. Neurology 2002; 58 : 504 \200\2235 . 154. Williams ER, Jones RE, Baker SN, Baker MR. Slow orthostatic tremor can persist when wa lking backward. Mov Disord 2011; 25 : 788 \200\2239 0 . 155. Rodrigues JP, Edwards DJ, Walt ers SE, et al. Gabapentin can improve postural stability and quality of life in primary ort hostatic tremor. Mov Disord 2005; 20 : 865 \200\2237 0 . 180. Borggreve F, Hageman G. A case of idiopathic palatal myoclonus: treat- ment with sodium valproate. Eur Neurol 1991; 31 : 403 \200\2234 . 181. Cakmur R, Idiman E, Idiman F, Baklan B, Ozkiziltan S. Essential pala- tal tremor succe ssfully treated with fl unarizine. Eur Neurol 1997; 38 : 133 \200\2234 . 156. Poersch M. Orthostatic tremor: combined treatment with primidone and clonazepam. Mov Disord 1994; 9 : 467. 157. Katzenschlager R, Costa D, Gerschlager W, et al. [ 123 I]-FP-CIT-SPEC T demonstrates d opaminergic defi cit in orthostatic tremor. Ann Neurol 2003; 53 : 489 \200\2239 6 . 182. Gambardella A, Quattrone A. Treatment of palatal myoclonus with sumatriptan. Mov Disord 1998; 13 : 195 . 183. Scott BL, Evans RW, Jankovic J. Treatment of palatal myoclonus with sumatriptan. Mov Disord 1996; 11 : 748 \200\2235 1 . 158. Espay AJ, Duker AP, Chen R, et al. Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: preliminary observation s. Mov Disord 2008; 23 : 2357 \200\2236 2 . 159. Guridi J, Rodriguez-Oroz MC, Arbizu J, et al. Successful thalamic deep brain stimulation for orthostatic tremor. Mov Disord 2008; 23 : 1808 \200\22311 . 184. Pakiam AS, Lang AE. Essential palatal tremor: evidence of heterogene- ity based on cli nical features and response to sumatriptan. Mov Disord 1999; 14 : 179 \200\2238 0 . 185. Deuschl G, Lohle E, Heinen F, Lucking C. Ear click in palatal tremor: its origin and t reatment with botulinum toxin. Neurology 1991; 41 : 1677 \200\2239 . 160. Krauss JK, Weigel R, Blahak C, et al. Chronic spinal cord stimulation in medically int ractable orthostatic tremor. J Neurol Neurosurg Psychiatry 2006; 77 : 1013 \200\2231 6 . 186. Dalakas MC, Teravainen H, Engel WK. Tremor as a feature of chronic relapsing and dysga mmaglobulinemic polyneuropathies: incidence and management. Arch Neurol 1984; 41 : 711 \200 \2231 4 . 161. Miwa H, Hatori K, Kondo T, Imai H, Mizuno Y. Th alamic tremor: case reports and implic ations of the tremor-generatin g mechanism. Neurology 1996; 46 : 75 \200\2239 . 187. Cardoso FE, Jankovic J. Hereditary motor-sensor y neuropathy and movement disorders. Muscle Nerve 1993; 16 : 904 \200\2231 0 . Oxford Textbook of Movement Disorders 176 193. Zeuner KE, Shoge RO, Goldstein SR, Dambrosia JM, Hallett M. Accelerometry to distingui sh psychogenic from essential or parkinso- nian tremor. Neurology 2003; 61 : 548 \200\2235 0 . 188. Ruzicka E, Jech R, Zarubova K, Roth J, Urgosik D. VIM thalamic stimu- lation for tremo r in a patient with IgM paraproteinaemic demyelinating neuropathy. Mov Disord 2003; 18 : 11 92 \200\2235 . 194. Koller W, Lang A, Vetere-Overfi eld B, et al. Psychogenic tremors. 189. Kim YJ, Pakiam AS, Lang AE. Historical and clinical features of psycho- genic tremor: a review of 70 cases. Can J Neurol Sci 1999; 26 : 190 \200\2235 . 190. Factor SA, Podskaln y GD, Molho ES. Psychogenic movement disor- ders: frequency, clinical profi le, and charact eristics. J Neurol Neurosurg Psychiatry 1995; 59 : 406 \200\2231 2 . Neurology 1989; 39 : 1094 \200\2239 . 195. Voon V, Lang AE. Antidepressant treatment outcomes of psychogenic movement disorder. J Clin Psychiatry 2005; 66 : 1529 \200\2233 4 . 196. Feinstein A, Stergiopoulos V, Fine J, Lang AE. Psychiatric outcome in patients with a psychogenic movement disorder: a prospec- tive study. Neuropsychiatry Neuropsychol Behav Ne urol 2001; 14 : 169 \200\2237 6 . 191. Raethjen J, Kopper F, Govindan RB, Volkmann J, Deuschl G. Two diff er- ent pathogeneti c mechanisms in psychogenic tremor. Neurology 2004; 63 : 812 \200\2231 5 . 192. McAuley J, Rothwell J. Identifi cation of psychogenic, dystonic, and other organic tre mors by a coherence entrainment test. Mov Disord 2004; 19 : 253 \200\2236 7 . CHAPTER 17 Dystonia: An Overview K.P. Bhatia , M. Stamelou , and S. Bressman De \201 nition Dystonia is a movement disorder characterized by sustained muscle contracti ons, frequently causing twisting and repetitive movements or abnormal postures (1). Th e ab normal postures are typically not fi xed, are caused by co-contraction of agonist and antag onist mus- cles, and tend to be repetitive or patterned, consistently involv- ing the same muscle groups. Slow writhing movements can occur (athetosis), where the dominant muscle act ivity switches from agonist to antagonist and vise versa. Tremor occurs commonly with dysto nia and either involves the aff ected body part (dystonic tremor) or another body part not aff ected by dystonia (tremor asso- ciated with dystonia). Dystonic tremor is jerky, irregu lar, and vari- able in amplitude, and typically worsens in particular positions of the aff ected body part. Classi \201 cation Dystonia can be classifi ed in three parallel ways: by anatomical distr ibution, age of onset, and etiology (1). Anatomical distribu- tion is subclassifi ed into f ocal, segmental, multifocal, hemidys- tonia, and generalized dystonia. In focal dystonia, t he abnormal movements involve a single body region only (e.g. hand). In segmental dystonia, abnormal movements aff ect two or more contiguous body regions (e.g. arm and neck). When d ystonia is multifocal, two or more non-contiguous body areas are involved (e.g. right arm, left leg). Hemidystonia aff ects one side of the body, while generalized dystonia includes both legs or one leg and the trunk (i.e. crural dystonia) plus at least one other body regi on (usually one or both arms). Age at onset is divided into young- onset (<20 \200\22330 ye ars) and adult-onset dystonia. Etiology is usually divided into four groups: primary, dysto nia-plus, sec- ondary (or acquired), and heredodegenerative. In the primary group dystonia is the only sign (although most allow tremor to be present as well) and there is no seconda ry cause or neurodegen- eration; in dystonia-plus syndromes, which are similar to primary d ystonia, there is no evidence of a secondary cause or neurode- generation, but signs other than dystonia (e.g. parkinsonism, myoclonus) are present; in secondary dystonia a clear acq uired or exogenous cause is present (e.g. brain injury, drug exposure); and in heredodegene rative dystonia, dystonia is part of a neurodegen- erative syndrome that is oft en inherite d (e.g. Wilson disease). Th e European Federation of Neurological Societies (EFNS) has pro- posed including dystonia-plus syndromes and paroxysmal dysto- nias under the primary dysto nias (Table 17.1). Th e three diff erent ways of classifying dystonia occur in parallel in clinical practice and are essential for diagnosis, prognosis, guiding therapy, and genetic counseling. Psychogenic dystonia is not described in the classifi cation of dystonia. It oc curs as part of a conversion disor- der, tends to be fi xed, and is accompanied by other si gns suggest- ive of a conversion disorder (18 \200\22321). Dystonia is oft en aggravated by voluntary movement. In action dystonia, the dystonic movem ents are elicited only with voluntary movement. When dystonia is evinced only with particul ar actions, it is called task-specifi c dystonia; examples include writer \200\231s cramp a nd the embouchure dystonia of woodwind and brass musicians. Activation of dystonic movement s by actions in remote parts of the body is called overfl ow; examples include leg dystonia while writ- ing or axial dystonia with talking. Factors that tend to exacerbate dystonia i nclude fatigue and emotional stress, whereas the move- ments usually decrease with relaxati on or sleep. Dystonia can oft en improve by tactile or proprioceptive sensory tricks ( gest e antago- niste ). Oft en a patient will be able to improve the abnormal posture to some de gree by touching, or even sometimes thinking about touching, the aff ected body part (2 \200\2236). Despite the \200\230motor \200\231 definition of primary dystonia, there are other, non-mo tor, features in many patients with primary dys- tonia, but these are less studied in secon dary/heredodegenera- tive dystonias (7, 8). Disease-related pain occurs in 30 \200\22370% o f patients, and mild sensory symptoms such as discomfort in the neck, irritation of the eye s or throat before the development of cervical dystonia, blepharospasm, and spasmodic dysph onia, respectively, are common (9, 10). Depressive disorders and a family history of depres sion are more frequent in adult-onset focal dystonia (11 \200\22314) and in manifesting and non-manifesting DYT1 mutation carriers (15). These non-motor symptoms are clinically relev ant, since they may impair quality of life equally to the motor symptoms (10, 16, 17). Genetic classi \201 cation of dystonia Th e DYT loci represent a clinically heterogeneous group of dis- orders including primary dystonia (DYT1, 2, 4, 6, 7, 13, 17, 21), dystonia-pl us (DYT3, 5/14, 11, 12, 15, 16), and paroxysmal dys- tonias (DYT8, 9, 10, 18, 19, 20) (Tabl e 17.2). Th erefore a genetic classifi cation of dystonia is not clinically useful. With re gard to Oxford Textbook of Movement Disorders 178 Table 17.1 Classi \201 cations of dystonia Fahn et al. 1998 (22) 1. Childhood 2. Adolescen ce 3. Adulthood Fahn et al. 2011 (23) 1. Young-onset (<26) 2. Adult-onset (>26) EFNS guidelines 2011 (24) 1. Early-onset (variably de \201 ned as <20 \200\22330 years) 2. Late-onset Age at onset Distribution Focal Segmental Multifocal Generalized hemidystonia Focal Segmental Multifocal Generalized hemidystonia Focal Segmental Multifocal Generalized hemidystonia Etiology Primary (a) Familial (b) Sporadic Primary Primary (a) Primary pure (e.g. DYT1, 6) (a) Primary paroxysmal (e.g. DYT8, 10, 18) Dystonia-plus Dystonia-plus (c) Primary-plus (former dystonia-plus syndromes, e.g. DYT5,11) Secondary Secondary Secondary Heredodegenerative Heredodegenerative Feature of another neurological disease (e.g. dystonic tics, paroxysmal dyskinesias, PD, PSP, etc.) Heredodegenerative Table 17.2 Th e DYT genes, phenotype, and transmission Primary dystonia DYT1 Gene or locus Phenotype Generalized early-limb-onset dystonia Transmissio n AD TOR1A None DYT2 Early-onset generalized dystonia AR DYT4 None Whispering dysphonia AD DYT6 Craniocervical and limb dystonia AD THAP1 18p DYT7 Adult-onset cervical dystonia AD DYT13 1p36.13 \200\22336.32 Craniocervical, laryngeal, and limb dystonia AD DYT17 20p11.2-q13.12 Segmental or generalized dystonia, severe dysphonia AR DYT21 2q14.3-q21.3 Adult-onset generalized or multifocal dystonia, starting with blepharospasm AD Dystonia-plu s syndromes DYT3 Dystonia \200\223parkinsonism (neurodegeneration) XR TAF1 DYT5a Dopa-responsive dystonia AD GTPCH1 DYT5b Dopa-responsive dystonia AR TH DYT11 Myoclonus \200\223dystonia AD SGCE DYT12 Rapid-onset dystonia \200\223parkinsonism AD ATP1A3 18p11 DYT15 Myoclonus \200\223dystonia AD DYT16 Early-onset dystonia \200\223parkinsonism AR PRKRA Paroxysmal dystonias DYT8 Paroxysmal non-kinesigenic dyskinesia AD MR1 DYT9/DYT18 Paroxysmal exercise-induced dystonia with wide phenotypical spectrum (e.g. spasticity, atax ia, seizures) AD SLC2A1 (GLUT1) DYT10 Paroxysmal kinesigenic dyskinesia AD PRRT2 16q DYT19 Paroxysmal kinesigenic dyskinesia 2 AD DYT20 2q Paroxysmal non-kinesigenic dyskinesia 2 AD disorder usually plateaus 5 \200\22310 years aft er onset. Prevalence reports of primary dy stonia vary widely from 3 to over 7000 per million depending on dystonia subtype (e.g. foca l vs generalized), ethnicity, and ascertainment methodology; most point to an estimated cru de prevalence of about 300 \200\223500 per million with focal dystonias being about seven t o ten times more common than generalized dystonia (27 \200\22329). However, the prevalence of primary dystonia is thought to be underestimated (29). genetic causes of heredodegenerative dystonias, many genes have been identifi ed (Table 17. 3). Primary dystonia Th e phenotypic spectrum of primary dystonia is wide, ranging from young-o nset generalized to adult-onset focal dystonia (25, 26). As per the defi nition, there are no additional signs and the CHAPTER 17 Dystonia: an overview 179 Young-onset primary dystonia Age at onset is usually in childhood or adolescence. Limb onse t is typical, with spread of symptoms over some years which then pla- teaus, oft en resulti ng in generalized dystonia. However, some patients may only develop focal or segmental dyst onia. Young-onset primary dystonia does not usually involve cranial or bulbar structures. DYT17 is autosomal recessive and was mapped to chromosome 20 in a consanguineous Lebanese f amily with cervical dystonia and progression to segmental dystonia in two siblings and gene ralized dystonia in a third sibling who also featured severe dysphonia and dysarthria (55).