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Orthostatic Tremor: Pathophysiology Guiding Treatment

  • Movement Disorders (A Videnovich, Section Editor)
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Abstract

Purpose of review

Orthostatic tremor (OT) is a rare disorder characterized by tremor and a feeling of unsteadiness while standing that resolve upon walking or sitting. A pathognomonic 13–18 Hz tremor is seen on surface EMG while standing. Though its clinical features have been better defined over time, much of its pathophysiology remains unknown and treatment options are limited. We review here recent developments in both of these areas.

Recent findings

Several recent studies have furthered our understanding of the central oscillatory network involved in OT. fMRI and 18F-FDG-PET studies have identified a ponto-cerebello-thalamo-cortical network underlying OT, though the nature of its dysfunction remains unknown.

Randomized trials of treatments for OT are few, so most data are from case reports or small case series. Clonazepam and gabapentin are likely the most effective medical therapies, while bilateral ventral intermediate nucleus deep brain stimulation shows promise for refractory cases.

Summary

Though much about OT remains unknown, our understanding of its pathophysiology has improved through recent studies. Treatment benefit is overall modest and inconsistent, though better understanding of the disease could lead to new avenues for treatment.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Heilman KM. Orthostatic tremor. Arch Neurol. 1984;41(8):880–1.

    Article  PubMed  CAS  Google Scholar 

  2. Pazzaglia P, Sabattini L, Lugaresi E. On an unusual disorder of erect standing position (observation of 3 cases). Riv Sper Freniatr Med Leg Alien Ment. 1970;94(2):450–7.

    PubMed  CAS  Google Scholar 

  3. Ganos C, Maugest L, Apartis E, Gasca-Salas C, Caceres-Redondo MT, Erro R, et al. The long-term outcome of orthostatic tremor. J Neurol Neurosurg Psychiatry. 2016;87(2):167–72. https://doi.org/10.1136/jnnp-2014-309942.

    Article  PubMed  Google Scholar 

  4. •• Hassan A, Ahlskog JE, Matsumoto JY, Milber JM, Bower JH, Wilkinson JR. Orthostatic tremor: clinical, electrophysiologic, and treatment findings in 184 patients. Neurology. 2016;86(5):458–64. https://doi.org/10.1212/wnl.0000000000002328. Large case series of clinical findings, electrophysiological data, and treatment outcomes.

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  6. McManis PG, Sharbrough FW. Orthostatic tremor: clinical and electrophysiologic characteristics. Muscle Nerve. 1993;16(11):1254–60. https://doi.org/10.1002/mus.880161117.

    Article  PubMed  CAS  Google Scholar 

  7. Koster B, Lauk M, Timmer J, Poersch M, Guschlbauer B, Deuschl G, et al. Involvement of cranial muscles and high intermuscular coherence in orthostatic tremor. Ann Neurol. 1999;45(3):384–8.

    Article  PubMed  CAS  Google Scholar 

  8. Brown P. New clinical sign for orthostatic tremor. Lancet. 1995;346(8970):346–7.

    Article  Google Scholar 

  9. Yarrow K, Brown P, Gresty MA, Bronstein AM. Force platform recordings in the diagnosis of primary orthostatic tremor. Gait Posture. 2001;13(1):27–34.

    Article  PubMed  CAS  Google Scholar 

  10. Karlberg M, Fransson PA, Magnusson M. Posturography can be used to screen for primary orthostatic tremor, a rare cause of dizziness. Otol Neurotol. 2005;26(6):1200–3.

    Article  PubMed  Google Scholar 

  11. Sander HW, Masdeu JC, Tavoulareas G, Walters A, Zimmerman T, Chokroverty S. Orthostatic tremor: an electrophysiological analysis. Mov Disord. 1998;13(4):735–8. https://doi.org/10.1002/mds.870130422.

    Article  PubMed  CAS  Google Scholar 

  12. Jones L, Bain PG. Orthostatic tremor. Pract Neurol. 2011;11(4):240–3. https://doi.org/10.1136/practneurol-2011-000022.

    Article  PubMed  Google Scholar 

  13. Balachandar A, Fasano A. Characterizing orthostatic tremor using a smartphone application. Tremor Other Hyperkinet Mov (N Y). 2017;7:488. https://doi.org/10.7916/d8v12grj.

    Article  PubMed Central  Google Scholar 

  14. Leu-Semenescu S, Roze E, Vidailhet M, Legrand AP, Trocello JM, Cochen V, et al. Myoclonus or tremor in orthostatism: an under-recognized cause of unsteadiness in Parkinson’s disease. Mov Disord. 2007;22(14):2063–9. https://doi.org/10.1002/mds.21651.

    Article  PubMed  Google Scholar 

  15. Rigby HB, Rigby MH, Caviness JN. Orthostatic tremor: a spectrum of fast and slow frequencies or distinct entities? Tremor Other Hyperkinet Mov (N Y). 2015;5:324. https://doi.org/10.7916/d8s75fhk.

    Article  Google Scholar 

  16. Bhatti D, Srikanth-Mysore C, Bertoni JM, Torres-Russotto D. Ataxia is common in patients with orthostatic tremor [abstract]. Mov Disord. 2013;28(Suppl 1):978.

    Google Scholar 

  17. Britton TC, Thompson PD, van der Kamp W, Rothwell JC, Day BL, Findley LJ, et al. Primary orthostatic tremor: further observations in six cases. J Neurol. 1992;239(4):209–17.

    Article  PubMed  CAS  Google Scholar 

  18. Benito-Leon J, Porta-Etessam J. Shaky-leg syndrome and vitamin B12 deficiency. N Engl J Med. 2000;342(13):981. https://doi.org/10.1056/nejm200003303421318.

    Article  PubMed  CAS  Google Scholar 

  19. Tan EK, Lo YL, Chan LL. Graves disease and isolated orthostatic tremor. Neurology. 2008;70(16 Pt 2):1497–8. https://doi.org/10.1212/01.wnl.0000310405.36026.92.

    Article  PubMed  CAS  Google Scholar 

  20. Lee HM, Kwon DY, Park MH, Koh SB, Kim SH. Symptomatic orthostatic tremor with progressive cognitive impairment in spinal cord lesions. Clin Neurol Neurosurg. 2012;114(10):1329–31. https://doi.org/10.1016/j.clineuro.2012.03.021.

    Article  PubMed  Google Scholar 

  21. Mestre TA, Lang AE, Ferreira JJ, Almeida V, de Carvalho M, Miyasaki J, et al. Associated movement disorders in orthostatic tremor. J Neurol Neurosurg Psychiatry. 2012;83(7):725–9. https://doi.org/10.1136/jnnp-2012-302436.

    Article  PubMed  Google Scholar 

  22. FitzGerald PM, Jankovic J. Orthostatic tremor: an association with essential tremor. Mov Disord. 1991;6(1):60–4. https://doi.org/10.1002/mds.870060111.

    Article  PubMed  CAS  Google Scholar 

  23. McAuley JH, Britton TC, Rothwell JC, Findley LJ, Marsden CD. The timing of primary orthostatic tremor bursts has a task-specific plasticity. Brain. 2000;123(Pt 2):254–66.

    Article  PubMed  Google Scholar 

  24. Wee AS, Subramony SH, Currier RD. ‘Orthostatic tremor’ in familial-essential tremor. Neurology. 1986;36(9):1241–5.

    Article  PubMed  CAS  Google Scholar 

  25. Papa SM, Gershanik OS. Orthostatic tremor: an essential tremor variant? Mov Disord. 1988;3(2):97–108. https://doi.org/10.1002/mds.870030201.

    Article  PubMed  CAS  Google Scholar 

  26. Bhatti D, Thompson R, Xia Y, Hellman A, Schmaderer L, Suing K, et al. Comprehensive, blinded assessment of balance in orthostatic tremor. Parkinsonism Relat Disord. 2017;47:22–5. https://doi.org/10.1016/j.parkreldis.2017.11.335.

    Article  PubMed  Google Scholar 

  27. Thompson PD, Rothwell JC, Day BL, Berardelli A, Dick JP, Kachi T, et al. The physiology of orthostatic tremor. Arch Neurol. 1986;43(6):584–7.

    Article  PubMed  CAS  Google Scholar 

  28. Walker FO, McCormick GM, Hunt VP. Isometric features of orthostatic tremor: an electromyographic analysis. Muscle Nerve. 1990;13(10):918–22. https://doi.org/10.1002/mus.880131006.

    Article  PubMed  CAS  Google Scholar 

  29. Boroojerdi B, Ferbert A, Foltys H, Kosinski CM, Noth J, Schwarz M. Evidence for a non-orthostatic origin of orthostatic tremor. J Neurol Neurosurg Psychiatry. 1999;66(3):284–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Wu YR, Ashby P, Lang AE. Orthostatic tremor arises from an oscillator in the posterior fossa. Mov Disord. 2001;16(2):272–9.

    Article  PubMed  CAS  Google Scholar 

  31. Deuschl G, Raethjen J, Lindemann M, Krack P. The pathophysiology of tremor. Muscle Nerve. 2001;24(6):716–35.

    Article  PubMed  CAS  Google Scholar 

  32. Wills AJ, Thompson PD, Findley LJ, Brooks DJ. A positron emission tomography study of primary orthostatic tremor. Neurology. 1996;46(3):747–52.

    Article  PubMed  CAS  Google Scholar 

  33. Muthuraman M, Hellriegel H, Paschen S, Hofschulte F, Reese R, Volkmann J, et al. The central oscillatory network of orthostatic tremor. Mov Disord. 2013;28(10):1424–30. https://doi.org/10.1002/mds.25616.

    Article  PubMed  Google Scholar 

  34. • Gallea C, Popa T, Garcia-Lorenzo D, Valabregue R, Legrand AP, Apartis E, et al. Orthostatic tremor: a cerebellar pathology? Brain. 2016;139(Pt 8):2182–97. https://doi.org/10.1093/brain/aww140. fMRI and 18F-FDG-PET studies establishing structures involved in OT pathophysiology.

    Article  PubMed  PubMed Central  Google Scholar 

  35. •• Schoberl F, Feil K, Xiong G, Bartenstein P, la Fougere C, Jahn K, et al. Pathological ponto-cerebello-thalamo-cortical activations in primary orthostatic tremor during lying and stance. Brain. 2017;140(1):83–97. https://doi.org/10.1093/brain/aww268. 18F-FDG-PET study demonstrating ponto-cerebello-thalamo-cortical network underlying OT and particular role of pontine tegmentum.

    Article  PubMed  Google Scholar 

  36. Gerschlager W, Katzenschlager R, Schrag A, Lees AJ, Brown P, Quinn N, et al. Quality of life in patients with orthostatic tremor. J Neurol. 2003;250(2):212–5. https://doi.org/10.1007/s00415-003-0980-9.

    Article  PubMed  CAS  Google Scholar 

  37. Benito-Leon J, Louis ED, Puertas-Martin V, Romero JP, Matarazzo M, Molina-Arjona JA, et al. Cognitive and neuropsychiatric features of orthostatic tremor: a case-control comparison. J Neurol Sci. 2016;361:137–43. https://doi.org/10.1016/j.jns.2015.12.031.

    Article  PubMed  Google Scholar 

  38. Gerschlager W, Munchau A, Katzenschlager R, Brown P, Rothwell JC, Quinn N, et al. Natural history and syndromic associations of orthostatic tremor: a review of 41 patients. Mov Disord. 2004;19(7):788–95. https://doi.org/10.1002/mds.20132.

    Article  PubMed  Google Scholar 

  39. Katzenschlager R, Costa D, Gerschlager W, O'Sullivan J, Zijlmans J, Gacinovic S, et al. [123I]-FP-CIT-SPECT demonstrates dopaminergic deficit in orthostatic tremor. Ann Neurol. 2003;53(4):489–96. https://doi.org/10.1002/ana.10475.

    Article  PubMed  Google Scholar 

  40. Spiegel J, Behnke S, Fuss G, Becker G, Dillmann U. Echogenic substantia nigra in patients with orthostatic tremor. J Neural Transm (Vienna). 2005;112(7):915–20. https://doi.org/10.1007/s00702-004-0236-6.

    Article  CAS  Google Scholar 

  41. Onofrj M, Thomas A, Paci C, D’Andreamatteo G. Gabapentin in orthostatic tremor: results of a double-blind crossover with placebo in four patients. Neurology. 1998;51(3):880–2.

    Article  PubMed  CAS  Google Scholar 

  42. Rodrigues JP, Edwards DJ, Walters SE, Byrnes ML, Thickbroom GW, Stell R, et al. Blinded placebo crossover study of gabapentin in primary orthostatic tremor. Mov Disord. 2006;21(7):900–5. https://doi.org/10.1002/mds.20830.

    Article  PubMed  Google Scholar 

  43. Hellriegel H, Raethjen J, Deuschl G, Volkmann J. Levetiracetam in primary orthostatic tremor: a double-blind placebo-controlled crossover study. Mov Disord. 2011;26(13):2431–4. https://doi.org/10.1002/mds.23881.

    Article  PubMed  Google Scholar 

  44. Bertram K, Sirisena D, Cowey M, Hill A, Williams DR. Safety and efficacy of botulinum toxin in primary orthostatic tremor. J Clin Neurosci. 2013;20(11):1503–5. https://doi.org/10.1016/j.jocn.2012.12.025.

    Article  PubMed  CAS  Google Scholar 

  45. Gates PC. Orthostatic tremor (shaky legs syndrome). Clin Exp Neurol. 1993;30:66–71.

    PubMed  CAS  Google Scholar 

  46. Espay AJ, Duker AP, Chen R, Okun MS, Barrett ET, Devoto J, et al. Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: preliminary observations. Mov Disord. 2008;23(16):2357–62. https://doi.org/10.1002/mds.22271.

    Article  PubMed  Google Scholar 

  47. Evidente VG, Adler CH, Caviness JN, Gwinn KA. Effective treatment of orthostatic tremor with gabapentin. Mov Disord. 1998;13(5):829–31. https://doi.org/10.1002/mds.870130513.

    Article  PubMed  CAS  Google Scholar 

  48. Piboolnurak P, Yu QP, Pullman SL. Clinical and neurophysiologic spectrum of orthostatic tremor: case series of 26 subjects. Mov Disord. 2005;20(11):1455–61. https://doi.org/10.1002/mds.20588.

    Article  PubMed  Google Scholar 

  49. Athauda D, Georgiev D, Aviles-Olmos I, Peters A, Day B, Brown P, et al. Thalamic-caudal zona incerta deep brain stimulation for refractory orthostatic tremor: a report of 3 cases. Mov Disord Clin Pract. 2017;4(1):6–110. https://doi.org/10.1002/mdc3.12345.

    Article  Google Scholar 

  50. Blahak C, Sauer T, Baezner H, Wolf ME, Saryyeva A, Schrader C, et al. Long-term follow-up of chronic spinal cord stimulation for medically intractable orthostatic tremor. J Neurol. 2016;263(11):2224–8. https://doi.org/10.1007/s00415-016-8239-4.

    Article  PubMed  Google Scholar 

  51. Yaltho TC, Ondo WG. Thalamic deep brain stimulation for orthostatic tremor. Tremor Other Hyperkinet Mov (N Y). 2011;1 https://doi.org/10.7916/d8nz86c1.

  52. Lehn AC, O'Gorman C, Olson S, Salari M. Thalamic ventral intermediate nucleus deep brain stimulation for orthostatic tremor. Tremor Other Hyperkinet Mov (N Y). 2017;7:479. https://doi.org/10.7916/d8280jhr.

    Article  Google Scholar 

  53. Gabellini AS, Martinelli P, Gulli MR, Ambrosetto G, Ciucci G, Lugaresi E. Orthostatic tremor: essential and symptomatic cases. Acta Neurol Scand. 1990;81(2):113–7.

    Article  PubMed  CAS  Google Scholar 

  54. Cabrera-Valdivia F, Jimenez-Jimenez FJ, Garcia Albea E, Tejeiro-Martinez J, Vaquero Ruiperez JA, Ayuso-Peralta L. Orthostatic tremor: successful treatment with phenobarbital. Clin Neuropharmacol. 1991;14(5):438–41.

    Article  PubMed  CAS  Google Scholar 

  55. Rodrigues JP, Edwards DJ, Walters SE, Byrnes ML, Thickbroom G, Stell R, et al. Gabapentin can improve postural stability and quality of life in primary orthostatic tremor. Mov Disord. 2005;20(7):865–70. https://doi.org/10.1002/mds.20392.

    Article  PubMed  Google Scholar 

  56. Lyons MK, Behbahani M, Boucher OK, Caviness JN, Evidente VG. Orthostatic tremor responds to bilateral thalamic deep brain stimulation. Tremor Other Hyperkinet Mov (N Y). 2012;2 https://doi.org/10.7916/d8tq608k.

  57. Yague S, Veciana M, Pedro J, Campdelacreu J. Importance of electromyographic studies in the diagnosis of orthostatic tremor. Neurologia. 2011;26(1):53–5. https://doi.org/10.1016/j.nrl.2010.06.005.

    Article  PubMed  CAS  Google Scholar 

  58. Coleman RR, Starr PA, Katz M, Glass GA, Volz M, Khandhar SM, et al. Bilateral ventral intermediate nucleus thalamic deep brain stimulation in orthostatic tremor. Stereotact Funct Neurosurg. 2016;94(2):69–74. https://doi.org/10.1159/000444127.

    Article  PubMed  Google Scholar 

  59. Wills AJ, Brusa L, Wang HC, Brown P, Marsden CD. Levodopa may improve orthostatic tremor: case report and trial of treatment. J Neurol Neurosurg Psychiatry. 1999;66(5):681–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Apartis E, Tison F, Arne P, Jedynak CP, Vidailhet M. Fast orthostatic tremor in Parkinson's disease mimicking primary orthostatic tremor. Mov Disord. 2001;16(6):1133–6.

    Article  PubMed  CAS  Google Scholar 

  61. Finkel MF. Pramipexole is a possible effective treatment for primary orthostatic tremor (shaky leg syndrome). Arch Neurol. 2000;57(10):1519–20.

    Article  PubMed  CAS  Google Scholar 

  62. Guridi J, Rodriguez-Oroz MC, Arbizu J, Alegre M, Prieto E, Landecho I, et al. Successful thalamic deep brain stimulation for orthostatic tremor. Mov Disord. 2008;23(13):1808–11. https://doi.org/10.1002/mds.22001.

    Article  PubMed  Google Scholar 

  63. Nasrallah KM, Mitsias PD. Orthostatic tremor due to thiamine deficiency. Mov Disord. 2007;22(3):440–1. https://doi.org/10.1002/mds.21193.

    Article  PubMed  Google Scholar 

  64. Pfeiffer G, Hinse P, Humbert T, Riemer G. Neurophysiology of orthostatic tremor. Influence of transcranial magnetic stimulation. Electromyogr Clin Neurophysiol. 1999;39(1):49–53.

    PubMed  CAS  Google Scholar 

  65. Setta F, Jacquy J, Hildebrand J, Manto MU. Orthostatic tremor associated with cerebellar ataxia. J Neurol. 1998;245(5):299–302.

    Article  PubMed  CAS  Google Scholar 

  66. Zeuner KE, Deuschl G. An update on tremors. Curr Opin Neurol. 2012;25(4):475–82. https://doi.org/10.1097/WCO.0b013e3283550c7e.

    Article  PubMed  Google Scholar 

  67. Follett MA, Torres-Russotto D, Follett KA. Bilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus for posttraumatic midbrain tremor. Neuromodulation. 2014;17(3):289–91. https://doi.org/10.1111/ner.12096.

    Article  PubMed  Google Scholar 

  68. Chiang HL, Tai YC, McMaster J, Fung VS, Mahant N. Primary orthostatic tremor: is deep brain stimulation better than spinal cord stimulation? J Neurol Neurosurg Psychiatry. 2017;88(9):804–5. https://doi.org/10.1136/jnnp-2016-315188.

    Article  PubMed  Google Scholar 

  69. •• Merola A, Fasano A, Hassan A, Ostrem JL, Contarino MF, Lyons M, et al. Thalamic deep brain stimulation for orthostatic tremor: a multicenter international registry. Mov Disord. 2017;32(8):1240–4. https://doi.org/10.1002/mds.27082. Multicenter review of treatment outcomes for VIM DBS in OT patients.

    Article  PubMed  Google Scholar 

  70. Krauss JK, Weigel R, Blahak C, Bazner H, Capelle HH, Grips E, et al. Chronic spinal cord stimulation in medically intractable orthostatic tremor. J Neurol Neurosurg Psychiatry. 2006;77(9):1013–6. https://doi.org/10.1136/jnnp.2005.086132.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Magarinos-Ascone C, Ruiz FM, Millan AS, Montes E, Regidor I, del Alamo de Pedro M, et al. Electrophysiological evaluation of thalamic DBS for orthostatic tremor. Mov Disord. 2010;25(14):2476–7. https://doi.org/10.1002/mds.23333.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Movement Disorders Section, Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA

    David Whitney MD, Danish Bhatti MD & Diego Torres-Russotto MD

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  1. David Whitney MD
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  2. Danish Bhatti MD
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Correspondence to Diego Torres-Russotto MD.

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David Whitney declares no conflict of interest.

Danish Bhatti has received personal fees from AbbVie, ACADIA, Adamas, Merz, Teva, and Allergan Pakistan.

Diego Torres-Russotto has received personal fees from Allergan, Ipsen, Merz, Revance, Sunovion, Teva, and AbbVie.

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Whitney, D., Bhatti, D. & Torres-Russotto, D. Orthostatic Tremor: Pathophysiology Guiding Treatment. Curr Treat Options Neurol 20, 35 (2018). https://doi.org/10.1007/s11940-018-0524-3

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