Essential tremor
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
no dysfunction or embarrassment
observation
Medicine therapy is not indicated for mild cases that do not cause dysfunction or embarrassment.[6]Louis ED. Clinical practice. Essential tremor. N Engl J Med. 2001 Sep 20;345(12):887-91. http://www.ncbi.nlm.nih.gov/pubmed/11565522?tool=bestpractice.com For these patients, observation is all that is required.
dysfunction or embarrassment
medical treatment
Medical therapy may be used to improve function (e.g., using a smartphone, performing work-related tasks) or reduce embarrassment (e.g., the inability to eat or drink in public without making a mess) associated with the disorder. Choice of treatment depends on concurrent medical conditions and potential adverse effects.[82]Zesiewicz TA, Elble RJ, Louis ED, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology. Neurology. 2011 Nov 8;77(19):1752-5. http://www.neurology.org/content/77/19/1752.long http://www.ncbi.nlm.nih.gov/pubmed/22013182?tool=bestpractice.com
Propranolol has been shown to be more effective than placebo at doses of 120 mg/day or greater.[83]Tolosa ES, Loewenson RB. Essential tremor: treatment with propranolol. Neurology. 1975 Nov;25(11):1041-4. http://www.ncbi.nlm.nih.gov/pubmed/1237822?tool=bestpractice.com Relative contraindications include bradycardia, asthma, diabetes mellitus, atrioventricular block, and congestive heart failure. Periodic monitoring of heart rate to evaluate for the development of bradycardia is advisable in older patients.
Propranolol should be started at 10 mg/day and increased up to 320 mg/day to achieve tremor control, or until troublesome adverse effects develop.[129]Louis ED. Essential tremor. Clin Geriatr Med. 2006 Nov;22(4):843-57. http://www.ncbi.nlm.nih.gov/pubmed/17000339?tool=bestpractice.com Adverse effects include depression and fatigue in addition to bradycardia.
Primidone in doses of up to 750 mg/day is effective in controlling essential tremor (ET).[130]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 Sep;48(9):911-5. http://www.ncbi.nlm.nih.gov/pubmed/3900296?tool=bestpractice.com In 23% to 73% of patients starting primidone, nausea, vomiting, and ataxia occur, but this acute reaction is short-lived.[35]Boecker H, Wills AJ, Ceballos-Baumann A, et al. The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study. Ann Neurol. 1996 May;39(5):650-8. http://www.ncbi.nlm.nih.gov/pubmed/8619551?tool=bestpractice.com [131]Sasso E, Perucca E, Fava R, et al. Primidone in the long-term treatment of essential tremor: a prospective study with computerized quantitative analysis. Clin Neuropharmacol. 1990 Feb;13(1):67-76. http://www.ncbi.nlm.nih.gov/pubmed/2306749?tool=bestpractice.com
Several second-line agents can be used to treat ET if primidone and propranolol are either ineffective or not tolerated. These include gabapentin, alprazolam, and topiramate.[91]Bruno E, Nicoletti A, Quattrocchi G, et al. Topiramate for essential tremor. Cochrane Database Syst Rev. 2017 Apr 14;4:CD009683. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009683.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/28409827?tool=bestpractice.com However, all may cause sedation.
Primary options
propranolol: 10 mg/day orally given in 2-4 divided doses initially, increase by 20 mg/day increments every 7 days as tolerated and according to response, maximum 320 mg/day
OR
primidone: 12.5 to 25 mg orally once daily initially, increase by 12.5 to 25 mg/day increments every 7 days as tolerated and according to response, maximum 750 mg/day
Secondary options
gabapentin: 300 mg orally three times daily initially, increase by 600 mg/day increments every 2 weeks as tolerated and according to response, maximum 3600 mg/day
OR
alprazolam: 0.5 mg orally three times daily initially, increase by up to 1 mg/day increments every 3-4 days as tolerated and according to response, maximum 4 mg/day
OR
topiramate: 25 mg/day orally given in 2 divided doses initially, increase by up to 25 mg/day increments every 7 days as tolerated and according to response, usual dose 100 mg/day, maximum 400 mg/day
deep brain stimulation (DBS)
DBS of the nucleus ventralis intermedius (VIM) of the thalamus is a highly successful neurosurgical method for the treatment of medicine-refractory essential tremor (ET).[116]Sixel-Doring F, Benecke R, Fogel W, et al; German Deep Brain Stimulation Association. Tiefe Hirnstimulation bei essenziellem Tremor. Empfehlungen der Deutschen Arbeitsgemeinschaft Tiefe Hirnstimulation. [Deep brain stimulation for essential tremor. Consensus recommendations of the German Deep Brain Stimulation Association]. Nervenarzt. 2009 Jun;80(6):662-5. [In German] http://www.ncbi.nlm.nih.gov/pubmed/19404603?tool=bestpractice.com
As this is an elective procedure, determining a favourable risk-to-benefit ratio is paramount. This includes accurately diagnosing the patient's tremor, establishing that appropriate medical therapy was not successful, estimating the improvement in the patient's functional capacity and quality of life that would result with tremor control, and assessing the patient's suitability for surgery (i.e., age, cognitive function, and medical comorbidities).
A multidisciplinary team that includes a movement disorders-specialised neurologist, a neurosurgeon, and a neuropsychologist should be involved. For centres where such specialists are not readily available, simpler screens have been designed to help identify potential candidates for DBS.[93]Deuschl G, Bain P. Deep brain stimulation for tremor [correction of trauma]: patient selection and evaluation. Mov Disord. 2002;17 (Suppl 3):S102-11. http://www.ncbi.nlm.nih.gov/pubmed/11948763?tool=bestpractice.com [94]Okun MS, Fernandez HH, Pedraza O, et al. Development and initial validation of a screening tool for Parkinson disease surgical candidates. Neurology. 2004 Jul 13;63(1):161-3. http://www.ncbi.nlm.nih.gov/pubmed/15249630?tool=bestpractice.com [95]Okun MS, Fernandez HH, Rodriguez RL, et al. Identifying candidates for deep brain stimulation in Parkinson's disease: the role of the primary care physician. Geriatrics. 2007 May;62(5):18-24. http://www.ncbi.nlm.nih.gov/pubmed/17489644?tool=bestpractice.com [96]Okun MS, Rodriguez RL, Mikos A, et al. Deep brain stimulation and the role of the neuropsychologist. Clin Neuropsychol. 2007 Jan;21(1):162-89. http://www.ncbi.nlm.nih.gov/pubmed/17366283?tool=bestpractice.com [97]Rodriguez RL, Fernandez HH, Haq I, et al. Pearls in patient selection for deep brain stimulation. Neurologist. 2007 Sep;13(5):253-60. http://www.ncbi.nlm.nih.gov/pubmed/17848865?tool=bestpractice.com
An alternative target for DBS is the caudal zona incerta (cZi), also known as the posterior subthalamic area. A new strategy whereby the DBS lead is implanted through the VIM thalamic nucleus into the cZi has been proposed, which allows stimulation in either or both targets. This new target shows substantial promise as an effective target for suppressing contralateral tremor in these patients, with a long-lasting effect.[117]Fytagoridis A, Sandvik U, Aström M, et al. Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor. J Neurol Neurosurg Psychiatry. 2012 Mar;83(3):258-62. http://www.ncbi.nlm.nih.gov/pubmed/22205676?tool=bestpractice.com [118]Barbe MT, Liebhart L, Runge M, et al. Deep brain stimulation of the ventral intermediate nucleus in patients with essential tremor: stimulation below intercommissural line is more efficient but equally effective as stimulation above. Exp Neurol. 2011 Jul;230(1):131-7. http://www.ncbi.nlm.nih.gov/pubmed/21515262?tool=bestpractice.com [119]Chang WS, Chung JC, Kim JP, et al. Simultaneous thalamic and posterior subthalamic electrode insertion with single deep brain stimulation electrode for essential tremor. Neuromodulation. 2013 May-Jun;16(3):236-43. http://www.ncbi.nlm.nih.gov/pubmed/22985104?tool=bestpractice.com
focused ultrasound thalamotomy with MRI guidance
Magnetic resonance imaging (MRI)-guided focused ultrasound thalamotomy is an alternative to deep brain stimulation (DBS) surgery.
In the UK, transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) thalamotomy is a treatment option for refractory essential tremor (ET) in patients not eligible for DBS where special arrangements for clinical governance, consent, and audit or research are in place.[124]National Institute for Health and Care Excellence. Unilateral MRI-guided focused ultrasound thalamotomy for treatment-resistant essential tremor. Jun 2018 [internet publication]. https://www.nice.org.uk/guidance/ipg617 [125]NHS England. Transcranial magnetic resonance guided focused ultrasound thalamotomy for treatment of medication-refractory essential tremor. Nov 2020 [internet publication]. https://www.england.nhs.uk/publication/transcranial-magnetic-resonance-guided-focused-ultrasound-thalamotomy-for-treatment-of-medication-refractory-essential-tremor
The American Society for Stereotactic and Functional Neurosurgery (ASSFN) recommends TcMRgFUS thalamotomy as a treatment option for patients with refractory ET, who have an appendicular tremor that interferes with quality of life, and that are expected to have a significant improvement with unilateral treatment.[126]Pouratian N, Baltuch G, Elias WJ, et al. American Society for Stereotactic and Functional Neurosurgery position statement on magnetic resonance-guided focused ultrasound for the management of essential tremor. Neurosurgery. 2020 Aug 1;87(2):E126-9. https://academic.oup.com/neurosurgery/article/87/2/E126/5674970 http://www.ncbi.nlm.nih.gov/pubmed/31832649?tool=bestpractice.com
Similar to DBS, the relative risk and benefits should be considered. The long-term effects and side effects are unclear.[120]Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016 Aug 25;375(8):730-9. http://www.nejm.org/doi/full/10.1056/NEJMoa1600159#t=article http://www.ncbi.nlm.nih.gov/pubmed/27557301?tool=bestpractice.com [124]National Institute for Health and Care Excellence. Unilateral MRI-guided focused ultrasound thalamotomy for treatment-resistant essential tremor. Jun 2018 [internet publication]. https://www.nice.org.uk/guidance/ipg617
gamma knife thalamotomy
Another surgical option for refractory essential tremor is gamma knife thalamotomy, which is especially suitable for older patients or those with high surgical risk for deep brain stimulation or radiofrequency thalamotomy.[127]Niranjan A, Raju SS, Kooshkabadi A, et al. Stereotactic radiosurgery for essential tremor: retrospective analysis of a 19-year experience. Mov Disord. 2017 May;32(5):769-77. http://www.ncbi.nlm.nih.gov/pubmed/28319282?tool=bestpractice.com
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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