Essential tremor: Difference between revisions

Essential tremor is a [[progressive disease|progressive]]<ref name="UF Health">{{cite web | vauthors = Shukla AW |title=Essential Tremor Information |url=https://movementdisorders.ufhealth.org/for-patients/movement-disorder-information/essential-tremor-information/ |website=Unified Health |access-date=17 June 2018}}</ref><ref name="NORD">{{cite web |vauthors=Louis ED |title=Essential Tremor |url=https://rarediseases.org/rare-diseases/essential-tremor/ |publisher=National Organization for Rare Disorders |access-date=17 June 2018}}</ref><ref name="NCBI2">{{cite journal | vauthors = Gironell A, Ribosa-Nogué R, Gich I, Marin-Lahoz J, Pascual-Sedano B | title = Severity stages in essential tremor: a long-term retrospective study using the glass scale | journal = Tremor and Other Hyperkinetic Movements | volume = 5 | pages = 299 | year = 2015 | pmid = 25793146 | pmc = 4361372 | doi = 10.7916/D8DV1HQC }}</ref> [[neurological disorder]], and the most common [[movement disorder]]. Though not life-threatening, it can certainly be debilitating. Its onset is usually between 40 and 50 years of age, but it can occur at any age.<ref>{{cite web |title=Tremor |url=https://www.ninds.nih.gov/health-information/disorders/tremor |website=National Institute of Neurological Disorders and Stroke}}</ref> The cause is poorly understood. Diagnosis is made by observing the typical pattern of the tremor coupled with the exclusion of known causes of such a tremor. There is currently no medical test available to identify an essential tremor.

In mild cases, ET can manifest as the inability to stop the tongue or hands from shaking, the ability to sing only in [[vibrato]], and difficulty doing small, precise tasks such as threading a needle. Even simple tasks such as cutting in a straight line or using a ruler can range from difficult to impossible, depending on the severity of the condition. In disabling cases, ET can interfere with a person's [[activities of daily living]], including feeding, dressing, and taking care of personal hygiene. Essential tremor generally presents as a rhythmic tremor (4–12 [[Hertz|Hz]]) that occurs only when the affected [[muscle]] is exerting effort. Any sort of physical or mental [[stress (medicine)|stress]] tends to make the tremor worse.<ref name="hopkinsmedicine">{{cite web | title = Essential Tremor Treatment at the Johns Hopkins Movement Disorders Center in Baltimore, MD | publisher = hopkinsmedicine.org | url = http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/movement_disorders/conditions/essential_tremor.html | access-date = 27 October 2014 }}</ref>

Essential Tremor was once thought to be a single disease state, however, research shows that there are multiple factors that are associated with causing Essential Tremor. This leads to the consideration that Essential Tremor is more akin to a family of diseases, due to the presence of both genetic (familial) and sporadic Essential Tremors.<ref name="'Essential tremor' or 'the essentia">{{cite journal | vauthors = Louis ED | title = 'Essential tremor' or 'the essential tremors': is this one disease or a family of diseases? | journal = Neuroepidemiology | volume = 42 | issue = 2 | pages = 81–89 | date = 2014 | pmid = 24335621 | pmc = 3945103 | doi = 10.1159/000356351 }}</ref> Currently, there are multiple main hypotheses behind Essential Tremor, being the degeneration of the [[cerebellum]], inheriting the tremor, ingestion of toxins, or the presence of [[Lewy body|Lewy Bodies]] in the brainstem.<ref name=":3">{{cite journal | vauthors = Ong YL, Deng X, Tan EK | title = Etiologic links between environmental and lifestyle factors and Essential tremor | journal = Annals of Clinical and Translational Neurology | volume = 6 | issue = 5 | pages = 979–989 | date = May 2019 | pmid = 31139697 | pmc = 6529929 | doi = 10.1002/acn3.758 }}</ref> However, ''post mortem'' studies showed that only a small number of patients had Lewy Bodies, and was more common for patients not to exhibit them.<ref>{{cite journal | vauthors = Louis ED | title = Essential Tremor: A Common Disorder of Purkinje Neurons? | journal = The Neuroscientist | volume = 22 | issue = 2 | pages = 108–118 | date = April 2016 | pmid = 26044399 | pmc = 5467972 | doi = 10.1177/1073858415590351 }}</ref>

It is unknown how the degeneration of the cerebellum leads to Essential Tremor, however, it is hypothesized that it may be due to the loss of [[Purkinje cell]]s, as they release gamma-aminobutyric acid ([[GABA]]), which is an inhibitory neurotransmitter meant to control the firing of neurons in the cerebellum. In certain Essential Tremor clinical studies which augment the GABA pathway, only some participants exhibited a reduction of tremor.<ref>{{cite journal | vauthors = Gironell A, Kulisevsky J, Barbanoj M, López-Villegas D, Hernández G, Pascual-Sedano B | title = A randomized placebo-controlled comparative trial of gabapentin and propranolol in essential tremor | journal = Archives of Neurology | volume = 56 | issue = 4 | pages = 475–480 | date = April 1999 | pmid = 10199338 | doi = 10.1001/archneur.56.4.475 }}</ref><ref>{{cite journal | vauthors = Zesiewicz TA, Ward CL, Hauser RA, Sanchez-Ramos J, Staffetti JF, Sullivan KL | title = A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor | journal = Movement Disorders | volume = 22 | issue = 2 | pages = 279–282 | date = January 2007 | pmid = 17149715 | doi = 10.1002/mds.21282 }}</ref> Some patients have responded to alcohol, claiming alcohol has reduced the tremor, however the reduction is only short term.<ref name=":0" /> However, alcohol might only be beneficial for those with an impacted GABA pathway, and may not be benefit patients who developed the tremor via other pathways.

The main underlying cause of essential tremor is not clear, but many cases seem to be familial.<ref>{{cite journal | vauthors = Deng H, Le W, Jankovic J | title = Genetics of essential tremor | journal = Brain | volume = 130 | issue = Pt 6 | pages = 1456–1464 | date = June 2007 | pmid = 17353225 | doi = 10.1093/brain/awm018 | doi-access = free }}</ref> About half of the cases are due to a genetic mutation and the pattern of inheritance is most consistent with [[autosomal]] [[Dominant gene|dominant]] transmission, meaning patients with Essential Tremor have around a 50% chance to pass it on to their children.<ref>{{cite book |title=Genes and Disease |date=1998 |publisher=National Center for Biotechnology Information |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK22186/ |chapter=Essential tremor }}</ref> There are multiple gene mutations and presentations on various chromosomes that lead to Essential Tremor.<ref>{{cite web |title=Entry - #190300 - Tremor, Hereditary Essential, 1; ETM1 |url=https://omim.org/entry/190300 |website=OMIM }}</ref> These include genes present on chromosomes 1–3, 6, 11, and 16. Each presentation or mutation of different genes were associated with families from different regions. For example, presentation of a gene associated with Essential Tremor on chromosome 6 has been noted in North American families, while a Canadian family was noted with mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene.<ref name=":3" /> Other mutations in genes such as the HTRA Serine Peptidase 2 ([[HTRA2]]) and the teneurin transmembrane protein 4 ([[TENM4 (gene)|TENM4]]), have been observed in a Turkish family and the Spanish population respectively.<ref name=":3" /> Recent ''post mortem'' studies have displayed alterations in the leucine-rich repeat and immunoglobulin-like domain-containing protein 1 (''[[LINGO1]]'') gene<ref>{{cite journal | vauthors = Delay C, Tremblay C, Brochu E, Paris-Robidas S, Emond V, Rajput AH, Rajput A, Calon F | title = Increased LINGO1 in the cerebellum of essential tremor patients | journal = Movement Disorders | volume = 29 | issue = 13 | pages = 1637–1647 | date = November 2014 | pmid = 24531928 | doi = 10.1002/mds.25819 | s2cid = 27331090 }}</ref><ref>{{cite journal | vauthors = Kuo SH, Tang G, Louis ED, Ma K, Babji R, Balatbat M, Cortes E, Vonsattel JP, Yamamoto A, Sulzer D, Faust PL | title = Lingo-1 expression is increased in essential tremor cerebellum and is present in the basket cell pinceau | journal = Acta Neuropathologica | volume = 125 | issue = 6 | pages = 879–889 | date = June 2013 | pmid = 23543187 | pmc = 3663903 | doi = 10.1007/s00401-013-1108-7 }}</ref> and GABA receptors<ref>{{cite journal | vauthors = Paris-Robidas S, Brochu E, Sintes M, Emond V, Bousquet M, Vandal M, Pilote M, Tremblay C, Di Paolo T, Rajput AH, Rajput A, Calon F | title = Defective dentate nucleus GABA receptors in essential tremor | journal = Brain | volume = 135 | issue = Pt 1 | pages = 105–116 | date = January 2012 | pmid = 22120148 | doi = 10.1093/brain/awr301 | doi-access = free }}</ref> in the cerebellum of people with essential tremor. ''HAPT1 ''mutations have also been linked to ET, as well as to Parkinson's disease, [[multiple system atrophy]], and [[progressive supranuclear palsy]].<ref>{{cite journal | vauthors = Vilariño-Güell C, Soto-Ortolaza AI, Rajput A, Mash DC, Papapetropoulos S, Pahwa R, Lyons KE, Uitti RJ, Wszolek ZK, Dickson DW, Farrer MJ, Ross OA | title = MAPT H1 haplotype is a risk factor for essential tremor and multiple system atrophy | journal = Neurology | volume = 76 | issue = 7 | pages = 670–672 | date = February 2011 | pmid = 21321341 | pmc = 3053340 | doi = 10.1212/WNL.0b013e31820c30c1 }}</ref>

Some environmental [[poison]]s, including [[toxin]]s, are also under active investigation, as they may play a role in the disease's cause.<ref>{{cite journal | vauthors = Louis ED | title = Etiology of essential tremor: should we be searching for environmental causes? | journal = Movement Disorders | volume = 16 | issue = 5 | pages = 822–829 | date = September 2001 | pmid = 11746611 | doi = 10.1002/mds.1183 | s2cid = 38809483 }}</ref> Exposure to heavy metals, specifically [[lead]], has been associated with causation of ET.<ref name=":3" /><ref>{{cite journal | vauthors = Dogu O, Louis ED, Tamer L, Unal O, Yilmaz A, Kaleagasi H | title = Elevated blood lead concentrations in essential tremor: a case-control study in Mersin, Turkey | journal = Environmental Health Perspectives | volume = 115 | issue = 11 | pages = 1564–1568 | date = November 2007 | pmid = 18007985 | pmc = 2072853 | doi = 10.1289/ehp.10352 | bibcode = 2007EnvHP.115.1564D }}</ref> Lead is a heavy metal that can cross the [[central nervous system]]'s (CNS) main line of defense, the [[blood–brain barrier]], even increasing its permeability, allowing other harmful substances to access the CNS.<ref>{{cite web |title=Chronic Lead Exposure: A Non-Traumatic Brain Injury |url=https://www.biausa.org/public-affairs/public-awareness/news/chronic-lead-exposure-a-non-traumatic-brain-injury |website=Brain Injury Association of America |access-date=2024-08-02}}</ref> This allows lead access to the CNS, permitting it to disturb processes that utilize calcium, including synaptic activity, and causes intracellular disruption, both of which may lead to irreversible damage to the CNS.<ref>{{cite journal | vauthors = Marambaud P, Dreses-Werringloer U, Vingtdeux V | title = Calcium signaling in neurodegeneration | journal = Molecular Neurodegeneration | volume = 4 | issue = 1 | pages = 20 | date = May 2009 | pmid = 19419557 | pmc = 2689218 | doi = 10.1186/1750-1326-4-20 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sanders T, Liu Y, Buchner V, Tchounwou PB | title = Neurotoxic effects and biomarkers of lead exposure: a review | journal = Reviews on Environmental Health | volume = 24 | issue = 1 | pages = 15–45 | date = January 2009 | pmid = 19476290 | pmc = 2858639 | doi = 10.1515/REVEH.2009.24.1.15 | bibcode = 2009RvEH...24.1.15S }}</ref> This would include cerebellar damage which could cause ET. There are other poisons that work in a similar manner to lead such as other heavy metals like mercury and aluminum, as well as toxic chemicals like certain pesticides and alcohol. In particular, excessive alcohol consumption can worsen essential tremor due to  damage to the cerebellum.<ref>{{cite journal | vauthors = Luo J | title = Effects of Ethanol on the Cerebellum: Advances and Prospects | journal = Cerebellum | volume = 14 | issue = 4 | pages = 383–385 | date = August 2015 | pmid = 25933648 | pmc = 4492805 | doi = 10.1007/s12311-015-0674-8 }}</ref>

Essential tremor is one of the most prevalent and poorly-understood neurological disorders.<ref name=disorder>{{cite journal | vauthors = Louis ED, Vonsattel JP | title = The emerging neuropathology of essential tremor | journal = Movement Disorders | volume = 23 | issue = 2 | pages = 174–182 | date = January 2008 | pmid = 17999421 | pmc = 2692583 | doi = 10.1002/mds.21731 }}</ref> Clinical, physiological and imaging studies point to involvement of the [[cerebellum]] and/or [[cerebellothalamocortical]] circuits.<ref name=disorder/> The traditional model for essential tremor, the olivary hypothesis, suggests that ET is caused by abnormal electrical activity in the [[inferior olivary nucleus]]. This activity makes neurons fire in a regular, [[Synchronization|synchronized]] way, which then disrupts signals to the [[cerebellum]] and leads to [[tremor]]s.<ref>{{cite journal | vauthors = Louis ED | title = Re-thinking the biology of essential tremor: from models to morphology | journal = Parkinsonism & Related Disorders | volume = 20 Suppl 1 | issue = 1 | pages = S88–S93 | date = January 2014 | pmid = 24262197 | doi = 10.1016/S1353-8020(13)70023-3 }}</ref> However, recent studies, especially those examining brain tissue, propose a new hypothesis that ET may be a [[neurodegenerative disease]] focused in the cerebellum, differing from the old theory<ref name=":6" />'''.''' Changes in the cerebellum could also be mediated by alcoholic beverage consumption. [[Purkinje cell]]s are especially susceptible to ethanol [[excitotoxicity]].<ref name="pmid20721919">{{cite journal | vauthors = Mostile G, Jankovic J | title = Alcohol in essential tremor and other movement disorders | journal = Movement Disorders | volume = 25 | issue = 14 | pages = 2274–2284 | date = October 2010 | pmid = 20721919 | doi = 10.1002/mds.23240 | s2cid = 39981956 }}</ref> Impairment of Purkinje synapses is a component of cerebellar degradation that could underlie essential tremor.<ref name="pmid20721919" /> Some cases have [[Lewy bodies]] in the [[locus ceruleus]].<ref>{{cite journal | vauthors = Louis ED | title = Essential tremors: a family of neurodegenerative disorders? | journal = Archives of Neurology | volume = 66 | issue = 10 | pages = 1202–1208 | date = October 2009 | pmid = 19822775 | pmc = 2762114 | doi = 10.1001/archneurol.2009.217 }}</ref><ref name="'Essential tremor' or 'the essentia"/><ref name=pmid18025031>{{cite journal | vauthors = Louis ED, Faust PL, Vonsattel JP, Honig LS, Rajput A, Robinson CA, Rajput A, Pahwa R, Lyons KE, Ross GW, Borden S, Moskowitz CB, Lawton A, Hernandez N | title = Neuropathological changes in essential tremor: 33 cases compared with 21 controls | journal = Brain | volume = 130 | issue = Pt 12 | pages = 3297–3307 | date = December 2007 | pmid = 18025031 | doi = 10.1093/brain/awm266 | doi-access = free }}</ref> ET cases that progress to Parkinson's disease are less likely to have had cerebellar problems.<ref name=pmid26336614>{{cite journal | vauthors = Ghika A, Kyrozis A, Potagas C, Louis ED | title = Motor and Non-motor Features: Differences between Patients with Isolated Essential Tremor and Patients with Both Essential Tremor and Parkinson's Disease | journal = Tremor and Other Hyperkinetic Movements | volume = 5 | pages = 335 | year = 2015 | pmid = 26336614 | pmc = 4548968 | doi = 10.7916/D83777WK }}</ref> Recent neuroimaging studies<ref>{{cite journal | vauthors = Benito-León J, Sanz-Morales E, Melero H, Louis ED, Romero JP, Rocon E, Malpica N | title = Graph theory analysis of resting-state functional magnetic resonance imaging in essential tremor | journal = Human Brain Mapping | volume = 40 | issue = 16 | pages = 4686–4702 | date = November 2019 | pmid = 31332912 | pmc = 6865733 | doi = 10.1002/hbm.24730 }}</ref> have suggested that the efficiency of the overall brain functional network in ET is disrupted.

Usually, the diagnosis is established on clinical grounds. Although ET was long considered a single-symptom illness, recent studies have shown that some patients also experience other additional motor symptoms and non-motor features.<ref name=":6">{{cite journal | vauthors = Louis ED, Lenka A | title = The Olivary Hypothesis of Essential Tremor: Time to Lay this Model to Rest? | journal = Tremor and Other Hyperkinetic Movements | volume = 7 | pages = 473 | date = 13 July 2017 | pmid = 28966877 | pmc = 5618117 | doi = 10.7916/D8FF40RX }}</ref> According to recent medical literature, besides isolated essential tremor, there are two additional classifications: 'ET plus' and 'ET-PD.' 'ET plus' is diagnosed when patients show cognitive impairments or other motor symptoms like [[ataxia]], [[dystonia]], or resting tremor. 'ET-PD' is used for those who meet the criteria for both ET and [[Parkinson's disease]].<ref name="The Pathophysiology and Treatment o">{{cite journal | vauthors = Kosmowska B, Wardas J | title = The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models | journal = Biomolecules | volume = 11 | issue = 12 | pages = 1813 | date = December 2021 | pmid = 34944457 | pmc = 8698799 | doi = 10.3390/biom11121813 | doi-access = free }}</ref> The clinical features of tremor in a patient include medical history (such as age of onset, family history, progression over time, and exposure to drugs or toxins), tremor characteristics (like which parts of the body are affected, when the tremor occurs, and its frequency), and any associated signs (such as signs of systemic illness, neurological signs, and soft signs). For some types of tremors, additional tests like recording tremor frequency, imaging for [[lesion]]s, receptor imaging, and biomarkers in blood or tissue may help identify the cause.<ref>{{cite journal | vauthors = Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, Raethjen J, Stamelou M, Testa CM, Deuschl G | title = Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society | journal = Movement Disorders | volume = 33 | issue = 1 | pages = 75–87 | date = January 2018 | pmid = 29193359 | pmc = 6530552 | doi = 10.1002/mds.27121 }}</ref> Tremors can start at any age, from birth through advanced ages (senile tremor).<ref>{{cite journal | vauthors = Louis ED, Dure LS, Pullman S | title = Essential tremor in childhood: a series of nineteen cases | journal = Movement Disorders | volume = 16 | issue = 5 | pages = 921–923 | date = September 2001 | pmid = 11746623 | doi = 10.1002/mds.1182 | s2cid = 30848508 }}</ref><ref>{{cite journal | vauthors = Bain PG, Findley LJ, Thompson PD, Gresty MA, Rothwell JC, Harding AE, Marsden CD | title = A study of hereditary essential tremor | journal = Brain | volume = 117 ( Pt 4) | issue = 4 | pages = 805–824 | date = August 1994 | pmid = 7922467 | doi = 10.1093/brain/117.4.805 }}</ref> Any [[voluntary muscle]] in the body may be affected, although the tremor is most commonly seen in the hands and arms and slightly less commonly in the [[neck]] (causing the person's head to shake), [[tongue]], and legs. A resting tremor of the hands is sometimes present.<ref name=pmid8334571/><ref>{{cite journal | vauthors = Cohen O, Pullman S, Jurewicz E, Watner D, Louis ED | title = Rest tremor in patients with essential tremor: prevalence, clinical correlates, and electrophysiologic characteristics | journal = Archives of Neurology | volume = 60 | issue = 3 | pages = 405–410 | date = March 2003 | pmid = 12633153 | doi = 10.1001/archneur.60.3.405 | doi-access = free }}</ref> Tremor occurring in the legs might be diagnosable as orthostatic tremor. Tremors in the lower limbs are quite rare in ET and are more likely to indicate Parkinson's disease.<ref>{{cite journal | vauthors = Rajalingam R, Breen DP, Chen R, Fox S, Kalia LV, Munhoz RP, Slow E, Strafella AP, Lang AE, Fasano A | title = The clinical significance of lower limb tremors | journal = Parkinsonism & Related Disorders | volume = 65 | pages = 165–171 | date = August 2019 | pmid = 31201091 | doi = 10.1016/j.parkreldis.2019.06.007 | hdl-access = free | hdl = 20.500.11820/fcbc5316-6d53-418f-ba3a-a73208c6f186 }}</ref>

"Focused Ultrasound" is a treatment that was approved for coverage in the U.S. in 2022 for those with Medicare insurance.  Totally non-surgical, the treatment process is performed on a conscious patient and takes 2 to 3 hours.

The first approach in helping people to improve tremor symptoms is the discontinuation of triggering and exacerbating factors like medications including certain antidepressants, anti-epileptics, beta-agonists; or substances like caffeine.<ref name=":1">{{cite journal | vauthors = Hopfner F, Deuschl G | title = Managing Essential Tremor | journal = Neurotherapeutics | volume = 17 | issue = 4 | pages = 1603–1621 | date = October 2020 | pmid = 32915385 | pmc = 7851235 | doi = 10.1007/s13311-020-00899-2 }}</ref> In addition, getting adequate sleep and utilizing relaxation techniques can also help improve and reduce tremor symptoms in individuals who reported an increase in tremors following physical activities.<ref name=":1" />

Since tremors can affect different parts of the body (like limbs, head, chin/jaw, and vocal),<ref name=":2">{{cite journal | vauthors = Wagle Shukla A | title = Diagnosis and Treatment of Essential Tremor | journal = Continuum | volume = 28 | issue = 5 | pages = 1333–1349 | date = October 2022 | pmid = 36222768 | doi = 10.1212/CON.0000000000001181 }}</ref> different non-pharmacological therapeutic techniques are available that can support patients with the management of tremors including occupational therapy, speech therapy, and psychotherapy.<ref name=":1" /> Occupational therapy provides support to help people manage everyday tasks more easily through different approaches and interventions.<ref name=":2" /> Speech therapy is helpful in people with vocal tremor to help manage and maintain the vocal changes associated with tremor symptoms. Psychological impacts like embarrassment and anxiety are also important concerns of many people with ET which can lead to social isolation and depression. Psychotherapy can be very beneficial and play a key role in helping people to improve the mental health of ET people.<ref name=":2" />

Alcohol had been known to help provide short-term relief of tremor symptoms in some people, however, the therapeutic effects of alcohol on ET had not been studied in many clinical trials. It has been proposed that alcohol can help reduce tremors through the agonism mechanism of the gamma-aminobutyric acid GABAergic.<ref>{{cite journal | vauthors = Ondo WG | title = Current and Emerging Treatments of Essential Tremor | journal = Neurologic Clinics | volume = 38 | issue = 2 | pages = 309–323 | date = May 2020 | pmid = 32279712 | doi = 10.1016/j.ncl.2020.01.002 }}</ref> Since GABA can decrease neural activity, it is believed that alcohol can increase the activity of GABA which then can reduce involuntary muscle movements or tremors. However, the duration of action of alcohol on ET is around 3–4 hours, alcohol also had been associated with the rebound of tremor, not to mention the risk of development of long-term alcohol consumption and abuse.<ref name=":0" /> The use of alcohol as a possible treatment for ET is not recommended by healthcare providers.

===Pharmacological Treatments===

|+Summary of main drugs used in pharmacological treatment of essential tremor<ref>{{cite journal | vauthors = Hedera P, Cibulčík F, Davis TL | title = Pharmacotherapy of essential tremor | journal = Journal of Central Nervous System Disease | volume = 5 | pages = 43–55 | date = December 2013 | pmid = 24385718 | pmc = 3873223 | doi = 10.4137/JCNSD.S6561 }}</ref><ref>{{cite journal | vauthors = Ondo WG | title = Current and Emerging Treatments of Essential Tremor | journal = Neurologic Clinics | volume = 38 | issue = 2 | pages = 309–323 | date = May 2020 | pmid = 32279712 | doi = 10.1016/j.ncl.2020.01.002 | series = Treatment of Movement Disorders }}</ref><ref>{{cite journal | vauthors = Alonso-Navarro H, García-Martín E, Agúndez JA, Jiménez-Jiménez FJ | title = Current and Future Neuropharmacological Options for the Treatment of Essential Tremor | journal = Current Neuropharmacology | volume = 18 | issue = 6 | pages = 518–537 | date = 2020-06-22 | pmid = 31976837 | pmc = 7457404 | doi = 10.2174/1570159X18666200124145743 }}</ref><ref name="The Pathophysiology and Treatment o"/>

! colspan="4" |'''First-line therapies'''

'''FDA-approved or supported by double-blinded, placebo-controlled studes (class I evidence)'''

|[[propranolol]]

|non-selective [[Beta blocker|β-adrenergic receptor antagonist]] (probable mechanism: antagonism at peripheral [[Beta-2 adrenergic receptor|β₂ receptors]])

|[[primidone]]

|[[topiramate]]

|[[gabapentin]], [[pregabalin]]

|[[alprazolam]], [[clonazepam]]

|[[atenolol]]

|[[nadolol]], [[sotalol]], [[indenolol]], [[artinolol]], [[timolol]]

|[[nimodipine]], [[flunarizine]], [[nicardipine]]

|[[clozapine]]

|[[Atypical antipsychotic|atypical antypsychotic]] (complex mechanism)

|[[olanzapine]], [[quetiapine]]

|atypical antypsychotics (complex mechanism)

[[File:Propranolol.svg|thumb|Chemical structure of Propranolol, one of the most effective medication for treating ET]]

When symptoms are sufficiently troublesome to warrant treatment, the first choice medication is [[propranolol]], a non-selective beta-blocker, which has been shown effective in reducing tremor by 70% in 50% of patients in clinical studies.<ref name=":7">{{cite journal | vauthors = Sharma S, Pandey S | title = Treatment of essential tremor: current status | journal = Postgraduate Medical Journal | volume = 96 | issue = 1132 | pages = 84–93 | date = February 2020 | pmid = 31575730 | doi = 10.1136/postgradmedj-2019-136647 }}</ref> Based on the guidelines from the American Academy of Neurology and the Italian Movement Disorders Association, propranolol is most effective in limb tremors, also there is little to no effect on head tremors. The recommended doses of propranolol range from 60 to 360&nbsp;mg daily, and it is based on the patient's specific factors.<ref name=":7" /> The commonly reported side effects of propranolol are bradycardia, bronchospasm, fatigue, and hypotension.<ref name=":8">{{cite journal | vauthors = Patel MD, Patel M, Jani R, Patel KG, Patel P, Gandhi SK | title = Essential Tremors: A Literature Review of Current Therapeutics | journal = Cureus | volume = 16 | issue = 5 | pages = e59451 | date = May 2024 | pmid = 38826876 | pmc = 11141324 | doi = 10.7759/cureus.59451 | doi-access = free }}</ref> In patients that have contraindicated comorbidities to propranolol, other beta-blockers such as [[Atenolol]], [[pindolol]], [[Sotalol]], and [[nadolol]] have shown some potential efficacy, but they are not very well studied and have limited evidence in their efficacy on the treatment of ET.<ref name=":0" />

Additional medications that have been reported to show efficacy in treating ET are [[gabapentin]], [[benzodiazepines]] such as [[alprazolam]], [[clonazepam]], and [[zonisamide]], and [[pregabalin]].<ref name=":0" /> However, most of the medications have limited evidence-based to support their clinical usage as treatments for ET. Some systematic reviews of medications for the treatment of ET have been conducted.  A 2017 review of [[topiramate]] found limited data and low-quality evidence to support its efficacy and the occurrence of treatment-limiting adverse effects,<ref>{{cite journal | vauthors = Bruno E, Nicoletti A, Quattrocchi G, Allegra R, Filippini G, Colosimo C, Zappia M | title = Topiramate for essential tremor | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 4 | pages = CD009683 | date = April 2017 | pmid = 28409827 | pmc = 6478240 | doi = 10.1002/14651858.CD009683.pub2 }}</ref> a 2017 review of [[zonisamide]] found insufficient information to assess efficacy and safety,<ref>{{cite journal | vauthors = Bruno E, Nicoletti A, Filippini G, Quattrocchi G, Colosimo C, Zappia M | title = Zonisamide for essential tremor | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 8 | pages = CD009684 | date = August 2017 | pmid = 28836659 | pmc = 6483684 | doi = 10.1002/14651858.CD009684.pub2 }}</ref> and a 2016 review of [[pregabalin]] determined the effects to be uncertain due to the low quality of evidence.<ref>{{cite journal | vauthors = Bruno E, Nicoletti A, Quattrocchi G, Filippini G, Colosimo C, Zappia M | title = Pregabalin for essential tremor | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | pages = CD009682 | date = October 2016 | pmid = 27763691 | pmc = 6461190 | doi = 10.1002/14651858.CD009682.pub2 }}</ref>

[[Botulinum toxin]] is a neurotoxin produced by a gram-positive, rod-shaped bacteria called [[Clostridium botulinum]]. BoNT works by inhibiting acetylcholine release at the presynaptic terminal by inactivating the SNARE proteins (SNAP-25), which interfere with muscle contraction.<ref>{{cite journal | vauthors = Anandan C, Jankovic J | title = Botulinum Toxin in Movement Disorders: An Update | journal = Toxins | volume = 13 | issue = 1 | pages = 42 | date = January 2021 | pmid = 33430071 | pmc = 7827923 | doi = 10.3390/toxins13010042 | doi-access = free }}</ref> BoNT type A injections have shown benefits in several clinical trials for the treatments of limb, voice, and head. However, the associated side effects included muscle weakness, stiffness reported within studies of limb tremors, and neck muscle pain, weakness, and dysphagia in clinical trials of head tremors.<ref name=":8" /> Botulinum toxin type A has been found to be helpful in treating voice tremors.<ref>{{cite journal | vauthors = Adler CH, Bansberg SF, Hentz JG, Ramig LO, Buder EH, Witt K, Edwards BW, Krein-Jones K, Caviness JN | title = Botulinum toxin type A for treating voice tremor | journal = Archives of Neurology | volume = 61 | issue = 9 | pages = 1416–1420 | date = September 2004 | pmid = 15364688 | doi = 10.1001/archneur.61.9.1416 }}</ref>

Additionally, [[MRI]]-guided [[high-intensity focused ultrasound]] is a nonsurgical treatment option for people with essential tremor who are medication refractory.<ref name=pmid28503363>{{cite journal | vauthors = Rohani M, Fasano A | title = Focused Ultrasound for Essential Tremor: Review of the Evidence and Discussion of Current Hurdles | journal = Tremor and Other Hyperkinetic Movements | volume = 7 | pages = 462 | year = 2017 | pmid = 28503363 | pmc = 5425801 | doi = 10.7916/D8Z89JN1 }}</ref><ref name=FDA2016>{{cite press release |title=FDA approves first MRI-guided focused ultrasound device to treat essential tremor |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-mri-guided-focused-ultrasound-device-treat-essential-tremor |archive-url=https://web.archive.org/web/20201108091524/https://www.fda.gov/news-events/press-announcements/fda-approves-first-mri-guided-focused-ultrasound-device-treat-essential-tremor |url-status=dead |archive-date=November 8, 2020 |publisher=FDA |date=24 March 2020 }}</ref> MRI-guided high-intensity focused ultrasound does not achieve healing, but can improve the quality of life by reducing the tremor manifestation.<ref name=FDA2016 /><ref>{{cite journal|date=2023|volume=9|issue=1|pages=17–20|doi=10.1515/cdbme-2023-1005|vauthors=Aharonson V, Postema M, Gebbie R, Van Der Merwe J, Schlesinger I|title=Sobel edge detection for quantifying the effectiveness of focused ultrasound thalamotomy for tremor relief|journal=Current Directions in Biomedical Engineering|doi-access=free}}</ref> While its long-term effects are not yet established, the improvement in tremor score from baseline was durable at 1 year and 2 years following the treatment.<ref name=pmid29265546>{{cite journal | vauthors = Chang JW, Park CK, Lipsman N, Schwartz ML, Ghanouni P, Henderson JM, Gwinn R, Witt J, Tierney TS, Cosgrove GR, Shah BB, Abe K, Taira T, Lozano AM, Eisenberg HM, Fishman PS, Elias WJ | title = A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up | journal = Annals of Neurology | volume = 83 | issue = 1 | pages = 107–114 | date = January 2018 | pmid = 29265546 | doi = 10.1002/ana.25126 | s2cid = 4437809 | url = https://ir.ymlib.yonsei.ac.kr/handle/22282913/161679 }}</ref> To date, reported adverse events and side effects have been mild to moderate. Possible adverse events include gait difficulties, balance disturbances, [[paresthesia]]s, [[headache]], skin burns with ulcerations, skin retraction, scars, and blood clots.<ref name=pmid28503363/><ref name="FDA2016" /><ref name="Hedera2017">{{cite journal | vauthors = Hedera P | title = Emerging strategies in the management of essential tremor | journal = Therapeutic Advances in Neurological Disorders | volume = 10 | issue = 2 | pages = 137–148 | date = February 2017 | pmid = 28382111 | pmc = 5367648 | doi = 10.1177/1756285616679123 | type = Review }}</ref> This procedure is contraindicated in pregnant women, persons who have non-MRI compatible implanted metallic devices, allergy to MR contrast agents, cerebrovascular disease, abnormal bleeding, hemorrhage and/or blood clotting disorders, advanced kidney disease or on dialysis, heart conditions, severe hypertension, and ethanol or substance abuse, among others.<ref name="FDA2016" /> The US Food and Drug Administration ([[Food and Drug Administration|FDA]]) approved Insightec's Exablate Neuro system to treat essential tremor in 2016.<ref name="FDA2016" />

Another nonsurgical treatment option that has been suggested as a less invasive alternative to DBS is electrically stimulating the peripheral limbs most affected by ET.<ref>{{Cite journal |last1=Toglia |first1=J. U. |last2=Izzo |first2=K. |date=1985-03-01 |title=Treatment of myoclonic dystonia with transcutaneous electrical nerve stimulation |url=https://doi.org/10.1007/BF02229221 |journal=The Italian Journal of Neurological Sciences |volume=6 |issue=1 |pages=75–78 |doi=10.1007/BF02229221 |pmid=3873445 |issn=1126-5442}}</ref><ref>{{Cite journal |last=Shukla |first=Aparna Wagle |date=2022-06-14 |title=Rationale and Evidence for Peripheral Nerve Stimulation for Treating Essential Tremor |journal=Tremor and Other Hyperkinetic Movements |volume=12 |issue=1 |article-number=20 |doi=10.5334/tohm.685 |doi-access=free |issn=2160-8288 |pmc=9205368 |pmid=35949227}}</ref> This stimulation has been explored using different stimulation intensities, either above the motoneuron activation threshold (thus directly activating the muscles in peripheral limbs), or below the motoneuron activation threshold but above the sensory afferent neuron threshold. While electrical stimulation above the activation motoneuron threshold can reduce tremor by up to 73%,<ref>{{Cite journal |last1=Dosen |first1=Strahinja |last2=Muceli |first2=Silvia |last3=Dideriksen |first3=Jakob Lund |last4=Romero |first4=Juan Pablo |last5=Rocon |first5=Eduardo |last6=Pons |first6=Jose |last7=Farina |first7=Dario |date=May 2015 |title=Online Tremor Suppression Using Electromyography and Low-Level Electrical Stimulation |journal=IEEE Transactions on Neural Systems and Rehabilitation Engineering |volume=23 |issue=3 |pages=385–395 |doi=10.1109/TNSRE.2014.2328296 |pmid=25051555 |bibcode=2015ITNSR..23..385D |hdl=10261/129838 |issn=1558-0210}}</ref><ref>{{Cite journal |last1=Javidan |first1=Manouchehr |last2=Elek |first2=Josef |last3=Prochazka |first3=Arthur |date=1992-03-01 |title=Attenuation of pathological tremors by functional electrical stimulation II: Clinical evaluation |url=https://doi.org/10.1007/BF02368522 |journal=Annals of Biomedical Engineering |volume=20 |issue=2 |pages=225–236 |doi=10.1007/BF02368522 |pmid=1575378 |issn=1573-9686}}</ref><ref>{{Cite journal |last1=Popović Maneski |first1=Lana |last2=Jorgovanović |first2=Nikola |last3=Ilić |first3=Vojin |last4=Došen |first4=Strahinja |last5=Keller |first5=Thierry |last6=Popović |first6=Mirjana B. |last7=Popović |first7=Dejan B. |date=2011-10-01 |title=Electrical stimulation for the suppression of pathological tremor |url=https://doi.org/10.1007/s11517-011-0803-6 |journal=Medical & Biological Engineering & Computing |volume=49 |issue=10 |pages=1187–1193 |doi=10.1007/s11517-011-0803-6 |issn=1741-0444}}</ref><ref>{{Cite journal |last1=Bó |first1=Antônio Padilha Lanari |last2=Azevedo-Coste |first2=Christine |last3=Geny |first3=Christian |last4=Poignet |first4=Philippe |last5=Fattal |first5=Charles |date=2014 |title=On the Use of Fixed-Intensity Functional Electrical Stimulation for Attenuating Essential Tremor |url=https://onlinelibrary.wiley.com/doi/abs/10.1111/aor.12261 |journal=Artificial Organs |volume=38 |issue=11 |pages=984–991 |doi=10.1111/aor.12261 |pmid=24571719 |issn=1525-1594}}</ref> it causes muscle fatigue and discomfort. Stimulating below the motoneuron activation threshold on the other hand requires precise timing to counteract the descending pathological neuronal signals driving ET in the peripheral limbs.<ref>{{Cite journal |last1=Metzner |first1=Christian |last2=Stringham |first2=Adam |last3=Hislop |first3=Brenna |last4=Bonham |first4=Joseph |last5=Chatterton |first5=Larrisa |last6=DeFigueiredo |first6=Ryan |last7=Charles |first7=Steven K. |date=2023 |title=Brief Submotor-Threshold Electrical Stimulation Applied Synchronously Over Wrist Flexor and Extensor Muscles does Not Suppress Essential Tremor, Independent of Stimulation Frequency |journal=Tremor and Other Hyperkinetic Movements (New York, N.Y.) |volume=13 |article-number=30 |doi=10.5334/tohm.740 |doi-access=free |issn=2160-8288 |pmc=10473161 |pmid=37663530}}</ref> Thus, while this treatment option shows promise it still requires rigorous investigation.

Essential tremor (ET) is a common neurological disorder, affecting up to 5% of the global population, with approximately 24.91 million people affected worldwide in 2020.<ref name=":4">{{cite journal | vauthors = Song P, Zhang Y, Zha M, Yang Q, Ye X, Yi Q, Rudan I | title = The global prevalence of essential tremor, with emphasis on age and sex: A meta-analysis | journal = Journal of Global Health | volume = 11 | article-number = 04028 | date = April 2021 | pmid = 33880180 | pmc = 8035980 | doi = 10.7189/jogh.11.04028 }}</ref> The prevalence of ET increases significantly with age, particularly in individuals aged 60 and above.<ref name=":4" /> It affects around 4% of people aged 40 and older, and the [[prevalence]] rises to 2.87% in those over 80, reaching up to 20% in individuals in their 90s and beyond.<ref>{{cite journal | vauthors = Louis ED, Ferreira JJ | title = How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor | journal = Movement Disorders | volume = 25 | issue = 5 | pages = 534–541 | date = April 2010 | pmid = 20175185 | doi = 10.1002/mds.22838 }}</ref> ET is more common in males than females across all age groups.<ref name=":4" />

Family history plays a significant role in the development of ET, with around 50% of cases being [[Heredity|hereditary]] and a 90% [[Concordance (genetics)|concordance]] rate in identical twins.<ref name=":5">{{cite book | vauthors = Agarwal S, Biagioni MC | chapter = Essential Tremor |date=2024 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK499986/ |access-date=2024-07-29 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29763162 }}</ref> While the likelihood of developing ET increases with age, it can also occur in younger individuals, especially if there is a family history of the disorder.<ref name=":5" /> ET is one of the most common types of tremor, aside from enhanced [[Physiologic tremor|physiological tremor]], and is among the most frequently observed [[movement disorder]]s.<ref>{{cite journal | vauthors = Benito-León J, Louis ED | title = Essential tremor: emerging views of a common disorder | journal = Nature Clinical Practice. Neurology | volume = 2 | issue = 12 | pages = 666–78; quiz 2p following 691 | date = December 2006 | pmid = 17117170 | doi = 10.1038/ncpneuro0347 }}</ref> Although not all studies show this trend, i.e. the majority of studies (70%) indicate that there are no sex differences in prevalence.<ref>{{Cite journal |last1=Louis |first1=Elan D. |last2=McCreary |first2=Morgan |date=2021 |title=How Common is Essential Tremor? Update on the Worldwide Prevalence of Essential Tremor |journal=Tremor and Other Hyperkinetic Movements |volume=11 |article-number=28 |doi=10.5334/tohm.632 |doi-access=free |issn=2160-8288 |pmc=8269764 |pmid=34277141}}</ref>