Editing Essential tremor (section)

==Cause==
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>

'''<big>Cerebellar</big>'''

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.

===Genetic===
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>

===Poisons and toxins===
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 }}</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>