Editing Ataxia (section)

== Causes ==
The three types of ataxia have overlapping causes, so can either coexist or occur in isolation. Cerebellar ataxia can have many causes despite normal neuroimaging.<ref>{{Cite web |title=Ataxia: What It Is, Causes, Symptoms, Treatment & Types |url=https://my.clevelandclinic.org/health/symptoms/17748-ataxia |access-date=2024-02-08 |website=Cleveland Clinic |language=en}}</ref>

=== Focal lesions ===
Any type of focal lesion of the [[central nervous system]] (such as [[stroke]], [[brain tumor]], [[multiple sclerosis]], inflammatory [such as [[sarcoidosis]]], and "chronic lymphocytyc inflammation with pontine perivascular enhancement responsive to steroids syndrome" [CLIPPERS<ref>{{cite journal | vauthors = Maenhoudt W, Ramboer K, Maqueda V | title = A Rare Cause of Dizziness and Gait Ataxia: CLIPPERS Syndrome | journal = Journal of the Belgian Society of Radiology | volume = 100 | issue = 1 | pages = 20 | date = February 2016 | pmid = 30151443 | pmc = 6102946 | doi = 10.5334/jbr-btr.997 | doi-access = free }}</ref>]) will cause the type of ataxia corresponding to the site of the lesion: cerebellar if in the cerebellum; sensory if in the dorsal spinal cord...to include cord compression by thickened ligamentum flavum or stenosis of the boney spinal canal...(and rarely in the [[thalamus]] or [[parietal lobe]]); or vestibular if in the vestibular system (including the vestibular areas of the [[cerebral cortex]]).{{citation needed|date=August 2021}}

=== Exogenous substances (metabolic ataxia) ===
[[Exogenous]] substances that cause ataxia mainly do so because they have a depressant effect on central nervous system function. The most common example is [[ethanol]] (alcohol), which is capable of causing reversible cerebellar and vestibular ataxia. Chronic intake of [[ethanol]] causes atrophy of the [[cerebellum]] by oxidative and endoplasmic reticulum stresses induced by [[thiamine]] deficiency.<ref name="pmid34444449">{{cite journal | vauthors = Mitoma H, Manto M, Shaikh AG | title = Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum | journal = International Journal of Environmental Research and Public Health | volume = 18 | issue = 16 | pages = 8678 | date = August 2021 | pmid = 34444449 | pmc = 8391842 | doi = 10.3390/ijerph18168678 | doi-access = free }}</ref>

Other examples include various prescription drugs (e.g. most [[antiepileptic drugs]] have cerebellar ataxia as a possible [[adverse effect (medicine)|adverse effect]]), Lithium level over 1.5mEq/L, [[synthetic cannabinoid]] [[Dexanabinol|HU-211]] ingestion<ref name="Inadvertent Ingestion of Marijuana --- Los Angeles, California, 2009">{{cite web |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5834a2.htm?s_cid=mm5834a2 |title=Inadvertent Ingestion of Marijuana --- Los Angeles, California, 2009 |access-date=3 September 2009 |url-status=live |archive-url=https://web.archive.org/web/20110511211253/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5834a2.htm?s_cid=mm5834a2 |archive-date=11 May 2011}}</ref> and various other medical and recreational drugs (e.g. [[ketamine]], [[Phencyclidine|PCP]] or [[dextromethorphan]], all of which are [[NMDA receptor antagonist]]s that produce a dissociative state at high doses). A further class of pharmaceuticals which can cause short term ataxia, especially in high doses, are [[benzodiazepine]]s.<ref name="pmid817697">{{cite journal | vauthors = Browne TR | title = Clonazepam. A review of a new anticonvulsant drug | journal = Archives of Neurology | volume = 33 | issue = 5 | pages = 326–332 | date = May 1976 | pmid = 817697 | doi = 10.1001/archneur.1976.00500050012003 }}</ref><ref name="pmid1888441">{{cite journal | vauthors = Gaudreault P, Guay J, Thivierge RL, Verdy I | title = Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment | journal = Drug Safety | volume = 6 | issue = 4 | pages = 247–265 | year = 1991 | pmid = 1888441 | doi = 10.2165/00002018-199106040-00003 | s2cid = 27619795 }}</ref> Exposure to high levels of [[methylmercury]], through consumption of fish with high [[Mercury (element)|mercury]] concentrations, is also a known cause of ataxia and other [[neurological disorders]].<ref name="pmid19253038">{{cite book | vauthors = Díez S | chapter = Human Health Effects of Methylmercury Exposure | title = Reviews of Environmental Contamination and Toxicology Volume 198 | volume = 198 | pages = 111–32 | year = 2009 | pmid = 19253038 | doi = 10.1007/978-0-387-09647-6_3 | isbn = 978-0-387-09646-9 }}</ref>

=== Radiation poisoning ===
Ataxia can be induced as a result of severe [[Acute radiation syndrome|acute radiation poisoning]] with an absorbed dose of more than 30 [[Gray (unit)|grays]].<ref>{{cite web |title=Radiation Exposure and Contamination - Injuries; Poisoning |url=https://www.merckmanuals.com/professional/injuries-poisoning/radiation-exposure-and-contamination/radiation-exposure-and-contamination |website=Merck Manuals Professional Edition |access-date=26 December 2022}}</ref> Furthermore, those with [[Ataxia–telangiectasia|ataxia telangiectasia]] may have a high sensitivity towards [[gamma ray]]s and [[x-ray]]s.<ref>{{cite journal | vauthors = Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM | title = Ataxia telangiectasia: a review | journal = Orphanet Journal of Rare Diseases | volume = 11 | issue = 1 | pages = 159 | date = November 2016 | pmid = 27884168 | pmc = 5123280 | doi = 10.1186/s13023-016-0543-7 |doi-access=free}}</ref>

=== Vitamin B<sub>12</sub> deficiency ===
[[Vitamin B12 deficiency|Vitamin B<sub>12</sub> deficiency]] may cause, among several neurological abnormalities, overlapping cerebellar and sensory ataxia.<ref>{{cite journal | vauthors = Crawford JR, Say D | title = Vitamin B12 deficiency presenting as acute ataxia | journal = BMJ Case Reports | volume = 2013 | pages = bcr2013008840 | date = March 2013 | pmid = 23536622 | pmc = 3618829 | doi = 10.1136/bcr-2013-008840 }}</ref> Neuropsychological symptoms may include sense loss, difficulty in [[proprioception]], poor balance, loss of sensation in the feet, changes in [[reflex]]es, dementia, and [[psychosis]], which can be reversible with treatment.<ref>{{cite journal | vauthors = Osimani A, Berger A, Friedman J, Porat-Katz BS, Abarbanel JM | title = Neuropsychology of vitamin B12 deficiency in elderly dementia patients and control subjects | journal = Journal of Geriatric Psychiatry and Neurology | volume = 18 | issue = 1 | pages = 33–38 | date = March 2005 | pmid = 15681626 | doi = 10.1177/0891988704272308 | s2cid = 29983253 }}</ref> Complications may include a neurological complex known as [[subacute combined degeneration of spinal cord]], and other neurological disorders.<ref>{{cite book | vauthors = Qudsiya Z, De Jesus O | chapter = Subacute Combined Degeneration of the Spinal Cord |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK559316/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32644742 |access-date=2022-07-17 }}</ref>

=== Hypothyroidism ===
Symptoms of neurological dysfunction may be the presenting feature in some patients with [[hypothyroidism]]. These include reversible [[cerebellar ataxia]], [[dementia]], [[peripheral neuropathy]], [[psychosis]] and [[coma]]. Most of the neurological complications improve completely after [[thyroid hormone]] replacement therapy.<ref name="isbn0-07-149992-X">{{cite book |vauthors=Victor M, Ropper AH, Adams RD, Samuels M | title = Adams and Victor's Principles of Neurology | edition = Ninth  | publisher = McGraw-Hill Medical | year = 2009 | pages = 78–88 | isbn = 978-0-07-149992-7 }}</ref><ref name="Pavan_2012">{{cite journal| vauthors =Pavan MR, Deepak M, Basavaprabhu A, Gupta A| year =2012| title =Doctor i am swaying – An interesting case of ataxia| journal =Journal of Clinical and Diagnostic Research| url =http://www.jcdr.net/article_fulltext.asp?issn=0973-709x&year=2012&volume=6&issue=4&page=702&issn=0973-709x&id=2120| access-date =2 May 2013| url-status =live| archive-url =https://web.archive.org/web/20140508025330/http://www.jcdr.net/article_fulltext.asp?issn=0973-709x&year=2012&volume=6&issue=4&page=702&issn=0973-709x&id=2120| archive-date =8 May 2014}}</ref>

=== Causes of isolated sensory ataxia ===
[[Peripheral neuropathy|Peripheral neuropathies]] may cause generalised or localised sensory ataxia (e.g. a limb only) depending on the extent of the neuropathic involvement. Spinal disorders of various types may cause sensory ataxia from the lesioned level below, when they involve the dorsal columns.<ref>{{cite journal | vauthors = Spinazzi M, Angelini C, Patrini C | title = Subacute sensory ataxia and optic neuropathy with thiamine deficiency | journal = Nature Reviews. Neurology | volume = 6 | issue = 5 | pages = 288–293 | date = May 2010 | pmid = 20308997 | doi = 10.1038/nrneurol.2010.16 | s2cid = 12333200 }}</ref><ref>{{cite journal | vauthors = Sghirlanzoni A, Pareyson D, Lauria G | title = Sensory neuron diseases | journal = The Lancet. Neurology | volume = 4 | issue = 6 | pages = 349–361 | date = June 2005 | pmid = 15907739 | doi = 10.1016/S1474-4422(05)70096-X | s2cid = 35053543 }}</ref><ref>{{cite journal | vauthors = Moeller JJ, Macaulay RJ, Valdmanis PN, Weston LE, Rouleau GA, Dupré N | title = Autosomal dominant sensory ataxia: a neuroaxonal dystrophy | journal = Acta Neuropathologica | volume = 116 | issue = 3 | pages = 331–336 | date = September 2008 | pmid = 18347805 | doi = 10.1007/s00401-008-0362-6 | s2cid = 22881684 }}</ref>

=== Non-hereditary cerebellar degeneration ===
Non-hereditary causes of cerebellar degeneration include chronic [[alcohol use disorder]], [[head injury]], [[paraneoplastic cerebellar degeneration|paraneoplastic]] and non-paraneoplastic [[autoimmunity|autoimmune]] ataxia,<ref name="Medusa head ataxia - Part 1">{{cite journal | vauthors = Jarius S, Wildemann B | title = 'Medusa-head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: Anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1 and anti-CARP VIII | journal = Journal of Neuroinflammation | volume = 12 | issue = 1 | pages = 166 | date = September 2015 | pmid = 26377085 | pmc = 4574226 | doi = 10.1186/s12974-015-0356-y | doi-access = free }}</ref><ref name="Medusa head ataxia - Part 2">{{cite journal | vauthors = Jarius S, Wildemann B | title = 'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC | journal = Journal of Neuroinflammation | volume = 12 | issue = 1 | pages = 167 | date = September 2015 | pmid = 26377184 | pmc = 4574118 | doi = 10.1186/s12974-015-0357-x | doi-access = free }}</ref><ref name="Medusa head ataxia - Part 3">{{cite journal | vauthors = Jarius S, Wildemann B | title = 'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook | journal = Journal of Neuroinflammation | volume = 12 | issue = 1 | pages = 168 | date = September 2015 | pmid = 26377319 | pmc = 4573944 | doi = 10.1186/s12974-015-0358-9 | doi-access = free }}</ref> [[high-altitude cerebral edema]],<ref name="Sharma_2019">{{cite journal | vauthors = Sharma R, Cramer NP, Perry B, Adahman Z, Murphy EK, Xu X, Dardzinski BJ, Galdzicki Z, Perl DP, Dickstein DL, Iacono D | title = Chronic Exposure to High Altitude: Synaptic, Astroglial and Memory Changes | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 16406 | date = November 2019 | pmid = 31712561 | pmc = 6848138 | doi = 10.1038/s41598-019-52563-1 | bibcode = 2019NatSR...916406S }}</ref> [[celiac disease]],<ref name="Hermaszewski_1991">{{cite journal | vauthors = Hermaszewski RA, Rigby S, Dalgleish AG | title = Coeliac disease presenting with cerebellar degeneration | journal = Postgraduate Medical Journal | volume = 67 | issue = 793 | pages = 1023–1024 | date = November 1991 | pmid = 1775412 | pmc = 2399130 | doi = 10.1136/pgmj.67.793.1023 }}</ref> [[normal-pressure hydrocephalus]],<ref name="Lv_2022">{{cite journal | vauthors = Lv M, Yang X, Zhou X, Chen J, Wei H, Du D, Lin H, Xia J | title = Gray matter volume of cerebellum associated with idiopathic normal pressure hydrocephalus: A cross-sectional analysis | journal = Frontiers in Neurology | volume = 13 | pages = 922199 | date = 2022-09-07 | pmid = 36158963 | pmc = 9489844 | doi = 10.3389/fneur.2022.922199 | doi-access = free }}</ref> and infectious or post-infectious [[Post viral cerebellar ataxia|cerebellitis]].<ref name="Parvez_2022">{{cite journal | vauthors = Parvez MS, Ohtsuki G | title = Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology | journal = Brain Sciences | volume = 12 | issue = 3 | page = 367 | date = March 2022 | pmid = 35326323 | pmc = 8946185 | doi = 10.3390/brainsci12030367 | doi-access = free }}</ref>

=== Hereditary ataxias ===
Ataxia may depend on [[hereditary]] disorders consisting of degeneration of the cerebellum or of the spine; most cases feature both to some extent, and therefore present with overlapping cerebellar and sensory ataxia, even though one is often more evident than the other. Hereditary disorders causing ataxia include [[autosomal dominant]] ones such as [[spinocerebellar ataxia]], [[episodic ataxia]], and [[dentatorubropallidoluysian atrophy]], as well as [[autosomal recessive]] disorders such as [[Friedreich's ataxia]] (sensory and cerebellar, with the former predominating) and [[Niemann–Pick disease]], [[ataxia–telangiectasia]] (sensory and cerebellar, with the latter predominating), autosomal recessive spinocerebellar ataxia-14<ref>{{cite journal | vauthors = Sait H, Moirangthem A, Agrawal V, Phadke SR | title = Autosomal recessive spinocerebellar ataxia-20 due to a novel SNX14 variant in an Indian girl | journal = American Journal of Medical Genetics. Part A | volume = 188 | issue = 6 | pages = 1909–1914 | date = June 2022 | pmid = 35195341 | doi = 10.1002/ajmg.a.62701 | s2cid = 247058153 }}</ref> and [[abetalipoproteinaemia]]. An example of X-linked ataxic condition is the rare [[fragile X-associated tremor/ataxia syndrome]] or FXTAS.

=== Arnold–Chiari malformation (congenital ataxia) ===
[[Arnold–Chiari malformation]] is a malformation of the [[Human brain|brain]]. It consists of a downward displacement of the [[cerebellar tonsils]] and the [[medulla oblongata|medulla]] through the [[foramen magnum]], sometimes causing [[hydrocephalus]] as a result of obstruction of [[cerebrospinal fluid]] outflow.<ref>{{cite journal | vauthors = Langridge B, Phillips E, Choi D | title = Chiari Malformation Type 1: A Systematic Review of Natural History and Conservative Management | journal = World Neurosurgery | volume = 104 | pages = 213–219 | date = August 2017 | pmid = 28435116 | doi = 10.1016/j.wneu.2017.04.082 | url = https://discovery.ucl.ac.uk/id/eprint/1555498/ }}</ref>

=== Succinic semialdehyde dehydrogenase deficiency ===
[[Succinic semialdehyde dehydrogenase deficiency]] is an [[autosomal]]-[[recessive gene]] disorder where mutations in the ALDH5A1 gene results in the accumulation of [[gamma-Hydroxybutyric acid]] (GHB) in the body. GHB accumulates in the nervous system and can cause ataxia as well as other [[neurological]] dysfunction.<ref name="urlSSADH ">{{cite journal | vauthors = Parviz M, Vogel K, Gibson KM, Pearl PL | title = Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies | journal = Journal of Pediatric Epilepsy | volume = 3 | issue = 4 | pages = 217–227 | date = November 2014 | pmid = 25485164 | pmc = 4256671 | doi = 10.3233/PEP-14097 }}</ref>

=== Wilson's disease ===
[[Wilson's disease]] is an [[autosomal]]-[[recessive gene]] disorder whereby an alteration of the ATP7B gene results in an inability to properly excrete [[copper]] from the body.<ref name="urlwww.birminghammodis.com">{{cite web|url=http://www.birminghammodis.com/handbook/Chapter12.pdf |title=Wilson's Disease | vauthors = Walshe JM | veditors = Clarke CE, Nicholl DJ |work=Birmingham Movement Disorders Coursebook |url-status=dead |archive-url= https://web.archive.org/web/20110910171019/http://www.birminghammodis.com/handbook/Chapter12.pdf |archive-date=10 September 2011}}</ref> Copper accumulates in the [[liver]] and raises the toxicity levels in the nervous system causing demyelination of the nerves.<ref>{{cite journal | vauthors = Ortiz JF, Morillo Cox Á, Tambo W, Eskander N, Wirth M, Valdez M, Niño M | title = Neurological Manifestations of Wilson's Disease: Pathophysiology and Localization of Each Component | journal = Cureus | volume = 12 | issue = 11 | pages = e11509 | date = November 2020 | pmid = 33354453 | pmc = 7744205 | doi = 10.7759/cureus.11509 |doi-access=free}}</ref> This can cause ataxia as well as other [[neurological]] and organ impairments.<ref name="urlWilsons disease2">{{cite web |title=Wilson's disease – PubMed Health |url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001789/ |url-status=live |archive-url=https://web.archive.org/web/20140727172514/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001789/ |archive-date=27 July 2014 |work=PubMed Health |vauthors=Haldeman-Englert C}}</ref>

=== Gluten ataxia ===
[[File:Gluten ataxia eng.ogg|thumb|A male with gluten ataxia: previous situation and evolution after three months of a gluten-free diet]]
Gluten ataxia is an [[autoimmune disease]] derived from [[celiac disease]],<ref>{{cite journal | vauthors = Giuffrè M, Gazzin S, Zoratti C, Llido JP, Lanza G, Tiribelli C, Moretti R | title = Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation | journal = International Journal of Molecular Sciences | volume = 23 | issue = 24 | pages = 15564 | date = December 2022 | pmid = 36555205 | pmc = 9779232 | doi = 10.3390/ijms232415564 |doi-access=free}}</ref> which is triggered by the ingestion of [[gluten]].<ref name="MitomaAdhikari2016">{{cite journal | vauthors = Mitoma H, Adhikari K, Aeschlimann D, Chattopadhyay P, Hadjivassiliou M, Hampe CS, Honnorat J, Joubert B, Kakei S, Lee J, Manto M, Matsunaga A, Mizusawa H, Nanri K, Shanmugarajah P, Yoneda M, Yuki N | title = Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias | journal = Cerebellum | volume = 15 | issue = 2 | pages = 213–232 | date = April 2016 | pmid = 25823827 | pmc = 4591117 | doi = 10.1007/s12311-015-0664-x | type = Review }}</ref><ref name="sapone-etal-2010-b">{{cite journal | vauthors = Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, Kaukinen K, Rostami K, Sanders DS, Schumann M, Ullrich R, Villalta D, Volta U, Catassi C, Fasano A | title = Spectrum of gluten-related disorders: consensus on new nomenclature and classification | journal = BMC Medicine | volume = 10 | pages = 13 | date = February 2012 | pmid = 22313950 | pmc = 3292448 | doi = 10.1186/1741-7015-10-13 | doi-access = free | type = Review }}</ref> Early diagnosis and treatment with a [[gluten-free diet]] can improve ataxia and prevent its progression. The effectiveness of the treatment depends on the elapsed time from the onset of the ataxia until diagnosis, because the death of [[Purkinje cells|neurons in the cerebellum]] as a result of gluten exposure is irreversible.<ref name="MitomaAdhikari2016" /><ref name="HadjivassiliouSanders2015" /> It accounts for 40% of ataxias of unknown origin and 15% of all ataxias.<ref name="HadjivassiliouSanders2015">{{cite journal | vauthors = Hadjivassiliou M, Sanders DD, Aeschlimann DP | title = Gluten-related disorders: gluten ataxia | journal = Digestive Diseases | volume = 33 | issue = 2 | pages = 264–268 | year = 2015 | pmid = 25925933 | doi = 10.1159/000369509 | type = Review | s2cid = 207673823 }}</ref> Less than 10% of people with gluten ataxia present any gastrointestinal symptom and only about 40% have intestinal damage.<ref name="MitomaAdhikari2016" /><ref name="HadjivassiliouSanders2015" /> This entity is classified into primary auto-immune cerebellar ataxias (PACA).<ref>{{cite journal | vauthors = Hadjivassiliou M, Graus F, Honnorat J, Jarius S, Titulaer M, Manto M, Hoggard N, Sarrigiannis P, Mitoma H | title = Diagnostic Criteria for Primary Autoimmune Cerebellar Ataxia-Guidelines from an International Task Force on Immune-Mediated Cerebellar Ataxias | journal = Cerebellum | volume = 19 | issue = 4 | pages = 605–610 | date = August 2020 | pmid = 32328884 | pmc = 7351847 | doi = 10.1007/s12311-020-01132-8 }}</ref> There is a continuum between presymptomatic ataxia and immune ataxias with clinical deficits.<ref>{{cite journal | vauthors = Manto M, Mitoma H | title = Immune Ataxias: The Continuum of Latent Ataxia, Primary Ataxia and Clinical Ataxia | journal = Journal of Integrative Neuroscience | volume = 23 | issue = 79 | date = April 2024 | page = 79 | doi = 10.31083/j.jin2304079 | doi-access = free | pmid = 38682229 }}</ref>

=== Potassium pump ===
Malfunction of the [[sodium-potassium pump]] may be a factor in some ataxias. The {{chem2|Na+/K+}} pump has been shown to control and set the intrinsic activity mode of [[cerebellar]] [[Purkinje neurons]].<ref>{{cite journal | vauthors = Forrest MD, Wall MJ, Press DA, Feng J | title = The sodium-potassium pump controls the intrinsic firing of the cerebellar Purkinje neuron | journal = PLOS ONE | volume = 7 | issue = 12 | pages = e51169 | date = December 2012 | pmid = 23284664 | pmc = 3527461 | doi = 10.1371/journal.pone.0051169 | doi-access = free | bibcode = 2012PLoSO...751169F }}</ref> This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computational element in the [[cerebellum]] and the [[brain]].<ref>{{cite journal | vauthors = Forrest MD | title = The sodium-potassium pump is an information processing element in brain computation | journal = Frontiers in Physiology | volume = 5 | issue = 472 | pages = 472 | date = December 2014 | pmid = 25566080 | pmc = 4274886 | doi = 10.3389/fphys.2014.00472 | doi-access = free }}</ref> Indeed, a [[ouabain]] block of {{chem2|Na+/K+}} pumps in the cerebellum of a live [[mouse]] results in it displaying ataxia and [[dystonia]].<ref>{{cite journal | vauthors = Calderon DP, Fremont R, Kraenzlin F, Khodakhah K | title = The neural substrates of rapid-onset Dystonia-Parkinsonism | journal = Nature Neuroscience | volume = 14 | issue = 3 | pages = 357–365 | date = March 2011 | pmid = 21297628 | pmc = 3430603 | doi = 10.1038/nn.2753 }}</ref> Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations.

=== Cerebellar ataxia associated with anti-GAD antibodies ===
Antibodies against the enzyme glutamic acid decarboxylase (GAD: enzyme changing glutamate into GABA) cause cerebellar deficits.<ref>{{cite journal | vauthors = Mitoma H, Manto M, Hampe CS | title = Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias | journal = Journal of Immunology Research | volume = 2017 | pages = 2913297 | date = 2017 | pmid = 28386570 | pmc = 5366212 | doi = 10.1155/2017/2913297 | doi-access = free }}</ref> The antibodies impair motor learning and cause behavioral deficits.<ref>{{cite journal | vauthors = Manto M, Honnorat J, Hampe CS, Guerra-Narbona R, López-Ramos JC, Delgado-García JM, Saitow F, Suzuki H, Yanagawa Y, Mizusawa H, Mitoma H | title = Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions | journal = Frontiers in Behavioral Neuroscience | volume = 9 | pages = 78 | date = 2015 | pmid = 25870548 | pmc = 4375997 | doi = 10.3389/fnbeh.2015.00078 | doi-access = free }}</ref>
[[Glutamate decarboxylase|GAD antibodies]] related ataxia is part of the group called immune-mediated cerebellar ataxias.<ref>{{cite journal | vauthors = Mitoma H, Manto M, Hampe CS | title = Immune-mediated Cerebellar Ataxias: Practical Guidelines and Therapeutic Challenges | journal = Current Neuropharmacology | volume = 17 | issue = 1 | pages = 33–58 | date = 2019 | pmid = 30221603 | pmc = 6341499 | doi = 10.2174/1570159X16666180917105033 }}</ref> The antibodies induce a synaptopathy.<ref>{{cite journal | vauthors = Mitoma H, Honnorat J, Yamaguchi K, Manto M | title = Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias | journal = International Journal of Molecular Sciences | volume = 21 | issue = 14 | pages = E4936 | date = July 2020 | pmid = 32668612 | pmc = 6341499 | doi = 10.3390/ijms21144936 | doi-access = free }}</ref> The cerebellum is particularly vulnerable to autoimmune disorders.<ref>{{cite journal | vauthors = Mitoma H, Manto M, Hadjivassiliou M | title = Immune-Mediated Cerebellar Ataxias: Clinical Diagnosis and Treatment Based on Immunological and Physiological Mechanisms | journal = Journal of Movement Disorders | volume = 14 | issue = 1 | pages = 10–28 | date = January 2021 | pmid = 33423437 | pmc = 7840241 | doi = 10.14802/jmd.20040 | doi-access = free }}</ref> Cerebellar circuitry has capacities to compensate and restore function thanks to cerebellar reserve, gathering multiple forms of plasticity. LTDpathies gather immune disorders targeting [[long-term depression]] (LTD), a form of plasticity.<ref>{{cite journal | vauthors = Hirano T | title = Long-term depression and other synaptic plasticity in the cerebellum | journal = Proceedings of the Japan Academy. Series B, Physical and Biological Sciences | volume = 89 | issue = 5 | pages = 183–195 | date = 2013 | pmid = 23666089 | pmc = 3722574 | doi = 10.2183/pjab.89.183 }}</ref>