Editing Cerebellum (section)

==Clinical significance==
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{{Main|Cerebellar ataxia}}
Damage to the cerebellum often causes motor-related symptoms, the details of which depend on the part of the cerebellum involved and how it is damaged. Damage to the [[vestibulocerebellum|flocculonodular lobe]] may show up as a loss of equilibrium and in particular an altered, irregular walking gait, with a wide stance caused by difficulty in balancing.<ref name=Ghez /> Damage to the [[cerebrocerebellum|lateral zone]] typically causes problems in skilled voluntary and planned movements which can cause errors in the force, direction, speed and amplitude of movements. Other manifestations include [[hypotonia]] (decreased muscle tone), [[dysarthria]] (problems with speech articulation), [[dysmetria]] (problems judging distances or ranges of movement), [[dysdiadochokinesia]] (inability to perform rapid alternating movements such as walking), impaired check reflex or rebound phenomenon, and [[intention tremor]] (involuntary movement caused by alternating contractions of opposing muscle groups).<ref>{{cite book | vauthors = Schmitz TJ |year=2007 |chapter=Examination of Coordination |veditors=O'Sullivan SB, Schmitz TJ |title=Physical Rehabilitation | url = https://archive.org/details/physicalrehabili00osul | url-access = limited |pages=[https://archive.org/details/physicalrehabili00osul/page/n199 193]–225 |location=Philadelphia |publisher=F. A. Davis|isbn=9780803612471 }}</ref><ref>{{Cite book|title=The linguistic cerebellum| vauthors = Mariën P, Manto M|publisher=Academic Press|year=2016|isbn=978-0-12-801608-4|location=London, UK|pages=337–351 }}</ref> Damage to the midline portion may disrupt whole-body movements, whereas damage localized more laterally is more likely to disrupt fine movements of the hands or limbs. Damage to the upper part of the cerebellum tends to cause gait impairments and other problems with leg coordination; damage to the lower part is more likely to cause uncoordinated or poorly aimed movements of the arms and hands, as well as difficulties in speed.<ref name=Ghez>{{cite book |title=Principles of Neural Science, 2nd edition |chapter=The cerebellum |veditors=Kandel ER, Schwartz JH |location=New York |publisher=Elsevier |year=1985 |pages=502–522 |vauthors=Ghez C, Fahn S }}</ref> This complex of motor symptoms is called ''[[ataxia]]''.

To identify cerebellar problems, [[neurological examination]] includes assessment of gait (a broad-based gait being indicative of ataxia), finger-pointing tests and assessment of posture.<ref name="Fine"/> If cerebellar dysfunction is indicated, a [[magnetic resonance imaging]] scan can be used to obtain a detailed picture of any structural alterations that may exist.<ref>{{cite journal | vauthors = Gilman S | title = Imaging the brain. Second of two parts | journal = New England Journal of Medicine | volume = 338 | issue = 13 | pages = 889–96 | date = March 1998 | pmid = 9516225 | doi = 10.1056/NEJM199803263381307 }}</ref>

The list of medical problems that can produce cerebellar damage is long, including [[stroke]], [[hemorrhage]], swelling of the brain ([[cerebral edema]]), [[neoplasm|tumors]], [[alcoholism]], physical [[trauma (medicine)|trauma]] such as gunshot wounds or explosives, and chronic [[degeneration (medical)|degenerative]] conditions such as [[olivopontocerebellar atrophy]].<ref name="NINDS-ataxias"/><ref>{{Cite web|url = http://www.scientificamerican.com/article/veterans-of-iraq-afghanistan-show-brain-changes-related-to-explosion-exposure/|title = Veterans of Iraq, Afghanistan Show Brain Changes Related to Explosion Exposure|date = January 15, 2016|access-date = January 21, 2016|website = Scientific American| vauthors = Yuhas D | url-status = live|archive-url = https://web.archive.org/web/20160120194938/http://www.scientificamerican.com/article/veterans-of-iraq-afghanistan-show-brain-changes-related-to-explosion-exposure/|archive-date = January 20, 2016 }}</ref> Some forms of [[migraine]] headache may also produce temporary dysfunction of the cerebellum, of variable severity.<ref>{{cite journal | vauthors = Vincent M, Hadjikhani N | title = The cerebellum and migraine | journal = Headache | volume = 47 | issue = 6 | pages = 820–33 | date = June 2007 | pmid = 17578530 | pmc = 3761082 | doi = 10.1111/j.1526-4610.2006.00715.x }}</ref> Infection can result in cerebellar damage in such conditions as [[transmissible spongiform encephalopathy|the prion diseases]]<ref name="NINDS-degen"/> and Miller Fisher syndrome, a variant of [[Guillain–Barré syndrome]].

===Aging===
The human cerebellum changes with age. These changes may differ from those of other parts of the brain.
The cerebellum is the youngest brain region (and body part) in centenarians according to an epigenetic biomarker of tissue age known as [[epigenetic clock]]: it is about 15 years younger than expected in a centenarian.<ref>{{cite journal | vauthors = Horvath S, Mah V, Lu AT, Woo JS, Choi OW, Jasinska AJ, Riancho JA, Tung S, Coles NS, Braun J, Vinters HV, Coles LS | title = The cerebellum ages slowly according to the epigenetic clock | journal = Aging | volume = 7 | issue = 5 | pages = 294–306 | date = May 2015 | pmid = 26000617 | pmc = 4468311 | doi = 10.18632/aging.100742 | url = https://www.aging-us.com/article/100742/text }}</ref> Further, [[gene expression]] patterns in the human cerebellum show less [[aging brain|age-related]] alteration than that in the [[cerebral cortex]].<ref>{{cite journal | vauthors = Fraser HB, Khaitovich P, Plotkin JB, Pääbo S, Eisen MB | title = Aging and gene expression in the primate brain | journal = PLOS Biology | volume = 3 | issue = 9 | pages = e274 | date = September 2005 | pmid = 16048372 | pmc = 1181540 | doi = 10.1371/journal.pbio.0030274 | author-link4 = Svante Pääbo | doi-access = free }}</ref>
Some studies have reported reductions in numbers of cells or volume of tissue, but the amount of data relating to this question is not very large.<ref>{{cite journal | vauthors = Andersen BB, Gundersen HJ, Pakkenberg B | title = Aging of the human cerebellum: a stereological study | journal = Journal of Comparative Neurology | volume = 466 | issue = 3 | pages = 356–65 | date = November 2003 | pmid = 14556293 | doi = 10.1002/cne.10884 | s2cid = 7091227 }}</ref><ref>{{cite journal | vauthors = Raz N, Gunning-Dixon F, Head D, Williamson A, Acker JD | title = Age and sex differences in the cerebellum and the ventral pons: a prospective MR study of healthy adults | journal = American Journal of Neuroradiology | volume = 22 | issue = 6 | pages = 1161–7 | year = 2001 | pmid = 11415913 | pmc = 7974784 | url = http://www.ajnr.org/cgi/reprint/22/6/1161.pdf | archive-url = https://web.archive.org/web/20081217005530/http://www.ajnr.org/cgi/reprint/22/6/1161.pdf | url-status = live | archive-date = 2008-12-17 }}</ref>

===Developmental and degenerative disorders===
[[File:Cervelletto e cisterna magna ecografia ad ultrasuoni Dr. Wolfgang Moroder.jpg|thumb|right|Ultrasound image of the fetal head at 19 weeks of pregnancy in a modified axial section, showing the normal fetal cerebellum and [[cisterna magna]]]]
Congenital malformation, hereditary disorders, and acquired conditions can affect cerebellar structure and, consequently, cerebellar function. Unless the causative condition is reversible, the only possible treatment is to help people live with their problems.<ref name="Merck 1886-1887">{{cite book|title=The Merck Manual of Diagnosis and Therapy|year=2006|publisher=Merck Research Libraries|location=Whitehouse Station, New Jersey| veditors = Albert RK, Porter RS |edition=18th |pages=1886–1887 |title-link=The Merck Manual of Diagnosis and Therapy}}</ref> Visualization of the fetal cerebellum by [[Medical ultrasound|ultrasound scan]] at 18 to 20 weeks of pregnancy can be used to [[Screening (medicine)|screen]] for fetal [[neural tube defect]]s with a [[Sensitivity and specificity|sensitivity]] rate of up to 99%.<ref>{{cite journal | vauthors = Campbell J, Gilbert WM, Nicolaides KH, Campbell S | title = Ultrasound screening for spina bifida: cranial and cerebellar signs in a high-risk population | journal = Obstetrics and Gynecology | volume = 70 | issue = 2 | pages = 247–50 | date = August 1987 | pmid = 3299184 }}</ref>

In normal development, endogenous [[Sonic hedgehog (protein)|sonic hedgehog]] signaling stimulates rapid proliferation of cerebellar granule neuron progenitors (CGNPs) in the external granule layer (EGL). Cerebellar development occurs during late embryogenesis and the early postnatal period, with CGNP proliferation in the EGL peaking during early development (postnatal day 7 in the mouse).<ref name=":0" /> As CGNPs terminally differentiate into [[cerebellar granule cell]]s (also called cerebellar granule neurons, CGNs), they migrate to the internal granule layer (IGL), forming the mature cerebellum (by post-natal day 20 in the mouse).<ref name=":0">{{cite journal | vauthors = Hatten ME, Heintz N | title = Mechanisms of neural patterning and specification in the developing cerebellum | journal = Annual Review of Neuroscience | volume = 18 | pages = 385–408 | date = 1995 | pmid = 7605067 | doi = 10.1146/annurev.ne.18.030195.002125 }}</ref> Mutations that abnormally activate Sonic hedgehog signaling predispose to cancer of the cerebellum ([[medulloblastoma]]) in humans with [[Gorlin Syndrome]] and in genetically engineered [[Mouse models of human disease|mouse models]].<ref>{{cite journal | vauthors = Polkinghorn WR, Tarbell NJ | title = Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification | journal = Nature Clinical Practice. Oncology | volume = 4 | issue = 5 | pages = 295–304 | date = May 2007 | pmid = 17464337 | doi = 10.1038/ncponc0794 | s2cid = 24461280 }}</ref><ref>{{Cite journal | vauthors = Roussel MF, Hatten ME | title = Cerebellum development and medulloblastoma | journal = Current Topics in Developmental Biology | volume = 94 | pages = 235–82 | date = 2011 | pmid = 21295689 | pmc = 3213765 | doi = 10.1016/B978-0-12-380916-2.00008-5 | isbn = 9780123809162 }}</ref>

Congenital malformation or underdevelopment ([[hypoplasia]]) of the cerebellar vermis is a characteristic of both [[Dandy–Walker syndrome]] and [[Joubert syndrome]].<ref>{{cite web|url=http://www.ninds.nih.gov/disorders/joubert/joubert.htm|title=NINDS Joubert Syndrome Information Page|publisher=National Institutes of Health|date=23 December 2013|access-date=9 January 2015|url-status=dead|archive-url=https://web.archive.org/web/20150104180444/http://www.ninds.nih.gov/disorders/joubert/joubert.htm|archive-date=4 January 2015}}</ref><ref>{{cite web|url=http://www.ninds.nih.gov/disorders/dandywalker/dandywalker.htm|title=NINDS Dandy-Walker Information Page|publisher=National Institutes of Health|date=14 February 2014|access-date=9 January 2015|url-status=dead|archive-url=https://web.archive.org/web/20150104180320/http://www.ninds.nih.gov/disorders/dandywalker/dandywalker.htm|archive-date=4 January 2015}}</ref> In very rare cases, the entire cerebellum [[Cerebellar agenesis|may be absent]].<ref>{{cite web|url=http://www.ninds.nih.gov/disorders/cerebellar_hypoplasia/cerebellar_hypoplasia.htm|title=NINDS Cerebellar Hypoplasia Information Page|publisher=National Institutes of Health|date=29 September 2011|access-date=9 January 2015|url-status=dead|archive-url=https://web.archive.org/web/20150104180252/http://www.ninds.nih.gov/disorders/cerebellar_hypoplasia/cerebellar_hypoplasia.htm|archive-date=4 January 2015}}</ref> The inherited neurological disorders [[Machado–Joseph disease]], [[ataxia telangiectasia]], and [[Friedreich's ataxia]] cause progressive neurodegeneration linked to cerebellar loss.<ref name="NINDS-ataxias">{{cite web|url=http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm|title=NINDS Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page|publisher=National Institutes of Health|date=16 April 2014|access-date=2 February 2015|url-status=live|archive-url=https://web.archive.org/web/20150209002034/http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm|archive-date=9 February 2015}}</ref><ref name="Merck 1886-1887" /> Congenital brain malformations outside the cerebellum can, in turn, cause [[brain herniation#Tonsillar herniation|herniation of cerebellar tissue]], as seen in some forms of [[Arnold–Chiari malformation]].<ref>{{cite web|url=http://www.ninds.nih.gov/disorders/chiari/detail_chiari.htm|title=Chiari Malformation Fact Sheet|publisher=National Institutes of Health|date=10 December 2014|access-date=9 January 2015|url-status=live|archive-url=https://web.archive.org/web/20111027111506/http://www.ninds.nih.gov/disorders/chiari/detail_chiari.htm|archive-date=27 October 2011}}</ref>

Other conditions that are closely linked to cerebellar degeneration include the idiopathic progressive neurological disorders [[multiple system atrophy]] and [[Ramsay Hunt syndrome type I]],<ref>{{cite web|url=http://www.ninds.nih.gov/disorders/dyssynergia/dyssynergia.htm|title=NINDS Dyssynergia Cerebellaris Myoclonica Information Page|publisher=National Institutes of Health|date=14 February 2011|access-date=1 February 2015|url-status=dead|archive-url=https://web.archive.org/web/20150216103415/http://www.ninds.nih.gov/disorders/dyssynergia/dyssynergia.htm|archive-date=16 February 2015}}</ref><ref>{{cite web|url=http://www.ninds.nih.gov/disorders/opca/opca.htm|title=NINDS Olivopontocerebellar Atrophy Information Page|publisher=National Institutes of Health|date=16 April 2014|access-date=9 January 2015|url-status=dead|archive-url=https://web.archive.org/web/20120127104017/http://www.ninds.nih.gov/disorders/opca/opca.htm|archive-date=27 January 2012}}</ref> and the [[autoimmune disease|autoimmune disorder]] [[paraneoplastic cerebellar degeneration]], in which tumors elsewhere in the body elicit an autoimmune response that causes neuronal loss in the cerebellum.<ref>{{cite web|url=http://www.ninds.nih.gov/disorders/paraneoplastic/paraneoplastic.htm|title=NINDS Paraneoplastic Syndromes Information Page|publisher=National Institutes of Health|date=12 March 2009|access-date=9 January 2015|url-status=dead|archive-url=https://web.archive.org/web/20150104180539/http://www.ninds.nih.gov/disorders/paraneoplastic/paraneoplastic.htm|archive-date=4 January 2015}}</ref> Cerebellar atrophy can result from an acute deficiency of vitamin B1 ([[thiamine#Deficiency|thiamine]]) as seen in [[beriberi]] and in [[Wernicke–Korsakoff syndrome]],<ref>{{cite web|url=http://www.ninds.nih.gov/disorders/wernicke_korsakoff/wernicke-korsakoff.htm|title=NINDS Wernicke-Korsakoff Syndrome Information Page|publisher=National Institutes of Health|date=14 February 2007|access-date=9 January 2015|url-status=dead|archive-url=https://web.archive.org/web/20150104180255/http://www.ninds.nih.gov/disorders/wernicke_korsakoff/wernicke-korsakoff.htm|archive-date=4 January 2015}}</ref> or [[vitamin E]] deficiency.<ref name="Merck 1886-1887"/>

Cerebellar atrophy has been observed in many other neurological disorders including [[Huntington's disease]], [[multiple sclerosis]],<ref name="NINDS-degen">{{cite web|url=http://www.ninds.nih.gov/disorders/cerebellar_degeneration/cerebellar_degeneration.htm|title=NINDS Cerebellar Degeneration Information Page|publisher=National Institutes of Health|date=28 February 2014|access-date=2 February 2015|url-status=dead|archive-url=https://web.archive.org/web/20150218075325/http://www.ninds.nih.gov/disorders/cerebellar_degeneration/cerebellar_degeneration.htm|archive-date=18 February 2015}}</ref> [[essential tremor]], [[progressive myoclonus epilepsy]], and [[Niemann–Pick disease]]. Cerebellar atrophy can also occur as a result of exposure to toxins including [[toxic heavy metal|heavy metals]] or [[pharmaceutical drug|pharmaceutical]] or [[psychoactive drug|recreational drugs]].<ref name="Merck 1886-1887"/>

===Pain===
There is a general consensus that the cerebellum is involved in pain processing.<ref>{{cite journal | vauthors = Moulton EA, Schmahmann JD, Becerra L, Borsook D | title = The cerebellum and pain: passive integrator or active participator? | journal = Brain Research Reviews | volume = 65 | issue = 1 | pages = 14–27 | date = October 2010 | pmid = 20553761 | pmc = 2943015 | doi = 10.1016/j.brainresrev.2010.05.005 }}</ref><ref>{{cite journal | vauthors = Baumann O, Borra RJ, Bower JM, Cullen KE, Habas C, Ivry RB, Leggio M, Mattingley JB, Molinari M, Moulton EA, Paulin MG, Pavlova MA, Schmahmann JD, Sokolov AA | title = Consensus paper: the role of the cerebellum in perceptual processes | journal = Cerebellum | volume = 14 | issue = 2 | pages = 197–220 | date = April 2015 | pmid = 25479821 | pmc = 4346664 | doi = 10.1007/s12311-014-0627-7 }}</ref> The cerebellum receives pain input from both descending cortico-cerebellar pathways and ascending spino-cerebellar pathways, through the pontine nuclei and inferior olives. Some of this information is transferred to the motor system inducing a conscious motor avoidance of pain, graded according to pain intensity.

These direct pain inputs, as well as indirect inputs, are thought to induce long-term pain avoidance behavior that results in chronic posture changes and consequently, in functional and anatomical remodeling of vestibular and proprioceptive nuclei. As a result, chronic neuropathic pain can induce macroscopic anatomical remodeling of the hindbrain, including the cerebellum.<ref name="ReferenceA"/> The magnitude of this remodeling and the induction of neuron progenitor markers suggest the contribution of [[Adult neurogenesis#Tracking neurogenesis|adult neurogenesis]] to these changes.