Editing Cerebellum (section)

===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"/>