Editing Human brain (section)

==Clinical significance==
===Injury===
[[Brain damage|Injury to the brain]] can manifest in many ways. [[Traumatic brain injury]], for example received in [[contact sport]], after a [[Falling (accident)|fall]], or a [[traffic collision|traffic]] or [[work accident]], can be associated with both immediate and longer-term problems. Immediate problems may include [[intracerebral haemorrhage|bleeding within the brain]], this may compress the brain tissue or damage its blood supply. [[Cerebral contusion|Bruising]] to the brain may occur. Bruising may cause widespread damage to the nerve tracts that can lead to a condition of [[diffuse axonal injury]].<ref name="GE Health">{{cite web|url=http://www.medcyclopaedia.com/library/topics/volume_vi_1/b/BRAIN_INJURY_TRAUMATIC.aspx|archive-url=https://archive.today/20110526162429/http://www.medcyclopaedia.com/library/topics/volume_vi_1/b/BRAIN_INJURY_TRAUMATIC.aspx|url-status=dead|archive-date=May 26, 2011|title=Brain Injury, Traumatic|publisher=[[General Electric|GE]]|work=Medcyclopaedia}}</ref> A [[skull fracture|fractured skull]], injury to a particular area, [[deafness]], and [[concussion]] are also possible immediate developments. In addition to the site of injury, the opposite side of the brain may be affected, termed a [[Coup contrecoup injury|contrecoup injury]]. Longer-term issues that may develop include [[posttraumatic stress disorder]], and [[hydrocephalus]]. [[Chronic traumatic encephalopathy]] can develop following multiple [[head injury|head injuries]].<ref>{{Cite journal |last1=Dawodu |first1=S.T. |title=Traumatic Brain Injury (TBI) – Definition and Pathophysiology: Overview, Epidemiology, Primary Injury |url=http://emedicine.medscape.com/article/326510-overview#a3 |website=Medscape |date=March 9, 2017 |url-status=live |archive-url=https://web.archive.org/web/20170409021001/http://emedicine.medscape.com/article/326510-overview#a3 |archive-date=April 9, 2017  }}</ref>

===Disease===
[[Neurodegenerative disease]]s result in progressive damage to, or loss of neurons affecting  different functions of the brain, that [[Aging brain|worsen with age]]. Common types are [[dementia]]s including [[Alzheimer's disease]], [[alcoholic dementia]], [[vascular dementia]], and  [[Parkinson's disease dementia]]. Other rarer infectious, genetic, or metabolic types include [[Huntington's disease]], [[motor neuron disease]]s, [[HIV dementia]], [[Neurosyphilis|syphilis-related dementia]] and [[Wilson's disease]]. Neurodegenerative diseases can affect different parts of the brain, and can affect movement, [[memory]], and cognition.{{sfn|Davidson's|2010|pp=1196-7}} Rare [[prion disease]]s including [[Creutzfeldt–Jakob disease]] and its [[Variant Creutzfeldt–Jakob disease|variant]], and [[Kuru (disease)|kuru]] are fatal neurodegenerative diseases.{{sfn|Davidson's|2010|pp=1205-15}}

[[Cerebral atherosclerosis]] is [[atherosclerosis]] that affects the brain. It results from the build-up of [[atheroma|plaques]] formed of [[cholesterol]], in the large arteries of the brain, and can be mild to significant. When significant, arteries can become narrowed enough to reduce blood flow. It contributes to the development of dementia, and has protein similarities to those found in Alzheimer's disease.<ref name="NN2020">{{cite journal |vauthors=Wingo AP, Fan W, Duong DM, Gerasimov ES, Dammer EB, Liu Y, Harerimana NV, White B, Thambisetty M, Troncoso JC, Kim N, Schneider JA, Hajjar IM, Lah JJ, Bennett DA, Seyfried NT, Levey AI, Wingo TS |title=Shared proteomic effects of cerebral atherosclerosis and Alzheimer's disease on the human brain |journal=Nat Neurosci |volume=23 |issue=6 |pages=696–700 |date=June 2020 |pmid=32424284 |pmc=7269838 |doi=10.1038/s41593-020-0635-5 |url=}}</ref>

The brain, although protected by the blood–brain barrier, can be affected by infections including [[virus]]es, [[bacteria]] and [[fungi]]. Infection may be of the [[meninges]] ([[meningitis]]), the brain matter ([[encephalitis]]), or within the brain matter (such as a [[cerebral abscess]]).{{sfn|Davidson's|2010|pp=1205-15}}

===Tumours===
[[Brain tumor|Brain tumours]] can be either [[benign]] or [[malignant|cancerous]]. Most malignant tumours [[metastasis|arise from another part of the body]], most commonly from the [[lung cancer|lung]], [[breast cancer|breast]] and [[melanoma|skin]].{{sfn|Davidson's|2010|pp=1216-7}} Cancers of brain tissue can also occur, and originate from any tissue in and around the brain. [[Meningioma]], cancer of the meninges around the brain, is more common than cancers of brain tissue.{{sfn|Davidson's|2010|pp=1216-7}} Cancers within the brain may cause symptoms related to their size or position, with symptoms including headache and nausea, or the gradual development of focal symptoms such as gradual difficulty seeing, swallowing, talking, or as a change of mood.{{sfn|Davidson's|2010|pp=1216-7}} Cancers are in general investigated through the use of CT scans and MRI scans. A variety of other tests including blood tests and lumbar puncture may be used to investigate for the cause of the cancer and evaluate the type and [[cancer staging|stage]] of the cancer.{{sfn|Davidson's|2010|pp=1216-7}} The [[corticosteroid]] [[dexamethasone]] is often given to decrease the [[oedema|swelling]] of brain tissue around a tumour. Surgery may be considered, however given the complex nature of many tumours or based on tumour stage or type, [[radiotherapy]] or [[chemotherapy]] may be considered more suitable.{{sfn|Davidson's|2010|pp=1216-7}}

===Mental disorders===
[[Mental disorder]]s, such as [[major depressive disorder|depression]], [[schizophrenia]], [[bipolar disorder]], [[posttraumatic stress disorder]], [[attention deficit hyperactivity disorder]], [[obsessive-compulsive disorder]], [[Tourette syndrome]], and [[addiction]], are known to relate to the functioning of the brain.<ref name="NHMH_3e – Addiction and ADHD">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE, Holtzman DM | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2015 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-182770-6 | edition = 3rd | chapter = Chapter 14: Higher Cognitive Function and Behavioral Control | quote =In conditions in which prepotent responses tend to dominate behavior, such as in drug addiction, where drug cues can elicit drug seeking (Chapter 16), or in attention deficit hyperactivity disorder (ADHD; described below), significant negative consequences can result.&nbsp;... ADHD can be conceptualized as a disorder of executive function; specifically, ADHD is characterized by reduced ability to exert and maintain cognitive control of behavior. Compared with healthy individuals, those with ADHD have diminished ability to suppress inappropriate prepotent responses to stimuli (impaired response inhibition) and diminished ability to inhibit responses to irrelevant stimuli (impaired interference suppression).&nbsp;... Functional neuroimaging in humans demonstrates activation of the prefrontal cortex and caudate nucleus (part of the dorsal striatum) in tasks that demand inhibitory control of behavior.&nbsp;... Early results with structural MRI show a thinner cerebral cortex, across much of the cerebrum, in ADHD subjects compared with age-matched controls, including areas of [the] prefrontal cortex involved in working memory and attention.}}</ref><ref name=NIMH2017>{{cite web |title=NIMH » Brain Basics |url=https://www.nimh.nih.gov/health/educational-resources/brain-basics/brain-basics.shtml |website=www.nimh.nih.gov |access-date=March 26, 2017 |url-status=live |archive-url=https://web.archive.org/web/20170326230311/https://www.nimh.nih.gov/health/educational-resources/brain-basics/brain-basics.shtml |archive-date=March 26, 2017  }}</ref><ref name="Addiction - brain disease review">{{cite journal | last1=Volkow |first1=N.D. |last2=Koob |first2=G.F. |last3=McLellan |first3=A.T. | title=Neurobiologic advances from the brain disease model of addiction | journal=[[The New England Journal of Medicine]] | volume=374 | issue=4 | pages=363–371 | date=January 2016 | pmid=26816013 | pmc=6135257 | doi=10.1056/NEJMra1511480}}</ref> Treatment for mental disorders may include [[psychotherapy]], [[psychiatry]], [[social interventionism|social intervention]] and personal [[Recovery model|recovery]] work or [[cognitive behavioural therapy]]; the underlying issues and associated prognoses vary significantly between individuals.<ref name="Simpson">{{cite book |last1=Simpson |first1=J.M. |last2=Moriarty |first2=G.L. |title=Multimodal Treatment of Acute Psychiatric Illness: A Guide for Hospital Diversion |publisher=[[Columbia University Press]] |year=2013 |pages=22–24 |isbn=978-0-231-53609-7 |url=https://books.google.com/books?id=MbtkAgAAQBAJ&pg=PA22}}</ref>

===Epilepsy===
[[Epileptic seizure]]s are thought to relate to abnormal electrical activity.{{sfn|Davidson's|2010|pp=1172-9}} Seizure activity can manifest as [[absence seizure|absence of consciousness]], [[focal seizure|focal]] effects such as limb movement or impediments of speech, or be [[generalised seizure|generalized]] in nature.{{sfn|Davidson's|2010|pp=1172-9}} [[Status epilepticus]] refers to a seizure or series of seizures that have not terminated within five minutes.<ref name="foundation">{{cite web |title=Status Epilepticus |url=https://www.epilepsy.com/learn/challenges-epilepsy/seizure-emergencies/status-epilepticus |website=Epilepsy Foundation}}</ref> Seizures have a large number of causes, however many seizures occur without a definitive cause being found. In a person with [[epilepsy]], risk factors for further seizures may include sleeplessness, drug and alcohol intake, and stress. Seizures may be assessed using [[blood test]]s, [[EEG]] and various [[medical imaging]] techniques based on the [[medical history]] and [[medical examination]] findings.{{sfn|Davidson's|2010|pp=1172-9}} In addition to treating an underlying cause and reducing exposure to risk factors, [[anticonvulsant]] medications can play a role in preventing further seizures.{{sfn|Davidson's|2010|pp=1172-9}}

===Congenital===
Some brain disorders, such as [[Tay–Sachs disease]],<ref name="Moore">{{cite book |last=Moore |first=S.P. |title=The Definitive Neurological Surgery Board Review |publisher=[[Lippincott Williams & Wilkins]] |isbn=978-1-4051-0459-3 |page=112 |year=2005 |url=https://books.google.com/books?id=mkK1a4mEx3IC&pg=PA112}}</ref> are [[congenital disorder|congenital]] and linked to [[Mutation|genetic]] and [[chromosome abnormality|chromosomal]] mutations.<ref name="Pennington">{{cite book |last=Pennington |first=B.F. |title=Diagnosing Learning Disorders, Second Edition: A Neuropsychological Framework |publisher=[[Guilford Press]] |isbn=978-1-60623-786-1 |pages=3–10 |year=2008 |url=https://books.google.com/books?id=LVV10L62z6kC&pg=PA3}}</ref> A rare group of congenital [[cephalic disorder]]s known as [[lissencephaly]] is characterised by the lack of, or inadequacy of, cortical folding.<ref name="Govaert">{{cite book |last1=Govaert |first1=P. |last2=de Vries |first2=L.S. |title=An Atlas of Neonatal Brain Sonography: (CDM 182–183) |publisher=[[John Wiley & Sons]] |isbn=978-1-898683-56-8 |pages=89–92 |year=2010 |url=https://books.google.com/books?id=FzcaxpvV1JUC&pg=PA89}}</ref> Normal [[prenatal development|development]] of the brain can be affected during [[pregnancy]] by [[nutritional deficiencies]],<ref name="Perese">{{cite book |last=Perese |first=E.F. |title=Psychiatric Advanced Practice Nursing: A Biopsychsocial Foundation for Practice |publisher=[[F.A. Davis]] |isbn=978-0-8036-2999-8 |pages=82–88 |year=2012 |url=https://books.google.com/books?id=6X_2AAAAQBAJ&pg=PA82}}</ref> [[teratology|teratogen]]s,<ref name="Kearney">{{cite book |last1=Kearney |first1=C. |last2=Trull |first2=T.J. |title=Abnormal Psychology and Life: A Dimensional Approach |publisher=[[Cengage Learning]] |isbn=978-1-337-09810-6 |page=395 |year=2016  |url=https://books.google.com/books?id=B9q5DQAAQBAJ&pg=PA395}}</ref> [[infectious diseases]],<ref name="Stevenson">{{cite book |last1=Stevenson |first1=D.K. |last2=Sunshine |first2=P. |last3=Benitz |first3=W.E. |title=Fetal and Neonatal Brain Injury: Mechanisms, Management and the Risks of Practice |publisher=[[Cambridge University Press]] |isbn=978-0-521-80691-6 |page=191 |year=2003 |url=https://books.google.com/books?id=RuekFAj_tIAC&pg=PA191}}</ref> and by the use of [[Recreational drug use|recreational drugs]], including alcohol (which may result in [[fetal alcohol spectrum disorders]]).<ref name="Perese"/><ref name="Dewhurst">{{cite book |last=Dewhurst |first=John |title=Dewhurst's Textbook of Obstetrics and Gynaecology |publisher=[[John Wiley & Sons]] |isbn=978-0-470-65457-6 |page=43 |year=2012 |url=https://books.google.com/books?id=HfakBRceodcC&pg=PA43}}</ref>
Most [[cerebral arteriovenous malformation]]s are congenital, these tangled networks of blood vessels may remain without symptoms but at their worst may rupture and cause [[intracranial hemorrhage|intracranial hemorrhaging]].<ref name="NINDS">{{cite web |title=Arteriovenous Malformations (AVMs) {{!}} National Institute of Neurological Disorders and Stroke |url=https://www.ninds.nih.gov/health-information/disorders/arteriovenous-malformations-avms?search-term=arteriovenous%20mal |website=www.ninds.nih.gov |access-date=8 February 2023}}</ref>

===Stroke===
{{Main|Stroke}}
[[File:Parachemableedwithedema.png|thumb|upright|[[CT scan]] of a [[cerebral hemorrhage]], showing an [[intraparenchymal bleed]] (bottom arrow) with surrounding [[edema]] (top arrow)]]

<!--Definitions and symptoms-->A [[stroke]] is a [[ischemia|decrease in blood supply]] to an area of the brain causing [[cell death]] and [[Brain damage#Causes|brain injury]]. This can lead to a wide range of [[Stroke#Signs and symptoms|symptoms]], including the "[[FAST (stroke)|FAST]]" symptoms of facial droop, arm weakness, and speech difficulties (including [[dysarthria|with speaking]] and [[dysphasia|finding words or forming sentences]]).<ref>{{cite journal |last1=Harbison |first1=J. |last2=Massey |first2=A. |last3=Barnett |first3=L. |last4=Hodge |first4=D. |last5=Ford |first5=G.A. | title=Rapid ambulance protocol for acute stroke | journal=Lancet | volume=353 | issue=9168 | page=1935 | date=June 1999 | pmid=10371574 | doi=10.1016/S0140-6736(99)00966-6 |s2cid=36692451 }}</ref> Symptoms relate to the function of the affected area of the brain and can point to the likely site and cause of the stroke. Difficulties with movement, speech, or sight usually relate to the cerebrum, whereas [[ataxia|imbalance]], [[diplopia|double vision]], [[vertigo]] and symptoms affecting more than one side of the body usually relate to the brainstem or cerebellum.{{sfn|Davidson's|2010|p=1183}}

Most strokes result from loss of blood supply, typically because of an [[embolus]], rupture of a [[atheroma|fatty plaque]] causing [[thrombus]], or [[arteriosclerotic|narrowing of small arteries]]. Strokes can also result from [[Stroke#Hemorrhagic|bleeding within the brain]].{{sfn|Davidson's|2010|pp=1180-1}} [[Transient ischemic attack|Transient ischaemic attack]]s (TIAs) are strokes in which symptoms resolve within 24 hours.{{sfn|Davidson's|2010|pp=1180-1}} Investigation into the stroke will involve a [[medical examination]] (including a [[neurological examination]]) and the taking of a [[medical history]], focusing on the duration of the symptoms and risk factors (including [[Hypertension|high blood pressure]], [[atrial fibrillation]], and [[tobacco smoking|smoking]]).{{sfn|Davidson's|2010|pp=1181, 1183-1185}} Further investigation is needed in younger patients.{{sfn|Davidson's|2010|pp=1183-1185}} An [[ECG]] and [[biotelemetry]] may be conducted to identify [[atrial fibrillation]]; an [[ultrasound]] can investigate [[carotid stenosis|narrowing]] of the [[Common carotid artery|carotid arteries]]; an [[echocardiogram]] can be used to look for clots within the heart, [[Valvular heart disease|diseases of the heart valves]] or the presence of a [[patent foramen ovale]].{{sfn|Davidson's|2010|pp=1183-1185}} [[Blood test]]s are routinely done as part of the [[Medical diagnosis#Other diagnostic procedure methods|workup]] including [[Diabetes mellitus#Diagnosis|diabetes tests]] and a [[lipid profile]].{{sfn|Davidson's|2010|pp=1183-1185}}

Some treatments for stroke are time-critical. These include [[thrombolysis|clot dissolution]] or [[embolectomy|surgical removal of a clot]] for [[Brain ischemia|ischaemic strokes]], and [[decompression (surgery)|decompression]] for [[Intracranial hemorrhage|haemorrhagic strokes]].{{sfn|Davidson's|2010|pp=1185-1189}}<ref>{{cite journal |last1=Goyal |first1=M. |display-authors=etal |title=Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials |journal=The Lancet |date=April 2016 |volume=387 |issue=10029 |pages=1723–1731 |doi=10.1016/S0140-6736(16)00163-X |pmid=26898852 |s2cid=34799180 }}</ref> As stroke is time critical,<ref>{{cite journal |last1=Saver |first1=J. L. |title=Time is brain—quantified |journal=Stroke |date=December 8, 2005 |volume=37 |issue=1 |pages=263–266 |doi=10.1161/01.STR.0000196957.55928.ab|pmid=16339467 |doi-access=free }}</ref> hospitals and even pre-hospital care of stroke involves expedited investigations – usually a [[CT scan]] to investigate for a haemorrhagic stroke and a [[CT angiogram|CT]] or [[MR angiogram]] to evaluate arteries that supply the brain.{{sfn|Davidson's|2010|pp=1183-1185}} [[MRI scan]]s, not as widely available, may be able to demonstrate the affected area of the brain more accurately, particularly with ischaemic stroke.{{sfn|Davidson's|2010|pp=1183-1185}}

Having experienced a stroke, a person may be admitted to a [[stroke unit]], and treatments may be directed as [[secondary prevention|preventing]] future strokes, including ongoing [[anticoagulation]] (such as [[aspirin]] or [[clopidogrel]]), [[Antihypertensive drug|antihypertensives]], and [[lipid-lowering agent|lipid-lowering drugs]].{{sfn|Davidson's|2010|pp=1185-1189}} A [[multidisciplinary team]] including [[speech pathologist]]s, [[physiotherapists]], [[occupational therapist]]s, and [[psychologist]]s plays a large role in supporting a person affected by a stroke and their [[physical medicine and rehabilitation|rehabilitation]].<ref>{{cite journal |last1=Winstein |first1=C.J. |display-authors=etal |title=Guidelines for adult stroke rehabilitation and recovery |journal=Stroke |date=June 2016 |volume=47 |issue=6 |pages=e98–e169 |doi=10.1161/STR.0000000000000098|pmid=27145936 |s2cid=4967333 |doi-access=free }}</ref>{{sfn|Davidson's|2010|pp=1183-1185}} A history of stroke increases the risk of developing dementia by around 70%, and recent stroke increases the risk by around 120%.<ref>{{Cite journal|last1=Kuźma|first1=Elżbieta|last2=Lourida|first2=Ilianna|last3=Moore|first3=Sarah F.|last4=Levine|first4=Deborah A.|last5=Ukoumunne|first5=Obioha C.|last6=Llewellyn|first6=David J.|date=November 2018 |title=Stroke and dementia risk: A systematic review and meta-analysis|journal=Alzheimer's & Dementia |volume=14 |issue=11 |pages=1416–1426 |doi=10.1016/j.jalz.2018.06.3061 |pmid=30177276|pmc=6231970|issn=1552-5260}}</ref>

===Brain death===
{{Main|Brain death}}
Brain death refers to an irreversible total loss of brain function.<ref name="GOILA2009">{{cite journal |last1=Goila |first1=AK |last2=Pawar |first2=M |title=The diagnosis of brain death |journal=Indian Journal of Critical Care Medicine |date=2009 |volume=13 |issue=1 |pages=7–11 |doi=10.4103/0972-5229.53108|pmid=19881172 |pmc=2772257 |doi-access=free }}</ref><ref name=":0">{{Cite journal |last=Wijdicks |first=EFM |date=January 8, 2002 |title=Brain death worldwide: accepted fact but no global consensus in diagnostic criteria |journal=Neurology |volume=58 |issue=1 |pages=20–25 |pmid=11781400 |doi=10.1212/wnl.58.1.20|s2cid=219203458 }}</ref> This is characterised by [[coma]], loss of [[reflex]]es, and [[apnoea]],<ref name=GOILA2009/> however, the declaration of brain death varies geographically and is not always accepted.<ref name=":0" /> In some countries there is also a defined syndrome of [[brainstem death]].<ref>{{cite journal |last1=Dhanwate |first1=AD |title=Brainstem death: A comprehensive review in Indian perspective. |journal=Indian Journal of Critical Care Medicine |date=September 2014 |volume=18 |issue=9 |pages=596–605 |pmid=25249744 |doi=10.4103/0972-5229.140151 |pmc=4166875 |doi-access=free }}</ref> Declaration of brain death can have profound implications as the declaration, under the principle of [[Futile medical care|medical futility]], will be associated with the withdrawal of life support,{{sfn|Davidson's|2010|p=1158}} and as those with brain death often have organs suitable for [[organ donation]].<ref name=":0" />{{sfn|Davidson's|2010|p=200}} The process is often made more difficult by poor communication with patients' families.<ref name="Urden">{{cite book |last1=Urden |first1=L.D. |last2=Stacy |first2=K.M. |last3=Lough |first3=M.E. |title=Priorities in Critical Care Nursing – E-Book |publisher=[[Elsevier Health Sciences]] |isbn=978-0-323-29414-0 |pages=112–113 |year=2013 |url=https://books.google.com/books?id=lLvwAwAAQBAJ&pg=PA112}}</ref>

When brain death is suspected, reversible [[differential diagnosis|differential diagnoses]] such as, electrolyte, neurological and drug-related cognitive suppression need to be excluded.<ref name="GOILA2009" />{{sfn|Davidson's|2010|p=1158}} Testing for reflexes{{efn|Including the [[vestibulo-ocular reflex]], [[corneal reflex]], [[gag reflex]] and dilation of the pupils in response to light,{{sfn|Davidson's|2010|p=1158}}}} can be of help in the decision, as can the absence of response and breathing.{{sfn|Davidson's|2010|p=1158}} Clinical observations, including a total lack of responsiveness, a known diagnosis, and [[neural imaging]] evidence, may all play a role in the decision to pronounce brain death.<ref name="GOILA2009" />