View source for Medicine:Brain ischemia

{{Infobox medical condition (new)
| name            = Brain ischemia
| synonyms        = '''Cerebral ischemia''', '''Cerebrovascular ischemia'''
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| caption         = [[CT scan]] slice of the brain showing a right-hemispheric cerebral infarct (left side of image).
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| field           = vascular surgeon
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'''Brain ischemia''' is a condition in which there is insufficient bloodflow to the [[Biology:Brain|brain]] to meet metabolic demand.<ref>{{cite news | first=Jonathon | last=Sullivan | title=What is Brain Ischemia? | publisher=WSU Emergency Medicine Cerebral Resuscitation Laboratory | url=http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_1.html | access-date=2008-11-11 | archive-url=https://web.archive.org/web/20090106045751/http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_1.html | archive-date=2009-01-06 | url-status=dead }}</ref>  This leads to poor oxygen supply or [[Medicine:Cerebral hypoxia|cerebral hypoxia]] and thus leads to the death of brain tissue or [[Medicine:Cerebral infarction|cerebral infarction]]/ischemic stroke.<ref>{{cite news | title=Brain Ischemia (Cerebral Ischemia) | date=2003 | publisher=Cure Hunter Incorporated | url =http://www.curehunter.com/public/keywordSummaryD002545.do | pages =Relationship Network | access-date = 2008-11-11 }}</ref>  It is a sub-type of stroke along with [[Medicine:Subarachnoid hemorrhage|subarachnoid hemorrhage]] and  [[Medicine:Intracerebral hemorrhage|intracerebral hemorrhage]].<ref name=UTD>{{cite web |url=https://www.uptodate.com/contents/clinical-diagnosis-of-stroke-subtypes |title=Clinical diagnosis of stroke subtypes }}</ref>

Ischemia leads to alterations in brain metabolism, reduction in metabolic rates, and energy crisis.<ref>{{cite journal |last1=Vespa |first1=Paul |last2=Bergsneider |first2=Marvin |last3=Hattori |first3=Nayoa |last4=Wu |first4=Hsiao-Ming |last5=Huang |first5=Sung-Cheng |last6=Martin |first6=Neil A |last7=Glenn |first7=Thomas C |last8=McArthur |first8=David L |last9=Hovda |first9=David A |title=Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study |journal=Journal of Cerebral Blood Flow & Metabolism |volume=25 |issue=6 |pages=763–74 |year=2005 |pmid=15716852 |pmc=4347944 |doi=10.1038/sj.jcbfm.9600073 }}</ref>

There are two types of ischemia: focal ischemia, which is confined to a specific region of the brain; and global ischemia, which encompasses wide areas of brain tissue.

The main symptoms of brain ischemia involve impairments in [[Philosophy:Visual perception|vision]], body movement, and speaking. The causes of brain ischemia vary from sickle cell anemia to congenital heart defects. Symptoms of brain ischemia can include unconsciousness, blindness, problems with coordination, and weakness in the body. Other effects that may result from brain ischemia are [[Medicine:Stroke|stroke]], cardiorespiratory arrest, and irreversible brain damage.

An interruption of blood flow to the brain for more than 10 seconds causes unconsciousness, and an interruption in flow for more than a few minutes generally results in irreversible brain damage.<ref name=Raichle>{{cite news | first=Marcus | last=Raichle | title=The Pathophysiology of Brain Ischemia | date=1983 | url=http://www.nil.wustl.edu/labs/raichle/MER_chapters/C55_The%20Pathophysiology%20of%20Brain%20Ischemia.pdf | work=Neurological Progress | access-date=2008-11-11 | url-status=dead | archive-url=https://web.archive.org/web/20090219085703/http://www.nil.wustl.edu/labs/raichle/MER_chapters/C55_The%20Pathophysiology%20of%20Brain%20Ischemia.pdf | archive-date=2009-02-19 }}</ref>  In 1974, Hossmann and Zimmermann demonstrated that ischemia induced in mammalian brains for up to an hour can be at least partially recovered.<ref>{{Cite journal|last1=Hossmann|first1=Konstantin-Alexander|last2=Zimmermann|first2=Volker|year=1974|title=Resuscitation of the monkey brain after 1 H complete ischemia. I. Physiological and morphological observations|journal=Brain Research|language=en|volume=81|issue=1|pages=59–74|doi=10.1016/0006-8993(74)90478-8|pmid=4434196}}</ref> Accordingly, this discovery raised the possibility of intervening after brain ischemia before the damage becomes irreversible.<ref>{{cite news | first=Marcus | last=Raichle | author2=Ann Neurol | title=The pathophysiology of brain ischemia | date=1983 | url=http://www.nil.wustl.edu/labs/raichle/MER_chapters/C55_The%20Pathophysiology%20of%20Brain%20Ischemia.pdf | work=Neurological Process | access-date=2009-04-22 | url-status=dead | archive-url=https://web.archive.org/web/20090219085703/http://www.nil.wustl.edu/labs/raichle/MER_chapters/C55_The%20Pathophysiology%20of%20Brain%20Ischemia.pdf | archive-date=2009-02-19 }}</ref>

==Symptoms and signs==
The symptoms of brain ischemia reflect the anatomical region undergoing blood and oxygen deprivation. Ischemia within the arteries branching from the internal carotid artery may result in symptoms such as blindness in one eye, weakness in one arm or leg, or weakness in one entire side of the body. Ischemia within the arteries branching from the vertebral arteries in the back of the brain may result in symptoms such as [[Medicine:Dizziness|dizziness]], vertigo, [[Medicine:Diplopia|double vision]], or weakness on both sides of the body {{Citation needed|date=September 2009}}. Other symptoms include difficulty speaking, slurred speech, and the loss of coordination.<ref name=MerckManual>{{cite book | last = Beers | first = Mark |author2=Andrew Fletcher |author3=Thomas Jones |author4=Robert Porter  | title = The Merck Manual of Medical Information | publisher = Merck & Co. Inc | date = 2003 | location = New York, New York | pages = 458–461 | isbn = 84-494-3359-2 }}</ref>  The symptoms of brain ischemia range from mild to severe.  Further, symptoms can last from a few seconds to a few minutes or extended periods of time.  If the brain becomes damaged irreversibly and infarction occurs, the symptoms may be permanent.<ref>{{cite news | first=Louis | last=Caplan |author2=Scott Kasner|author3=John Dashe | title=Differential diagnosis of brain ischemia | publisher=UpToDate | url =https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke | work =Up to Date For Patients | access-date = 2008-11-11 }}</ref>

Similar to [[Medicine:Cerebral hypoxia|cerebral hypoxia]], severe or prolonged brain ischemia will result in [[Medicine:Unconsciousness|unconsciousness]], [[Medicine:Brain damage|brain damage]] or [[Biology:Death|death]],  mediated by the [[Biology:Ischemic cascade|ischemic cascade]].<ref>{{cite journal |last1=Lipton |first1=Peter |title=Ischemic cell death in brain neurons |journal=Physiological Reviews |volume=79 |issue=4 |pages=1431–568 |year=1999 |pmid=10508238 |doi=10.1152/physrev.1999.79.4.1431 }}</ref>

Multiple cerebral ischemic events may lead to subcortical ischemic depression, also known as vascular depression. This condition is most commonly seen in elderly depressed patients.{{Citation needed|date=September 2009}} Late onset depression is increasingly seen as a distinct sub-type of depression, and can be detected with an MRI.<ref>{{cite journal |last1=Baldwin |first1=Robert C. |title=Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence |journal=International Journal of Geriatric Psychiatry |volume=20 |issue=1 |pages=1–11 |year=2005 |pmid=15578670 |doi=10.1002/gps.1255 |s2cid=19083813 }}</ref>

==Causes==
Brain ischemia has been linked to a variety of diseases or abnormalities. <!-- maybe subdivisions into various types of abnormalities? --> Individuals with sickle cell anemia, compressed blood vessels, [[Medicine:Ventricular tachycardia|ventricular tachycardia]], plaque buildup in the arteries, blood clots, extremely low blood pressure as a result of heart attack, and congenital heart defects have a higher predisposition to brain ischemia in comparison to the average population. Sickle cell anemia may cause brain ischemia associated with the irregularly shaped blood cells. Sickle shaped blood cells clot more easily than normal blood cells, impeding blood flow to the brain.{{citation needed|date=February 2021}}

Compression of blood vessels may also lead to brain ischemia, by blocking the arteries that carry oxygen to the brain. [[Medicine:Tumors|Tumors]] are one cause of blood vessel compression.{{citation needed|date=February 2021}}

Ventricular tachycardia represents a series of irregular heartbeats that may cause the heart to completely shut down resulting in cessation of oxygen flow. Further, irregular heartbeats may result in formation of blood clots, thus leading to oxygen deprivation to all organs.{{citation needed|date=February 2021}}

Blockage of arteries due to plaque buildup may also result in ischemia.  Even a small amount of plaque build up can result in the narrowing of passageways, causing that area to become more prone to blood clots.{{Citation needed|date=September 2009}} Large blood clots can also cause ischemia by blocking blood flow.{{citation needed|date=February 2021}}

A heart attack can also cause brain ischemia due to the correlation that exists between heart attack and low blood pressure. Extremely low blood pressure usually represents the inadequate oxygenation of tissues. Untreated heart attacks may slow blood flow enough that blood may start to clot and prevent the flow of blood to the brain or other major organs. Extremely low blood pressure can also result from drug overdose and reactions to drugs. Therefore, brain ischemia can result from events other than heart attacks.{{citation needed|date=February 2021}}

Congenital heart defects may also cause brain ischemia due to the lack of appropriate artery formation and connection. People with congenital heart defects may also be prone to blood clots.{{citation needed|date=February 2021}}


Recently, [[Medicine:Moyamoya disease|Moyamoya disease]] has also been identified as a potential cause for brain ischemia.  Moyamoya disease is an extremely rare cerebrovascular condition that limits blood [[Biology:Circulatory system|circulation]] to the brain, consequently leading to oxygen deprivation.<ref>{{cite news | first=Gareth | last=Sparks | title=What is Moyamoya disease? | date=2002 | publisher=eSSORTMENT | url=http://www.essortment.com/family/moyamoyamoyadi_sxma.htm | access-date=2009-04-13 | url-status=dead | archive-url=https://web.archive.org/web/20090327140113/http://www.essortment.com/family/moyamoyamoyadi_sxma.htm | archive-date=2009-03-27 }}</ref>

==Pathophysiology==
During brain ischemia, the brain cannot perform aerobic metabolism due to the loss of [[Chemistry:Oxygen|oxygen]] and [[Biology:Substrate (biochemistry)|substrate]]. The brain is not able to switch to anaerobic metabolism and, because it does not have any long term energy stored, the levels of [[Chemistry:Adenosine triphosphate|adenosine triphosphate]] (ATP) drop rapidly, approaching zero within 4 minutes. In the absence of biochemical energy, cells begin to lose the ability to maintain electrochemical gradients. Consequently, there is a massive influx of [[Chemistry:Calcium|calcium]] into the [[Biology:Cytosol|cytosol]], a massive release of glutamate from synaptic vesicles, [[Biology:Lipolysis|lipolysis]], [[Biology:Calpain|calpain]] activation, and the arrest of protein synthesis.<ref>{{cite news | first=Jonathon | last=Sullivan | title=Bad Things Happen in Ischemia | publisher=Emergency Medicine Cerebral Resuscitation Lab | url =http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_7.html | work =WSU Emergency Medicine Cerebral Resuscitation Laboratory | access-date = 2008-11-11 }}</ref> Additionally, removal of metabolic wastes is slowed.<ref>{{cite news | title=Ischemic and Hemorrhagic | url=http://www.umassmed.edu/strokestop/module_one/Ischemic_Hemorrhagic.html | access-date=2008-11-11 | archive-url=https://web.archive.org/web/20090216132235/http://www.umassmed.edu/strokestop/module_one/Ischemic_Hemorrhagic.html | archive-date=2009-02-16 | url-status=dead }}</ref>  The interruption of blood flow to the brain for ten seconds results in the immediate loss of consciousness.  The interruption of blood flow for twenty seconds results in the stopping of electrical activity.<ref name=Raichle/> An area called a penumbra may result, wherein neurons do not receive enough blood to communicate, however do receive sufficient oxygenation to avoid cell death for a short period of time.<ref>{{cite journal |vauthors=Hakim AM |title=Ischemic penumbra: the therapeutic window |journal=Neurology |volume=51 |issue=3 Suppl 3 |pages=S44–6 |year=1998 |pmid=9744833 |doi=10.1212/wnl.51.3_suppl_3.s44|s2cid=44452236 }}</ref>

==Diagnosis==
===Classification===
The broad term, "[[Medicine:Stroke|stroke]]" can be divided into three categories: brain ischemia, [[Medicine:Subarachnoid hemorrhage|subarachnoid hemorrhage]] and  [[Medicine:Intracerebral hemorrhage|intracerebral hemorrhage]].  Brain ischemia can be further subdivided, by cause, into [[Medicine:Thrombosis|thrombotic]], embolic, and hypoperfusion.<ref name=UTD/>  Thrombotic and embolic are generally focal or multifocal in nature while hypoperfusion affects the brain globally.{{citation needed|date=February 2021}}

====Focal brain ischemia====
Focal brain ischemia occurs when a blood clot has occluded a cerebral vessel.<ref name=twoflavors>{{cite news | first=Jonathon | last=Sullivan | title=Two Flavors of Ischemia | publisher=Emergency Medicine Cerebral Resuscitation Lab | url =http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_2.html | work =Brain Ischemia 101 | access-date = 2008-10-13 }}</ref>  Focal brain ischemia reduces blood flow to a specific brain region, increasing the risk of [[Biology:Cell death|cell death]] to that particular area.<ref>{{cite journal |last1=Miettinen |first1=S. |last2=Fusco |first2=F. R. |last3=Yrjanheikki |first3=J. |last4=Keinanen |first4=R. |last5=Hirvonen |first5=T. |last6=Roivainen |first6=R. |last7=Narhi |first7=M. |last8=Hokfelt |first8=T. |last9=Koistinaho |first9=J. |title=Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2 |journal=Proceedings of the National Academy of Sciences |volume=94 |issue=12 |pages=6500–5 |year=1997 |pmid=9177247 |pmc=21079 |doi=10.1073/pnas.94.12.6500 |bibcode=1997PNAS...94.6500M |jstor=42387 |doi-access=free }}</ref>  It can be either caused by [[Medicine:Thrombosis|thrombosis]] or embolism.{{citation needed|date=February 2021}}

====Global brain ischemia====
Global brain ischemia occurs when blood flow to the brain is halted or drastically reduced. This is commonly caused by [[Medicine:Cardiac arrest|cardiac arrest]]. If sufficient [[Biology:Circulatory system|circulation]] is restored within a short period of time, symptoms may be transient. However, if a significant amount of time passes before restoration, brain damage may be permanent.  While [[Medicine:Reperfusion therapy|reperfusion]] may be essential to protecting as much brain tissue as possible, it may also lead to [[Medicine:Reperfusion injury|reperfusion injury]]. Reperfusion injury is classified as the damage that ensues after restoration of blood supply to ischemic tissue.<ref name=twoflavors/>

Due to different susceptibility to ischemia of various brain regions, a global brain ischemia may cause focal brain infarction. The [[Biology:Cerebral cortex|cerebral cortex]] and [[Biology:Striatum|striatum]] are more susceptible than the thalamus, and the thalamus in turn is more sensitive than the brainstem.<ref>{{cite web|url=https://neuropathology-web.org/chapter2/chapter2aHIE.html|title=Neuropathology - Chapter 2: Cerebral ischemia and stroke|author=Dimitri P. Agamanolis, M.D.}} Updated: October, 2017</ref> Partial cerebral cortex infarction from global brain ischemia typically manifests as [[Medicine:Watershed stroke|watershed stroke]].<ref name=":0">{{Cite book|title=Pathophysiology: Concepts of Altered Health States|last=Porth|first=C.M.|publisher=Wolters Kluwer Health {{!}} Lippincott Williams & Wilkins|year=2009|isbn=978-16054-7390-1|location=Philadelphia|pages=1301|edition=Eighth}}</ref>

====Biomarker====
Use of [[Biology:Biomarker|biomarker]] is one method that has been evaluated to predict the risk of stroke, diagnose stroke and its causes, predict stroke severity and outcome, and guide prevention therapy.

'''Blood Biomarkers''': Many proteins and RNA biomarkers identified are connected to ischemic stroke pathophysiology includes

''Central Nervous System Tissue Injury Biomarkers''- [[Biology:S100B|S100B]], [[Biology:Glial fibrillary acidic protein|Glial fibrillary acidic protein]], [[Biology:Enolase 2|enolase 2]], [[Medicine:Anti-NMDA receptor encephalitis|Anti-NMDA receptor encephalitis]].

''Inflammatory Biomarkers'' - [[Chemistry:C-reactive protein|c-reactive protein]], Interleukin 6, [[Biology:Tumor necrosis factor|Tumor necrosis factor]] α,VCAM-1.

''Coagulation / [[Medicine:Thrombosis|Thrombosis]] Biomarkers'' - [[Biology:Fibrinogen|Fibrinogen]], [[Chemistry:D-dimer|D-dimer]], [[Biology:Von Willebrand factor|Von Willebrand factor]]

''Other Biomarkers''- PARK7, B-type neurotrophic growth factor.<ref>{{cite journal |last1=Jickling |first1=Glen |last2=Sharp |first2=Frank |title=Blood Biomarkers of Ischemic stroke |journal=Neurotherapeutics  |volume=8 |pages=349–360 |year=2011 |issue=3 |doi=10.1007/s13311-011-0050-4|pmid=21671123 |pmc=3250275 }}</ref>

==Treatment==
[[Medicine:Alteplase|Alteplase]] (t-PA) is an effective medication for acute ischemic stroke.  When given within 3 hours, treatment with tpa significantly improves the probability of a favourable outcome versus treatment with placebo.{{citation needed|date=February 2021}}

The outcome of brain ischemia is influenced by the quality of subsequent supportive care.  Systemic blood pressure (or slightly above) should be maintained so that cerebral blood flow is restored.  Also, hypoxaemia and [[Medicine:Hypercapnia|hypercapnia]] should be avoided.  Seizures can induce more damage; accordingly, anticonvulsants should be prescribed and should a seizure occur, aggressive treatment should be undertaken.  Hyperglycaemia should also be avoided during brain ischemia.<ref>{{cite journal |vauthors=Hinds CJ |title=Prevention and treatment of brain ischaemia |journal=British Medical Journal |volume=291 |issue=6498 |pages=758–60 |year=1985 |pmid=3929929 |pmc=1417168 |doi=10.1136/bmj.291.6498.758}}</ref>

===Management===
When someone presents with an ischemic event, treatment of the underlying cause is critical for prevention of further episodes.{{citation needed|date=February 2021}}

Anticoagulation with [[Chemistry:Warfarin|warfarin]] or [[Chemistry:Heparin|heparin]] may be used if the patient has [[Medicine:Atrial fibrillation|atrial fibrillation]].{{citation needed|date=February 2021}}

Operative procedures such as [[Medicine:Carotid endarterectomy|carotid endarterectomy]] and [[Medicine:Carotid stenting|carotid stenting]] may be performed if the patient has a significant amount of plaque in the carotid arteries associated with the local ischemic events.{{citation needed|date=February 2021}}

==Research==

Therapeutic hypothermia has been attempted to improve results post brain ischemia {{Citation needed|date=September 2009}}.  This procedure was suggested to be beneficial based on its effects post cardiac arrest.  Evidence supporting the use of therapeutic hypothermia after brain ischemia, however, is limited.{{citation needed|date=October 2021}}

A closely related disease to brain ischemia is brain hypoxia.  Brain hypoxia is the condition in which there is a decrease in the oxygen supply to the brain even in the presence of adequate blood flow.  If hypoxia lasts for long periods of time, [[Medicine:Coma|coma]], seizures, and even [[Medicine:Brain death|brain death]] may occur.  Symptoms of brain hypoxia are similar to ischemia and include inattentiveness, poor judgment, memory loss, and a decrease in [[Engineering:Motor coordination|motor coordination]].<ref name="Cerebral Hypoxia Information Page">{{cite news | title=Cerebral Hypoxia Information Page | date=2008-05-07 | publisher=National Institutes of Health | url=http://www.ninds.nih.gov/disorders/anoxia/anoxia.htm | work=National Institute of Neurological Disorders and Stroke | access-date=2009-04-28 | archive-url=https://web.archive.org/web/20090505220610/http://www.ninds.nih.gov/disorders/anoxia/anoxia.htm | archive-date=2009-05-05 | url-status=dead }}</ref>  Potential causes of brain hypoxia are suffocation, [[Medicine:Carbon monoxide poisoning|carbon monoxide poisoning]], severe [[Medicine:Anemia|anemia]], and use of drugs such as [[Biology:Cocaine|cocaine]] and other amphetamines.<ref name=MerckManual/>  Other causes associated with brain hypoxia include [[Medicine:Drowning|drowning]], [[Social:Strangling|strangling]], [[Medicine:Choking|choking]], [[Medicine:Cardiac arrest|cardiac arrest]], head trauma, and complications during general [[Medicine:Anesthesia|anesthesia]].  Treatment strategies for brain hypoxia vary depending on the original cause of injury, primary and/or secondary.<ref name="Cerebral Hypoxia Information Page" />

==See also==
* [[Medicine:Anoxic depolarization in the brain|Anoxic depolarization in the brain]]
* [[Medicine:Watershed stroke|Watershed stroke]]

==References==
{{Reflist}}

==Bibliography==
* {{cite book |first1=Eugene I. |last1=Gusev |last2=Skvortsova |first2=Veronica I. |title=Brain ischemia |publisher=Kluwer Academic/Plenum Publishers |location=New York |year=2003 |isbn=0-306-47694-0}}

==Further reading==
* Chang, Steven; Doty, James; Skirboll, Stephen; Steinberg, Gary. [https://web.archive.org/web/20070221105824/http://cgi.stanford.edu/~amlin/cgi-bin/find_specialist?action=get_description&disease=cerebralischemia Cerebral ischemia ]. ''cgi.stanford.edu''. URL last accessed February 26, 2006.{{dead link|date=May 2016}}

== External links ==
{{Medical resources
|  DiseasesDB     =
|  ICD10          = G45.9, I67.8
|  ICD9           = {{ICD9|435X,437X}}
|  OMIM           =
|  MedlinePlus    =
|  eMedicineSubj  =
|  eMedicineTopic =
|  eMedicine_mult =
|  MeshID         = D002545
}}

{{Cerebrovascular diseases}}
{{Hemodynamics}}

[[Category:Vascular diseases]]
[[Category:Stroke]]

{{Sourceattribution|Brain ischemia}}