Brain ischemia

The clinical presentation of brain ischemia varies depending on the affected vascular territory. Ischemia in the anterior circulation, particularly branches of the internal carotid artery, may present with unilateral weakness, speech disturbances, or visual loss in one eye (amaurosis fugax).Posterior circulation ischemia, involving the vertebrobasilar arteries, often leads to symptoms such as vertigo, diplopia, dysarthria, or bilateral motor deficits.Transient symptoms may indicate a TIA, while prolonged or severe cases may progress to permanent deficits due to cerebral infarction.{{cite book |title=The Merck manual of medical information |date=2003 |publisher=Merck Research Laboratories |location=Whitehouse Station, NJ |isbn=9780911910353 |edition=2nd home, [all new & completely rev.]}} Sudden loss of consciousness can occur when cerebral blood flow ceases for over 10 seconds, and irreversible brain damage generally follows within minutes.{{cite journal |last1=Hakim |first1=Antoine M. |title=Ischemic penumbra |url=https://doi.org/10.1212/WNL.51.3_SUPPL_3.S44 |journal=Neurology |pages=S44–S46 |doi=10.1212/WNL.51.3_Suppl_3.S44 |date=September 1998|volume=51 |issue=3_suppl_3 |pmid=9744833 }}

Brain ischemia results from conditions that reduce or block cerebral blood flow. Common causes of focal ischemia include arterial thrombosis due to atherosclerosis, embolism from cardiac sources such as atrial fibrillation, and small vessel disease associated with hypertension or diabetes. Global ischemia usually arises from systemic hypoperfusion following cardiac arrest or severe hypotension.{{cite journal |last1=Murphy |first1=Robert |last2=Damasceno |first2=Albertino |last3=Reddin |first3=Catriona |last4=Hankey |first4=Graeme J |last5=Iversen |first5=Helle K |last6=Oveisgharan |first6=Shahram |last7=Lanas |first7=Fernando |last8=Czlonkowska |first8=Anna |last9=Langhorne |first9=Peter |last10=Ogunniyi |first10=Adesola |last11=Wasay |first11=Mohammad |last12=Rumboldt |first12=Zvonko |last13=Judge |first13=Conor |last14=Oguz |first14=Aytekin |last15=Mondo |first15=Charles |last16=Winter |first16=Yaroslav |last17=Rosengren |first17=Annika |last18=Pogosova |first18=Nana |last19=Avezum |first19=Alvaro |last20=Nilanont |first20=Yongchai |last21=Penaherrera |first21=Ernesto |last22=Xavier |first22=Denis |last23=Lopez-Jaramillo |first23=Patricio |last24=Wang |first24=Xingyu |last25=Yusuf |first25=Salim |last26=O’Donnell |first26=Martin |title=Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case–control study |url=https://doi.org/10.1177/17474930241227783 |journal=International Journal of Stroke |pages=559–568 |language=EN |doi=10.1177/17474930241227783 |date=1 June 2024|volume=19 |issue=5 |pmid=38204182 }} Additional risk factors include smoking, hyperlipidemia, advanced age, and a history of TIA or stroke. Rare etiologies include sickle cell anemia, which promotes vascular occlusion, and Moyamoya disease, a progressive cerebrovascular disorder affecting the intracranial arteries.{{cite journal |last1=Rupareliya |first1=Chintan |last2=Lui |first2=Forshing |title=Moyamoya Disease |url=https://www.ncbi.nlm.nih.gov/books/NBK535455/ |website=StatPearls |publisher=StatPearls Publishing |date=2025|pmid=30571076 }}

When blood supply to the brain is compromised, neurons are deprived of oxygen and glucose necessary for aerobic metabolism. This leads to rapid depletion of adenosine triphosphate (ATP) within minutes. The failure of ATP-dependent ion pumps disrupts electrochemical gradients, resulting in cellular depolarization and an influx of calcium. Elevated intracellular calcium triggers glutamate release, proteolysis, and ultimately, neuronal injury.{{cite journal |last1=Lipton |first1=Peter |title=Ischemic Cell Death in Brain Neurons |url=https://doi.org/10.1152/physrev.1999.79.4.1431 |journal=Physiological Reviews |pages=1431–1568 |doi=10.1152/physrev.1999.79.4.1431 |date=10 January 1999|volume=79 |issue=4 |pmid=10508238 }} Surrounding the infarcted core is the 'ischemic penumbra,' a zone of hypoperfused tissue that retains some metabolic activity and may be salvageable with timely intervention.

Diagnosis of brain ischemia begins with prompt clinical assessment of neurological deficits, often using tools such as the NIH Stroke Scale.{{cite web |last1=Caplan |first1=Louis R |last2=Kasner |first2=Scott E |last3=Dashe |first3=John F |title=Differential diagnosis of transient ischemic attack and acute stroke |url=https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke?search=Differential%20diagnosis%20of%20brain%20ischemia.%20UpToDate.&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 |website=www.uptodate.com |access-date=10 May 2025}} Immediate brain imaging is essential to confirm ischemia and exclude hemorrhage. Noncontrast computed tomography (CT) is typically the first step due to its availability and speed. Magnetic resonance imaging (MRI) with diffusion-weighted imaging offers higher sensitivity for detecting acute ischemia. Additional studies, including CT or MR angiography and carotid Doppler ultrasound, help identify vascular occlusions or stenosis. Cardiac evaluation, such as echocardiography and ECG monitoring, may be necessary in cases with suspected embolic sources.{{cite web |title=Pathophysiology Of Disease An Introduction To Clinical Medicine, 7th Ed [ PDF][tahir 99] VRG |url=https://archive.org/details/PathophysiologyOfDiseaseAnIntroductionToClinicalMedicine7thEdPDFtahir99VRG}}

Focal brain ischemia occurs when a blood clot has occluded a cerebral vessel.{{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 | archive-date=2009-01-06 | archive-url=https://web.archive.org/web/20090106045603/http://sullydog.com/sullysites/qm/brainischemia101syllabus/syllabus/presentation1_9_2.html | url-status=dead }} Focal brain ischemia reduces blood flow to a specific brain region, increasing the risk of cell death to that particular area.{{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 }} It can be either caused by thrombosis or embolism.{{citation needed|date=February 2021}}

Global brain ischemia occurs when blood flow to the brain is halted or drastically reduced. This is commonly caused by cardiac arrest. If sufficient 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 reperfusion may be essential to protecting as much brain tissue as possible, it may also lead to reperfusion injury. Reperfusion injury is classified as the damage that ensues after restoration of blood supply to ischemic tissue. Carotid artery stenosis may cause focal brain ischemia through artery-to-artery embolism or global brain ischemia if very severe stenosis with limited to no blood flow through the carotid artery.{{citation needed|date=February 2021}}

Due to different susceptibility to ischemia of various brain regions, a global brain ischemia may cause focal brain infarction. The cerebral cortex and striatum are more susceptible than the thalamus, and the thalamus in turn is more sensitive than the brainstem.{{cite web|url=https://neuropathology-web.org/chapter2/chapter2aHIE.html|title=Neuropathology - Chapter 2: Cerebral ischemia and stroke|author=Dimitri P. Agamanolis, M.D.|access-date=2020-07-14|archive-date=2022-02-17|archive-url=https://web.archive.org/web/20220217164648/https://neuropathology-web.org/chapter2/chapter2aHIE.html|url-status=live}} Updated: October, 2017 Partial cerebral cortex infarction from global brain ischemia typically manifests as watershed stroke.{{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}}

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 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.{{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}}

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, coma, seizures, and even brain death may occur. Symptoms of brain hypoxia are similar to ischemia and include inattentiveness, poor judgment, memory loss, and a decrease in motor coordination.{{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 }} Potential causes of brain hypoxia are suffocation, carbon monoxide poisoning, severe anemia, and use of drugs such as cocaine and other amphetamines.{{cite journal |last1=Tsatsakis |first1=Aristides |last2=Docea |first2=Anca Oana |last3=Calina |first3=Daniela |last4=Tsarouhas |first4=Konstantinos |last5=Zamfira |first5=Laura-Maria |last6=Mitrut |first6=Radu |last7=Sharifi-Rad |first7=Javad |last8=Kovatsi |first8=Leda |last9=Siokas |first9=Vasileios |last10=Dardiotis |first10=Efthimios |last11=Drakoulis |first11=Nikolaos |last12=Lazopoulos |first12=George |last13=Tsitsimpikou |first13=Christina |last14=Mitsias |first14=Panayiotis |last15=Neagu |first15=Monica |title=A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse |journal=Journal of Clinical Medicine |date=23 August 2019 |volume=8 |issue=9 |pages=1295 |doi=10.3390/jcm8091295|doi-access=free |pmid=31450861 |pmc=6780697 }} Other causes associated with brain hypoxia include drowning, strangling, choking, cardiac arrest, head trauma, and complications during general anesthesia. Treatment strategies for brain hypoxia vary depending on the original cause of injury, primary and/or secondary.

Treatment of brain ischemia depends on the type, location, and timing of the event. For acute ischemic stroke, intravenous thrombolysis with tissue plasminogen activator (tPA) is recommended within 4.5 hours of symptom onset.{{cite journal |last1=Powers |first1=William J. |last2=Rabinstein |first2=Alejandro A. |last3=Ackerson |first3=Teri |last4=Adeoye |first4=Opeolu M. |last5=Bambakidis |first5=Nicholas C. |last6=Becker |first6=Kyra |last7=Biller |first7=José |last8=Brown |first8=Michael |last9=Demaerschalk |first9=Bart M. |last10=Hoh |first10=Brian |last11=Jauch |first11=Edward C. |last12=Kidwell |first12=Chelsea S. |last13=Leslie-Mazwi |first13=Thabele M. |last14=Ovbiagele |first14=Bruce |last15=Scott |first15=Phillip A. |last16=Sheth |first16=Kevin N. |last17=Southerland |first17=Andrew M. |last18=Summers |first18=Deborah V. |last19=Tirschwell |first19=David L. |title=Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association |url=https://doi.org/10.1161/STR.0000000000000211 |journal=Stroke |pages=e344–e418 |doi=10.1161/STR.0000000000000211 |date=December 2019|volume=50 |issue=12 |pmid=31662037 }} In patients with large vessel occlusions, endovascular mechanical thrombectomy offers substantial benefits when performed within 6 to 24 hours, particularly if imaging shows viable penumbral tissue.{{cite journal |last1=Nogueira |first1=Raul G. |last2=Jadhav |first2=Ashutosh P. |last3=Haussen |first3=Diogo C. |last4=Bonafe |first4=Alain |last5=Budzik |first5=Ronald F. |last6=Bhuva |first6=Parita |last7=Yavagal |first7=Dileep R. |last8=Ribo |first8=Marc |last9=Cognard |first9=Christophe |last10=Hanel |first10=Ricardo A. |last11=Sila |first11=Cathy A. |last12=Hassan |first12=Ameer E. |last13=Millan |first13=Monica |last14=Levy |first14=Elad I. |last15=Mitchell |first15=Peter |last16=Chen |first16=Michael |last17=English |first17=Joey D. |last18=Shah |first18=Qaisar A. |last19=Silver |first19=Frank L. |last20=Pereira |first20=Vitor M. |last21=Mehta |first21=Brijesh P. |last22=Baxter |first22=Blaise W. |last23=Abraham |first23=Michael G. |last24=Cardona |first24=Pedro |last25=Veznedaroglu |first25=Erol |last26=Hellinger |first26=Frank R. |last27=Feng |first27=Lei |last28=Kirmani |first28=Jawad F. |last29=Lopes |first29=Demetrius K. |last30=Jankowitz |first30=Brian T. |last31=Frankel |first31=Michael R. |last32=Costalat |first32=Vincent |last33=Vora |first33=Nirav A. |last34=Yoo |first34=Albert J. |last35=Malik |first35=Amer M. |last36=Furlan |first36=Anthony J. |last37=Rubiera |first37=Marta |last38=Aghaebrahim |first38=Amin |last39=Olivot |first39=Jean-Marc |last40=Tekle |first40=Wondwossen G. |last41=Shields |first41=Ryan |last42=Graves |first42=Todd |last43=Lewis |first43=Roger J. |last44=Smith |first44=Wade S. |last45=Liebeskind |first45=David S. |last46=Saver |first46=Jeffrey L. |last47=Jovin |first47=Tudor G. |title=Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct |url=https://doi.org/10.1056/NEJMoa1706442 |journal=New England Journal of Medicine |pages=11–21 |doi=10.1056/NEJMoa1706442 |date=4 January 2018|volume=378 |issue=1 |pmid=29129157 }} Supportive care includes blood pressure optimization, oxygenation, and management of complications such as fever and seizures. In global ischemia due to cardiac arrest, targeted temperature management (32–36 °C) may improve neurologic outcomes.{{cite journal |last1=Bernard |first1=Stephen A. |last2=Gray |first2=Timothy W. |last3=Buist |first3=Michael D. |last4=Jones |first4=Bruce M. |last5=Silvester |first5=William |last6=Gutteridge |first6=Geoff |last7=Smith |first7=Karen |title=Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia |url=https://doi.org/10.1056/NEJMoa003289 |journal=New England Journal of Medicine |pages=557–563 |doi=10.1056/NEJMoa003289 |date=21 February 2002|volume=346 |issue=8 }} Long-term care focuses on secondary prevention through antithrombotic therapy, control of vascular risk factors, and rehabilitation.{{cite journal |last1=Powers |first1=William J. |last2=Rabinstein |first2=Alejandro A. |last3=Ackerson |first3=Teri |last4=Adeoye |first4=Opeolu M. |last5=Bambakidis |first5=Nicholas C. |last6=Becker |first6=Kyra |last7=Biller |first7=José |last8=Brown |first8=Michael |last9=Demaerschalk |first9=Bart M. |last10=Hoh |first10=Brian |last11=Jauch |first11=Edward C. |last12=Kidwell |first12=Chelsea S. |last13=Leslie-Mazwi |first13=Thabele M. |last14=Ovbiagele |first14=Bruce |last15=Scott |first15=Phillip A. |last16=Sheth |first16=Kevin N. |last17=Southerland |first17=Andrew M. |last18=Summers |first18=Deborah V. |last19=Tirschwell |first19=David L. |title=Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association |url=https://doi.org/10.1161/STR.0000000000000211 |journal=Stroke |pages=e344–e418 |doi=10.1161/STR.0000000000000211 |date=December 2019|volume=50 |issue=12 |pmid=31662037 }}

The clinical outcome of brain ischemia depends on the extent of injury, time to treatment, and patient comorbidities. Rapid reperfusion has been associated with significantly improved functional recovery and reduced mortality. However, delayed treatment or severe ischemia often results in long-term neurological deficits, including motor impairment, aphasia, and cognitive dysfunction. Approximately one-third of ischemic stroke survivors experience significant disability. In cases of global ischemia, outcomes are heavily influenced by the duration of cerebral hypoperfusion and the quality of post-resuscitation care.{{cite journal |last1=Hinds |first1=C J |title=Prevention and treatment of brain ischaemia. |url=https://doi.org/10.1136/bmj.291.6498.758 |journal=BMJ |pages=758–760 |language=en |doi=10.1136/bmj.291.6498.758 |date=21 September 1985|volume=291 |issue=6498 |pmid=3929929 |pmc=1417168 }} Vascular depression and vascular dementia may develop after multiple subcortical ischemic insults, particularly in older adults.{{cite journal |last1=Baldwin |first1=Robert C. |title=Is vascular depression a distinct sub-type of depressive disorder? A review of causal evidence |url=https://doi.org/10.1002/gps.1255 |journal=International Journal of Geriatric Psychiatry |pages=1–11 |language=en |doi=10.1002/gps.1255 |date=2005|volume=20 |issue=1 |pmid=15578670 }}

{{Reflist}}

{{Cerebrovascular diseases}}

{{Hemodynamics}}

{{Authority control}}

Category:Vascular diseases

Category:Stroke

Category:Ischemia