Acute Ischemic Stroke - Basics

Stroke is defined as “rapidly developed clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 h or leading to death, with no apparent cause other than of vascular origin”

Primary Category
Secondary Category


  • According to WHO definition, Stroke is defined as “rapidly developed clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 h or leading to death, with no apparent cause other than of vascular origin”
  • The second leading cause of death globally
  • Types of Stroke:
    • Ischemic (85%)
      • Transient ischemic attack (Lasting less than 24 hours and resolves completely)
      • Major ischemic stroke
    • Hemorrhagic (15%)
      • Intracerebral hemorrhage
      • Subarachnoid hemorrhage (Mostly traumatic)
  • Ischemic stroke is much more common in young adults than hemorrhagic stroke.

Ischemic Stroke

  • Can be a transient ischemic attack (TIA) or major ischemic stroke
  • TIA is defined by the National Institute of Health as “episodes of temporary and focal cerebral (including retinal) dysfunction of vascular origin, rapid in onset which commonly last 2–15 min but occasionally up to a day (24 h)” where “resolution is swift and leaves no permanent (clinical) neurologic deficit”
  • Acute presentation of symptoms
  • Time duration is critical to determine the course of treatment & administer anti-thrombolytic therapy
TOAST Classification of Stroke Subtypes
  • Large artery atherosclerosis
  • Cardioembolic stroke
  • Small vessel occlusion
  • Stroke of other determined etiology
  • Cryptogenic stroke (Stroke of unknown etiology)
Large artery atherosclerosis
  • 15% of all ischemic strokes
  • Divided into four subtypes based upon clinical features:
    • Asymptomatic extracranial carotid stenosis
    • Symptomatic extracranial carotid stenosis
    • Extracranial vertebral artery atherosclerotic disease
    • Intracranial atherosclerotic disease
Cardioembolic stroke
  • 14-30% of all ischemic strokes
  • Associated with early and long-term recurrence risk
  • Characterized by decreased consciousness and sudden onset to maximal deficit
  • Diagnosed by the absence of arterial disease and finding a cardiac source of embolism
Small vessel occlusion
  • 25% of all ischemic stroke cases
  • Causes subcortical infarcts
  • caused by arteriolosclerosis of cerebral arterioles due to various risk factors like hypertension, diabetes

Etiology of Ischemic Stroke

  • Thrombotic: Obstruction of vessel secondary to atherosclerosis, vasculitis of the vessel itself
  • Embolic: Obstruction secondary to emboli derived from other parts of the body
  • Prognosis and outcome of stroke are significantly affected by the etiology


  • Recent increased rate of ischemic stroke hospitalizations in people aged 25–44
  • 10%-12% of total stroke patients are young adults
  • Age differences:
    • Age < 35 Years ➨ Women ﹥Men
    • Age 35 - 50 Years ➨ Men ﹥Women
  • Racial differences :
    • In the age group 35-44 years  ➨ Relative risk of 5 in blacks compared to whites
    • In the age group < 34 years ➨ Relative risk of 2.2 in blacks compared to whites

Signs and Symptoms

  • Early symptoms of stroke can be recognized by the acronym FAST
    • F - Face drooping
    • A - Arm weakness
    • S - Speech difficulty
    • T - Time to consult a doctor
  • Other symptoms include:
    • Sudden onset of numbness or weakness
    • Confusion and dizziness
    • Trouble seeing and walking
    • Severe headache

Risk Factors

Non-Modifiable Risk Factors

  • Age (risk increases with age)
  • Sex (Men > Women)
  • Previous history of TIA (Increased risk with a family history or previous history of stroke)
  • Ethnicity (Black > White)
  • Hereditary Factors (Monogenic Disorders like Fabry Disease)

Modifiable Risk Factors

  • Hypertension (Every 10 mm Hg reduction in BP ➨ 1/3rd reduced risk of stroke)
  • Drug Abuse
    • Smoking ➝ Significantly increased risk (Women > Men)
    • Alcohol ➝ Protective at a low dose, Increased risk at high dose
    • Cocaine abuse  ➝ 5.7-fold higher risk
    • Cannabis abuse ➝ 2.3-fold higher risk
  • Diabetes (2 times increased risk of stroke)
  • Atrial Fibrillation (2-5 fold increased risk of stroke)
  • Hyperlipidemia (2 fold increased risk of stroke)
  • Poor diet and insufficient physical activity

Pathophysiology of Ischemic Stroke

  • Hypoperfusion causes disruption in aerobic respiration of cells thus depleting ATP.
  • ATP depletion causes failure of Na+/K+ ATPase pump and results in depolarization and calcium influx that starts a cascade of events which eventually ends in cell necrosis and release of intracellular content (e.g. Glutamate) in the extracellular environment (Excitotoxicity).

Workup for Stroke:

Initial Evaluation

  • Secure airway, breathing, and circulation (endotracheal intubation should be done if necessary)
  • Complete history and physical examination to determine risk factors for stroke
  • Rule out hypoglycemia as a cause of neurological symptoms
  • Perform a rapid and concise neurological examination such as NIHSS
    • The National Institutes of Health Stroke Scale (NIHSS) is used to determine the severity of the stroke on the basis of 11 categories.
  • Neurological examination should be done simultaneously along with IV access and sending labs
  • A CT brain plain should be done as soon as possible to rule out intracerebral hemorrhage
  • A negative CT scan doesn’t exclude ischemia as it has a poor resolution to detect small ischemic stroke
  • MRI (Specially Diffusion-weighted imaging) is more sensitive to detect ischemia but should be ordered only if it can be done as quickly as CT Scan

Table 1: National Institute of Health Stroke Scale (NIHSS)

Level of Consciousness
0 = Alert 1 = Drowsy 2 = Stuporous 3 = Coma
Ask Month and Age
0 = Answers both correctly 1 = Answers one correctly 2 = Incorrect
Open and Close Eyes Hand Grip Squeeze
0 = Obeys both correctly 1 = Obeys one correctly 2 = Incorrect
Horizontal Extraocular Movements
0 - Normal 1 = Partial gaze palsy 2 = Forced deviation
Visual Fields
0 - No visual loss 1 = Partial Hemianopia 2 = Complete Hemianopia 3 = Bilateral Hemianopia (Blind)
Facial Palsy
0 = Normal 1 = Minor 2 = Partial 3 - Complete
Left Arm
0 = No drift 1 = Drift 3 = Can't Resist Gravity 4 = No movement X = Untestable (Joint fusion or limb amp)
Left Leg
As above
Right Arm
As above
Right Leg
As above
Limb Ataxia
0 = No ataxia 1 = Present in one limb 2 = Present in two limbs
0 = Normal 1 = Partial loss 2 = Severe loss
0 = No aphasia 1 = Mild to moderate aphasia 2 = Severe aphasia 3 = Mute
0 = Normal articulation 1 = Mild to moderate slurring of words 2 = Near to unintelligible or worse X = Intubated or other physical barrier
0 = No neglect 1 = Partial neglect 2 = Complete neglect
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Table 2: Severity Score based on NIHSS Score evaluation

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Laboratory Testing

  • Diagnosis of stroke is usually made clinically by relating neurologic abnormalities with imaging findings.
  • Following tests can be performed but anti thrombolytic therapy shouldn't wait for the result of all tests unless there is some clear contraindication to start the treatment (tPA).
    • CBC to exclude polycythemia, infection
    • Clotting Profile i.e PT, PTT, and INR to exclude clotting disorders
    • Fasting Lipid Profile to exclude hyperlipidemia
    • Blood glucose level to exclude hypoglycemia that can mimic stroke symptoms
    • Toxicology screen to exclude drug abuse and overdose
    • Serum electrolytes to exclude renal cause of the neurological abnormality
  • In some specific patients, ANA, APL ACL antibodies, VDRL for syphilis, and genetic testing can be done

Figure 1: Stroke Intervention Flowchart

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  • If imaging confirms ischemic stroke, determine the cause (origin of thrombus or embolus)
  • Perform ECG and cardiac enzymes to exclude coronary artery disease as the cause of stroke
  • Determine the cause by:
    • Carotid artery evaluation by ultrasound
    • CTA, Magnetic resonance angiography
    • Telemetry monitoring
    • Transthoracic echocardiogram (Exclude PFO)
    • Color-coded transcranial or cervical arteries duplex
    • Transcranial doppler ultrasound (TCD)


  • Recognizing the signs of stroke and seeking early treatment is critical for prognosis.
  • Imaging is the mainstay of diagnostic tests for stroke.
  • A negative plain CT scan brain doesn't exclude the possibility of an ischemic stroke.
  • If there is no contraindication to start anti-thrombolytic therapy, it shouldn't be delayed.

Further Readings

  • Yew, K. S., & Cheng, E. (2009). Acute stroke diagnosis. American family physician, 80(1), 33–40
  • Ustrell, X., & Pellisé, A. (2010). Cardiac workup of ischemic stroke. Current cardiology reviews, 6(3), 175–183.


  • Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T. Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ (1980) 58:113–30
  • Bersano A, Markus HS, Quaglini S, et al. Clinical pregenetic screening for stroke monogenic diseases: results from Lombardia GENS Registry. Stroke 2016;47:1702–1709
  • Kissela BM, Khoury JC, Alwell K, et al. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology 2012;79:1781–1787
  • Hemachandra D, McKetin R, Cherbuin N, Anstey KJ. Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Aust N Z J Public Health 2016;40:226–230
  • Tibæk M, Dehlendorff C, Jørgensen HS, Forchhammer HB, Johnsen SP, Kammersgaard LP. Increasing incidence of hospitalization for stroke and transient ischemic attack in young adults: a registry-based study. J Am Heart Assoc 2016:5: e003158
  • George MG, Tong X, Kuklina EV, Labarthe DR. Trends in stroke hospitalizations and associated risk factors among children and young adults, 1995-2008. Ann Neurol 2011;70:713–721
  • Cheng YC, Ryan KA, Qadwai SA, et al. Cocaine use and risk of ischemic stroke in young adults. Stroke 2016;47:918–922
  • Nedeltchev K, der Maur TA, Georgiadis D, et al. Ischaemic stroke in young adults: predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry 2005;76: 191–195
  • Putaala J, Yesilot N, Waje-Andreassen U, et al. Demographic and geographic vascular risk factor differences in European young adults with ischemic stroke: the 15 cities young stroke study. Stroke 2012;43:2624–2630
  • George MG, Tong X, Bowman BA. Prevalence of cardiovascular risk factors and strokes in younger adults. JAMA Neurol 2017;74:695–703
  • Adams, H. P., Jr, Bendixen, B. H., Kappelle, L. J., Biller, J., Love, B. B., Gordon, D. L., & Marsh, E. E., 3rd (1993). Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke, 24(1), 35–41.
  • Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR imaging of the brain. Radiology. 2000;217(2):331–345. Medline
  • Ntaios G. Embolic Stroke of Undetermined Source: JACC Review Topic of the Week. J Am Coll Cardiol. 2020 Jan 28;75(3):333-340
  • C. Denier, C. Flamand-Roze, F. Dib, J. Yeung, M. Solignac, L. Bayon de la Tour, M. Sarov-Rivière, E. Roze, B. Falissard & F. Pico (2015) Aphasia in stroke patients: early outcome following thrombolysis, Aphasiology, 29:4, 442-456, DOI: 10.1080/02687038.2014.971220
  • Musuka, T. D., Wilton, S. B., Traboulsi, M., & Hill, M. D. (2015). Diagnosis and management of acute ischemic stroke: speed is critical. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 187(12), 887–893.
  • Pierik R, Algra A, van Dijk E, Erasmus ME, van Gelder IC, Koudstaal PJ, Luijckx GR, Nederkoorn PJ, van Oostenbrugge RJ, Ruigrok YM, Scheeren TWL, Uyttenboogaart M, Visser MC, Wermer MJH, van den Bergh WM., on behalf of the Parelsnoer Institute-Cerebrovascular Accident Study Group. Distribution of Cardioembolic Stroke: A Cohort Study. Cerebrovasc Dis. 2020;49(1):97-104
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  • Ferro JM. Cardioembolic stroke: an update. Lancet Neurol. 2003 Mar;2(3):177-88
  • Xing C, Arai K, Lo EH, Hommel M. Pathophysiologic cascades in ischemic stroke. Int J Stroke. 2012 Jul;7(5):378-85
  • Khaku, A. S., & Tadi, P. (2021). Cerebrovascular Disease. In StatPearls. StatPearls Publishing.
  • Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337(8756):1521–1526. Medline
  • Musuka, T. D., Wilton, S. B., Traboulsi, M., & Hill, M. D. (2015). Diagnosis and management of acute ischemic stroke: speed is critical. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 187(12), 887–893.
  • Nicol, M. B., & Thrift, A. G. (2005). Knowledge of risk factors and warning signs of stroke. Vascular health and risk management, 1(2), 137–147.
  • Advisory Council for the National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20014. A classification and outline of cerebrovascular diseases II. Stroke (1975) 6:564–616.10.1161/01.STR.6.5.564
  • Chen, Z., Mo, J., Xu, J., Qin, H., Zheng, H., Pan, Y., Meng, X., Jing, J., Xiang, X., & Wang, Y. (2019). Risk Profile of Ischemic Stroke Caused by Small-Artery Occlusion vs. Deep Intracerebral Hemorrhage. Frontiers in neurology, 10, 1213.
  • National Institute of Health Stroke Scale (NIHSS)
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Written by

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Founder NeuroCare.AI, Practicing Neurologist, sub-specialized in the field of Neurocritical Care, Stroke & Epilepsy

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