Ischemic Stroke

Ischemic stroke is the commonest form of stroke. It represents infarction of the brain or spinal cord due to interruption of blood supply. There are many causes including embolism of material such as thrombus, cholesterol or rarely other material. Other mechanisms include thrombosis and miscellaneous causes of interruption of blood flow.
The symptoms vary depending on which blood vessels are affected. Occlusion of proximal blood vessels such as the internal carotid artery (ICA), middle cerebral artery (MCA), anterior cerebral artery (ACA), basilar artery (BA) and posterior cerebral artery (PCA) cause large areas of infarction. These infarcts affect cortical areas as well as subcortical tracts and structures. Perforator blood vessel occlusion such as the lenticulostriate arteries, the recurrent artery of Heubner, thalamic perforators and brainstem perforators cause smaller areas of infarction that spare the cortical structures. These are lacunar strokes and have typical syndromes. However, the clinical deficits are often disabiling regardless of the blood vessel size. Occasionally, the cortical branches of the main arteries may be affected without involvement of the proximal portions. In these cases cortical infarcts that spare the subcortical structures occur.
By understanding the functional neuroanatomy of the central nervous system and the patterns of blood supply, stroke syndromes allow localization of the area of infarction in most cases. This is important in emergency settings when dealing with acute stroke to be able to distinguish between ischemic stroke and stroke mimics.
Here are the main goals of assessment of patients with ischemic stroke:

  1. Identification of ischemic stroke patients who may be candidates for emergent reperfusion therapies.
  2. Identification of mechanism of stroke and underlying etiology to guide secondary prevention strategies. This helps prevent early and late stroke recurrence.
  3. Identification of potential complications to prevent them and to institute early therapy.
  4. Identification of rehabilitation needs.


Cerebral infarction, ischaemic stroke.


Diagnosis is confirmed by imaging demonstrating areas of infarction.

Clinical features:

  • The clinical spectrum of ischemic stroke ranges through a spectrum from silent infarction to disabiling focal neurological deficits, coma and death. Symptoms with stroke may be transient but are usually persistant.
  • Typically there is sudden onset focal neurological deficit attributable to a vascular territory. Symptoms may be stuttering. Progression may occur.
  • Malignant middle cerebral artery (MCA) syndrome:
    • Infarction =or> 2 thirds MCA territory +/-ACA infarction
    • With decreased consciousness, GCS=or <13
    • NIHSS =or>16 for non-dominant hemisphere & =or>20 for dominant hemisphere.

Causes of ischemic stroke (ischemic stroke, focal cerebral ischemia, infarction, TIA):

Vascular disorders:

  • Vasculopathy:
    • Atherosclerosis
    • Fibromuscular dysplasia
    • Carotid or vertebral artery dissection
    • Post radiation syndrome
    • Cholesterol emboli syndrome
    • Reversible cerebral vasoconstriction syndrome RCVS
    • Progressive intracranial occlusions: moyamoya syndrome
    • Aortic dissection
    • Lacunar infarction
  • Vasculitidis (cerebral vasculitis a.k.a. cerebral vasculitidis):
    • Autoimmune Vasculitis:
      • Granulomatous angiitis of the CNS, primary angiitis of the CNS
    • Large vessels:
      • Giant cell arteritis
      • Takayasu arteritis
    • Connective tissue disease:
      • Systemic lupus erythematosus
      • Sjogren syndrome
      • Microscopic Polyarteritis
      • Wegener granulomatosis
      • Churg-Strauss syndrome
    • Kawasaki syndrome
    • Behcet disease
  • Infectious Vasculitis:
  •  Bacterial:
    • Lyme disease
    • Syphilitic arteritis (meningovascular syphilis)
    • Rickettsial
    • Meningovascular TB,
    • Viral: Varicella-Zoster Virus VZV, EBV
    • Fungal: Mucormycosis,
    • Parasitic: malaria, Schistosomiasis
    • Malignancy associated
    • Drug induced
    • Cerebral autosomal dominant angiopathy with subcortical infarcts & leukoencephalopathy CADASIL
    • Migraine
    • Drug abuse:
      • Cocaine, amfetamine
      • – Venous or venous sinus thrombosis
    • Mitochondrial encephalomyopathy lactic acidosis & stroke MELAS

Cardiac disorders

  • Arrhythmias
  • Mural thrombus
  • Rheumatic heart disease
  • Endocarditis
  • Mitral valve prolapse
  • Prosthetic heart valves
  • Paradoxic embolus
  • Atrial myxoma

Hematologic disorders:

  • Sickle cell disease
  • Thrombocytosis: >1,000,000/microL
  • Polycythemia: Hematocrit >46%
  • Leukocytosis >150,000/microL
  • Hypercoagulable states
  • Intravascular lymphoma

Causes of deterioration after an ischemic stroke:

  • Cerebral edema of the stroke
  • Hemorrhagic transformation of the stroke
  • Metabolic
  • Infection

DDx. ischemic stroke ‘focal cerebral ischemia, ischemic stroke’:

  • Migraine
  • Vascular:
    • Intracerebral hemorrhage
    • Subdural hematoma
    • Extradural hematoma
    • Subarachnoid Masses:
    • Brain abscess
    • Tumor
  • Metabolic:
    • Hypoglycemia
    • Hyperosmolar nonketotic hyperglycemia

Findings on Investigations:

CT noncontrast:

  • Rules out hemorrhage
  • In the early phase, initial few hours: no changes on CT
  • Extensive hypodensity e.g. >1/3 area of MCA territory, is considered a contraindication to TPA
  • Early, after a few hours:
    • Loss of grey-white matter differentiation e.g. loss of insular ribbon
    • Effacement of sulci: vasogenic oedema.
    • +/-hemorrhage
    • Hyperdense arteries e.g. proximal MCA, basilar artery, vertebral arteries: thrombosis
  • By 24 hours:
    • Hypodensity that matches the territory of the involved artery. Typically wedge shaped in cortical infarcts
    • Posterior circulation: ‘tiger eye’ hypodensity of small part of the thalamus due to perforators, occipital area hypodensity
    • Lacunar infarct: Hypodensity in basal ganglia, thalami, periventricular white matter
  • By day 2-4:
    • Features of oedema +mass effect
    • Acute oedema: area hypodense to white matter but hyperdense to CSF
    • Mass effect: effacement of the cerebral sulci, sylvian fissure or other basal cisterns, or compression of the ventricular system (this lasts <4 weeks)
    • If CT with contrast: Gyral enhancement (enhancement of the gyri) occurs.
  • Chronic:
    • Focal volume loss +dilation of the adjacent ventricle: evidence of encephalomalacia

CT angiography (CTA):

  • Shows major vessel occlusion (ICA, MCA M1 M2, basilar) or dissections
  • Shows atherosclerosis & stenosis (carotid, MCA, PCA, Basilar)
  • Shows anatomic variations
  • Shows leptomeningeal collaterals

CTP, CT perfusion:

  • e.g. by TTP time-to-minimum-perfusion (Time to peak)
  • e.g. by MTT mean transit time: prolonged in affected area (core infarct+penumbra).
  • Cerebral blood volume CBV: reduced in core infarct
  • Shows the core infarct+ischemic penumbra
  • Uses contrast
  • CTP, MR perfusion PWI criteria for anterior circulation LVO stroke:
    • The core infarct lesion measured 50 ml or less,
    • The volume of tissue with a time to maximum delay of more than 10 seconds was 100 ml or less
    • And the mismatch volume was at least 15 ml
    • And the mismatch ratio was more than 1.8:1.0


  • Early: shows areas of infarction within minutes
  • Edema in gyri on T2
  • Effacement of adjacent subarrachnoid space
  • Loss of signal void in vessels a.k.a. Arterial enhancement (high signal in artery on noncontrast T1, T2): slow flow vs. thrombus
  • Lacunar infarct:
    • T1: low signal intensity
    • T2: high signal intensity
  • T1 +contrast: Gyral enhancement occurs at <6 weeks, nhancement of adjacent meninges with gadolinium
  • FLAIR: Distal Hyperintense vessels may indicate collateral perfusion.
  • Hemorrhagic transformation/Hemorrhagic conversion (HT): petechial or confluent hemorrhage within the ischemic lesion starts in the periphery
  • Parenchymal hemorrhage (PH): blood clots in the infarcted area with at least slight space-occupying effect.
  • DWI MRI (diffusion weighted MRI)
  • Shows the core infarct & shows it the earliest
  • Lasts up to 10 days
  • High signal on DWI within a vascular territory. On apparent diffusion coefficient ADC map it is low signal
  • Nonspecific
  • False negatives occur in brain stem strokes & vertebrobasilar strokes <24hrs. [312]

PWI MRI (Perfusion weighted MRI)

  • e.g. by TTP time-to-minimum-perfusion (Time to peak)
  • Shows the core infarct+ischemic penumbra
  • With gadolinium contrast reduce signal in areas with slow or no flow.
  • Diffusion/perfusion mismatch shows ischemic penumbra. [DIFFUSE]
  • CTP, MR perfusion PWI criteria for anterior circulation LVO stroke:
    • The core infarct lesion measured 50 ml or less,
    • The volume of tissue with a time to maximum delay of more than 10 seconds was 100 ml or less
    • And the mismatch volume was at least 15 ml
    • And the mismatch ratio was more than 1.8:1.0


  • Shows major vessel occlusion e.g. loss of signal void.
  • Can exclude 50-99% stenosis of large vessels. [SONIA]
  • Turbulant flow can look like stenosis
  • Tight focal stenosis can look like 2-3 cm stenosis because of turbulance

MRI vessel wall imaging:

  • T1 +fat saturated: hyperintense serpentine hemorrhage within the vessel wall

Transcranial dopper TCD:

  • Can exclude 50-99% stenosis of large vessels in some patients but other tests are preferable. [SONIA]

Catheter Angiography:

  • Demonstrates areas of occlusion. Occlusion of blood vessel, bare areas in capillary phase
  • Increased Capillary blush if a few hours from onset
  • Demonstrates collateral flow
  • Luxury perfusion (also seen on SPECT/angiography): early venous drainage, +transient blush. Occurs at 2-4 weeks

SPECT, acetazolamide for rCBF, IMP iodine amphetamine: [234]

  • Central area:
    • Acutely: Reduced uptake & blood flow rCBF
    • Subacute: Luxury perfusion (nonnutritional perfusion): increased perfusion rCBF of the infracted area after a stroke that disappears later on.
    • Chronic: decreased rCBF
  • Peripheral area (surrounds the infarct):
    • Slight decrease in rCBF & IMP uptake ~contrast enhancement.
  • If tPA is used:
    • Increased perfusion in areas that remain reperfused (nutritional perfusion) ~recovered tissue
    • Luxury perfursion (nonnutritional perfusion) occurs in areas that then become unperfused i.e. infarct


  • Acute 12-24 hrs: pallor, eosinophilic neurons “ischemic change a.k.a. red dead neurons”
  • Subacute 2 days- 2 weeks: macrophages, capillary proliferation, reactive astrocytes
  • Chronic months- years: cavitation, macrophages, reactive astrocytes
  • Lacunar stroke: lipohyalinosis

Useful scales and classifications:

National Institutes of Health Stroke Scale NIHSS:

0 is normal
1a. LOC Level of consciousness Alertness 0-3
1b. LOC responses 0-2
1.c LOC Following commands 0-2
2. Best Gaze 0-2

  •  Normal
  • Gaze palsy
  • Forced deviation or Gaze paralysis

3. Visual fields 0-3

  • Normal
  • Partial hemianopia
  • Completel hemianopia
  • Bilateral hemianopia or  cortical blindness

4. Facial palsy 0-3
5a. Motor arms drift in 10s left 0-4

  • Normal
  • Some drift
  • Some effort against gravity
  • No antigravity movement
  • No movement

5b. Motor arms drift in 10s right 0-4

  • Same scale as left arm

6a. Motor legs in 5s left 0-4

  • Same scale as left arm

6b. Motor legs in 5s right 0-4

  • Same scale as left arm

7. Limb ataxia 0-2

  • Finger-nose, heel-shin

8. Sensory 0-2

  • Pin-prick

9. Best language 0-3
10. Dysarthria 0-2
11. Extinction & hemi-inattention 0-2

  • Sensory & Visual stimulation
Modified Rankin scale:

0, No symptoms at all
1, No significant disability despite symptoms; able to carry out all usual duties and activities
2, Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
3, Moderate disability; requiring some help, but able to walk without assistance
4, Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
5, Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6, Dead

Oxfordshire Community Stroke Project Classification:
  • Total anterior circulation infarction
  • Partial anterior circulation infarction
  • Posterior infarction
  • Lacunar infarction
TOAST classification:
  • Large-artery atherosclerosis
  • Cardioembolism
  • Small-vessel occlusion
  • Stroke of other determined aetiology
  • Stroke of undetermined aetiology


Investigations in Ischemic Stroke

General points:

  • Basic investigations in every patient include vascular imaging of extracranial and intracranial blood vessels, ECG, echocardiogram and at least 24 hours of monitoring for paroxysmal atrial fibrillation
  • Extensive work up is still necessary in Lacunar stroke
  • In the ER CT non-contrast and CTA are necessary emergently to exclude intracerebral hemorrhage and identify large vessel occlusion respectively. This helps identify patients who may be candidates for emergent reprefusion therapies

Blood tests:

  • FBC, Coagulation screen, Blood Glucose, blood chemistry panel,
  • Fasting: Cholesterol, Lipids, glucose
  • ESR in some cases: vasculitides, giant cell arteritis.

Cardiac evaluation:

  • Necessary even in lacunar stroke
  • Initial evaluation includes ECG, echocardiogram and at least 24 hours of cardiac rhythm monitoring
  • ECG: assess for Atrial fibrillation, and signs of cardiac ischemia
  • Cardiac monitor for at least 24 hours. But subsequent trials show higher yield of detecting paroxysmal atrial fibrillation with longer monitoring

Holter monitor:

  • 24-48hrs. Detects additional patients with AF
  • If =or> 70 atrial premature beats/24hr, higher risk of Paroxysmal AF: 7 day event recorder
  • If no other cause on vascular imaging and echocardiogram and >45 years old consider long-term holter monitor or implantable recorder

Transthoracic echocardiogram:

  • Valvular disease, left atrial thrombus, mural thrombus, aortic arch atheroma, patent foramen ovale

Transesophageal Echocardiogram TEE +bubble study:

  • Especially if other tests don’t reveal the mechanism
  • Valvular disease, left atrial thrombus, mural thrombus, aortic arch atheroma, patent foramen ovale
  • If there is contrast in right atrium & left atrium: shunt is present

Vascular evaluation:

  • Necessary in every patient. Must evaluate extracranial and intracranial vascular anatomy


  • Allows rapid evaluation of extracranial and intracranial circulation
  • Good screening test for extracranial internal carotid artery stenosis, vertebral artery stenosis, intracranial stenosis and for large vessel occlusion


  • Allows evaluation of extracranial and intracranial circulation
  • Good screening test
  • May mistakenly show high grade stenosis as occlusion

Carotid artery duplex ultrasound (B mode ultrasound +doppler)

  • Good for extracranial internal carotid artery atherosclerotic stenosis if validated in the insitution against catheter angiography
  • Poor test for vertebral artery disease
  • Poor test for intracranial stenosis
  • Difficult to interpret with multiple occlusion and with dissection

Catheter Angiography:

  • Useful if there are discrepencies between non-invasive tests
  • Useful if planning therapy
  • Useful in intracranial atherosclerotic disease
  • Useful in non-atherosclerotic stenosis


  • For cardiomegaly (chronic hypertension), aortic dissection
  • Not necessary prior to thrombolysis

Speech and language therapy assessment:

  • Dysphagia swallowing screen: can be performed by nurses
  • Test feeds
  • Formal evaluation by speech and language pathologist if positive screen or brainstem stroke
Investigations to consider if relevant:

Blood tests:

  • Homocysteine level
  • Vasculitic screen [ESR, CRP, ANA screen, ENA panel (anti- dsDNA, anti-Sm, anti-RNP, SSA, SSB, anti-Jo-1, antitopoisomerase ‘formerly anti Scl-70’, antinucleolar, anticentromere), ANCA (c-ANCA, p-ANCA), Complement C3, C4 and CH50],
  • Antiphospholipid antibodies: Anticardiolipin antibodies [APASS], lupus anticoagulant.
  • Serum protein electrophoresis SPEP, B2 microglobulin,
  • Plasma hemoglobin electrophoresis: Sickle cell disease
  • Cryoglobulins
  • Consider Thrombophilia screen (see below, except anticardiolipin antibodies): if young, not if old. Repeat test regardless of result and assess for venous thromboembolism
  • If suspecting vasculitis: lyme serology.

Thrombophilia screen in selected patients:

  • Factor V Leiden Mutation
  • Anticardiolipin antibody
  • Lupus-anticoagulant:
    • aPTT is usually prolonged. Also do a manual aPTT screen (different phospholipid composition), or hexagonal PL screen (uses very dilute aPTT reagent making it sensitive to phospholipids)
    • Do a mixing study aPTT (immediate and delayed mixing study) or dRVVT (see below): 1:1 (patient plasma:control plasma) Failure to correct indicates an inhibitor, Correction with mixing indicates factor deficiency. Delayed mixing study is to look for slow inhibitors (e.g. factor VIII inhibitor).
    • dilute Russelll Viper Venom Test (dRVVT) mixing study is prolonged in lupus anticoagulant or factor inhibitor. It’s a type of mixing study using snake venom (activates factor X).
    • Do Phospholipid (PL) dependence confirmatory test (adding phospholipid shortens/corrects the clotting time): e.g. dRVVT confirm ratio (i.e. dRVVT screen/dRVVT confirm). Or hexagonal PL confirm (basically hexagonal screen+PL, then calculate, Delta=hexagonal PL screen – hexagonal PL confirm). Or platelet neutralization (PNP).
    • Then Rule out inhibitors including factor VIII inhibitor
    • Then recheck panel in 12 weeks
  • Thrombin Time: necessary for lupus anticoagulant interpretation in some cases
  • Protein S: deficiency
  • Protein C antigen & activity: deficiency
  • Antithrombin (formerly Antithrombin III): deficiency
  • Prothrombin gene variant G20210A
  • Activated protein C ratio (APC ratio) i.e. effect of APC on PTT: poor response =Activated protein C resistance
  • Homocysteine levels
  • HITS antibody (IgG antibody against heparin-platelet factor 4 complex)
  • Also do: FBC, coagulation screen, fibrinogen levels
  • Consider:
    • Plasminogen activator inhibitor PAI-1 levels: PAI-1 deficiency

Urine toxicology: cocaine, amfetamines
CSF analysis, LP:

  • Subarachnoid hemorrhage, syphilis
  • Pleocytosis in VZV vasculopathy vasculitis
  • Anti-VZV IgG, serum/CSF ratio of VZV IgG & VZV PCR: IgG is more sensitive, VZV vasculopathy


  • Troponin T: associated with increase mortality.
  • 3 blood cultures: Infective Endocarditis even though hemorrhagic stroke is more common in infective endocarditis
  • Stress testing for coronary artery disease

Transcranial Doppler ultrasound TCD:

  • Decreased flow: proximal stenosis
  • Increased flow: spasm of the artery e.g. middle cerebral artery
  • Confirm crossfilling of MCA from contralateral carotid
  • With contrast: confirms Right to left shunt.

CT thorax, abdomen & pelvis::

  • for underlying cancer, Pulmonary AVM
  • for underlying neoplasm in paraneoplastic hypercoaguable states and paraneoplastic vasculitis

Videofluroscopy: for swallow assessment, be aware of normal aging changes


Assess for emergency reperfusion therapies:

This is an emergency, activate the stroke team protocol and proceed per local institution guidelines. Here are some points:

  • Emergent CT head and CTA head and neck to assess for emergency reperfusion therapies
  • Finger stick glucose test
  • Obtain IV access for CTA and potential thrombolysis

BP management prior to reperfusion:

  • Do not lower BP unless it is outside parameters for thrombolysis avoid hypotension
  • Non-thromboysis candidates:
    • Treat if >220/120 mmHg, but lower it slowly. consider Labetalol, or Nicardipine or other agents
  • Thrombolysis candidates:
    • Goal <185/110 mmHg. consider Labetalol, or Nicardipine or other agents

If patient meets criteria for thrombolysis proceed to thrombolysis without delay. [Multiple RCT and meta-analysis, standard of care]
If patient meets criteria for neuroendovascular stroke therapy proceed to endovascular therapy without delay. [Multiple RCT and meta-analysis, standard of care]

Reperfusion strategies:
  • Intravenous thrombolytic therapy I.V.: [NINDS-rtPA, ECASS-3, SITS-MOST, Meta-analysis]
  • Alteplase intravenously within 4.5 hours. Review indications, contraindications & post procedure care
  • Avoid Aspirin or anticoagulants for 24 hours

NeuroEndovascular stroke therapy:

  • Mechanical thrombectomy is proven efficacious for patients with proximal large vessel occlusion (LVO) ischemic stroke [multiple RCTs, MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT, and meta-analysis]
  • Stent-retrievers are more efficacious than MERCI device. [SWIFT, TREVO]. Studies using MERCI device along did not show benefit. [IMS3, MR RESCUE]
  • Intraarterial therapy with alteplase alone is probably not effective compared to intravenous alteplase. [IMS3, Synthesis]
  • Indicated for patients with large vessel occlusion LVO strokes in anterior circulation (ICA, MCA) within 6 hours of last known well (LKW) with CT/CTA selection [HERMES metaanalysis, MRCLEAN, ESCAPE, SWIFT PRIME, EXTEND IA, REVASCAT]
  • Indicated for patients with large vessel occlusion LVO strokes in anterior circulation (ICA, MCA) within 6-24 hours of last known well (LKW) with CT/CTA/CTP or MRI/PWI/DWI selection [DAWN trial].
  • Indicated for patients with posterior circulation LVO strokes within 24 hours depending on clinical-imaging criteria [observational studies]


Admit to stroke unit:

General measures:

  • Nurse head-down (flat) initially (<24hours) to improve perfusion vs. >30 degrees later to prevent pneumonia
  • Nothing by mouth & cough/gag/swallow assessment, then restart feeding
  • Temperature control: Acetaminophen/paracetamol if >37 degrees. [post hoc of RCT]
  • Monitor BP
  • Treat Hyperglycemia:
    • Insulin to prevent worsening of the pathology of the ‘ischemic penumbra’ [Theoretical basis]
    • GIK (GKI, glucose potassium insulin infusion) may be used safely. [GIST]
    • Insulin sliding scale is also an acceptable option and easier for most cases
  • Skin care, mobilize to prevent pressure ulcers
  • Early mobilization. Safe to start 24 hours after stroke onset. Safe to start rehabilitation 24 hours after stroke onset.
  • Prevention of contractures, range of motion exercise by nurses and care-givers
  • DVT prophylaxis:
    • Graduated compression stockings/thromboembolic deterrent stockings TED stockings are inefficacious. [CLOTS1].
    • LMW heparin rather than heparin [PROTECT, RCT]
    • Early mobilisation


Secondary prevention:

Antiplatelets VS anticoagulation depending on mechanism
Extracranial carotid artery stenosis:

  • Antiplatelets: Aspirin, clopidogrel, cilostazole. [IST,CAST, UK-TIA, NINDS-rtPA, ESPRIT,]
  • Statin
  • Blood pressure control
  • Smoking cessation if smoker
  • Diabetes mellitus control if diabetic
  • Plus revascularization with carotid artery stenting or carotid endarterctomy if stenosis is >70 % per NASCET criteria. [NASCET, ECST, CREST, ICSS, SAPPHIRE]

Extracranial vertebral artery stenosis:

  • Antiplatelets: Aspirin, clopidogrel, or cilostazole. [IST,CAST, UK-TIA, NINDS-rtPA, ESPRIT,]
  • Statin
  • Blood pressure control
  • Smoking cessation if smoker
  • Diabetes mellitus control if diabetic

Intracranial Atherosclerotic disease (ICAD):

  • Antiplatelets:
    • Aspirin, clopidogrel, or cilostazole. [WASID, IST,CAST, UK-TIA, NINDS-rtPA, ESPRIT,]
    • Consider aspirin plus clopidogrel for 3 months, then single antiplatelet after that. [SAMMPRIS]
    • Aspirin as effective as warfarin in this subtype but with lower hemorrhage risk. [WASID]
  • Statin
  • Blood pressure control
  • Smoking cessation if smoker
  • Diabetes mellitus control if diabetic

Small vessel disease:

  • Antiplatelets: Single antiplatelet therapy. Aspirin, clopidogrel, or cilostazole. [SPS3, MATCH]
  • Statin
  • Blood pressure control
  • Smoking cessation if smoker
  • Diabetes mellitus control if diabetic

Cardioembolic due to atrial fibrillation:

  • Anticoagulation:
    • Timing is controversial but should be initiated by 2 weeks at the most. Usually prior to guided by risk of hemorrhagic transformation
    • Apixaban, dabigatran, warfarin, rivaroxaban, or edoxaban. [ARISTOTLE, AVERROS, RE-LY, BAFTA, ACTIVE-W, ACTIVE-A, ROCKET-AF, RCTs]
    • Avoid therapeutic enoxaparin. [Meta-analysis shows NNT and NNH are similar 33 and 35]
  • Statin
  • Blood pressure control
  • Smoking cessation if smoker
  • Diabetes mellitus control if diabetic

Extracranial cervical artery dissection (carotid artery or vertebral artery):

  • Antiplatelets or anticoagulation are both effective. [CADISS]

Paradoxical embolism:

  • Anticoagulation or antiplatelets
  • No benefit to closure of patent foramen ovale (PFO)

Infective endocarditis:

  • Intravenous antibiotics
  • Avoid anticoagulations
  • Surgery in some patients


Risk factor optimization:

Blood pressure control:

  • No benefit to early rapid reduction of blood pressure, but significant benefit from long-term treatment of hypertension. [WASID, SAMMPRIS, PROGRESS]
  • Gradually reduce the blood pressure during the subacute phase of stroke.
  • Agents:
    • ACEi +thiazide: Perindopril P.O. +indapamide P.O. [PROGRESS]
    • Calcium channel blockers
    • Beta blockers
    • Direct vasodilators
    • Other agents

Lipid management:

  • Goal: LDL <1.8mmol/l (70mg/dl), or high does statin regardless of LDL.
  • Statin pravastatin P.O. to reduce coronary events & secondary prevention [HPS]
  • Agents: Atorvastatin P.O. [SPARCL]

Diabetes & hyperglycemia:

  • Acutely, avoid hyperglycemia
  • Chronically, screen for & treat diabetes

Smoking cessation
Alcohol: reduce if heavy alcohol consumption
Obesity: targets BMI of 18.5 to 24.9 kg/m2 and a waist circumference of <88cm (35inch) for women and <102cm (40 inch) for men
Diet, exercise

Complications and related issues:

Malignant MCA syndrome (space occupying middle cerebral artery infarction cerebral edmea) with hemispheric infarct & patients 18-60 years old within 48hrs and in some patients older than 60 years old:

  • Hemicraniectomy.[HAMLET, DECIMAL, DESTINY & metanalysis] [312]
  • Adjuncts to decompression:
    • Osmotherapy: 3% NaCl &/or Mannitol (see under cerebral oedema for dosing etc)
    • Hyperventilation, very temporary measure
    • Corticosteroids are not used

Impending herniation with cerebellar infarct:

  • Posterior fossa decompression, Suboccipital craniotomy
  • Osmotherapy: 3% NaCl &/or Mannitol 20% or 25%



Safe to start 24 hours after stroke onset
Core compoennts:

  • Early mobilization
  • Speech & language therapy
  • Physical therapy
  • Occupational therapy

3-9 months post stroke: Consider intensive 2-week program of constraint-induced movement therapy CIMT [EXCITE]:

  • Up to 6 h each weekday of using the paretic limb for functionally relevant repetitive tasks,including shaping procedures.
  • +Restraint of the less affected wrist & hand during most waking hours.


Primary prevention of stroke:

Risk factor control:

  • Blood pressure control
  • Smoking cessation if smoker
  • Lipid control [HPS, LIPID]
  • Diabetes mellitus control if diabetic
  • Physical activiy

Antiplatelet agents in selected patients.
Rapid evaulation and treatment of transient ischemic attacks (TIA) [CHANCE]

Related articles:


  1. Statins after ischemic stroke and transient ischemic attack: an advisory statement from the Stroke Council, American Heart Association and American Stroke Association. Stroke, 2004. 35(4): p. 1023.
  2. Adams, H.P., Jr., et al., Guidelines for the early management of patients with ischemic stroke: A scientific statement from the Stroke Council of the American Stroke Association. Stroke, 2003. 34(4): p. 1056-83.