Overview

Definition

An ischemic stroke is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism or, rarely, due to systemic hypoperfusion.

Epidemiology

• Incidence: 800,000 cases per year in the US
• 2nd leading cause of death worldwide
• 2nd most common cause of disability in adults
• Prevalence increases with age.
• Approximately 80%–85% of all strokes are ischemic (15%–20% are hemorrhagic).
• Of the ischemic strokes, approximately 80% are thrombotic (20% are embolic).
• The most common embolic cause is atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation with thromboembolism.

Etiology/classification

Thrombotic stroke:

• Large-vessel occlusion: middle cerebral artery (MCA), posterior cerebral artery, anterior cerebral artery
  • Causes:
    • Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis (most common cause) → large-vessel thrombosis due to a clot on an established plaque
    • Arteritis/vasculitis
    • Arterial dissection
    • Moyamoya disease (spontaneous occlusion of the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries around the circle of Willis (rare))
  • Most common locations:
    • Bifurcation of the common carotid artery
    • MCA
    • Intracranial vertebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries proximal to the middle basilar artery
    • Origin of the vertebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries
  • Less common locations:
    • Origin of the common carotid artery
    • Posterior cerebral artery
    • Origin of the major branches of the vertebral basilar arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries
    • Origin of the branches of the anterior, middle, and posterior cerebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries
• Small vessel occlusion = lacunar infarcts:
  • Causes:
    • Lipohyalinosis due to hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis at the origin of the small vessel or large parent artery
  • Least likely to have embolic occlusion
  • Location:
    • Small penetrating arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries that arise from the distal vertebral artery, basilar artery, stem of the MCA, or the circle of Willis
    • Most often in the deep penetrating vessels that reach the white matter and deep gray matter in the thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus, basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia, or pons

Embolic stroke:

• Cardiac sources:
  • Left atrial thrombi/ atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation (most frequent isolated cause)
  • Left ventricular thrombus
  • Atrial fibrillation
  • Recent MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction (< 1 month)
  • Rheumatic mitral or aortic valve disease
  • Bioprosthetic and mechanical heart valve emboli
  • Carotid atherosclerosis 
  • Bacterial endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis (septic emboli)
  • Patent foramen ovale Patent Foramen Ovale A patent foramen ovale (PFO) is an abnormal communication between the atria that persists after birth. The condition results from incomplete closure of the foramen ovale. Small, isolated, and asymptomatic PFOs are a common incidental finding on echocardiography and require no treatment. Patent Foramen Ovale
  • Arterial dissection (rupture of an arterial wall followed by thrombus formation and embolization)
• Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis may also be embolic (in addition to thrombotic).
  • Iatrogenic embolization after an angiogram or other vascular procedures
  • Emboli released during carotid artery surgery

Systemic hypoperfusion:

• Usually global/bilateral and does not affect isolated regions
• Watershed regions between major cerebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries are the most vulnerable.
• Causes:
  • Heart failure with severely reduced cardiac output
  • Cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest or serious arrhythmia

Risk factors

• Hypertension (most important)
• Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
• Smoking
• Hyperlipidemia
• Carotid stenosis
• Previous history of stroke or transient ischemic attack Transient ischemic attack Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA) ( TIA TIA Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA))
• Heart disease:
  • Atrial fibrillation
  • Valvular heart disease
  • Cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Overview of Cardiomyopathies
• Older age
• Migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache with aura
• Hypercoagulable states Hypercoagulable states Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States:
  • Antiphospholipid syndrome Antiphospholipid syndrome Antiphospholipid syndrome (APLS) is an acquired autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies, which create a hypercoagulable state. These antibodies are most commonly discovered during a workup for a thrombotic event or recurrent pregnancy loss, which are the 2 most common clinical manifestations. Antiphospholipid Syndrome
  • Cancer/malignancy
  • Pregnancy
  • Oral contraceptive use (especially in women > 35 years who smoke)
• Genetic conditions: cerebral autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
• Blood disorders:
  • Sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease
  • Protein C or protein S deficiency (usually congenital; can also be acquired)
  • Factor V Leiden (resistance to activated protein C)
  • Essential thrombocytosis
  • Polycythemia vera Polycythemia vera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of RBCs. In addition, the WBC and platelet counts are also increased, which differentiate PV from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera

Management

The goal of stroke management is to ensure prompt intervention and optimal outcomes. If possible, restoration of adequate blood flow to the injured regions and saving the ischemic penumbra from permanent injury should be attempted.

Initial management

• Assess airway, breathing, and circulation (ABC).
• Treat hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia or hyperglycemia accordingly (may masquerade as stroke).
• IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids
• Assess for reperfusion therapy: ideally administered within 60 minutes of arrival to the ED
• Criteria for thrombolysis with the recombinant tissue plasminogen activator (tPA) alteplase or other agents:
  • Diagnosis of ischemic stroke causing neurologic deficits (and not improving)
  • < 4.5 hours after the onset of symptoms
  • ≥ 18 years of age
  • Absolute contraindications to thrombolytic therapy:
    • Intracranial hemorrhage on CT
    • Clinical presentation suggestive of subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage (SAH)
    • Neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery, head trauma Head trauma Head trauma occurs when external forces are directed to the skull and brain structures, resulting in damage to the skull, brain, and intracranial structures. Head injuries can be classified as open (penetrating) or closed (blunt), and primary (from the initial trauma) or secondary (indirect brain injury), and range from mild to severe and life-threatening. Head Trauma, or stroke in the previous 3 months
    • Uncontrolled hypertension Uncontrolled hypertension Although hypertension is defined as a blood pressure of > 130/80 mm Hg, individuals can present with comorbidities of severe asymptomatic or "uncontrolled" hypertension (≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic) that carries with it a significant risk of morbidity and mortality. Uncontrolled Hypertension (systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg)
    • History of intracranial hemorrhage
    • Known intracranial arteriovenous malformation, neoplasm, or intracranial aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Extremity and Visceral Aneurysms
    • Active internal bleeding
    • Suspected or confirmed endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
    • Known bleeding diathesis with platelet count < 100,000/μL
    • Elevated PTT with heparin administered in the last 48 hours or with the use of oral anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
    • Glucose < 50 mg/dL
  • Relative contraindications:
    • Recent GI or urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract bleeding (past 21 days)
    • Minor or rapidly improving stroke symptoms
    • Major surgery or serious nonhead trauma in the past 14 days
    • Seizure at stroke onset
    • Recent arterial puncture at a noncompressible site
    • Recent lumbar puncture
    • Post- MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
    • Pregnancy
  • Other additional cautions:
    • Age > 80 years
    • History of prior stroke and diabetes
    • Use of any active anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants (even with INR < 1.7)
    • NIHSS score > 25 (severe stroke)
    • CT with multilobar infarction (hypodensity > ⅓ of a cerebral hemisphere)
• Continuous blood pressure monitoring:
  • < 180/105 mm Hg for the 1st 24 hours
  • If necessary, reduction of blood pressure with IV labetalol or other agents
• Endovascular therapy:
  • Mechanical embolectomy or angioplasty using catheters
  • Indicated in occlusion of larger vessels (e.g., MCA) regardless of previous tPA administration
  • Indications for procedure initiation:
    • Must be within 6 hours of symptom onset
    • High baseline level of function prior to the stroke
    • NIHSS > 6 and minimal tissue damage on CT
• Antithrombotic therapy if reperfusion is not feasible: Aspirin or other antiplatelet agents Antiplatelet agents Antiplatelet agents are medications that inhibit platelet aggregation, a critical step in the formation of the initial platelet plug. Abnormal, or inappropriate, platelet aggregation is a key step in the pathophysiology of arterial ischemic events. The primary categories of antiplatelet agents include aspirin, ADP inhibitors, phosphodiesterase/adenosine uptake inhibitors, and glycoprotein IIb/IIIa inhibitors. Antiplatelet Agents are given within 24–48 hours after symptom onset.
• Compression socks to prevent deep vein thrombosis Deep vein thrombosis Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis ( DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis) and pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism 
• Urgent neurologic consultation
• Neurosurgical consultation if evidence of brain edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema or herniation

Rehabilitation

• PT to improve neurologic function and reduce the risk of contractures
• Occupational therapy:
  • Improves the quality of life
  • May need splinting of hands to prevent contractures
• Swallowing assessment to prevent aspiration
• Speech therapy
• Careful attention to prevent complications due to immobility:
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Pressure ulcers
  • Limb contractures
• Careful assessment of the ability to drive safely
• Family and patient education:
  • Continuation of preventive measures at home
  • The FAST mnemonic is helpful for lay individuals to identify recurrence:
    • Facial droop
    • Arm weakness
    • Speech abnormality
    • Time

Prevention of recurrence

• Lifestyle changes:
  • Healthy diet (e.g., Mediterranean diet)
  • Exercise as tolerated; weight loss if obese
  • Smoking cessation counseling if applicable
• Risk-factor management with improved control of:
  • Diabetes
  • Hypertension
  • Hyperlipidemia
• Medications:
  • Dual antiplatelet therapy unless contraindicated
    • Aspirin
    • Clopidogrel or extended-release dipyridamole
  • Statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins (e.g., atorvastatin) in clinically important atherosclerotic disease
• Treatment of underlying causes (e.g., atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation) and anticoagulation as indicated

Complications and prognosis

Complications:

• Cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema:
  • Accumulation of water in the cerebral parenchyma if ischemic injury goes without management for the 1st few days
  • May lead to obstructing hydrocephalus or brain herniation
• Adverse reactions to tPA thrombolysis:
  • Bleeding complications
  • Decline in neurologic status

Prognosis depends on these predictors of outcomes:

• Stroke severity/extent of infarction
• Age
• Time elapsed from symptom onset to diagnosis and management
• Length and intensity of therapy
• Level of functioning before the event