Stroke and TIA: Characteristics and Pathophysiology

• Cerebrovascular disorders distinguish between transient ischemic attacks and cerebral infarctions.

Transient Ischemic Attacks (TIAs) vs. Cerebral Infarctions

• TIAs involve temporary reduction in blood flow to the brain, spinal cord, or retina, causing reversible neurological dysfunction.
• TIA symptoms resolve within 24 hours without permanent damage.
• Cerebral infarctions (stroke) involve a sustained decrease in blood flow to the brain, leading to irreversible damage and lasting neurological deficits.
• There are no signs of neuronal death with TIA
• Neuronal death occurs due to prolonged ischemia with cerebral infarction.
• TIA symptoms: temporary weakness, vision problems, or speech difficulties; fully resolve without intervention
• Cerebral infarction symptoms: persistent; vary depending on the affected brain region; e.g., hemiparesis, aphasia, visual disturbances, and dizziness
• Risk factors: hypertension, diabetes, smoking, and atrial fibrillation.
• TIAs are considered a warning sign, with a high risk (20%) of developing a cerebral infarction within three months.
• TIA pathophysiology: temporary blockage or reduction of blood flow; small emboli or vascular spasms that resolve spontaneously
• Cerebral infarction can result from thrombosis (blockage of a brain artery), embolism (clot traveling from elsewhere), or hemorrhage leading to sustained ischemia.
• TIA imaging: no permanent damage detected
• Cerebral infarction imaging: CT or MRI typically shows brain tissue damage.
• TIA treatment: prevent future strokes using antiplatelets, anticoagulants, or vascular interventions.
• Cerebral infarction treatment: acute intervention; thrombolytics (tPA) or endovascular therapy, with rehabilitation to address deficits.

Pathophysiology of Ischemic Strokes

• Ischemic strokes occur when there is a sustained reduction in blood flow to the brain, resulting in the death of neurons and glial cells.
• A key feature of an ischemic stroke is the formation of an ischemic core, where blood flow is entirely blocked and leads to rapid cell death.
• The penumbra is an area of partial blood flow reduction surrounding the ischemic core, where neurons are at risk but can recover if blood flow gets restored promptly.

Thrombotic Stroke

• Thrombotic strokes occur when a thrombus (blood clot) forms in one of the intracranial arteries or larger arteries supplying the brain.
• The most common cause is atherosclerotic plaque rupture, initiating thrombus formation.
• Portions of the thrombus break off and occlude more distal parts of the cerebral vasculature.
• The slow progression of blockage leads to ischemia and infarction.

Embolic Stroke

• Embolic strokes are caused by emboli that travel from a distant site, often from the heart (due to atrial fibrillation) or large arteries (the aorta or carotid arteries).
• These emboli lodge in cerebral arteries, usually smaller ones, causing sudden blockage of blood flow.
• Embolic strokes often result in sudden and severe symptoms.
• Embolic strokes are commonly followed by secondary strokes due to the persistence of the embolic source.

Lacunar Stroke

• Lacunar strokes occur due to the occlusion of small penetrating arteries that supply deeper brain structures such as the basal ganglia, thalamus, or brainstem.
• Causes associate with chronic hypertension, leads to the formation of small vessel disease.
• Infarcts are small and located deep within the brain.
• Lacunar strokes have a better prognosis but can cause significant deficits depending on the affected area.

Pathophysiological Process (Ischemic Cascade)

• Excitotoxicity: Due to lack of oxygen and ATP, neurons depolarize, allowing calcium to accumulate intracellularly, causing cell death.
• Oxidative Stress: Reactive oxygen species (ROS) are generated, damaging cellular components such as proteins, DNA, and membranes, leading to further necrosis.
• Inflammation: Dying cells release signals that recruit immune cells and activate glial cells, produce cytokines and ROS, exacerbating tissue damage and increasing blood-brain barrier permeability.

Ischemic Stroke Pathophysiology

• Ischemic strokes occur as a result of cerebral blood vessel occlusion; this leads to reduced or blocked blood flow and oxygen supply to brain tissue.
• Thrombosis, embolism, or global hypoperfusion are common causes.
• The ischemic core is the area where blood flow is completely stopped, leading to rapid neuronal death within minutes.
• The penumbra surrounds tissue of the ischemic core with reduced blood flow (60-80% reduction) and where neurons can survive, making intervention critical for recovery.
• Excitotoxicity from a loss of energy production leads to membrane depolarization, excessive glutamate release, and calcium influx, which triggers neuronal damage.
• Oxidative stress is a result of ischemia promoting reactive oxygen species (ROS) production, damaging cellular components (lipids, proteins, DNA).
• Neuronal death triggers an immune response involving microglia and cytokines, which exacerbates damage and disrupts the blood-brain barrier (BBB).
• The ischemic cascade results in irreversible necrosis and neuronal damage if timely reperfusion is not achieved.

Hemorrhagic Stroke Pathophysiology

• Hemorrhagic strokes result from the rupture of a blood vessel within the brain (intracerebral) or subarachnoid space.
• Hypertension, aneurysms, or traumatic brain injury often causes hemorrhages.
• Ruptures lead to pooling of blood, which increases intracranial pressure, and compression of surrounding brain tissue, disrupting normal perfusion and leading to ischemia in adjacent areas.
• Blood accumulation compresses neurons and vasculature, leading to ischemic damage in adjacent tissue.
• Hemoglobin and iron released from red blood cells become toxic to neurons, causing oxidative stress and apoptosis.
• The compression disrupts blood flow, triggering ischemic cascades.
• Immune cells and cytokines infiltrate the rupture site, promoting further damage and disruption of the BBB.

Ischemic vs Hemorrhagic Strokes

• Ischemic Stroke: Blood vessel blockage (thrombus, embolus), resulting in reduced oxygen and nutrient delivery, and leading to ischemic cascade
• Hemorrhagic Stroke: Blood vessel rupture and bleeding, resulting in mechanical compression and toxic blood effects, leading to mechanical pressure, ischemia, toxic blood products, and inflammation.
• Ischemic Stroke: progressive cell death from ongoing ischemia; BBB disruption through inflammatory processes; gradual onset
• Hemorrhagic Stroke: secondary ischemia, edema, and oxidative stress; BBB disruption occurs from mechanical rupture and inflammation; sudden onset with severe headaches or loss of consciousness
• Hemorrhagic Stroke: Variable, often worse due to increased intracranial pressure
• Ischemic Stroke: Better if treated promptly with reperfusion

Clinical Manifestations: Ischemic Stroke

• Caused by occlusion or significant reduction in cerebral blood flow due to thrombus or embolus.
• Core symptoms: hemiparesis, hemisensory loss, visual disturbances, and aphasia (if dominant hemisphere is affected)
• Progresses over minutes to hours and can cause permanent damage if there is no timely intervention.
• Early detection and treatment can help prevent progression
• The ischemic core is where blood flow is completely halted, leading to rapid cell death within minutes.
• The penumbra is can recover if blood flow gets restored.
• The ischemic cascade includes excitotoxicity, oxidative stress, and inflammatory responses.

Clinical Manifestations: Hemorrhagic Stroke

• Caused by the rupture of a cerebral blood vessel, leading to bleeding into the brain parenchyma or subarachnoid space.
• Key symptoms: sudden severe headache ("thunderclap" headache), nausea, vomiting, and altered consciousness
• Other symptoms: rapid onset of neurological deficits; hemiparesis, aphasia, or loss of vision.
• Signs of increased intracranial pressure (ICP) such as papilledema, seizures, or reduced consciousness.
• The rupture of blood vessels causes blood pooling, leading to compression of surrounding brain tissue and increased intracranial pressure.
• The ischemic cascade is initiated in surrounding regions due to disrupted blood flow.
• Released hemoglobin from damaged red blood cells becomes toxic to neurons and can exacerbate long-term injury.