Stroke — Ischemic and Hemorrhagic

Table of Contents

1. What is a Stroke?
2. Types: Ischemic vs Hemorrhagic
3. FAST Warning Signs
4. Risk Factors
5. Pathophysiology
6. Diagnosis and Brain Imaging
7. Emergency Treatment
8. Recovery and Rehabilitation
9. Secondary Prevention
10. Lifestyle and Natural Approaches
11. Key Research Papers
12. Connections
13. Featured Videos

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What is a Stroke?

A stroke is a sudden disruption of blood flow to part of the brain, causing brain cells to die within minutes. It is a medical emergency — every minute without treatment destroys roughly 1.9 million neurons and 14 billion synapses. Stroke is the second leading cause of death worldwide and the leading cause of adult disability in high-income countries.

Approximately 800,000 strokes occur annually in the United States. Of those, about 87% are ischemic (blockage) and 13% are hemorrhagic (bleeding). Survival and functional outcome depend almost entirely on how quickly the person receives definitive treatment.

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Types: Ischemic vs Hemorrhagic

Ischemic Stroke (87%)

Caused by a clot that blocks a cerebral artery. There are three main subtypes:

• Cardioembolic (30%): A clot forms in the heart — most commonly due to atrial fibrillation — and travels to the brain. These are often large, devastating strokes.
• Large-artery atherosclerosis (25%): Plaque buildup in a major artery (carotid or basilar) ruptures or causes local thrombosis.
• Small-vessel (lacunar) disease (20%): Blockage of tiny deep perforating arteries, typically from chronic hypertension. Often causes pure motor, pure sensory, or ataxic-hemiparesis syndromes.

Hemorrhagic Stroke (13%)

• Intracerebral hemorrhage (ICH): Bleeding directly into brain tissue, usually from chronic hypertension rupturing small arteries. Mortality is 40% at one month.
• Subarachnoid hemorrhage (SAH): Bleeding into the space surrounding the brain, most often from a ruptured aneurysm. Classic presentation is "thunderclap headache" — the worst headache of one's life. Mortality is 25–35%.

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FAST Warning Signs

The FAST acronym helps everyone recognize stroke quickly. Time lost is brain lost — call 911 immediately if any of these appear suddenly:

• F — Face drooping: Is one side of the face drooping or numb? Ask the person to smile. Is it uneven?
• A — Arm weakness: Is one arm weak or numb? Ask the person to raise both arms. Does one drift downward?
• S — Speech difficulty: Is speech slurred, garbled, or impossible to understand? Can the person repeat a simple sentence?
• T — Time to call 911: If ANY of these signs are present, call emergency services immediately. Note the time symptoms began.

Additional warning signs include sudden severe headache, sudden vision loss in one or both eyes, sudden dizziness or loss of balance, and sudden confusion or trouble understanding others.

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Risk Factors

• Hypertension: The single most important modifiable risk factor. Systolic BP above 140 mmHg more than doubles stroke risk.
• Atrial fibrillation: Increases stroke risk 4–5 fold; responsible for 15–20% of all ischemic strokes.
• Diabetes mellitus: Doubles stroke risk through accelerated atherosclerosis and endothelial dysfunction.
• Smoking: Doubles ischemic stroke risk and triples hemorrhagic stroke risk. Risk returns to baseline within 5 years of quitting.
• Dyslipidemia: High LDL cholesterol promotes carotid and cerebral artery atherosclerosis.
• Obesity and physical inactivity: BMI above 30 associated with 22% increased stroke risk.
• Prior TIA or stroke: TIA carries a 10–15% 90-day stroke risk; prior stroke increases recurrence risk by 25–35% within 5 years without treatment.
• Age and sex: Risk doubles each decade after age 55. Men have higher stroke rates overall, but women have higher lifetime risk due to longevity, and stroke mortality is higher in women.
• Carotid artery stenosis: Stenosis above 70% of the symptomatic carotid carries 26% two-year stroke risk without endarterectomy.

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Pathophysiology

When a cerebral artery is occluded, the core of the ischemic territory (where blood flow falls below 10 mL/100g/min) dies within minutes. Surrounding this core is the ischemic penumbra — tissue that is functionally silent but structurally viable, receiving just enough collateral blood flow to survive for hours. The goal of acute stroke therapy is to rescue the penumbra before it joins the infarct core.

Neuronal death in the penumbra is driven by excitotoxicity (excess glutamate), oxidative stress, mitochondrial failure, and inflammatory cascades including microglial activation and neutrophil infiltration. In hemorrhagic stroke, the expanding hematoma compresses surrounding tissue and releases blood breakdown products (iron, thrombin, hemoglobin) that are directly neurotoxic.

The National Institutes of Health Stroke Scale (NIHSS) is a standardized 42-point exam assessing level of consciousness, gaze, visual fields, facial palsy, arm and leg motor function, limb ataxia, sensory function, language, dysarthria, and extinction. Scores above 16 predict high mortality; scores below 6 predict good recovery. Every point increase roughly corresponds to a 17% decrease in the likelihood of an excellent outcome.

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Diagnosis and Brain Imaging

Stroke diagnosis requires urgent neuroimaging to distinguish ischemic from hemorrhagic stroke — a distinction that completely reverses treatment decisions.

• Non-contrast CT (NCCT): The first imaging obtained in the emergency department. Instantly identifies hemorrhage (bright white blood). Ischemic changes may be subtle in the first few hours — early signs include loss of the insular ribbon, hyperdense MCA sign, and blurring of the basal ganglia.
• CT Angiography (CTA): Obtained immediately after NCCT to identify large vessel occlusion (LVO) amenable to mechanical thrombectomy. Also shows carotid stenosis and intracranial aneurysms.
• CT Perfusion (CTP): Maps ischemic core versus salvageable penumbra. Used to select patients for thrombectomy beyond the 6-hour window (DAWN and DEFUSE-3 trials).
• MRI with DWI: Diffusion-weighted imaging is the gold standard for ischemic stroke detection, positive within minutes of onset. Also identifies brainstem and cerebellar strokes that CT can miss.
• Cardiac evaluation: 12-lead ECG (looking for atrial fibrillation), echocardiogram (looking for thrombus, PFO, valvular disease), and 30-day cardiac monitoring (detects paroxysmal AF in 15–20% of cryptogenic strokes).

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Emergency Treatment

Intravenous tPA (Alteplase)

Intravenous tissue plasminogen activator (tPA, alteplase) dissolves the clot by activating plasminogen. It is the standard of care for eligible ischemic stroke patients within 4.5 hours of symptom onset (or last known well time). The NNT to achieve one additional excellent outcome is approximately 8 within 3 hours and 14 within 4.5 hours.

Key contraindications to tPA: hemorrhagic stroke (obvious), recent major surgery within 14 days, INR above 1.7, platelet count below 100,000, blood pressure above 185/110 mmHg (must be lowered first), and prior intracerebral hemorrhage.

Tenecteplase (TNK) is a newer single-bolus alternative with equivalent or superior efficacy and is increasingly replacing alteplase in many centers.

Mechanical Thrombectomy

For large vessel occlusions (LVO) — typically M1, M2, or basilar artery — mechanical thrombectomy with stent retrievers or aspiration catheters is the most effective acute treatment ever demonstrated in stroke neurology. Success rates (TICI 2b-3 reperfusion) exceed 80% in experienced centers.

The DAWN trial (2018) extended the thrombectomy window to 24 hours in selected patients with favorable penumbra imaging (clinical-imaging mismatch). The DEFUSE-3 trial extended it to 16 hours. Both trials found dramatic reductions in disability at 90 days.

For ICH, management focuses on blood pressure control (systolic below 140 mmHg within 1 hour — INTERACT2 trial), reversal of anticoagulation, and neurosurgical consultation for selected cases.

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Recovery and Rehabilitation

Stroke rehabilitation begins as soon as the patient is medically stable — often within 24–48 hours. Early mobilization improves outcomes and reduces complications including deep vein thrombosis, pneumonia, and pressure ulcers.

• Physical therapy: Restores walking, balance, and motor control. Constraint-induced movement therapy (CIMT) forces use of the affected limb and can dramatically improve upper extremity function even years post-stroke.
• Occupational therapy: Retrains activities of daily living — dressing, bathing, cooking — and evaluates home modifications.
• Speech-language therapy: Addresses aphasia (language), dysarthria (speech motor), and dysphagia (swallowing). Post-stroke dysphagia affects 40–70% of patients and requires formal swallow evaluation before oral feeding begins.
• Cognitive rehabilitation: Addresses post-stroke cognitive impairment, which affects up to 30% of survivors at one year.
• Depression: Post-stroke depression occurs in 30–40% of survivors and is independently associated with worse functional recovery. SSRI treatment is indicated.

Most neurological recovery occurs in the first 3–6 months, but meaningful improvement can continue for 2 or more years with continued therapy. Neuroplasticity — the brain's ability to rewire — is the biological basis for recovery.

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Secondary Prevention

After a first stroke or TIA, preventing a second event is critical. The specific approach depends on stroke mechanism:

• Antiplatelet therapy (for non-cardioembolic ischemic stroke): Aspirin 81 mg daily remains the foundation. Dual antiplatelet therapy (aspirin plus clopidogrel) for 21–90 days after minor stroke or TIA (CHANCE and POINT trials) reduces early recurrence by approximately 25% compared to aspirin alone.
• Anticoagulation (for cardioembolic stroke from AF): Direct oral anticoagulants (DOACs — apixaban, rivaroxaban, dabigatran, edoxaban) are preferred over warfarin due to lower intracranial hemorrhage risk. NOACs reduce stroke recurrence by 50–70% in AF patients.
• Carotid endarterectomy (CEA): For symptomatic carotid stenosis ≥70%, CEA performed within 2 weeks of the index event reduces 5-year stroke risk from 26% to 9% (NASCET trial). Carotid stenting is an alternative for high surgical-risk patients.
• Statin therapy: High-intensity statin (atorvastatin 80 mg or rosuvastatin 40 mg) reduces recurrent stroke by 16–25% regardless of baseline LDL. Target LDL below 1.8 mmol/L (70 mg/dL) or below 1.4 mmol/L for very high-risk patients.
• Blood pressure control: Target below 130/80 mmHg for most stroke patients. ACE inhibitors and thiazide diuretics have strong evidence for stroke prevention.

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Lifestyle and Natural Approaches

Lifestyle modification addresses the root causes of stroke and works synergistically with medications:

• Mediterranean diet: Reduces stroke risk by 30% in the PREDIMED trial. Emphasizes olive oil, fish, legumes, vegetables, fruits, and nuts. Associated with lower carotid intima-media thickness and reduced atrial fibrillation incidence.
• Physical activity: 150 minutes per week of moderate-intensity exercise reduces stroke risk by 25%. Even regular walking significantly decreases risk.
• Sodium restriction: Reducing dietary sodium by 1,000 mg/day lowers systolic BP by 4–5 mmHg, translating to approximately 14% stroke risk reduction.
• Omega-3 fatty acids: EPA/DHA from fatty fish (salmon, mackerel, sardines) or supplements reduce triglycerides and may reduce cardioembolic stroke risk in patients with elevated triglycerides (REDUCE-IT trial).
• Magnesium: Each 100 mg increase in dietary magnesium is associated with 7% reduction in stroke risk in meta-analyses. Magnesium supports vascular tone and reduces atrial fibrillation burden.
• Smoking cessation: Risk returns to near-baseline within 5 years. Varenicline and combination NRT are more effective than willpower alone.
• Alcohol: Light consumption (1 drink/day) modestly reduces ischemic stroke risk, but even moderate drinking significantly increases hemorrhagic stroke risk. Heavy drinking is a major risk factor for both types.

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Key Research Papers

Foundational clinical trials and systematic reviews that shaped modern stroke care:

1. NINDS rt-PA Stroke Study Group, 1995 — tPA within 3 hours of stroke onset. PMID: 7477192
2. Hacke W et al., 2008 — ECASS 3: tPA 3–4.5 hours after stroke. PMID: 18815396
3. Goyal M et al., 2015 — MR CLEAN: Endovascular therapy for acute ischemic stroke. PMID: 26321104
4. Nogueira RG et al., 2018 — DAWN Trial: Thrombectomy 6–24 hours. PMID: 29129157
5. Albers GW et al., 2018 — DEFUSE-3: Thrombectomy 6–16 hours. PMID: 29129156
6. Anderson CS et al., 2013 — INTERACT2: Intensive blood pressure reduction in ICH. PMID: 22992589
7. Wang Y et al., 2013 — CHANCE Trial: Dual antiplatelet therapy after TIA/minor stroke. PMID: 26196118
8. Johnston SC et al., 2018 — POINT Trial: Clopidogrel + aspirin after minor ischemic stroke or TIA. PMID: 29766750
9. NASCET Collaborators, 1991 — Carotid endarterectomy for symptomatic stenosis. PMID: 12364352
10. Amarenco P et al., 2006 — SPARCL: Atorvastatin 80 mg for recurrent stroke prevention. PMID: 16441422
11. Estruch R et al., 2013 — PREDIMED: Mediterranean diet and cardiovascular/stroke risk. PMID: 23541526
12. Bhatt DL et al., 2019 — REDUCE-IT: Icosapentaenoic acid reduces cardiovascular events. PMID: 30404111

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Connections

• TIA (Transient Ischemic Attack)
• Epilepsy
• Alzheimer's Disease
• Peripheral Neuropathy
• ALS
• POTS
• Multiple Sclerosis
• Atrial Fibrillation
• Hypertension
• Atherosclerosis
• Magnesium
• Vitamin D3
• Vitamin B12
• Mediterranean Diet
• Potassium
• Salmon
• Trigeminal Neuralgia
• Bell's Palsy

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