STROKE

A Stroke is a sudden neurological impairment caused by an interruption in blood flow to the brain (ischemic
stroke) or bleeding into or around the brain (haemorrhagic stroke). This disruption deprives brain cells of
oxygen and nutrients, leading to rapid cell death and potentially permanent brain damage, disability, or
death.
Stroke is a leading cause of death and disability worldwide, making rapid recognition and treatment critical.
World Stroke day observed on October 29
Types & Etiology of Stroke
1. Ischemic Stroke (Most Common – ~85% of cases)
- Caused by a blockage in an artery supplying blood to the brain, often due to a blood clot (thrombosis or
embolism).
2. Haemorrhagic Stroke (~15% of cases)
- Occurs when a weakened blood vessel ruptures, causing bleeding in or around the brain (e.g.,
intracerebral or subarachnoid haemorrhage).
3. Transient Ischemic Attack (TIA) – “Mini-Stroke”
- A temporary blockage with stroke-like symptoms that resolve within 24 hours, but it is a warning sign
for future strokes.

Risk Factors for Ischemic Stroke

Ischemic stroke risk factors are classified as non-modifiable and modifiable.
A. Non-Modifiable Risk Factors
1. Age (Risk doubles every decade after 55).
2. Sex (Men > Women, but women have worse outcomes).
3. Race/Ethnicity (Higher risk in Black, Hispanic, and Asian populations).
4. Genetics (Family history of stroke, inherited clotting disorders).
5. Prior Stroke or TIA (10x higher risk of recurrence).

B. Modifiable Risk Factors (Most Important for Prevention)

1. Hypertension (HTN)
- 1 risk factor (accounts for ~50% of strokes).
- Chronic HTN accelerates atherosclerosis and small vessel disease.
2. Cardiac Conditions
- Atrial Fibrillation (AFib) (5x higher stroke risk due to emboli).
- Valvular Disease (e.g., mitral stenosis, mechanical valves).
- Recent MI (risk of mural thrombus embolism).
3. Diabetes Mellitus (DM)
- 2–4x higher stroke risk (accelerates atherosclerosis).
- Hyperglycaemia worsens ischemic injury.
4. Dyslipidaemia
- High LDL & low HDL → Atherosclerosis (plaque rupture → thrombosis).
5. Smoking
- Doubles stroke risk (promotes atherosclerosis, hypercoagulability).
6. Obesity & Metabolic Syndrome
- Linked to HTN, diabetes, and dyslipidaemia.
7. Physical Inactivity
- Increases risk of HTN, diabetes, and obesity.
8. Alcohol & Drug Abuse
- Heavy alcohol use → HTN, AFib.
- Cocaine/amphetamines → Vasospasm, HTN-induced haemorrhage.
9. Hypercoagulable States
 - Antiphospholipid syndrome, Factor V Leiden, Protein C/S deficiency.
10. Carotid/Intracranial Atherosclerosis
- Symptomatic carotid stenosis >70% → High stroke risk.

The cascade of cerebral ischemia in ischemic stroke occurs through a series of pathophysiological events
triggered by interrupted blood flow to the brain. Initially, the occlusion of a cerebral artery leads to hypoxia
and glucose deprivation, causing rapid depletion of ATP stores. This energy failure results in the breakdown
of ionic gradients across neuronal membranes as sodium-potassium pumps fail, leading to membrane
depolarization. The depolarization triggers excessive release of excitatory neurotransmitters, particularly
glutamate, which overstimulates NMDA and AMPA receptors. This excitotoxicity causes massive calcium
influx into cells, activating destructive enzymes including proteases, lipases, and endonucleases that degrade
cellular components. Concurrently, anaerobic metabolism produces lactic acid, creating intracellular
acidosis that exacerbates cellular damage. During reperfusion (if it occurs), oxidative stress generates
reactive oxygen species that attack cellular membranes through lipid peroxidation. The inflammatory
response follows, with microglial activation and cytokine release that further disrupt the blood-brain barrier
and promote edema formation. The ischemic penumbra - the hypo perfused but potentially salvageable
tissue surrounding the infarct core - gradually succumbs to these damaging processes if blood flow is not
restored. This cascade ultimately leads to both necrotic and apoptotic cell death, with the extent of damage
determined by the duration and severity of ischemia.

Signs & Symptoms

Ischemic stroke typically presents with sudden-onset neurological deficits depending on the affected brain
region. Common manifestations include:
- Focal Weakness: Hemiparesis (arm/leg weakness on one side)
- Speech Disturbances: Aphasia (Anterior circulation strokes) or dysarthria
- Visual Deficits: Homonymous hemianopia (vision loss in half of visual field)
- Vertigo & Ataxia (posterior circulation strokes)
- Facial Droop (unilateral lower face weakness)
- Severe Headache (less common than in haemorrhagic stroke)
FAST Mnemonic for Recognition:
- Face drooping
- Arm weakness
- Speech difficulty
- Time to call emergency

Diagnosis
Immediate assessment is critical to confirm stroke and rule out haemorrhage.
- Non-Contrast CT Head:
- First-line imaging to exclude haemorrhage.
- Early ischemic changes (e.g., hyperdense artery sign, loss of gray-white differentiation).
- MRI with Diffusion-Weighted Imaging (DWI):
- More sensitive for acute ischemia (shows restricted diffusion within minutes).
- Vascular Imaging (CTA/MRA):
- Identifies large vessel occlusions (e.g., MCA, basilar artery).
- Cardiac Workup:
- ECG (for atrial fibrillation), echocardiography (for cardioembolic sources).
- Laboratory Tests:
- CBC, coagulation profile, glucose, lipid panel.

Management
The goals of treatment of acute stroke are
(a)To reduce the ongoing neurologic injury in the acute setting to reduce mortality and long-term disability,
(b)To prevent complications secondary to immobility and neurologic dysfunction, and
(c) To prevent stroke recurrence.

Pharmacotherapy

Ischemic stroke
Acute Treatment (Time-Sensitive!)
A. Thrombolysis (Alteplase, tPA):
tPA (Alteplase) is the only FDA-approved pharmacological thrombolytic agent for acute ischemic stroke. It
works by dissolving blood clots to restore cerebral blood flow.
1. Mechanism of Action- It Converts plasminogen to plasmin, which breaks down fibrin in clots
(thrombolysis)
2. Time Window - Standard window: Within 4.5 hours of symptom onset. - Extended window (select
cases): Up to 9 hours with perfusion imaging
3. Dosing - 0.9 mg/kg (max 90 mg):
- 10% as bolus (over 1 min) and Remaining 90% infused over 1 hour.
4. Eligibility Criteria
- Inclusion: Clinical diagnosis of ischemic stroke.
- Clear onset time <4.5 hours. - No hemorrhage on CT.
- Exclusion (Major Contraindications):BP >185/110 mmHg (uncontrolled).
- Recent surgery/bleeding (e.g., GI bleed, stroke <3 months).
- INR >1.7 or platelets <100,000/mm³. - Severe hypoglycemia/hyperglycemia.
- IV tPA within 4.5 hours of symptom onset (if no contraindications).
- Dose: 0.9 mg/kg (max 90 mg), 10% as bolus, rest over 1 hour.

B. Blood Pressure Management

- Avoid aggressive lowering unless:
- BP >220/120 mmHg** (no thrombolysis given).
- BP >185/110 mmHg (if planned for tPA).
- Gradual reduction preferred to maintain cerebral perfusion.
C. Oxygen Therapy
- Only if hypoxia (SpO₂ <94%) – excessive O₂ can worsen oxidative stress.
D. Temperature Control
- Fever worsens outcomes → Antipyretics (paracetamol) + cooling devices if needed.
E. Glycemic Control
- Avoid hyperglycemia (>180 mg/dL)→ Insulin sliding scale.
- Avoid hypoglycemia (<70 mg/dL) → Glucose infusion if needed.
-
Secondary Prevention (Long-Term Therapy)
1. Antiplatelets:
- Aspirin (160–325 mg loading dose, then 75–100 mg/day).
- **Dual Antiplatelet Therapy (DAPT):
- Aspirin + Clopidogrel for 21 days (for high-risk TIA/minor stroke).
- Long-term monotherapy (clopidogrel or aspirin) thereafter.
2. Anticoagulation (for Cardioembolic Strokes):
- Atrial Fibrillation: DOACs (dabigatran, rivaroxaban, apixaban) or warfarin (INR 2–3).
- Mechanical Heart Valves: Warfarin (INR 2.5–3.5).
3. Risk Factor Management:
- Hypertension: ACEi/ARB (target BP <140/90 mmHg).
- Dyslipidemia: High-intensity statin (e.g., atorvastatin 40–80 mg).
- Diabetes: HbA1c target <7%.
4. Supportive Care
- BP Management: Avoid aggressive lowering in acute phase (unless >220/120 mmHg).
- Glycemic Control: Maintain glucose 140–180 mg/dL.
- DVT Prophylaxis: Compression stockings or LMWH (in immobilized patients).
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Non-Pharmacological Therapy for Ischemic Stroke
Non-pharmacological interventions play a critical role in acute stroke management, secondary prevention,
and rehabilitation. These include:

Acute Phase Interventions

Mechanical Thrombectomy
- For large vessel occlusion (LVO) (e.g., MCA, ICA, basilar artery).
- Time Window: Up to 24 hours in select patients with salvageable penumbra (confirmed by perfusion
imaging).
- Procedure: Endovascular retrieval of clot using stent retrievers (e.g., Solitaire, Trevo).

Secondary Prevention (Lifestyle & Interventions)

A. Dietary Modifications
- Mediterranean/DASH diet: Rich in fruits, vegetables, whole grains, and low-fat dairy.
- Salt restriction: <2.3 g/day (for hypertension control).
- Reduce saturated fats: To lower LDL cholesterol.
B. Smoking Cessation
- Doubles stroke risk → Counseling + nicotine replacement therapy/varenicline.
C. Physical Activity
- Aerobic exercise (30 min/day, 5 days/week) to improve vascular health.
- Supervised rehabilitation for post-stroke motor recovery.
D. Weight Management
- BMI target: 18.5–24.9 kg/m² (weight loss if obese).
E. Carotid Revascularization
- Carotid endarterectomy (CEA) or stenting for symptomatic carotid stenosis >50%.

Rehabilitation Therapies
A. Physiotherapy
- Early mobilization (within 24–48 hrs if stable).
- Constraint-Induced Movement Therapy (CIMT) for hemiparesis.
B. Occupational Therapy
- Improves activities of daily living (ADLs) (e.g., dressing, eating).
C. Speech & Swallowing Therapy
- For dysphagia (prevent aspiration) and aphasia recovery.
D. Cognitive Rehabilitation
- For memory, attention, and executive function deficits.
4. Psychological Support
- Post-stroke depression (PSD) affects ~30% of survivors → Counselling /SSRIs (e.g., fluoxetine).
- Caregiver education for long-term support.
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General Approach to Stroke Treatment
The management of stroke patients follows a time-sensitive, stepwise protocol to maximize recovery and
minimize disability. The approach differs for ischemic and haemorrhagic strokes but prioritizes rapid
assessment, acute intervention, and secondary prevention.

For patients with presumed acute stroke, the initial approach is to first ensure the patient is stable from a
respiratory and cardiac standpoint and then to quickly determine whether the injury is ischemic or
hemorrhagic, which is determined by a CT scan. Ischemic stroke patients presenting within hours of
symptom onset should be evaluated for pharmacologic and mechanical reperfusion therapy. Patients with
TIA require urgent assessment and intervention to reduce the risk of stroke, which is highest in the first few
days after TIA.
In patients with an ischemic stroke and a BP <220/120 mm Hg without comorbid conditions requiring acute
hypertensive treatment, the acute lowering of blood pressure in the first 48 to 72 hours after ischemic stroke
does not prevent death or improve the level of dependency. “Permissive hypertension” in these patients is
often part of routine care. However, for patients who are alteplase-treatment candidates or those with
comorbid conditions, such as aortic dissection, acute myocardial infarction, pulmonary edema, or
hypertensive encephalopathy, treatment of hypertension may be required. If BP is treated, the use of short-
acting and easily titrated agents, such as labetalol or nicardipine/clevidipine, is preferred.

In patients with ICH and elevated blood pressure, the acute lowering of SBP to 140 mm Hg has been shown
to be safe and may improve functional outcome. Once the patient is out of the hyperacute phase
management efforts are focused on preventing worsening of stroke, minimizing complications, and
instituting appropriate secondary prevention strategies. The acute phase of the stroke includes the first week
after the event.

Immediate Assessment & Stabilization

A. Pre-Hospital (FAST Recognition & EMS Activation)
- **FAST criteria** (Face drooping, Arm weakness, Speech difficulty, Time to call emergency).
- **Stroke alert activation** for rapid transport to a stroke center.
**B. Emergency Department (First 10 Minutes)**
- **ABCs** (Airway, Breathing, Circulation).
- **NIH Stroke Scale (NIHSS)** to assess severity.
- **Stat labs**: Glucose (rule out hypoglycemia), CBC, INR, electrolytes.

Rapid Imaging (Within 25 Minutes)**

- **Non-contrast CT head**:
- Rules out hemorrhage (for thrombolysis eligibility).
- Early signs of ischemia (e.g., hyperdense artery sign, loss of gray-white differentiation).
- **CTA/MRA** (if thrombectomy is considered).

Acute Treatment
A. Ischemic Stroke
1. **IV Thrombolysis (tPA/Alteplase)**
- **Window**: ≤4.5 hours from symptom onset.
- **Dose**: 0.9 mg/kg (max 90 mg; 10% bolus + 90% over 1h).
- **Exclusions**: Active bleeding, recent surgery, INR >1.7, platelets <100K.
2. **Mechanical Thrombectomy**
- **For large vessel occlusion (LVO)**: ICA, M1 MCA, basilar artery.
- **Window**: ≤6h (standard) or up to **24h with penumbral mismatch**
(DAWN/DEFUSE-3 criteria).
3. **Supportive Care**
 - **BP control**: <185/110 mmHg (if tPA given).
- **Temperature**: Treat fever (antipyretics).
- **Glucose**: Maintain 140–180 mg/dL.

B. Hemorrhagic Stroke
1. **BP Control**: Target SBP <140 mmHg (e.g., nicardipine, labetalol).
2. **Neurosurgical Intervention**:
- **EVD (external ventricular drain)** for hydrocephalus.
- **Clipping/coiling** for ruptured aneurysms (if SAH).
3. **Reverse Anticoagulation**:
- Vitamin K + PCC (for warfarin), idarucizumab (for dabigatran).

Secondary Prevention
A. Ischemic Stroke
- **Antiplatelets**:
- **Aspirin + Clopidogrel** (21 days for high-risk TIA/minor stroke).
- Long-term **monotherapy** (clopidogrel or aspirin).
- **Anticoagulation**: DOACs/warfarin for **AFib or cardioembolic strokes**.
- **Risk Factor Control**:
- **BP**: <140/90 mmHg (ACEi/ARB preferred).
- **LDL**: High-intensity statin (atorvastatin 40–80 mg).
- **Smoking cessation, diabetes management**.

B. Hemorrhagic Stroke
- **BP control**: SBP <130 mmHg (long-term).
- **Avoid antiplatelets/anticoagulants** (unless mandatory).
- **AVM/aneurysm repair** if needed.

Rehabilitation (Start Early!)

- **Physiotherapy**: Mobility training (within 24–48h if stable).
- **Occupational therapy**: ADL retraining (e.g., dressing, eating).
- **Speech therapy**: For dysphagia/aphasia.
- **Cognitive rehab**: Memory, attention deficits.
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Desired Outcomes in Stroke Treatment

The primary goals of stroke treatment are to **save lives, minimize disability, and prevent recurrence**.
Outcomes are measured using clinical scales, functional independence, and quality-of-life metrics.

1. Acute Phase (0–72 Hours)

**A. Reperfusion Success**
- **For ischemic stroke:**
- **tPA:** Complete or partial recanalization
- **Thrombectomy:** Successful clot removal
- **For hemorrhagic stroke:**
- **Hematoma stabilization** (no expansion on repeat CT).
**B. Neurological Stability**
- **Reduction in NIHSS score** (improved speech, motor function).
- **No clinical worsening** (e.g., no seizures).
2. Short-Term Outcomes (Hospital Discharge)
**A. Functional Independence**
- **Modified Rankin Scale (mRS) score 0–2** (no or mild disability):
- **mRS 0**: No symptoms.
- **mRS 1**: Minor symptoms (e.g., mild weakness) but fully independent.
- **mRS 2**: Slight disability but can walk/care for self.
**B. Survival & Complications Avoided**
- **Mortality rate reduction** (especially in large strokes).
- **Prevention of complications:**
- Aspiration pneumonia.
- Deep vein thrombosis (DVT).
- Pressure ulcers.

3. Long-Term Outcomes (3–12 Months)

**A. Sustained Functional Recovery**
- **Return to pre-stroke activities** (work, hobbies).
- **No need for institutional care** (nursing home).
**B. Secondary Prevention Success**
- **No recurrent stroke** (lifestyle + medication adherence).
- **Controlled risk factors:**
- BP <140/90 mmHg.
- LDL <70 mg/dL (for atherosclerotic strokes).
- HbA1c <7% (if diabetic).
**C. Quality of Life (QoL)**
- **Patient-reported outcomes**:
- Minimal depression/anxiety (e.g., PHQ-9 score <5).
- Social reintegration (family, community participation).
Evaluation of Therapeutic Outcomes and Monitoring the Therapeutic Care Plan
Patients with acute stroke must be closely monitored for Worsening of stroke (new or recurring stroke)
Complications like Blood clots (DVT or pulmonary embolism), Infections (mostly respiratory or urinary)
and side effects of medicines or treatments

Common problems in stroke patients include

Stroke extension (more brain area affected by bleeding or blockage)
Cerebral edema (brain swelling) and increased brain pressure
Hypertensive emergency (very high blood pressure)
Infections (common in lungs and urinary tract)
Blood clots in veins (DVT, embolism)
Electrolyte and heart rhythm issues (due to brain damage)
Recurrent strokes

The success of stroke treatment is assessed through **clinical, functional, and quality-of-life measures** at
different stages:
A. Acute Phase (0–72 Hours)**
- **Reperfusion Efficacy**
- **Ischemic Stroke:**
- Reduction in **NIH Stroke Scale (NIHSS) score** (e.g., ≥4-point drop =
significant improvement).
- **Glasgow Coma Scale (GCS)** for severe strokes.
B. Short-Term (Hospital Stay & Discharge)**
- **Functional Independence**
- **Modified Rankin Scale (mRS):**
- **mRS 0-2** = Good outcome (independent in daily activities).
- **mRS 3-5** = Moderate-severe disability.
- **mRS 6** = Death.
- **Barthel Index (BI):** Assesses activities of daily living (ADLs); score ≥85
= independence.
- **Complication Prevention**
- **No aspiration pneumonia, DVT, or pressure ulcers.**
##### **C. Long-Term (3–12 Months Post-Stroke)**
- **Sustained Recovery**
- **Return to work/social activities.**
- **Stroke-Specific Quality of Life (SS-QoL) Scale.**
- **Secondary Prevention Success**
- **No recurrent stroke/TIA.**
- **Controlled risk factors (BP, LDL, HbA1c).**

MONITORING STROKE THERAPY IN HOSPITALIZED PATIENTS

Temperature – every 8h, CBC – daily, electrolytes and ECG every 8h (All patients)
B.P, neurologic function, ICP, fluid status – every 2h in ICU (haemorrhagic stroke)

Drug - Main Side Effect – Monitoring- Frequency

Alteplase- Bleeding - BP, Neuro exam - Every 15 min–1 hour initially, 30min – 6 hrs &1hr – 17 hr
Aspirin Bleeding Daily check Daily
Clopidogrel Bleeding Daily check Daily
Aspirin + Dipyridamole Headache, bleeding Daily check Daily
Direct-acting oral anticoagulants Bleeding Daily check Daily
Warfarin- Bleeding - INR, Hemoglobin, Hematocrit- INR Daily-3 days, weekly until stable and monthly

BLEEDING RISK SCORING SYSTEMS

Score ≥3 = High bleeding risk, requires close monitoring.

For Antiplatelet Therapy (S₂TOP-BLEED)

Each factor has a point score to assess bleeding risk:
Risk Factor Points
Male sex 2
Smoking 1
Aspirin ± dipyridamole or aspirin + clopidogrel 5
Poor outcome (Rankin score ≥3) 2
Prior stroke 1
High BP 1
Low BMI (<20 or 20–25) 1
Elderly (45–85+ years) 2 to 12 based on age
Asian ethnicity 1
Diabetes 1

For Oral Anticoagulants (HAS-BLED)

Risk Factor Points
High BP (>160 mmHg) 1
Liver/kidney issues 1
Past stroke 1
Past bleeding 1
Unstable INR (for warfarin users) 1
Age >65 years 1
Drug/alcohol use 1
_______________________________________________________________________________________
 A Transient Ischemic Attack (TIA) is a temporary blockage of blood flow to the brain, causing stroke-
like symptoms that resolve within 24 hours (usually within minutes to hours) without permanent
damage.

TIAs are a warning sign — up to 1 in 3 people with TIA will have a full stroke, often within days or
weeks.

1. Immediate Assessments:
CT scan (non-contrast): To rule out hemorrhagic stroke.
MRI brain (Diffusion-weighted imaging): More sensitive to detect small infarcts.
Blood glucose, ECG, CBC, Renal function, Electrolytes, Lipid profile, HbA1c.

2. Further Testing:
Carotid Doppler ultrasound: To detect carotid artery stenosis.
Echocardiogram: To check for cardiac source of emboli (e.g., atrial fibrillation).
24-hour Holter monitor: If arrhythmia suspected.
ABCD² score to assess stroke risk post-TIA.

Component Points
Age ≥ 60 1
BP ≥ 140/90 1
Clinical features (unilateral weakness = 2, speech only = 1) 2 or 1
Duration ≥ 60 min = 2, 10–59 min = 1 2 or 1
Diabetes 1

Score ≥ 4 = moderate to high stroke risk → hospital admission

Pharmacotherapy
1.Antiplatelet therapy: Aspirin 150–325 mg/day (start immediately)
Consider dual antiplatelet (Aspirin + Clopidogrel) for 21 days if high risk
2.Statin: Start Atorvastatin 40–80 mg/day regardless of cholesterol
3.Antihypertensive: Control BP, but avoid rapid lowering acutely
4.Anticoagulation: If AF or cardioembolic source, start oral anticoagulant (e.g., DOAC or Warfarin)

Lifestyle and Risk Factor Modification

Smoking cessation
Glycemic control (if diabetic)
Weight management
Healthy diet (DASH/Mediterranean)
Physical activity