Pathophysiology of Ischemic Stroke

1. Initiating Event

2. Two Zones of Injury (Fig. 16.10)

Penumbra damage is worsened by inflammation and excitotoxicity (mediated by glutamate and sodium). Hyperglycemia and fever further worsen it - both must be controlled.

3. Cellular Cascade (Flowchart 16.6)

Thrombus/Embolus
       ↓
  Hypoperfusion
       ↓
  ATP Depletion
       ↓
Activation of:
  • Lipid peroxidases
  • Proteases
  • NO synthase
       ↓
Destruction of intracellular organelles,
cell membrane + Free radical release
       ↓
  LIQUEFACTIVE NECROSIS

4. CBF Thresholds & Functional Consequences

Key Takeaway

Lacunar (Small Vessel) Stroke

Definition & Basics

• Caused by occlusion of small penetrating arteries (200-800 µm) supplying deep brain parenchyma
• Occlusion occurs by:
  • Atherothrombotic disease at vessel origin
  • Lipohyalinosis thickening - a consequence of chronic hypertension
• Infarct size: 0.2 to 15 mm in diameter (these small cavities = "lacunes")
• Account for 20% of all strokes
• Risk factors: Hypertension (most important) and age
• Presentation: Fluctuating symptoms called "Capsular Warning Syndrome"

Lacunar Syndromes (Table 16.14)

Key Points to Remember

• No cortical signs (no aphasia, no hemianopia, no neglect) - because purely deep structures are involved
• Pure motor is the most common lacunar syndrome
• Dysarthria-clumsy hand and ataxic hemiparesis are classically pontine
• Lacunar infarcts are best seen on MRI (DWI) - often invisible on CT
• Management: BP control is the single most important preventive measure

Lacunar Stroke Syndromes

IC = Internal Capsule | MCA = Middle Cerebral Artery | PCA = Posterior Cerebral Artery | PCOM = Posterior Communicating Artery

A. DIAGNOSIS

1. FAST (Bedside Screening)

2. Neuroimaging

3. Blood Investigations

• CBC, ESR, glucose, RFT, LFT, PT-INR, aPTT, electrolytes
• Hypercoagulable workup: Protein C & S, Antithrombin III, Factor VII/VIII, Lupus anticoagulant, Anticardiolipin Ab, APCR, Factor V Leiden, Prothrombin G20210A, Sickle cell screen

4. Cardiac Investigations

• ECG (for AF), Echocardiogram (TTE/TEE) - for cardiac source of emboli, intracardiac thrombus, PFO

B. MANAGEMENT

1. IV Thrombolysis (r-tPA / Tenecteplase) - "Time is Brain"

• Clinical diagnosis of stroke
• Onset to treatment ≤ 4.5 hours
• Age ≥ 18 years
• CT: No hemorrhage or infarct > 1/3 MCA territory

• BP > 185/110 mmHg despite treatment
• Platelets < 1,00,000 / Hematocrit < 25%
• Glucose < 50 or > 400 mg%
• Prior ICH / head injury in 3 months / major surgery in 14 days
• Age > 80 years / Pregnancy / Coma

Tenecteplase: 0.25 mg/kg IV bolus (max 25 mg)

2. Endovascular Mechanical Thrombectomy

• Alternative when IV thrombolysis is contraindicated or failed
• Saves penumbra by direct clot removal

3. Antiplatelet Therapy

• Aspirin 150 mg + Clopidogrel 75 mg (dual antiplatelet)
• Avoid Glycoprotein IIb/IIIa inhibitors (abciximab) - causes excess ICH

4. Anticoagulation

• Routine use is NOT recommended in acute ischemic stroke
• Only use in: AF, crescendo TIAs, hypercoagulable states, cerebral venous sinus thrombosis (CVT)

5. Blood Pressure Management

Key rule: "Do not kill the penumbra to save the penumbra" - avoid aggressive BP lowering

6. Reduce Intracranial Tension

• Water restriction, IV Mannitol, oral Glycerol, head-end elevation

7. Hemicraniectomy

• For malignant MCA infarction (NIHSS > 15, age ≤ 60, infarct > 50% MCA territory, infarct volume > 145 cm³)
• Refer within 24 hrs, operate within 48 hrs

8. Statins

• Atorvastatin 40-80 mg / Rosuvastatin 20-40 mg

9. Rehabilitation

• Early physical, occupational, speech therapy
• Restraint therapy (immobilizing unaffected side) improves hemiparesis

C. SECONDARY PREVENTION

ABCD² Score (TIA risk stratification)

Score < 4 = low risk | Score > 6 = high risk for stroke

Clinical Features of Stroke

A. General Onset

• Sudden onset of focal neurological deficit (hallmark)
• Symptoms depend on which artery/territory is affected
• May present with "capsular warning syndrome" (fluctuating symptoms before major stroke)

B. Cortical Signs (Large Vessel / MCA territory)

C. Brainstem / Posterior Circulation Signs

D. Lacunar Stroke (Pure Subcortical - NO cortical signs)

E. Territory-Based Features

F. Hemorrhagic Stroke - Additional Features

• Sudden severe headache ("thunderclap" - SAH)
• Vomiting, neck stiffness (SAH)
• Rapid loss of consciousness
• Higher ICP signs - papilledema, Cushing reflex (bradycardia + hypertension)

G. Key Distinguishing Points

Remember: Stroke = sudden focal neurological deficit until proven otherwise. Any new sudden weakness, speech difficulty, visual loss, or unsteadiness = call FAST

Clinical Features of Stroke

(Boloor's Textbook of Medicine - Chapter 16: Neurology)

A. General Features

• Sudden onset focal neurological deficit
• Fluctuating symptoms = "Capsular Warning Syndrome" (precedes lacunar stroke)
• Symptoms depend on territory of arterial occlusion

B. Territory-Based Clinical Features

C. Lacunar Stroke Syndromes (No Cortical Signs)

D. Complications of Acute Stroke (Box 16.11)

E. "Time is Brain" - Neural Loss Per Stroke (Fig. 16.13)

F. Stroke Mimickers (Box 16.12 - Differential Diagnosis)

If you have the page showing the "Site of Occlusion vs Clinical Features" table (Table 16.15 from Boloor), please share it and I'll extract that as well.

Management of Stroke

(Boloor's Textbook of Medicine - Ch. 16)

ACUTE MANAGEMENT

1. IV Thrombolysis - r-tPA / Tenecteplase

"Time is Brain" - earlier treatment = better outcome

• Clinical diagnosis of stroke
• Onset to treatment ≤ 4.5 hours
• Age ≥ 18 years
• CT: No hemorrhage, infarct size < 1/3 MCA territory
• Patient/surrogate consent

• BP > 185/110 mmHg despite treatment (give Labetalol 20 mg IV × 2 doses)
• Platelets < 1,00,000 | Hematocrit < 25%
• Glucose < 50 or > 400 mg%
• Heparin/warfarin use within 48 hrs with raised aPTT/INR
• Prior ICH
• Stroke/head injury within 3 months
• Major surgery within 14 days
• GI bleed within 21 days
• Recent MI within 3 months
• Coma/stupor | Pregnancy | Age > 80 yrs
• Minor stroke symptoms

• r-tPA: 0.9 mg/kg IV (10% as bolus, 90% over 60 min; max 90 mg)
• Tenecteplase: 0.25 mg/kg IV bolus single dose (max 25 mg)
• No antithrombotic treatment for 24 hours after tPA
• Avoid urethral catheterization for 2 hours

2. Endovascular Mechanical Thrombectomy

• Alternative/adjunct when IV thrombolysis is contraindicated or failed
• Directly removes clot to restore blood flow
• Saves the ischemic penumbra

3. Antiplatelet Therapy (Dual)

• Aspirin 150 mg + Clopidogrel 75 mg daily
• Avoid Glycoprotein IIb/IIIa inhibitors (e.g., Abciximab) - causes excess ICH
• Routine anticoagulation is NOT recommended in acute ischemic stroke

4. Anticoagulation

• Atrial fibrillation (risk of cardiogenic re-embolization)
• Crescendo TIAs with arteriosclerotic stenosis
• Known hypercoagulable states
• Cerebral venous sinus thrombosis (CVT)

5. Blood Pressure Management

• First-line: Labetalol, Nicardipine, Clevidipine
• Second-line: Nitroprusside (if DBP > 120 mmHg)
• Do NOT over-lower BP → "Do not kill the penumbra to save the penumbra"
• Do NOT use antihypertensives unless: LV failure, aortic dissection, acute MI, renal failure, hypertensive encephalopathy

6. Reducing Intracranial Tension (ICT)

• Water restriction
• IV Mannitol
• Oral Glycerol
• Head-end elevation
• Treat fever (antipyretics, surface cooling)

7. Serum Glucose Control

• Treat hyperglycemia with insulin infusion (target ~110 mg/dL)
• Avoid hypoglycemia

8. Hemicraniectomy

• Age ≤ 60 years
• NIHSS > 15
• Decreased consciousness (NIHSS item 1a ≥ 1)
• MRI infarct ≥ 50% MCA territory or volume > 145 cm³
• Refer within 24 hours, operate within 48 hours

9. Statins

• Atorvastatin 40-80 mg or Rosuvastatin 20-40 mg

10. Neuroprotection

• Nimodipine, Magnesium, Citicoline, Sovateltide (Tyvalzi)
• Protect neurons by blocking excitatory amino acid pathways
• Not yet proven beneficial in humans

11. Medical Support (Bedridden Patients)

12. Rehabilitation

• Early physical + occupational + speech therapy
• Educate patient and family
• Restraint therapy (immobilizing unaffected side) → proven to improve hemiparesis even years after stroke
• Goal: Return patient home + maximize functional recovery

SECONDARY PREVENTION

ABCD² Score (TIA Risk)

< 4 = Low risk | ≥ 6 = High risk for stroke → urgent anticoagulation/antiplatelet

TRANSIENT ISCHEMIC ATTACK (TIA)

A. Definition

Key point: ~50% of TIA patients have MRI evidence of ischemia even when symptoms last only a few hours. TIA may herald a stroke.

B. Risk Factors

• Atheroma
• Hypertension
• Postural hypotension
• Bradycardia / low cardiac output
• Diabetes mellitus

C. Clinical Features

• Hemiparesis and aphasia - most common
• Amaurosis fugax - sudden transient loss of vision in one eye (hallmark of anterior circulation TIA)
• Hemisensory loss
• Hemianopic visual loss
• Diplopia
• Vertigo
• Vomiting, choking
• Dysarthria
• Ataxia

D. Types (Box 16.15)

Recurrent same side + same territory TIA = suggestive of vessel disease TIA in both anterior + posterior circulation = suggestive of cardioembolism

E. Diagnosis

• Primarily clinical - based on description of episode
• Look for embolic source:
  • Carotid arterial bruit / stenosis
  • Atrial fibrillation or other dysrhythmia
  • Valvular heart disease / endocarditis
  • Recent myocardial infarction
• ROSIER score to establish diagnosis in emergency
• FAST (Face, Arm, Speech, Time)
• Exclude hypoglycemia first

F. ABCD² Score (Stroke Risk after TIA)

< 4 = Low risk | > 4 = High risk → urgent investigation + secondary prevention

G. Management (Flowchart 16.7)

Suspected TIA
     ↓
Exclude Hypoglycemia
     ↓
History + FAST
  ├── Negative → Consider alternative diagnosis
  └── Positive → ROSIER to confirm TIA
                      ↓
              Symptoms completely resolved?
              ├── No → Stroke Pathway
              └── Yes → Start Aspirin 300 mg/day
                              ↓
                     Assess ABCD² Score
                    ↙              ↘
             ABCD² < 4          ABCD² > 4
         • Aspirin 300 mg     • Aspirin 300 mg
         • Go home            • Admit stroke unit
         • Specialist review  • Assessment within
           within 1 WEEK        24 HOURS
                    ↓
           Brain MRI with DWI
                    ↓
        Candidate for carotid intervention?
          ↙                        ↘
         No                        Yes
          ↓                         ↓
  Best Medical Rx          Carotid stenosis level (ECST)
  (BP control,             ↙              ↘
   antiplatelets,      < 70%           > 70-99%
   statins,          Best medical    Carotid endarterectomy
   lifestyle)          treatment      OR Angioplasty + stenting

H. Best Medical Treatment (Secondary Prevention)

• BP control
• Antiplatelet drugs (Aspirin 300 mg → then 75-150 mg long-term)
• Cholesterol lowering - diet + statins
• Lifestyle changes: Smoking cessation, exercise regimen
• Anticoagulation if AF present (Warfarin / DOACs)

Bottom line: TIA = "stroke warning." ABCD² score guides urgency. High-risk TIA (score > 4) needs same-day investigation and treatment to prevent imminent stroke.

SUBARACHNOID HEMORRHAGE (SAH)

Boloor's Textbook of Medicine - Ch. 16

A. Definition

B. Etiology (Table 16.22)

C. Risk Factors (Box 16.16)

• Hypertension, cigarette smoking, oral contraceptives
• Pregnancy, cocaine abuse, alcohol
• Polycystic kidneys, Ehlers-Danlos syndrome, moyamoya, AVM, coarctation of aorta
• Fibromuscular dysplasia

D. Saccular (Berry) Aneurysm

• Develops within Circle of Willis and adjacent arteries
• 3 most common sites:
  1. Terminal internal carotid artery
  2. MCA bifurcation
  3. Top of basilar artery
• Annual rupture risk: < 10 mm = 0.1% | > 10 mm = 0.5-1%

• First 2 weeks: 20%
• First month: 30%
• Per year thereafter: 3%
• Peak rebleed: first 7 days

E. Clinical Features

Headache triggered by: physical exertion, straining, sexual excitement

F. Investigations

G. Complications

• Obstructive hydrocephalus - may need shunting
• Arterial vasospasm - cause of coma/hemiparesis; poor prognostic sign
• Hyponatremia

H. Differential Diagnosis (Box 16.18)

• Migraine
• Acute bacterial meningitis
• Cervical arterial dissection

I. Management

• Absolute bed rest for 4 weeks
• Protect airway, manage BP + raised ICP
• Treat seizures, pain management, sedation
• Urgently discuss with neurosurgical team

• Target MAP = 130 mmHg
• Drugs: Labetalol, Esmolol, Nicardipine
• Avoid Sodium Nitroprusside (increases ICP)

• Hypovolemia, hypotension, hyperthermia, hyperglycemia, hyponatremia

• 30-60 mg IV for 5-14 days → then 360 mg orally for 7 days
• Given for 3 weeks total
• Reduces cerebral vasospasm → prevents delayed ischemia → decreases mortality

For unruptured aneurysms > 8 mm: risk of treatment < risk of hemorrhage if untreated

• Vasospasm → vasodilators
• Hydrocephalus → drainage via shunt
• Hyponatremia → fluid restriction
• Immobility complications → prevent chest infection, DVT, PE

Key mnemonics:

• "Worst headache of my life" = SAH until proven otherwise
• Xanthochromia = confirms SAH when CT negative
• Nimodipine = only drug proven to reduce mortality in SAH
• Clip or Coil = definitive treatment

HEMIPLEGIA

Etiology, Clinical Features & Management

A. Definition

• Almost always due to Upper Motor Neuron (UMN) lesion in the contralateral corticospinal pathway

B. Etiology

Most Common Causes

Other Causes

• Hypertensive intracerebral hemorrhage
• Todd's (postictal) paralysis - transient, follows seizure
• Alternating hemiplegia of childhood
• Migraine (hemiplegic migraine)
• Functional/psychogenic (conversion disorder)
• Brown-Séquard syndrome (spinal cord)

C. Site of Lesion & Clinical Pattern

Crossed signs (ipsilateral CN palsy + contralateral hemiplegia) = brainstem lesion

D. Clinical Features

Acute (Flaccid) Phase

• Flaccid paralysis - loss of tone (shock phase)
• Absent deep tendon reflexes
• Plantar reflex - may be absent or extensor

Established (Spastic) Phase - UMN Pattern

Associated Cortical Signs (if cortical lesion)

• Aphasia (dominant hemisphere)
• Homonymous hemianopia
• Hemineglect / anosognosia (non-dominant)
• Sensory loss / astereognosis
• Seizures

E. Investigations

F. Management

1. Treat Underlying Cause

• Ischemic stroke → IV tPA (if within 4.5 hrs) / thrombectomy
• Hemorrhagic stroke → control BP, surgical evacuation if indicated
• Tumor → surgery/radiotherapy/chemotherapy
• Abscess → antibiotics ± drainage

2. Acute General Care

• Airway, breathing, circulation (ABC)
• BP control (avoid excessive lowering)
• Treat seizures, fever, hyperglycemia
• DVT prophylaxis (SC heparin + compression stockings)
• Prevent aspiration (nasogastric feeding if dysphagia)
• Pressure sore prevention
• Urinary catheterization if needed

3. Antispasticity (Established Phase)

4. Rehabilitation (Most Important for Recovery)

• Early physiotherapy - passive → active exercises, prevent contractures
• Occupational therapy - ADL retraining, adaptive devices
• Speech therapy - if aphasia/dysphagia
• Constraint-induced movement therapy (CIMT) - restraint of unaffected limb, proven to improve hemiparesis
• Gait training - parallel bars, walking aids
• Goal: maximize functional independence

5. Secondary Prevention

• Antiplatelets (aspirin + clopidogrel)
• Statins (atorvastatin 80 mg)
• Anticoagulation if AF
• Control HTN, DM, dyslipidemia
• Smoking cessation

Key point: Hemiplegia = UMN lesion above the level of decussation (contralateral). The initial flaccid phase gives way to spastic hemiplegia. Rehabilitation started early gives the best functional outcome.

• Adams and Victor's Principles of Neurology, 12th Ed.
• Bradley and Daroff's Neurology in Clinical Practice

HEMIPLEGIA

As per Boloor's Textbook of Medicine - Ch. 16

A. Definition

• Hemiplegia = Complete paralysis of one side of body (face + arm + leg)
• Hemiparesis = Incomplete weakness of same distribution
• Results from UMN lesion of the contralateral corticospinal tract
• Lesion can be at: Cortex → Corona radiata → Internal capsule → Brainstem → Spinal cord

B. Etiology

Vascular (Most Common)

Non-Vascular

C. Stages & Clinical Features

Stage 1 - Acute (Flaccid) Hemiplegia

• Flaccid paralysis (loss of tone) - due to "cerebral shock"
• Loss of all reflexes - DTRs absent
• Plantar reflex - extensor (Babinski positive) from onset

Stage 2 - Established (Spastic) Hemiplegia

Posture in Established Hemiplegia

• Upper limb: Adducted shoulder, flexed elbow, flexed wrist, clenched fist
• Lower limb: Extended hip + knee, plantar flexed foot

D. Localizing the Lesion

E. Investigations

• CT brain - first-line (rules out hemorrhage)
• MRI + DWI - confirms ischemic infarct, posterior fossa
• CBC, glucose, LFT, RFT, PT-INR
• ECG + Echocardiography - cardiac source
• Carotid Doppler / MRA / CTA - vascular stenosis

F. Management

Acute Phase

• Treat underlying cause (tPA / thrombectomy for ischemic stroke)
• Airway protection, BP control
• Control fever, hyperglycemia
• DVT prophylaxis, pressure sore care
• RT feeding if dysphagia

Spasticity Management

Rehabilitation (Most Important)

• Early physiotherapy - prevent contractures, restore movement
• Occupational therapy - ADL training
• Speech therapy - aphasia / dysphagia
• CIMT (Constraint Induced Movement Therapy) - restraining unaffected limb improves hemiplegic limb
• Gait training - walking aids, parallel bars

Secondary Prevention

• Antiplatelets (Aspirin + Clopidogrel)
• Statins (Atorvastatin 80 mg)
• Control HTN, DM, dyslipidemia
• Anticoagulation if AF

If you share the Boloor pages on hemiplegia, I can give you the exact text, tables, and flowcharts from that book specifically.