Prophylactic Antiepileptic Drugs in Hemorrhagic Stroke (ICH)

Current Recommendation: Avoid Routine Prophylaxis

• The 2025 Neurocritical Care Society (NCS) Clinical Practice Guideline (Frontera et al., PMID 39707127) — the most current authoritative guidance — conducted a systematic review and meta-analysis across 15 studies and concluded:

"We suggest avoidance of prophylactic ASM in hospitalized adult patients with acute nontraumatic ICH." (Weak recommendation, very low quality of evidence)

• Meta-analyses showed no significant reduction in early seizures (≤14 days), late seizures (>14 days), or mortality with prophylactic ASM.
• Prophylactic ASMs were associated with increased adverse events and a higher relative risk of poor functional outcomes at 90 days.

If Prophylaxis Is Used Despite the Above

Why LEV Over Phenytoin?

• Phenytoin is associated with worse cognitive outcomes, drug interactions, and a narrow therapeutic window.
• LEV has a more favorable adverse effect profile, fewer drug interactions, and no requirement for therapeutic drug level monitoring.
• A 2023 meta-analysis (Mota Telles et al., PMID 36337029, Int J Stroke) found PASDs reduced seizures only in studies with continuous EEG monitoring (OR 0.36), but this benefit did not translate into improved functional outcomes — even with newer, less toxic drugs.

When Should Treatment (Not Prophylaxis) Be Given?

• Lorazepam 0.1 mg/kg IV (max 4 mg) — first-line to abort an acute seizure
• Followed by a loading dose of LEV (preferred), valproic acid, or fosphenytoin as second-line

Special Note: SAH vs ICH

Summary Table

• Frontera JA et al. Neurocrit Care 2025 — NCS 2025 Guideline (PMID 39707127)
• Mota Telles JP et al. Int J Stroke 2023 (PMID 36337029)
• Fang T et al. Neurocrit Care 2022 (PMID 34286461)

Levetiracetam Dosing

Adult Dosing by Indication

Formulations Available

• Oral: Immediate-release tablets (250, 500, 750, 1000 mg), oral solution (100 mg/mL)
• IV: 500 mg/5 mL (100 mg/mL concentrate); infuse over 15 minutes
• Extended-release tablets also available (once-daily dosing)

Renal Dose Adjustment

Key Pharmacokinetic Points

• Half-life: 6–8 hours (longer in elderly)
• No hepatic metabolism — no CYP interactions, no drug-drug interactions
• Not protein-bound — linear pharmacokinetics across the dosing range
• No need for therapeutic drug level monitoring in routine use (though reference range is ~12–46 mg/L)

Blood Pressure Control in Stroke — Ischemic vs. Hemorrhagic

Part 1: Ischemic Stroke

Pathophysiology of Hypertension in Acute Ischemic Stroke

Targets

Why Such Permissive Targets Without Thrombolysis?

Preferred Agents (Ischemic Stroke)

• IV labetalol — intermittent bolus (first-line)
• IV nicardipine — continuous infusion (preferred for precise titration)
• IV hydralazine — intermittent doses
• IV sodium nitroprusside — only when DBP >140 mmHg

Part 2: Hemorrhagic Stroke (ICH)

Why Active BP Lowering IS Indicated

Targets (AHA/ASA & Current Evidence)

Key Trial Data (ICH)

Preferred Agents (ICH)

• IV labetalol
• IV nicardipine (preferred — smooth titration, no reflex tachycardia)
• IV clevidipine
• IV enalaprilat

Summary Comparison Table

• Bradley & Daroff's Neurology in Clinical Practice
• Goldman-Cecil Medicine (22nd Ed.)
• Comprehensive Clinical Nephrology, 7th Ed. — AHA/ASA & ESO guideline comparison table
• Reginato PH et al. Neurocrit Care 2025 (PMID 40739079) — meta-analysis of intensive BP lowering in ICH

Carotid Stenosis — Overview and Treatment

Epidemiology and Clinical Significance

• 5–10% of patients >65 years have >50% carotid stenosis; ~1% have ≥75%
• Symptomatic patients have a 5–10× increased stroke risk vs asymptomatic; TIA carries a 20% risk of stroke within 90 days
• Asymptomatic patients outnumber symptomatic by 4:1
• ~90% of stroke risk is attributable to modifiable risk factors

Imaging Diagnosis

Grading of Stenosis

Treatment

1. Guideline-Directed Medical Therapy (GDMT) — Foundation for ALL patients

• Antiplatelet therapy: Aspirin 75–325 mg/day ± clopidogrel
• Statin therapy: High-intensity statin — target LDL <70 mg/dL
• BP control: Target SBP <140 mmHg (<130 in diabetics)
• HbA1c <7.0% in diabetics
• Smoking cessation
• Weight management, exercise (≥30 min moderate activity × 3/week)

2. Revascularization — Carotid Endarterectomy (CEA) vs Carotid Artery Stenting (CAS)

Symptomatic Carotid Stenosis

• NASCET: CEA reduced 2-year ipsilateral stroke rate from 26% → 9% for 70–99% stenosis (absolute risk reduction 17%)
• ECST: Confirmed benefit for 70–99% stenosis
• VA Cooperative Study: Corroborated NASCET findings

Asymptomatic Carotid Stenosis

3. CEA vs CAS — Comparative Data

4. Transcarotid Artery Revascularization (TCAR)

Indications Summary

Symptomatic + 70–99% stenosis → CEA (within 2 weeks)
Symptomatic + 50–69% stenosis → CEA (if perioperative risk <6%)
Symptomatic + <50% stenosis  → Medical therapy only
Asymptomatic + >70% stenosis → GDMT ± CEA if periop risk <3%
High surgical risk (any)      → Consider CAS or TCAR

• Fuster & Hurst's The Heart, 15th Ed.
• Bradley & Daroff's Neurology in Clinical Practice
• Grainger & Allison's Diagnostic Radiology
• Paraskevas KI et al. J Vasc Surg 2024 (PMID 37939746) — recent advances in asymptomatic carotid stenosis

3% Hypertonic Saline in Suspected CSVT — 13-Year-Old with Intellectual Disability

Understanding the Problem: Why Is 3% NaCl Being Considered?

• Increases venous back-pressure → impairs CSF absorption
• Elevates cerebral blood volume
• Can cause hemorrhagic venous infarcts and cerebral edema

Role of 3% Hypertonic Saline in CSVT — Is It Appropriate?

Standard management of raised ICP in CSVT:

"Treatment must be individualized, but anticoagulation is the cornerstone to prevent progression of thrombosis even in the presence of intracranial hemorrhage. Additional treatment should be directed at the management of secondary effects such as elevated ICP." — Plum & Posner's Diagnosis and Treatment of Stupor and Coma

3% NaCl — Dosing (Pediatric)

• Bolus: ~90–250 mL of 3% NaCl over 15–20 min (2–5 mL/kg)
• Infusion: 4.5–50 mL/hr titrated to response

Special Considerations: Intellectual Disability

1. Cannot reliably report headache — ICP may be underrecognized until late
2. Baseline neurological exam is altered — detecting clinical deterioration requires familiarity with baseline behavior
3. Agitation/behavioral change may be the only sign of worsening ICP or seizure
4. Seizure threshold may be lower — CSVT-associated seizures are more likely; continuous EEG monitoring should be considered
5. Consent and cooperation — IV access, monitoring, and medications may require additional support

Clinical pearl: In a non-verbal or minimally verbal child with ID, do not wait for the classic triad of raised ICP. Act on behavioral change + fundoscopy findings + imaging.

Important Cautions with 3% NaCl in CSVT Specifically

1. Do not delay anticoagulation in favor of osmotherapy — anticoagulation (LMWH or UFH) should be started promptly once CSVT is confirmed (or strongly suspected) even if hemorrhagic transformation is present
2. Avoid hypotonic fluids — they worsen cerebral edema; all maintenance fluids should be isotonic
3. Monitor sodium closely — rapid sodium correction carries risk of osmotic demyelination; aim for gradual, controlled rises
4. Mannitol is a less preferred alternative in CSVT with raised ICP — it causes osmotic diuresis and can worsen dehydration, which may propagate venous thrombosis. HTS is therefore preferred over mannitol in this specific context.
5. Imaging first if time permits: MRI + MRV is gold standard; CT venography is acceptable emergently

Summary Decision Framework

Suspected CSVT + raised ICP signs in 13-yr-old with ID
│
├─ Secure airway/IV access
├─ Urgent MRI-MRV or CT-venography
├─ Head of bed 30°, avoid hypotonic fluids
│
├─ ICP crisis present (GCS drop, herniation signs)?
│   YES → 3% NaCl 2–5 mL/kg IV bolus over 15–20 min
│         Monitor Na+, osmolality; repeat if needed
│         Avoid mannitol (worsens dehydration → propagates CSVT)
│
├─ Start anticoagulation (LMWH preferred) — do NOT delay
│   Even if hemorrhagic infarct present
│
├─ Seizure? → Treat with LEV (preferred)
│   No routine prophylaxis
│
└─ Acetazolamide for chronic ICP elevation (post-acute phase)