Treatment of Vasogenic Oedema

1. Corticosteroids (Primary Treatment)

Dexamethasone

• Mechanism: Rapidly closes the BBB; effect on permeability can be seen as early as 1 hour after administration.
• Indication: Oedema surrounding brain tumours (primary or metastatic), cerebral abscess, multiple sclerosis exacerbations.
• Dose (brain tumour): Start at 8-12 mg/day, adjusted to the lowest effective dose. Clinical improvement often begins within minutes to hours; dramatic improvement occurs within 24-48 hours (Goldman-Cecil Medicine).
• Harrison's protocol: Dexamethasone 4 mg q6h for vasogenic oedema from tumour or abscess.
• Contraindications: Corticosteroids are not effective in cytotoxic oedema and are contraindicated in:
  • Head trauma (worsens outcome)
  • Ischaemic stroke
  • Intracerebral/subarachnoid haemorrhage (systemic complications can worsen the patient's condition)
  • Vasogenic oedema from trauma also typically does not respond.

Methylprednisolone (MS Exacerbations)

• Dose: 1 g/day for 3-5 days for acute MS exacerbations with vasogenic oedema component.
• Dramatic reduction in BBB enhancement on MRI may be seen. Effect is, however, lost after several months.

Side Effects to Monitor

• Insomnia, steroid myopathy, GI complications, hyperglycaemia (monitor blood glucose closely).
• If corticosteroids are required for >6 weeks, give prophylaxis against Pneumocystis jirovecii.

2. Osmotic Therapy (Acute ICP Reduction)

Mannitol

• Dose: 0.25-1 g/kg IV (low doses as effective as older high doses of 3 g/kg, with fewer electrolyte disturbances).
• Mechanisms: Increases serum osmolality, reduces brain tissue volume (particularly non-infarcted tissue), reduces CSF and interstitial fluid secretion by ~50%, rheological blood changes, antioxidant effect.
• Target: Serum osmolality 300-315 mOsm/L; do not exceed 320 mOsm/L.
• Cautions: Avoid in ICH, aneurysms, or AVMs before craniotomy (can expand haematoma as normal brain shrinks); may precipitate pulmonary oedema in patients with cardiac or renal impairment; rebound oedema may occur on discontinuation.

Hypertonic Saline

• Dose: 30 mL of 23.4% NaCl bolus; or 3% NaCl infusion.
• Increasingly advocated especially in patients where mannitol is contraindicated.
• Caution: Monitor serum sodium and osmolality carefully; risk of osmotic demyelination syndrome if used in hyponatraemic patients.

3. General Measures for Raised ICP

4. Second-Line / Refractory ICP

• Decompressive craniectomy - shown to reduce mortality in TBI with refractory ICP.
• High-dose barbiturate ("pentobarb coma") - metabolic suppression.
• Hypothermia to 33°C.

5. Anti-VEGF Therapy (Tumour-Associated Oedema)

• Bevacizumab (anti-VEGF antibody) is effective for symptomatic cerebral oedema in brain tumours and can significantly reduce corticosteroid requirements.
• Particularly useful in recurrent glioblastoma or radiation-induced oedema.

6. Treat the Underlying Cause (Definitive)

Key Distinctions

Treatment of PRES (Posterior Reversible Encephalopathy Syndrome)

Core Principles

1. Blood pressure control
2. Remove/treat the precipitating cause
3. Seizure management

1. Blood Pressure Control

• Agents of choice: IV labetalol or IV nicardipine (both recommended by Harrison's 22E as first-line IV agents)
• Target: Lower the MAP by approximately 20% initially - do NOT aim for rapid normalisation, as overshoot below the patient's autoregulatory lower limit can cause secondary cerebral ischaemia and infarction.
• Monitoring: Continuous BP monitoring; repeat neuroimaging if clinical worsening occurs despite treatment.
• Hypertensive crisis is the most common trigger, but blood pressure may not always be markedly elevated at presentation (especially in drug-induced or eclampsia-related PRES).

2. Remove the Precipitating Cause

Note from Harrison's: Calcineurin inhibitor neurotoxicity can occur even at normal serum drug levels, so normal levels do not exclude them as the cause.

3. Seizure Management

• Seizures occur in up to 90% of patients with PRES (Brenner & Rector).
• Non-convulsive seizures are common - maintain a low threshold for continuous EEG monitoring.
• Standard anticonvulsants are effective (levetiracetam is commonly used as it avoids hepatic metabolism and has fewer drug interactions).
• Special case - Eclampsia: Magnesium sulfate is preferred over conventional anticonvulsants for seizure control, with evidence supporting its superiority in this context.
• Duration of anticonvulsant therapy: Can typically be weaned once the PRES resolves radiologically, as seizures do not usually persist after the underlying cause is treated.

4. General Supportive Care

• Elevate head of bed to 30°
• Avoid hypotonic IV fluids (worsen cerebral oedema)
• Correct any metabolic disturbances (hyponatraemia, hypomagnesaemia, hypocalcaemia) that lower the seizure threshold
• Maintain airway if consciousness is impaired; ICU-level monitoring for severe cases

5. Monitoring and Prognosis

• Repeat MRI typically shows complete radiological resolution after BP control and removal of the offending agent.
• Prognosis is generally favourable, but a 2025 Lancet Neurology review by Fugate, Hawkes & Rabinstein highlights that complications including epilepsy and stroke can follow severe or recurrent PRES, and that novel agents (CAR-T, tyrosine kinase inhibitors) are expanding the spectrum of presentations.
• Emerging biomarkers (IL-6, IL-10, VEGF) may help predict severity and outcome.

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