High Altitude Cerebral Edema

High altitude cerebral edema is a life-threatening encephalopathy that develops in the setting of acute mountain sickness, as the severe end of a continuum, usually at over 4000 m and after 2 or more days at altitude. Incidence is 0.5 to 1% of climbers at 4000 to 5000 m, and higher over 5500 m. It is defined by ataxia and altered mental status in a person with recent ascent, with or without symptoms of acute mountain sickness.

Mechanism: hypoxemia causes cerebral vasodilation and raises cerebral blood flow and capillary pressure. Vasogenic edema follows from disruption of the blood-brain barrier by hypoxia-induced mediators (vascular endothelial growth factor, nitric oxide and free radicals), and cytotoxic edema contributes later.

The raised intracranial pressure and the white matter involvement (particularly the corpus callosum, the splenium in particular) cause the ataxia and confusion.

Magnetic resonance imaging shows hemosiderin deposits from microhemorrhages that persist for years in survivors.

Without treatment, coma and death follow within 24 hours of the onset of ataxia. With early descent, most patients recover, but deficits (ataxia, cognitive impairment) can persist for weeks. High altitude pulmonary edema coexists in about half of cases. Complications: coma, herniation, seizures (uncommon), retinal hemorrhage, cranial nerve palsies and persistent cognitive deficits.

• Truncal ataxia (inability to walk heel to toe in a straight line, the earliest sign), severe headache unresponsive to analgesics, vomiting and extreme fatigue
• Confusion, irritability, hallucinations, drowsiness, stupor and coma
• Papilledema in about 50%, retinal hemorrhage, sixth nerve palsy and focal deficits
• Coexisting dyspnea and cough from pulmonary edema
• Red flags: any ataxia or altered mentation at altitude, a climber who lags behind or behaves oddly, and rapid deterioration at night

1. Clinical diagnosis: recent ascent with ataxia, altered mental status or both. Test tandem gait and observe behavior, and use a self-reported symptom score (headache, gastrointestinal symptoms, fatigue, dizziness, sleep disturbance, each scored 0 to 3).
2. Bedside tests: capillary glucose (to exclude hypoglycemia), pulse oximetry and temperature.
3. MRI brain: T2 hyperintensity in the white matter, particularly the splenium of the corpus callosum, with later hemosiderin on susceptibility sequences. CT shows a reduction in ventricular size and sulci, and is less sensitive.
4. Chest examination and imaging for coexisting pulmonary edema.
5. Exclusion of other causes: hypoglycemia, hyponatremia, stroke, meningitis, intoxication, carbon monoxide poisoning (from tents and stoves), hypothermia and exhaustion.

Differentials: acute mountain sickness, migraine, stroke, hypoglycemia, hyponatremia (from overhydration), hypothermia and meningitis.

1. Immediate descent: at least 300 to 1000 m, as fast as is safe, with escort and no exertion. Do not wait for improvement overnight.
2. Oxygen: 2 to 4 L/min by mask to keep saturation over 90%.
3. Dexamethasone: 8 mg orally, IV or IM once, then 4 mg every 6 hours until the patient is symptom free and descent is complete, then taper over 3 to 5 days if given longer than 5 days. Children: 0.4 mg/kg (maximum 8 mg) once, then 0.1 mg/kg (maximum 4 mg) every 6 hours.
4. Portable hyperbaric chamber at 2 psi (13.8 kPa) when descent is delayed, in 2 to 4 hour sessions, then continue descent.
5. Acetazolamide 250 mg orally every 12 hours as an adjunct once the patient is able to take oral medication (children 2.5 mg/kg every 12 hours, maximum 125 mg a dose). It is not a substitute for descent.
6. Coexisting pulmonary edema: add nifedipine 30 mg modified-release orally every 12 hours.
7. Airway and supportive care: protect the airway in coma, give IV glucose 50% 25 to 50 mL for hypoglycemia, and warm the patient. Intubation and controlled ventilation to a PaCO2 of 35 mmHg and hypertonic saline 3% 2 to 5 mL/kg IV over 10 to 20 minutes in a hospital setting for severe edema.
8. Seizures: lorazepam 4 mg IV (children 0.1 mg/kg).
9. Avoid sedatives and opioids, which obscure mental state and depress breathing.
10. Recovery: do not re-ascend until fully recovered, and rest at a lower altitude for several days.

Prevention: slow ascent with an average gain in sleeping altitude of 300 to 500 m a day over 3000 m with a rest day every 3 to 4 days, avoiding rapid ascent after symptoms, and drug prophylaxis for high-risk ascents.

Acetazolamide 125 mg orally every 12 hours starting the day before ascent and continuing for 2 days at the top (250 mg every 12 hours for very rapid ascent).

Dexamethasone 4 mg orally every 6 hours (or 8 mg every 12 hours) starting on the day of ascent, for rescue and selected groups.

Follow-up with MRI and cognitive review at 3 months for survivors of severe cases.