High Altitude Cerebral Oedema (HACE)

AUTHOR: DR JENNY BAKER

What is HACE?

HACE can occur from 2500m above sea level although more commonly presents at altitudes of 5000m and above. One in five with HAPE have concurrent HACE and up to 50% of those that die from HAPE are also found to have HACE on autopsy(1). It is often thought of as ‘end-stage AMS’ and is characterised by symptoms of AMS combined with neurological signs(1). It’s a severe form of HAI and, if not treated quickly, can result in death.

Pathophysiology

The pathophysiology of HACE is poorly understood. It is thought that normal adaptations to altitude, AMS and HACE are each along a spectrum of these changes that occur. These adaptations are stimulated by a decrease in the concentration of oxygen in inspired air at altitude(2). This reduces gas exchange and results in progressive hypoxia(2). For more information about this, check out our blog on physiological adaptations to altitude! 

Hypoxia causes increased cerebral blood flow and cerebral arterial and venous dilation(1). This in turn results in increased capillary pressure which, combined with an increase in the permeability of the blood-brain-barrier causes cerebral oedema. Vessel dilatation increases the volume occupied, increasing intracranial pressure(1). The extent to which this occurs dictates the susceptibility of individuals to AMS and HACE (2). 

The ‘tight fit’ hypothesis suggests that the ability to tolerate cerebral swelling within the skull, i.e. the brain-to-intracranial space ratio, will also contribute to a person’s likelihood of developing HACE(2). However, the evidence base for this is poor and it has not currently been proven.

Additionally, there is ongoing research into the genetics that may contribute to a person’s response to hypobaric hypoxia, and susceptibility to HAI. It is likely that multiple genes each contribute in a small way, with hypoxia-inducible factor alpha (HIF-a) and angiotensin-converting enzyme being of particular interest(2)

Presentation

HACE is seen as a development of acute mountain sickness (AMS) and often follows a deterioration of the symptoms associated with it(3): 

• Sleep disturbance 
• Anorexia 
• Nausea and vomiting 
• Dizziness 
• Fatigue 

HACE is characterised by the presence of these symptoms associated with neurological signs(3) 

• Ataxia 
• Lassitude 
• Behavioural changes 
  •  irritability, confusion, disorientation, inability to care for oneself 
• Cranial nerve palsies 
  • Often III, IV and VI
• Decline in cognitive function  
• Progressive loss of consciousness, eventually resulting in coma

Investigations

While there are changes on radiological imaging(4), and retinal haemorrhages are common(2), assessment in the field is likely to depend on good clinical skills: i.e. excellent history taking, and examination(3). Sharpened Romberg’s(5) has been found to be sensitive for ataxia in HACE:

• • Standing with their feet heel-to-toe and arms crossed over their chest, ask the patient to close their eyes for 60 seconds (See here for further information). Any movement to balance themselves amounts to a ‘fail’. 

In addition, Quigley and Zafren(6) found that a clock drawing test illuminated cognitive deficit in a patient who seemed otherwise well (Figure 1), although this has not been validated as a test for HACE.

Figure 1: Abnormal clock face drawn by the patient on day 1(left), despite no ataxia and ability to converse normally. Collateral history from a friend reported ataxia and abnormal behaviour the previous day. After treatment with oral dexamethasone and supplemental oxygen overnight the patient was able to draw a normal clock face (right).

Management

Early recognition and treatment are essential – the earlier treatment is initiated the greater the treatment response (3). 

Gold standard management for any high-altitude illness is descent. 

Dexamethasone 8 mg initially, then 4 mg 6 hourly helps to reduce oedema(3).

If descent is not feasible:

• Supplemental oxygen, aiming for saturations >90%
• If available a portable hyperbaric chamber can be used. These do not cure HACE, and symptoms return in the hours after leaving but this can be used to buy time if descent is not safe due to weather or to gain enough neurological improvement that the patient may be able to mobilise and descend with aid. 

Remember, co-existent HAPE is common – add nifedipine 20mg MR if there is any suspicion. Please see our article on HAPE for further details

Complications

The neurological deficit caused by HACE increases with the severity of cerebral oedema. Untreated, this can result in coma, and eventually death, usually secondary to brain herniation(1). 

The main concern when climbing is the loss of insight into the condition and there are frequent stories of climbers having to be persuaded to descend or, sadly, who fail to recognise the onset of HACE and do not descend in time. 

While there have been reports of long-term cognitive effects following ascent to extreme altitude, these have focussed on those who have been well during repeated exposure rather than those suffering from HACE.

Prevention

Prevention is always better than cure; and makes your job as the expedition medic much easier! 

• Slow ascent 
  • Above 3000m, sleeping elevation should not increase by more than 500m/day – see wilderness medical guidelines(3).   
  • Rest every 3-4 days to allow acclimatisation 
• Prophylactic measurements including: 
  • Acetazolamide as prophylaxis 
    • 125mg BD or 250mg OD from 1 day before ascent >3500m(3)
    • Stimulates ventilation and aids acclimatisation
    • Side effects include tingling in peripheries, diuresis, taste alterations
    • Those with anaphylaxis to sulphonamides should avoid it. 
  • Dexamethasone can be used as an alternative to acetazolamide 
    • While it reduces symptoms of HAI it does not aid acclimatisation
    • Think about the length of administration – adrenal suppression can occur after 2 weeks. 
• Early management of HACE/HAPE
  • Descent
  • Acetazolomide 250mg BD

See our article on AMS for the Wilderness Medicine Society’s risk stratification regarding chemical prophylaxis

Differentials to consider

It has been said that anyone who appears slightly drunk at altitude should be suspected of having HACE. Ensure you take a thorough history and examination and rule out any differential diagnosis. 

Differentials related to the expedition

• Hypoglycaemia 
• Hyponatraemia
• Dehydration
• Hypothermia 
• Exhaustion 

Other medical diagnoses

• CNS infection 
• Trauma + head injury 
• Space occupying lesion 
• Intracranial haemorrhage/Stroke 

Any suspicion of HACE should be met with descent where at all possible.

Take home messages

• HACE occurs due to an excessive response to hypoxia at altitude.
• Prevention is better than cure! 
  • Ascend slowly and consider chemical prophylaxis in susceptible team members or on expeditions with rapid ascent profiles.
• Suspect AMS/HACE in any team member who seems tired, confused or ‘just not right’.
• Early treatment is more effective. 
• Descent is the best treatment if there are any concerns about HACE.
• Consider concurrent HAPE and adding nifedipine to treatment.

Are you interested in learning more about AMS and other high altitude conditions?

If so, why not check out our Altitude Medicine Course? Whilst you’re there, why don’t you take a look at our other courses too?