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High Altitude Cerebral Edema

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Last Update: July 17, 2023.

Continuing Education Activity

High altitude cerebral edema (HACE) is a severe and potentially fatal condition associated with high altitude illness that is often thought of as a late or end-stage acute mountain sickness (AMS). It is often characterized by ataxia, fatigue, and altered mental status. HACE represents the least common form of altitude illness, however it is critical that it be rapidly diagnosed and managed, as it can progress to coma and death as a result of brain herniation within 24 hours. This activity reviews the presentation, evaluation, and management of high altitude cerebral edema and stresses the role of an interprofessional team approach to the care of affected patients.


  • Explain the importance of rapid detection of high altitude cerebral edema.
  • Review the history and physical exam findings typically seen in patients with high altitude cerebral edema.
  • Describe the treatment of high altitude cerebral edema.
  • Explain modalities to enhance care coordination among interprofessional team members in order to improve outcomes for patients affected by high altitude cerebral edema.
Access free multiple choice questions on this topic.


High Altitude Cerebral Edema (HACE) is a severe and potentially fatal manifestation of high altitude illness and is often characterized by ataxia, fatigue, and altered mental status. HACE is often thought of as an extreme form/end-stage of Acute Mountain Sickness (AMS). Although HACE represents the least common form of altitude illness, it may progress rapidly to coma and death as a result of brain herniation within 24 hours, if not promptly diagnosed and treated. [1][2][3][4]


HACE generally occurs after 2 days above 4000m but can occur at lower elevations (2500m) and with faster onset.   Some, but not all, individuals will suffer from symptoms of AMS such as headache, insomnia, anorexia, nausea prior to transitioning to HACE.  Some may also have concomitant High Altitude Pulmonary Edema (HAPE).  HACE in isolation is rare, but the absence of concomitant HAPE or symptoms of AMS prior to deterioration does not rule-out the presence of HACE.   [5][6][7]


Incidence of HACE is 0.5-1% at altitudes of 4000-5000 m.  HACE affects those of all ages and genders, though younger males may be at higher risk due to continuation of ascent despite symptoms of AMS and faster rate of ascent. Risk factors include prior history of high altitude illness, lack of acclimatization, heavy physical exertion, rapid rate of ascent, and abrupt ascent from lower altitudes. 


Although the exact mechanism of development of HACE is not fully understood, it is thought to be the extreme form/end-stage of AMS. Hypoxia at altitude elicits neuro-hormonal (VEG-F, Nitric Oxide, reactive cytokines, free radicals) and hemodynamic responses resulting in hypoxia-induced cerebral vasodilation leading to over perfusion of microvascular cerebral beds.  This leads to intracranial hypertension with elevated capillary pressure and capillary leakage. The disruption of the blood-brain barrier from these stressors leads to subsequent cerebral edema.  The “tight fit” hypothesis suggests that one’s susceptibility to AMS/HACE is dependent upon the individual’s intracranial space available to compensate for increasing edema. This theory would help to explain the seemingly random nature of AMS that can evolve into HACE.  The “revised theory” to the development of HACE argues against volume overload and intracranial hypertension as the leading cause.  In this model, hypoxia induces free radical formation causing damage/failure of the Na+/K+ ATPase Pump with resultant astrocyte swelling from osmotic-oxidative stress, with subsequent cytotoxic edema. Neither theory is considered the standard by which HACE is fully understood.

History and Physical

Most cases develop as a progression of AMS and will include a history of recent ascent to altitude and prior complaints/findings of AMS including a headache, fatigue, nausea, insomnia, and/or lightheadedness.  Some may also have signs/symptoms of HAPE.  Transition to HACE is heralded by signs of encephalopathy including ataxia (usually the earliest clinical finding) and altered mentation which may range from mild to severe.  Other symptoms may include a more severe headache, difficulty speaking, lassitude, a decline in the level of consciousness, and/or focal neurological deficits or seizures.


HACE is a clinical diagnosis with the patient typically presenting with signs of encephalopathy, preceeded by signs and symptoms of Acute Mountain Sickness. The onset of neurological findings such as progressive decline in cognitive/mental function, declining level of consciousness, impaired coordination, slurred speech, and/or lassitude signify the transition from AMS to HACE.  Typical evaluation consists of an abnormal neurological exam, with ataxia often being the earliest finding. Early symptoms may be misinterpreted as exhaustion and it is important to exclude these, as well as other disorders such as dehydration, hypoglycemia, hypothermia, or hyponatremia which all may have signs and symptoms that overlap with that of HACE.  Though rarely available, laboratory testing may show an elevated white blood cell count in the setting of HACE, whereas any number of metabolic abnormalities may be present with the aforementioned others within the differential diagnosis.  Lumbar puncture may have an increased opening pressure with otherwise normal laboratory findings. CT may show cerebral edema, but MRI is a better study to evaluate for more subtle signs of edema and can remain abnormal for days up to weeks.  To date, there has been no direct correlation with the severity of edema with clinical outcome.

Treatment / Management

The mainstay of treatment is the immediate descent of at least 1000m or until symptoms improve. One should not descend alone and should have assistance to minimize physical exertion, which may worsen the patient’s condition. If descent is not an option, one may use a portable hyperbaric chamber and/or supplemental oxygen to temporize illness, but this should never replace or delay evaluation/descent when possible. If available, dexamethasone 8mg for one dose, followed by 4mg every 6 hours should be given to adults via PO, IM, or IV routes. Pediatric dosing is 0.15 mg/kg every 6 hours. Acetazolamide has proven to be beneficial in only a single clinical study. The suggested dosing regimen for Acetazolamide is 250 mg PO, given twice daily. Though effective in alleviating or temporizing symptoms, none of the adjunct treatment modalities are definitive or a replacement for an immediate descent.[8][1][9]

Differential Diagnosis

  • Acute psychosis
  • Brain tumour
  • Carbon monoxide poisoning
  • Central nervous system infection
  • Cerebrovascular bleed or infarct
  • Cerebrovascular spasm
  • Diabetic ketoacidosis
  • Hypoglycemia
  • Hyponatremia
  • Ingestion of drugs
  • Seizure disorder

Pearls and Other Issues

Acclimatization is the best means by which to prevent HACE and all other forms of AMS.  Considerations for prevention of AMS and subsequent HACE is to have a slow rate of ascent with the altitude one sleeps at being more important than the altitude reached.  Final ascent rates of 300-500m per day are recommended for safe and preventative acclimatization.  If signs of AMS develop, stop ascent and if debilitating or severe, descend immediately.   Prophylaxis for HACE/AMS includes both Acetazolamide and Dexamethasone. Ibuprofen is recommended for those with a history of altitude illness. There is less evidence for natural remedies such as ginkgo balboa and coca leaves.  Most advocate training regimens and slow rate of ascent to optimize acclimatization.  This often requires an intense time commitment and is difficult for many to achieve, particularly for those engaged in recreational climbing. Some studies have shown benefit to sleeping in specialized tents at home that provide normobaric hypoxia before departure to higher altitudes, although this has not been validated as a primary preventative measure of AMS or HACE.  

Enhancing Healthcare Team Outcomes

High Altitude Cerebral Edema (HACE) is a severe and potentially fatal manifestation of high altitude illness and is often characterized by ataxia, fatigue, and altered mental status. HACE is often thought of as an extreme form/end-stage of Acute Mountain Sickness (AMS). Although HACE represents the least common form of altitude illness, it may progress rapidly to coma and death as a result of brain herniation within 24 hours, if not promptly diagnosed and treated. The condition is best managed by an interprofessional team that includes a neurologist, internist and an emergency department physician

Even with robust training regimens, acclimatization, and prophylactic medications, HACE can strike any individual at any altitude, at any time. Even those with considerable experience at altitude may fall prey to the wares of HACE. Thus careful attention to the signs and symptoms of AMS and HACE should always be given proper consideration and respect. 

Review Questions


Gonzalez Garay A, Molano Franco D, Nieto Estrada VH, Martí-Carvajal AJ, Arevalo-Rodriguez I. Interventions for preventing high altitude illness: Part 2. Less commonly-used drugs. Cochrane Database Syst Rev. 2018 Mar 12;3(3):CD012983. [PMC free article: PMC6494375] [PubMed: 29529715]
Nieto Estrada VH, Molano Franco D, Medina RD, Gonzalez Garay AG, Martí-Carvajal AJ, Arevalo-Rodriguez I. Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs. Cochrane Database Syst Rev. 2017 Jun 27;6(6):CD009761. [PMC free article: PMC6481751] [PubMed: 28653390]
Jensen JD, Vincent AL. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 17, 2023. High Altitude Cerebral Edema. [PubMed: 28613666]
Khodaee M, Grothe HL, Seyfert JH, VanBaak K. Athletes at High Altitude. Sports Health. 2016 Mar-Apr;8(2):126-32. [PMC free article: PMC4789936] [PubMed: 26863894]
Derby R, deWeber K. The athlete and high altitude. Curr Sports Med Rep. 2010 Mar-Apr;9(2):79-85. [PubMed: 20220348]
Gallagher SA, Hackett PH. High-altitude illness. Emerg Med Clin North Am. 2004 May;22(2):329-55, viii. [PubMed: 15163571]
Basnyat B, Murdoch DR. High-altitude illness. Lancet. 2003 Jun 07;361(9373):1967-74. [PubMed: 12801752]
Li Y, Zhang Y, Zhang Y. Research advances in pathogenesis and prophylactic measures of acute high altitude illness. Respir Med. 2018 Dec;145:145-152. [PubMed: 30509704]
Zafren K, Pun M, Regmi N, Bashyal G, Acharya B, Gautam S, Jamarkattel S, Lamichhane SR, Acharya S, Basnyat B. High altitude illness in pilgrims after rapid ascent to 4380 M. Travel Med Infect Dis. 2017 Mar-Apr;16:31-34. [PubMed: 28285976]

Disclosure: Jacob Jensen declares no relevant financial relationships with ineligible companies.

Disclosure: Andrew Vincent declares no relevant financial relationships with ineligible companies.

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Bookshelf ID: NBK430916PMID: 28613666


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