Pediatric High Altitude Cerebral Edema in the Nepal Himalayas

Introduction

An increasing number of people, including children and adolescents, are traveling to high altitude (above 2500 m) throughout the world. Nepal alone had over 1.1 million foreign visitors in 2018, many of whom visited high altitude areas, with just over 35,000 visitors between the ages of 1 d and 15 y. ¹ There are limited data and few guidelines regarding children and adolescents at high altitude. However, many clinicians are increasingly being asked questions such as “Can our child visit her grandparents at a resort in the mountains?” or “Can our daughter go to Everest Base Camp?” ² There is little epidemiologic evidence to guide clinicians in answering these questions, but the evidence available suggests that the incidence of acute mountain sickness (AMS) in children is similar to that in adults. ^{3 –}5 High altitude cerebral edema (HACE), a life-threatening condition, is on the severe end of the AMS spectrum ⁶ The incidence of HACE in adults ranges from 0.5 to 3.4%, or to as high as 34% depending on the altitude and the rate of ascent. ⁷ HACE is much more likely to occur in people who have high altitude pulmonary edema (HAPE). ⁶

We report 2 cases consistent with HACE in patients younger than 18 y. We are not aware of a previous case report of HACE in a patient under the age of 18 y. The 2 patients presented while one of the authors was volunteering at the Himalayan Rescue Association Manang clinic (3500 m) in spring 2018.

Case Report 1

A healthy 16-y-old girl from Norway with no significant medical history presented to our clinic in Manang (3500 m). She was experiencing a gradually worsening headache associated with anorexia, nausea, vomiting, and dizziness that had begun 2 d before arrival. She had mild upper respiratory symptoms 1 wk previously, including rhinorrhea and cough, that had resolved before arrival in Manang. She had felt well at the beginning of the trek at 759 m. The patient and her father ascended via jeep from 759 m to 3500 m in 1 day and then trekked to 3800 m the following day. During this time she developed poor appetite, nausea, and mild headache. She denied shortness of breath or respiratory symptoms. On arrival at 3800 m, her headache was generalized; 9 of 10 in severity; and associated with persistent vomiting, dizziness, and difficulty sleeping. She and her father left their tea house at 3800 m early in the morning and arrived at the clinic on a chartered motorbike. She reported that she had only been drinking approximately 500 mL of fluid daily over the previous 2 d because of nausea.

Vital signs were as follows: blood pressure 138/70 mm Hg, heart rate 100 beats·min⁻¹, respiratory rate 18 breaths·min⁻¹, temperature 37.8°C, and peripheral capillary oxygen saturation (SpO₂) 69% on room air. Normal SpO₂ at the elevation of Manang is approximately 90% on room air. She appeared ill, with a withdrawn and apathetic affect. She had no respiratory distress. Her lungs were clear to auscultation. She was alert and followed commands. She had ataxia with tandem gait (heel-to-toe walking) and dysmetria with finger-to-nose testing bilaterally. She was given ondansetron 4 mg and acetazolamide 250 mg by mouth and was encouraged to drink fluids. She was given oxygen at 2 L·min⁻¹ via nasal cannula without a repeat SpO₂ recorded. The treating physician recommended administration of dexamethasone, but the patient's father refused because the patient was reported to be a high-performance athlete and had been told by her coach “not to take steroids.” The patient and her father descended immediately via jeep because helicopter evacuation was not possible owing to bad weather. The patient reported that her symptoms improved gradually during descent and had completely resolved 24 h later when she arrived below 800 m.

Case Report 2

A healthy 12-y-old boy from Germany who had no significant medical history presented to our clinic with 2 d of a gradually worsening headache associated with vomiting and dizziness that had begun at 4500 m. The boy and his father had ascended to 2600 m via jeep and then took 3 d to arrive at 4500 m. The boy felt well during the ascent, but when he reached 4500 m he developed headache and nausea. The next morning the patient and his father attempted to ascend, but the patient began to report blurry vision. At that time the patient and his father descended, hoping this would improve the blurry vision. They made another attempt to ascend 2 h later, but the blurry vision persisted. They then descended to 4200 m, where the patient's father gave him acetazolamide 125 mg by mouth. The patient and his father stayed at 4200 m that night. Overnight, the child developed nonbloody, nonbilious vomiting and became increasingly unsteady on his feet with a “wobbly” gait, as per the father. The patient took a second dose of acetazolamide the following morning. He continued to have a headache and began to report diplopia, which he described as seeing “2 rivers” when he looked down the valley. Diplopia progressed to intermittent loss of vision. The boy and his father then descended to our clinic. The visual disturbances improved during the descent. The boy took a third dose of acetazolamide on arrival to the clinic.

Vital signs on arrival were blood pressure 95/60 mm Hg, heart rate 122 beats·min⁻¹, temperature 37.5°C, and SpO₂ 84% on room air. SpO₂ improved to 99% with supplemental oxygen via a nonrebreather face mask. The respiratory rate was not recorded. Examination revealed an unwell-appearing boy who was lethargic, listless, and at times difficult to arouse. He occasionally needed physical stimuli to stay awake. The pupils were equal and reactive to light. Extraocular movements were intact. He had no signs of respiratory distress. The lungs were clear to auscultation. Neurologic examination revealed normal tandem gait and finger-to-nose testing bilaterally. In addition to acetazolamide and supplemental oxygen, dexamethasone 8 mg was recommended but was refused by the patient's father for unclear reasons. Immediate helicopter evacuation was not possible because the patient presented in the late evening hours. Jeep evacuation was arranged, and the patient began further descent immediately. The patient was lost to follow-up.

Discussion

We believe that this is the first published description of HACE in children. Our cases illustrate the variable features of HACE. HACE is distinguished from AMS by the presence of altered mental status or ataxia, which can occur separately or together. The girl in the first case had ataxia but a relatively normal mental status, whereas the boy in the second case had a depressed level of consciousness without ataxia. Other diagnoses that can mimic HACE in children include dehydration, hypoglycemia, migraine, hyponatremia, hypothermia, carbon monoxide poisoning, diabetic ketoacidosis, brain tumor, and seizure.

Both patients had normal oral temperatures, eliminating hypothermia as a diagnosis. Lack of fever made an infectious etiology less likely. There was no history of carbon monoxide exposure, making carbon monoxide toxicity unlikely. Dehydration can mimic AMS, but neurologic features made this diagnosis less likely. Neither patient had a history of diabetes, so diabetic ketoacidosis or hypoglycemia were both improbable. New-onset diabetes was unlikely. In retrospect, fingerstick glucose determination would have been appropriate in both cases. Neither patient had a history consistent with seizures. The acute onset of headache is not consistent with a brain tumor. Subarachnoid hemorrhage was unlikely because the headaches were not maximal or thunderclap at onset. Neither patient had a history of a medical condition that might cause sodium imbalance. Both had decreased fluid intake, making hyponatremia unlikely. Migraine equivalent with visual disturbances was a possibility, especially in the second case. The patient in the first case had a strong family history of migraines but had never before experienced one herself. Unfortunately, family history was not elicited in the second patient and he was lost to follow-up.

The first patient had an oxygen saturation of 69%. The presence of low oxygen saturation suggests that she also had HAPE without clinical signs or symptoms. An abnormally low SpO₂ in a patient with HACE is presumptive evidence of HAPE. ⁶ HACE is much more likely in those with HAPE. Young patients also have an increased incidence of respiratory illnesses, such as pneumonia and bronchiolitis. ^{8 –}10 It is possible that the upper respiratory illness that our 16-y-old patient experienced early in the trip predisposed her to HAPE, which led to HACE.

Insufficient descent after the onset of symptoms seems to be the main contributing factor to the development of HACE in the second patient. The patient and his father had a reasonable ascent profile of no more than 500 m per night above 2500 m, but they ascended rapidly via jeep to 2600 m. The patient and his father descended appropriately after the onset of symptoms but only after a flawed attempt to reascend. The lack of significant improvement in symptoms after a 300 m descent should have prompted further descent, as evidenced by the fact that the patient's gait and visual symptoms improved significantly with an additional 700 m descent. A common sense approach to descent for the treatment of AMS/HACE features no hard cutoff but rather descent until symptoms improve or resolve.

Prevention and treatment of AMS and HACE are summarized in the high altitude guidelines of the Wilderness Medical Society. ¹¹ The most effective method of preventing AMS and HACE is gradual ascent of no more than 500 m increase in sleeping elevation each night above 2500 m, with an extra day at the same altitude every 3 to 4 nights. Acetazolamide can also be used for prevention at the pediatric dose of 2.5 mg·kg⁻¹ to a maximum of 125 mg dose every 12 h. Dexamethasone is not recommended for prevention of AMS and HACE in children.

There are no treatment guidelines specific for HACE in children. A patient with HACE should be treated with immediate descent until symptoms resolve, although ataxia may persist for days or even weeks in severe cases. Oxygen therapy via nasal cannula or nonrebreather should be given immediately in addition to dexamethasone (oral, intramuscular, or intravenous) at a dose of 0.15 mg·kg⁻¹ up to 8 mg initially, then 0.075 mg·kg⁻¹ up to 4 mg every 6 h. Simulated descent in a portable hyperbaric therapy can be used also if actual descent is not possible. ¹²

Conclusion

Our cases suggest that HACE can occur in children and adolescents. Because there are no specific guidelines for treatment of AMS and HACE in patients under the age of 18 y, we recommend treatment as for adults: immediate descent, oxygen, and dexamethasone. Dexamethasone was declined in both cases but may have led to more rapid resolution. Simulated descent in a portable hyperbaric chamber can be used if actual descent is impossible.