Transient Cerebral Ischemia at High Altitude and Hyper-Responsiveness to Hypoxia

Introduction

Transient neurological disorders occurring at high altitude but not presenting the characteristics of acute mountain sickness (AMS) or high-altitude cerebral edema have been scarcely described at high altitude, mostly as case reports (Hackett et al., 1987; Basnyat et al., 2004; Firth and Bolay, 2004). Their mechanisms are still debated. The present case report describes an unusual rapidly resolving neurological disorder at high altitude in a young woman who had an extensive diagnostic work-up after returning home.

Case Report

Mrs. M.D., 36 years old (53 kg, 1.55 m), participated in a trekking in Ladakh in August 2018. After 4 days of acclimatization at Leh (3700 m) and 15 days of walking between 3800 and 5300 m above sea level, without any particular problem or AMS symptom, Mrs. M.D. started with her companions the ascent of a 6000 m peak in Zanskar. After three nights at 4800 m without any problem, she had to make an intense effort for 10 minutes, during a climb to 5300 m, to catch up with the group that had taken the lead. She arrived panting at the group level and remained breathless for a few minutes. Then, she complained of sudden unilateral visual disturbances (left eye), characterized by altered vision, abnormal forms in the visual field (“kaleidoscope”), and a feeling of pressure around the left eye. She felt exhausted, severely dizzy, then slurred speech appeared as well as some confusion (according to her companions). For a few minutes, she could not find her words or the names of the people around her. She felt tingling and numbness in the right arm.

The group decided to get her down quickly. During the descent, as she became nearly unconscious and collapsed several times, she had to be supported by her companions. She did not respond to pats on the hand but finally to pats on the cheek.

Arriving at 4800 m after 3 hours of descent, she felt better. She was given oxygen for 20 minutes and was prevented from falling asleep. Then her condition seemed to improve and she slept continuously for 14 hours. No medication was given to her. She drank and ate slightly. The next day, she woke up without any symptom, no visual or other neurological signs. She walked for 20 km with the rest of the group at altitudes between 4800 and 4500 m, without any neurological symptom or fatigue. At no time since her malaise, she felt any breathing difficulty.

She had taken aspirin during the trekking only occasionally (e.g., 500 mg in the morning of the malaise), but no other medication. She does not take oral contraception.

A brain magnetic resonance imaging (MRI) was performed 1 month after her episode (T1 sagittal slices, axial FLAIR, T2 * diffusion, and coronal STIR) that evidenced no abnormalities and gave no argument for a recent ischemic episode.

Two months after the episode, she came to the altitude consultation. She is well and has resumed her engineering job. On her return from Ladakh, she complained of being a little “awkward” in some fine gestures and her entourage told her that her voice had changed a bit, but at the time of the consultation, all these troubles have disappeared, and the neurological examination is normal.

In her medical history, nothing special is worth mentioning, no hypertension, no hypercholesterolemia, no familial history of vascular event, and no migraine. She has an unexplored Raynaud's syndrome, some episodes of vagal malaise. She occasionally complains of sinusitis (incidentally found on the MRI: left maxillary sinusitis with hydroaeric level). She takes no medication.

On examination, her lung auscultation was normal. Her EKG was normal, with a sinus rhythm and a qRS axis at 90°.

During the hypoxia exercise test, a very high ventilatory response to hypoxia at exercise was found (HVRe = 1.47 L/[min·kg]), the standard (mean ± standard deviation [SD]) value being 0.68 ± 0.33 L/(min·kg) (Fig. 1) (Richalet et al., 2012). End tidal PCO₂ at exercise in hypoxia was low (23.7 mmHg), the standard (mean ± SD) value being 35.2 ± 3.0 mmHg.

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FIG. 1.

(A) Typical hypoxic exercise test on a normal subject. (B) Hypoxic exercise test on the patient. V ̇ e = minute ventilation; SaO₂ = arterial O₂ saturation, P_ETCO₂: end-tidal PCO₂. HVRe is calculated as Δ V ̇ e_e/ Δ SaO_2e/body weight × 100 [see Richalet et al. (2012) for more details].

A transthoracic and transesophageal echocardiography revealed normal cardiac dimensions and contractility. Valves were normal. There was no persistence of foramen ovale (PFO, as explored by microbubbles injection). The Doppler of supra-aortic arteries was normal. A 24-hour EKG Holter revealed no rhythm disturbances. An assessment of hemostasis did not seem necessary.

Discussion

Altogether, this is a rapidly resolving neurological disorder occurring at high altitude, in a young woman without medical history and perfectly acclimatized to high altitude.

The probable diagnoses were the following: 1.

Embolic transient ischemic attack in the left carotid artery territory, given the visual disturbance in the left eye and the right arm sensory disturbances, but this does not explain the dizziness and the disorders of consciousness. Furthermore, no potential cause was found at the cardiovascular work-up (no PFO, normal EKG Holter, Doppler of supra-aortic arteries, and MRI).

The hypothesis of a transient cerebral ischemic/hypoxic event seems the most likely to be the cause of this neurological disorder. It calls our attention about the possible harmful effect of excessive hyperventilation at high altitude on cerebral tissue, combining hypoxemia and hypocapnia-induced vasoconstriction. Dizziness is a symptom that is part of the Lake Louise scoring system (The Lake Louise, 1992). However, it might be confusing since dizziness is likely due to hyperventilation-induced hypocapnia and hyperventilation is rather a sign of good acclimatization to high altitude, as shown in this case report. A hypoxia exercise test that evidenced a hyper-responsiveness to hypoxia is another argument in favor of this hypothesis.

Cases of transient ischemic attacks have been previously reported (Botella De Maglia et al., 1993; Cauchy et al., 2002), but this is the first case wherein the patient has been extensively explored at his return home. Focal manifestations of migraine have been described at high altitude (Cauchy et al., 2002; Broessner et al., 2016). The first symptoms (positive visual signs, dysphasia, and right arm sensory disturbances) indeed suggest a migrainous aura but a migraine attack would not explain that she soon after became unconscious. However the absence of migraine attacks before or after this episode is not in favor of this hypothesis. High-altitude global amnesia has been evoked in rare circumstances (Litch and Bishop, 2000; Bucuk et al., 2008). However, in this case, amnesia is not the pre-eminent symptom. Similar neurological symptoms may be caused by intense neuronal discharge or neuronal synchronization as a feature of cortical spreading depression (Firth and Bolay, 2004).

In conclusion, special attention should be given to subjects who show a hyper-responsiveness to hypoxia before a sojourn at high altitude: they should avoid any kind of stress, emotion, or exhaustive exercise that would induce inappropriate hyperventilation.