High-altitude cerebral edema manifesting as T2/FLAIR hyperintensity and microbleeds in the white matter on MRI brain

Abstract

High-altitude cerebral edema is a rare type of acute mountain illness characterized by consciousness disruption and truncal ataxia. Here we discuss a 40-year-old nondiabetic, nonsmoker male who went on a tour to Nanga Parbat. On returning home, the patient developed symptoms of headache, nausea, and vomiting. His symptoms worsened with time and he developed lower limb weakness and shortness of breath. Later, he underwent a computerized tomography chest scan. On the basis of CT scan findings, the doctors decided that the patient was suffering from COVID-19 Pneumonia despite having negative COVID-19 PCR tests multiple times. Later, the patient presented to our hospital with similar complaints. MRI of the brain revealed T2/fluid-attenuated inversion recovery hyperintense and T1 hypointense signals in the bilateral semioval centrum, posterior periventricular white matter, and corpus callosum genu, body, and splenium. These abnormal signals were discovered to be more evident in the corpus callosum's splenium. Moreover, susceptibility-weighted imaging revealed micro hemorrhages in the corpus callosum. This verified the diagnosis that the patient is suffering from high-altitude cerebral edema. Within 5 days, his symptoms resolved and he was discharged with full recovery.

Introduction

Living at sea level while traveling on a tour to high altitudes could have dire consequences if adequate measures are not taken on time. At higher altitudes, our body is exposed to low atmospheric pressure that results in a low partial pressure of oxygen which may impede adaptation to high-altitude regions [1]. Although acclimatization is a natural physiological adaptation to certain environmental situations, the body requires a certain time to adapt to a new environment. High-altitude cerebral edema (HACE) is a rare type of acute mountain illness characterized by consciousness disruption and truncal ataxia [2]. These symptoms are caused by vasogenic edema, and microbleeds in the white matter and corpus callosum are frequent MRI findings [3]. Sometimes, verbal and visual memory deficits can be identified in a patient with corpus callosum splenium lesions [4].

The risk of “acute mountain sickness” increases to 25% at 3500 m (11,500 feet) altitude and 50% at 6000 m (19,700 feet) [5,6]. According to research, the prevalence of HACE was found to be 0.5%-1.0% in a selected group of individuals traveling to heights over 4500 m [7]. HACE affects people of all ages and both sexes, while younger males may be at a higher risk due to continued ascent despite having acute mountain sickness symptoms and a faster ascend rate. Risk factors for HACE include a previous history of high altitude illness, lack of acclimatization, excessive physical exercise, rapid ascend rate, and sudden ascent from lower altitudes [4].

Although the specific mechanism by which HACE develops is not entirely understood, it is believed to be the most severe form/final stage of acute mountain sickness [8]. Hypoxia at altitude evokes neuro-hormonal such as free radicals, nitric oxide, cytokines and Vascular endothelial growth factor, and hemodynamic responses, leading to “hypoxia-induced cerebral vasodilation” and over perfusion of microvascular cerebral beds. This results in intracranial hypertension accompanied by increased capillary pressure and leakage. This breach of the blood-brain barrier caused by these stressors results in cerebral edema [8].

However, HACE occurs under specific conditions, there is limited research detailing its clinical course and neuroimaging changes. Here we discussed neuroimaging features of a case of HACE also having high-altitude pulmonary edema.

Case report

A 40-year-old nondiabetic, nonsmoker adult male went on a tour to Nanga Parbat (3850-8126 m in height) situated in the higher altitudes of northern Pakistan. The patient stated that he was fine during the tour but on his way to returning home, the patient suddenly experienced fever, vomiting, nausea, and headache. With the passage of time, his symptoms started to worsen. Due to these worrisome symptoms, the patient was presented to the local hospital and was managed but later his condition deteriorated and he developed lower limb weakness and shortness of breath. There was no other significant past medical history of any chronic disorders. The doctors suspected that it could be due to the COVID-19. To confirm the diagnosis, the patient underwent a computerized tomography chest scan. The findings revealed: perihilar airspace shadowing with smooth interlobular septal thickening. The doctors made the diagnosis that the patient is suffering from COVID-19 pneumonia despite having negative COVID-19 PCR tests multiple times.

The patient then presented to our hospital with similar complaints. Routine hematological testing was performed. All the hematological tests findings including complete blood count, serum electrolytes, liver function tests, renal function tests, coagulation profile, and blood culture were unremarkable. COVID-19 PCR was also found to be negative. However, biochemical tests showed raised creatine phosphokinase and lactate dehydrogenase representing underlying tissue injury. Arterial blood gases were performed which showed a Ph of 7.4, HCO3 of 21 mmol, PCO2 of 34.5 (35-48 mmHg), and PO2 of 72 (83-108 mmHg). His blood pressure was measured and it was 100/70 mmHg.

Later, an MRI brain and whole spine were performed followed by nerve conduction studies. MRI brain showed T2/fluid-attenuated inversion recovery (FLAIR) hyperintense and T1 hypointense signals in the bilateral centrum semioval, posterior periventricular white matter, genu, body, and splenium of the corpus callosum. These abnormal signals were found to be more prominent in the splenium of the corpus callosum. Additionally, microhemorrhages were seen in the corpus callosum on susceptibility-weighted imaging. This confirmed the diagnosis that the patient is suffering from high altitude sickness.

The oxygen saturation of the patient was maintained up to 98% on 1 L of oxygen. Within 5 days of his admission to the hospital, his chest symptoms resolved followed by an improvement in neurologic symptoms. He was discharged after the stabilization of symptoms and requested for follow-up after 2 weeks. After 2 weeks the patient came for a follow-up with a complete resolution of his symptoms. The patient seemed to be fully recovered (Figs. 1 and 2).

Fig. 1.

(A-D) T2/FLAIR Hyperintense signals in the periventricular deep white matter and the genu, splenium and splenium of the corpus callosum. (E) T1 hypointense signals in the genu, body and splenium of the corpus callosum. (F) Diffuse micro hemorrhages in the corpus callosum on SWI. (G, H) Diffusion restriction in the splenium of corpus callosum. SWI, susceptibility-weighted imaging.

Fig. 2.

(A, B) Bilateral perihilar airspace opacification with smooth interlobular septal thickening representing interstitial pulmonary edema. (C) Interval resolution of pulmonary edema.

Discussion

HACE is described as an end-stage acute high-altitude illness. At high altitudes, the “partial pressure of the oxygen” is 13.3 kPa (68%) at 3000 m height while at sea level it is 19.6kPa [9,10]. This difference in partial pressure disrupts the autoregulatory vascular system in nonacclimatized individuals. Additionally, the reduced partial pressure of oxygen at extreme heights induces vasodilation followed by transient failure of the autoregulatory mechanism making an increase in the capillary hydrostatic pressure causing cerebral edema with further injury to the blood-brain barrier [11]. Our patient also traveled to a high altitude of 3850-8126 m in height, this reduction in oxygen pressure at such height could be responsible for the worsening of his situation.

Studies have proposed 2 theories regarding the pathogenesis of HACE. These theories include vasogenic and cytotoxic edema. Vasogenic edema occurs due to the release of multiple neurohormones responsible for hemodynamic instability including nitric oxide, free radicals, growth factors, and cytokines. All these neurohormones collectively disrupt the cerebral blood-brain barrier and cause cerebral edema.

Vasogenic edema tends to impact the “splenium” of the “corpus callosum,” and “white matter tract,” and enhanced capillary permeability can also result in microhemorrhages. Microhemorrhages generally involve the “corpus callosum,” “cerebral white matter,” and “centrum semiovale” as indicated by imaging investigations [12,13]. In the current case, microhemorrhages were observed in the “corpus callosum.” Hefti et al. [12] noted microhemorrhages in the “middle cerebellar peduncles.” It is possible that the ordered organization of the “splenium” and “middle cerebral peduncle” is responsible for its greater involvement [12]. Moreover, the supply of the “corpus callosum” by “short perforating arteries” devoid of adrenergic tone may make this structure more vulnerable to microhemorrhages and edema [14] than “middle cerebellar peduncles.” However, the patient in Hefti et al. [12] research underwent an MRI 2 months after the onset of sickness, while our patient underwent an MRI during the acute phase.

Cytotoxic edema occurs due to disruption of the Na+/K+ ATPase pump caused by inadequate oxygen supply to the tissues [15]. Reduced oxygen supply causes tissue injury by free radicals formation. This breach in the blood-brain barrier results in extensive microhemorrhages which have a predilection of corpus callosum [15].

Different Imaging investigations have been introduced such as MRI and CT scan that not only aid in the diagnosis but also in determining the disease's progression and any complications. For example, transiently elevated SI on “fluid-attenuated inversion recovery” (FLAIR) and “T2-weighted images with diffusion restriction in the corpus callosum,” particularly the splenium, is a characteristic MRI finding of HACE [8]. The MRI findings can help in assessing the clinical recovery, allowing the diagnosis of HACE to be made even after the patient has recovered in order to describe the nature of their disorders.

Conclusion

The exceptional imaging features in our case were the presence of microhemorrhages in the corpus callosum and T2/FLAIR hyperintense and T1 hypointense signals in the bilateral semioval centrum, posterior periventricular white matter, and corpus callosum genu, body, and splenium. These abnormal signals were discovered to be more evident in the corpus callosum's splenium.

Consequently, in an appropriate clinical setting, if any of these structures are involved with microhemorrhages and cerebral edema on MRI, HACE should be promptly recognized and the patient should be treated with the utmost urgency due to the fatality of the condition.

Guarantor

Ubaid Khan.

Ethical approval

For this case ethical approval was not required from hospital, and we have patient father consent form.

Registration of research studies

As this is case report the registration not required.

Provenance and peer review

Not commissioned, externally peer reviewed.

Authors' contribution

All authors contributed toward data analysis, drafting, and revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Patient consent

Written informed consent was obtained from the parent of patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.