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Ann Med
Ann Med
Annals of Medicine
0785-3890
1365-2060
Taylor & Francis

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10.1080/07853890.2024.2401107
2401107
Version of Record
Research Article
Neurology
Altitude-related features and prognosis in patients with reversible splenial lesion syndrome
H.-X. Wang et al.
Wang Hao-Xiang a*
https://orcid.org/0000-0002-7214-7779
Li Yi-Ding b*
Liang Jun b
Xue Yuan-Zheng b
Zhu Li b
Xiong Ting-Wei c
Chen Peng-De b
Kang Xun b
Huang Jian-Ping b
Gong Zi-Li a
https://orcid.org/0000-0002-8438-283X
Sun Hao-Lun b
a Department of Neurology, Xinqiao Hospital & The Second Affiliated Hospital, Army Medical University, Chongqing, China
b Shigatse Branch, Xinqiao Hospital, Army Medical University, Shigatse, China
c Department of Medical Imaging, Xinqiao Hospital & The Second Affiliated Hospital, Army Medical University, Chongqing, China
* These authors contributed equally to this work.

Supplemental data for this article can be accessed online at https://doi.org/10.1080/07853890.2024.2401107.

CONTACT Hao-Lun Sun sunhaolu1994@gmail.com Shigatse Branch, Xinqiao Hospital, Army Medical University, Shigatse 857000, China
10 9 2024
2024
10 9 2024
56 1 240110712 4 2024
14 5 2024
15 5 2024
KnowledgeWorks Global Ltd.9 9 2024
published online in a building issue9 9 2024
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
2024
The Author(s)
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Abstract

Introduction

RESLES (Reversible splenial lesion syndrome) can be observed secondary to various diseases, and intramyelinic edema may play a crucial role in the pathogenesis of SCC (Splenium of the corpus callosum). Some studies have suggested that hypoxic-ischaemic encephalopathy may constitute a risk factor for SCC lesions. However, the potential impact of high-altitude environments on SCC, especially during chronic exposure, remain obscure.

Methods

Our study included 19 patients who satisfied the diagnostic criteria of RESLES at high altitudes. Ten low-altitude patients with RESLES were included as controls. All participants received MRI (Magnetic resonance imaging) scans twice. Routine blood tests, liver, kidney and thyroid function, coagulation function, electrolytes and vitamins were detected during hospitalization and before discharge. In addition, the patients were followed up in May 2023.

Results

Hypoxic environments at high altitudes may increase the risk of RESLES. The two groups showed different clinical symptoms. High-altitude patients had significantly higher CRP levels than low-altitude patients. The lesion size in high-altitude patients showed a positive correlation with SaO2 levels. However, the patients at low altitudes had positive correlation trends between lesion size and several inflammatory markers (WBC, NEU and CRP). All patients had a benign prognosis that may not be affected by the use of prednisone acetate.

Conclusions

Hypoxic environments at high altitudes may play a role in the aetiology of RESLES. Additionally, RESLES is a reversible disease and the administration of glucocorticoids may be dispensable for its treatment.

Keywords

Reversible splenial lesion syndrome
splenium of the corpus callosum
hypoxia
high altitude
intramyelinic edoema
National Natural Science Foundation of China 10.13039/501100001809 82101499 This study was supported by the National Natural Science Foundation of China (grant no. 82101499).
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pmcIntroduction

Reversible splenial lesion syndrome (RESLES) is a rare clinical radiological syndrome characterized by a transient lesion in the splenium of the corpus callosum (SCC) on magnetic resonance imaging (MRI) [1]. Recent studies indicate that RESLES can be observed secondary to a variety of diseases including infection, poisoning, electrolyte disturbance and vitamin deficiency [2,3]. The pathophysiological mechanism of RESLES remains unclear, and some research attributes the lesion of SCC to cytotoxic brain edema [4,5]. However, increased evidence suggests that intramyelinic edema, highlighted by its reversible nature, indeed provides a compelling alternative to the cytotoxic edema model. [6,7]. The splenium is also relatively sensitive to hypoxia in the corpus callosum [8]. Some studies suggest that hypoxic-ischemic encephalopathy may be a risk factor for SCC lesions, especially in infants [9]. In addition, patients with high-altitude cerebral edema (HACE) are reported to be susceptible to edema of SCC and RESLES due to acute hypoxic exposure [10,11]. Although recent research has explored the pathogenesis of RESLES, the potential effects of high-altitude environments on SCC, particularly during prolonged exposure, remain unclear. In this study, we explored the features of patients who underwent RESLES at two different altitudes.

Materials and methods

RESLES diagnosis

RESLES diagnosis was made based on the criterion proposed by Garcia-Monco et al. (2011) [12]. In brief, patients who had transient lesions of SCC revealed by MRI were diagnosed with RESLES. To obtain a definite diagnosis of reversibility, suspected patients received unenhanced MRI and diffusion weighted imaging (DWI) scans (UMR560 1.5 T, China) at least twice. All diagnoses were confirmed by two radiologists.

The exclusion criteria were as follows: (1) concomitant neurological disorders, asymmetrical lesions, any acute lesions other than those involving SCC, or a family history of encephalopathy; (2) severe cardiac, pulmonary, hepatic, or other systemic diseases; (3) any type of tumour; (4) any type of head trauma or craniocerebral surgery; (5) a history of anticonvulsants usage and do not have the history of epilepsy; and (6) unwillingness to participate in the present study. Written consent was obtained from all participants or their legal representatives. This study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice. This study was approved by the Institutional Review Board of Xinqiao Hospital and its Shigatse Branch (2023-004).

Study participants selection and evaluation

A total of 466 patients at high altitudes underwent brain MRI scans at Shigatse Branch, Xinqiao Hospital (3,800 m above sea level) from May 2022 to March 2023. Among these patients, we observed 19 who met the diagnostic criteria for RESLES. For comparison, we reviewed 100,000 brain MRI subjects in Xinqiao Hospital (approximately 300 m) from January 2019 to March 2023, in which 10 patients were diagnosed with RESLES and included these patients as controls. None of the patients had received any treatment prior to hospital arrival. Additionally, owing to the pandemic, we conducted nucleic acid tests for coronavirus disease 2019 (COVID-19) in all patients after 2020.

The high-altitude participants received MRI scans on days 1 and 10 of the hospital stay. Low-altitude subjects underwent MRI examinations on days 1 and 1–2 months after admission. We collected demographic characteristics, medical history data (including hypertension, diabetes, hyperlipidaemia and other chronic diseases), education level (the amount of time accrued through formal school education, starting from primary school) and clinical features of all participants. The severity of infections was assessed using the national early warning score (NEWS) upon admission [13]. All patients had full resolution of their clinical symptoms before discharge from the hospital. Additionally, follow-up was conducted through video calls and hospital revisits during May 2023, during which the Mini-Mental State Examination (MMSE) was conducted to assess cognitive function [14].

Clinical specimens sampling and processing

The levels of SaO2 (saturation of oxygen saturation) were assessed using a fingertip oximeter after the patients refrained from pure oxygen for at least 30 min on admission. Fasting blood was collected on the day of admission and the day prior to discharge from the hospital between 06:00 and 07:00 to avoid potential circadian rhythm effects. Cerebrospinal fluid (CSF) was collected by lumbar puncture from six low-altitude patients who provided informed consent, and subsequently analyzed. While, the remaining patients declined due to the invasive nature of the procedure. Unfortunately, we were unable to obtain CSF samples from high-altitude subjects because of limited objective conditions. Routine blood tests were performed using an automatic blood analyzer at the Clinical Laboratory of the hospital. An automatic biochemical analyzer was used to measure liver, kidney and thyroid function, while an automatic hemostasis analyzer was used to measure coagulation function. We also analyzed blood samples using electrolytes and vitamin analyzers.

Statistical analysis

Data are presented as mean ± standard deviation (SD) unless otherwise stated. We first evaluated the normality of the data using the Kolmogorov–Smirnov test. A two-tailed independent t-test was used to compare data with a normal distribution, while the Mann-Whitney U test was used for non-normal data. The chi-square test was used to compare categorical variable data. Correlations of lesion size with SaO2 and inflammatory indicators were tested by partial correlation analyses adjusted for age and sex, where r represents the partial correlation coefficient. Two-sided p values less than 0.05 were defined as statistically significant. All statistical analyses were performed using Statistical Product Service Solutions (SPSS), version 25.0 (SPSS Software, USA).

Results

Characteristics and clinical features of the study subjects

The flow chart outlining the process for including and excluding patients was displayed in Figure 1. As shown, there were 20 patients at high altitudes with a reversible lesion in SCC on MRI, compared to 32 patients at low altitudes. After filtering by exclusion criteria, the number of enrolled RESLES patients was 19 at high altitudes and 10 at low altitudes. The incidence rate at high altitudes was approximately 4077/100,000 patients, while at low altitudes it was 10 per 100,000. Based on our retrospective study, hypoxic conditions at high altitudes may increase the risk of developing RESLES. As shown in Table 1, there were no significant differences in age or education level between the two groups. The RESLES patients were primarily men at high altitudes, while females constituted the predominant proportion at low altitudes. All patients in the high altitude (HA) group resided in the Shigatse city and had no experience at higher altitudes within 3 months prior to hospital admission except for those with high altitude pulmonary edema (HAPE) and HACE. None of the patients in the low altitude (LA) group reported a history of mountain climbing or visiting high-altitude areas within 3 months prior to hospital admission. This suggests that these infected patients did not have a history of acute mountain sickness in either group. As expected, the high-altitude participants resided in a higher living environment (4021 ± 452.9 m vs. 300 ± 0 m, p < 0.001). As altitude increased, blood oxygen significantly decreased. Therefore, the SaO2 level of high-altitude patients was significantly lower than that of controls (87.25 ± 5.79% vs. 99.22 ± 0.83%, p < 0.001). There were no comorbidities such as hypertension, diabetes, hyperlipidaemia, or chronic diseases in either group.

Figure 1. The flow chart outlining the process for including and excluding patients. RESLES, reversible splenial lesion syndrome; SCC, splenium of the corpus callosum.

Table 1. Characteristics and symptoms in subjects of LA and HA.

Characteristics	LA(n = 10)	HA (n = 19)	p value	
Age, mean (SD), y	26.30(7.45)	25.32(6.53)	0.473	
Female, n (%)	8(80.00)	1(5.26)	<0.001	
Education level, mean (SD), y	12.1(2.6)	13.42(2.84)	0.200	
Altitude, mean (SD), m	300(0)	4021(452.9)	<0.001	
SaO2, mean (SD), %	99.20(0.79)	83.79(5.76)	<0.001	
Comorbidities	None	None	–	
Predisposing causes	 	 	 	
 Infection, n (%)	10(100)	14(73.68)	0.075	
 HAPE, n (%)	0(0)	3(15.79)	0.185	
 HACE, n (%)	0(0)	2(10.53)	0.288	
Clinical symptoms	 	 	 	
 Fever, n (%)	1(10.00)	18(94.74)	<0.001	
 Cephalalgia, n (%)	2(20.00)	18(94.74)	<0.001	
 Visual impairment, n (%)	7(70.00)	3(15.79)	0.004	
 Cognitive impairment, n (%)	2(20.00)	2(10.53)	0.482	
 Epileptic seizures, n (%)	2(20.00)	0(0)	0.043	
A two-tailed independent t-test or Mann-Whitney U test was used to compare age, education level and altitude after the Kolmogorov–Smirnov test. The chi-square test was used to compare percentage data.

LA: low altitude; HA: high altitude; SaO2: oxygen saturation; HAPE: high-altitude pulmonary edoema; HACE: high-altitude cerebral edoema; SD: standard deviation.

Regarding predisposing causes, all low-altitude subjects were infected before the SCC lesion, which were mainly upper respiratory tract infections and pulmonary infections. In previous research, acute cerebral edema has been proven to be the main inducer of RESLES at high altitudes [15]. However, we found that only two patients were diagnosed with HACE. A significant proportion of high-altitude patients also have coexisting infection or pulmonary edema. Infections of the HA group included upper respiratory tract infections, pulmonary infections and one case of urinary tract infection. The severity of the infections was assessed using the NEWS, a reliable scoring system for patients with suspected sepsis. All patients in the study were classified as having a relatively low risk of deterioration (score < 5 points). A few studies have reported that COVID-19 may lead to cytotoxic lesions in SCC [16]. However, the influence of COVID-19 infection was not analyzed and discussed in this study. This is because the medical history of all patients indicated that none had been infected with COVID-19 within 14 days prior to hospitalization, and all had tested negative for the virus through nucleic acid tests before hospitalization.

Over 90% of high-altitude patients exhibited clinical symptoms of fever and cephalalgia, which occurred with a diminished probability in low-altitude patients. However, a higher risk of visual impairment and epileptic seizures has been observed in patients at low altitudes. In addition, there were no significant differences in cognitive impairment between the two groups.

We further performed haematology testing to identify possible aetiological factors. In both groups, no abnormalities were detected in the B vitamins, glucose, liver function, kidney function, thyroid function and coagulation function. Hyponatremia was reported to be a contributing factor in the development of reversible splenial lesions [17]. However, we found the serum sodium levels are comparable between HA and LA group (138.0 ± 4.03 mmol/L vs. 138.1 ± 4.26 mmol/L, p = 0.795) (Supplemental Figure 1). Most subjects in both groups had elevated levels of inflammatory indicators. Moreover, high-altitude patients had significantly higher levels of CRP (C-reactive protein) than patients at low-altitude (58.83 ± 53.14 mg/L vs. 6.73 ± 7.18 mg/L, p = 0.001), while no differences in WBC (white blood cell count) (9.56 ± 6.07 × 10^9/L vs. 7.66 ± 4.81 × 10^9/L, p = 0.400), NEU (neutrophil count) (7.18 ± 5.56 × 10^9/L vs. 5.20 ± 4.52 × 10^9/L, p = 0.251) and LYM (lymphocyte count) (1.64 ± 0.80 × 10^9/L vs. 1.77 ± 0.75 × 10^9/L, p = 0.680) (Figure 2). Moreover, no obvious abnormalities were found in the examine of partially low-altitude patients (Supplemental Figure 2).

Figure 2. Comparisons of inflammatory indicators between subjects of LA and HA. (A) Comparisons of WBC between subjects of LA and HA. (B) Comparisons of NEU between subjects of LA and HA. (C) Comparisons of LYM between subjects of LA and HA. (D) Comparisons of CRP between subjects of LA and HA. LA: low altitude; HA: high altitude; WBC: white blood cell count; NEU: neutrophil count; LYM: lymphocyte count; CRP: C-reactive protein. ∗∗ denotes p < 0.01. NS denotes no statistical significance.

Lesion size and its correlations of the study subjects

Furthermore, we performed a detailed analysis of lesion size in SCC based on MRI scans. The small lesion (<150 mm2) was around the oval size and the large lesion (>150 mm2) had a crescent shape on each image, regardless of altitudes (Figure 3). MRI examination of the corpus callosum showed high signal intensity on T2 weighted imaging (T2WI) and DWI scans, and low signal intensity on T1 weighted imaging (T1WI) and ADC (apparent diffusion coefficient) scans.

Figure 3. Scans of SCC lesion in MRI. (A-D) The small lesion size of SCC on T2WI (A), T1WI (B), DWI (C) and ADC (D) of MRI scans both in subjects of LA and HA. (E-F) The large lesion size of SCC on T2WI (E), T1WI (F), DWI (G) and ADC (H) of MRI scans both in subjects of LA and HA. LA: low altitude; HA: high altitude; SCC: splenium of the corpus callosum; MRI: magnetic resonance imaging; T2WI: T2 weighted imaging; T1WI: T1 weighted imaging; DWI: diffusion weighted imaging; ADC: apparent diffusion coefficient.

We subsequently measured the largest lesion area in the two groups. Subjects of LA and HA had no significant differences in the lesion size (93.60 ± 12.30 mm2 vs. 110.32 ± 60.92 mm2, p = 0.402) (Figure 4A). However, greater dispersion was observed among high-altitude patients. Notably, the two largest lesions in the high-altitude patients were caused by HACE. The correlations of lesion size with SaO2 and inflammatory indicators are shown in Figure 4B-F. Lesion size in high-altitude patients was negatively correlated with SaO2 levels (r = −0.516, p = 0.034). There was also a negative correlation between lesion size and SaO2 level in all subjects (r = −0.375, p = 0.054). However, no correlation was observed between lesion size and SaO2 in the low-altitude group (r = 0.204, p = 0.628). The patients at low altitudes had positive correlation trends between lesion size and WBC (r = 0.689, p = 0.059), NEU (r = 0.697, p = 0.055) and CRP (r = 0.668, p = 0.070). Additionally, the lesion size of high-altitude patients (WBC: r = 0.032, p = 0.903; NEU: r = −0.006, p = 0.982; CRP: r = −0.017, p = 0.948) and all groups (WBC: r = 0.160, p = 0.427; NEU: r = 0.151, p = 0.451; CRP: r = 0.108, p = 0.590) showed a poor correlation with inflammatory indicators. As for LYM, there was no correlation between the lesion size in the two groups. These findings further indicated that the severity of RESLES may be related to hypoxia at high altitudes and inflammation at low altitudes.

Figure 4. Comparisons and correlations of the SCC lesion’s largest area in subjects of LA and HA. (A) Comparisons of the SCC lesion’s largest area between subjects of LA and HA. (B-F) Correlations of SaO2 (B), WBC (C), NEU (D), LYM (E) and CRP (F) with the SCC lesion’s largest area in subjects of LA and HA. LA: low altitude; HA: high altitude; SCC: splenium of the corpus callosum; SaO2: saturation of oxygen; WBC: white blood cell count; NEU: neutrophil count; LYM: lymphocyte count; CRP: C-reactive protein. NS indicates no statistically significant difference. Partial correlation analysis was adjusted for age and sex. The shaded areas represent the 95% confidence intervals.

Treatment and prognosis of the study subjects

The optimal treatment approach for RESLES remains unclear, and the main controversy is the use of glucocorticoids [18,19]. Given the divergent views among the administration of glucocorticoids in RESLES patients, the subjects at high altitudes were divided into two groups for analysis. Importantly, this study was retrospective, and the treatment administered was determined by the patients and their physicians, with no intervention provided by the researchers. Seven patients were exclusively subjected to symptomatic treatment, including anti-infective, antipyretic and mask oxygen therapy. The rest were administered low-dose glucocorticoids (Prednisone Acetate, 20 mg/day) in addition to symptomatic treatment within 1 week. The glucocorticoid group showed no statistical difference in characteristics, clinical features and serum sodium levels (Supplemental Table 1). All patients were closely monitored, and none showed any signs of worsening or increased risk of related infections.

Just as shown in Figure 5A, there were also no significant differences in lesion size before treatment (88.43 ± 38.87 mm2 vs. 123.08 ± 69.04 mm2, p = 0.242). Lesions of both groups were obviously diminished within 10 days (glucocorticoids group: 44.58 ± 50.51 mm2 vs. 123.08 ± 69.04 mm2, p = 0.008; no-glucocorticoids group: 14.00 ± 25.24 mm2 vs. 88.43 ± 38.87 mm2, p = 0.002) (Figure 5B-C). In addition, the size change of SCC lesions had no differences between two groups (74.43 ± 33.41 mm2 vs. 78.50 ± 46.45 mm2, p = 0.842) (Figure 5D). Concurrently, all low-altitude subjects were managed exclusively using symptomatic measures. The lesions almost completely resolved after 1 month of treatment.

Figure 5. Comparisons of lesion size before and after treatment between subjects of Non-GCs and GCs in HA. (A) Comparisons of lesion size before treatment between subjects of Non-GCs and GCs in HA. (B) Comparisons of lesion size before and after treatment in Non-GCs of HA. (C) Comparisons of lesion size before and after treatment in GCs of HA. (D) Comparisons of lesion size change before and after treatment between subjects of Non-GCs and GCs in HA. GCs: glucocorticoids; HA: high altitude. ∗∗ denotes p < 0.01. NS denotes no statistical significance.

Finally, we evaluated low- and high-altitude patients before discharge. The average hospital stay was approximately 2 weeks. The abnormal hematological and symptomatic parameters improved before discharge. Previous studies have indicated that SCC disorders may cause cognitive impairment [20]. Thus, all patients were followed up in May 2023, and there were no significant abnormalities and differences in MMSE scores of two groups (28.00 ± 1.56 vs. 28.53 ± 1.26, p = 0.380) (Supplemental Figure 3). This proved the benign course of RESLES, the prognosis of which may not correlate with the use of glucocorticoids.

Discussion

To our knowledge, this is the first study to compare the features and prognoses of patients with RESLES at different altitudes. Individuals exposed to chronic hypoxia at high altitudes seem to be more susceptible to SCC lesions. Consistent with previously published research, we contribute clinical evidence supporting the notion that RESLES may be a benign entity [21,22]. Furthermore, our findings indicate that the prognosis of RESLES is not influenced by glucocorticoid therapy even in cases arising in high-altitude regions.

Previous investigations have indicated that myelin and extracellular compartments in SCC have a higher water fraction, thus increasing their vulnerability to edema [23]. The poor supply of the splenium from the end arteries of the vertebrobasilar system, independent from other regions of the corpus callosum, presents an increased risk to the development of pathology [24]. Accordingly, a growing number of reports have found that various factors can lead to lesions in SCC and symptoms of transient encephalopathy [25]. Inflammation or metabolic abnormalities can significantly contribute to edema of the myelin sheath [26]. Our research suggests correlations between inflammatory indicators and lesion size and provides clinical evidence for the important role of inflammation in the pathogenesis of RESLES in low-altitude patients.

Acute cell hypoxia at high altitudes can lead to dysfunction of the Na-K-ATPase pump, which is associated with the swelling of astrocytes and development of edema [27]. Moreover, capillary endothelial injury induced by hypoxia may aggravate SCC lesions [28]. This may explain the enhanced permeability of blood vessels observed in severe mountain sickness or edema. [29]. The disruption of the blood-brain barrier (BBB) in patients with HACE further contributes to microhemorrhage and edema [30]. Consistent with this evidence, our research observed that the lesion size in RESLES patients caused by HAPE is less than that caused by HACE.

Possibly due to limited objective medical conditions and mild symptoms, the occurrence of RESLES has not been reported in long-term plateau environments in previous studies. However, long stays at high altitudes may result in severe chronic hypoxia. This may cause prominently distended capillary patterns, leading to hyperaemia and cellular edema in the cerebrum [31]. Increased levels of oxidation and nitrosation, induced by hypoxaemia, further exacerbate vessel dysfunction. The subsequent systemic inflammatory response plays a critical role in the development of SCC lesions [32]. The compensatory increase in haemoglobin concentration also enhances susceptibility to inflammatory indicators [33]. Thus, it is expected that the prevalence of RESLES will be higher among high-altitude residents. Our study found that lesion size was associated with the degree of hypoxia. Additionally, plasma CRP levels were significantly increased in high-altitude patients, consistent with previous studies. An intriguing phenomenon that is difficult to explain is that most patients at high altitudes are diagnosed with mild clinical symptoms. Further investigation is warranted to elucidate it.

A previous imaging research has shown that a small lesion can appear as a round or oval shape located in the center of the SCC, while the large lesion may extend laterally through the callosal fibres into the contiguous white matter and present a crescent shape [34]. The MRI images appear to be consistent at different altitudes. The lesions in both groups displayed obvious boundaries such as restricted diffusion of DWI scans and decreased signal intensity of ADC scans. The high signal intensity of DWI is commonly associated with metabolic or energy dysfunction, especially in patients with ischemic stroke [35]. In contrast to stroke, RESLES lesions are usually reversible, indicating no neuronal death or permanent damage in SCC [36]. We found no abnormalities in CSF leukocyte levels or biochemical examinations, which provided additional evidence for this finding. The imaging findings support the hypothesis that intramyelinic edema may be the principal pathological mechanism of RESLES, in contrast to irreversible cytotoxic cerebral edema, which typically culminates in the formation of a permanent glial scar [37]. A recent study measuring local glucose metabolism in SCC further confirms this theory [7].

Glucocorticoids are commonly used in treating brain edema, and have a remarkable effect on preventing lipid peroxidation and subsequent damage [38]. However, our study indicates that the prognosis of patients may not be affected by the use of prednisone acetate. Additionally, we did not observe any patients with cognitive impairment or other sequelae. One possible explanation for this could be the limited sample size. Moreover, cases with lesions outside the SCC, indicating poor prognosis, were excluded from our criteria [4]. In summary, RESLES, in the absence of severe comorbidities, is a self-limiting disease that may not require excessive treatment.

Notably, our retrospective study did not allow for the detection of additional biomarkers or further elucidation of the pathology of RESLES. In addition, the limited sample size led to a narrow disease spectrum and unavoidable missed factors in this study. Further research is needed to determine whether women residing in LA areas are more susceptible to RESLES. A larger sample size with clinical follow-up at various altitudes should be conducted to explore the impact of the extent of hypoxia at varying high altitudes. Additional samples are also required for the precise impact of infection type and severity on the occurrence of RESLES. Moreover, the effects of other confounding factors, such as hyponatremia and the type or severity of the infection, must also be taken into consideration and eliminated. Chronic diseases among young populations, including asthma and obstructive sleep apnoea syndrome (OSAS), can also lead to oxygen deprivation. Whether these diseases increase the risk of RESLES is also an intriguing concern to be investigated in the future.

Conclusions

Our study found that hypoxic environments at high altitudes may play a role in the aetiology of RESLES and further brought attention to the different clinical manifestations in high-altitude patients. People at high altitudes appear to be more vulnerable to SCC lesions. This study provides evidence that RESLES is a reversible disease and that glucocorticoid administration may be dispensable for its treatment.

Supplementary Material

Supplemental informention.docx

Ethical approval

The study was approved by the Institutional Review Board of Xinqiao Hospital and its Shigatse Branch, China.

Consent form

All participants granted verbal consent for the publication of the study.

Patient consent

All participants provided written consent to participate in the study.

Authors contributions

H-XW, Z-LG and H-LS conceived and designed the project. T-WX, P-DC and XK performed the MRI testing, diagnosis and data collection. Y-ZX, LZ and J-PH performed clinical specimen testing and data collection. H-XW, Y-DL and JL analyzed the data. Y-DL and H-LS drafted the manuscript All authors have contributed to the manuscript and approved the submitted version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data for this study are available from the corresponding author upon reasonable request.
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