高原紧急情况下对大批急进高原人群急性重症高原病的现场救治

目的：对高原紧急情况下大批急进高原人群急性重症高原病的现场救治进行探讨。方法：对＂4.14＂玉树抗震救灾期间在结古镇救治的18例急性重症高原病（高原肺水肿、高原脑水肿）患者的高原现场治疗情况进行分析。结果：现场救治18例急性重症高原病患者（其中高原肺水肿17例、高原肺水肿合并脑水肿1例）,治愈17例,现场治愈率94.44%,好转后送1例,好转率5.56%,无一例死亡。结论：高原紧急情况下大批急进高原人群因高原低压缺氧等引起的急性重症高原病,在高原现场救治的基础上,并积极地实施综合的救治措施,对有效地提高治愈率,降低死亡率具有重要的意义。     

Transient high altitude neurological dysfunction: an origin in the temporoparietal cortex

This case report describes three separate episodes of isolated ataxia, hallucinations of being accompanied by another person, and bilateral dressing apraxia occurring in a single individual without prior warning signs. These symptoms are attributable to disruption of vestibular processing in the temporoparietal cortex or associated limbic structures. Neurological dysfunction at high altitude is usually ascribed to high altitude cerebral edema or acute mountain sickness. However, transient neurological symptoms occur abruptly at more extreme altitudes, often following vigorous exertion, without overt altitude-induced prodromes. These symptoms may be caused by intense neuronal discharge or neuronal synchronization as a feature of epileptic discharges or cortical spreading depression. Transient high altitude neurological dysfunction should be recognized as a separate complication of extreme altitude, distinct from high altitude cerebral edema.     

Statistical parametric mapping in brain single photon computed emission tomography after carbon monoxide intoxication

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml x 100 g(-1) x min(-1) with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.     

急性高原反应症状及体征变化对高原脑水肿早期诊断意义的研究

目的观察和随访急进高原后疑似高原脑水肿者（HACE）的症状、体征变化,为制定HACE的早期诊断标准提供依据。方法对24200名急进高原人员进行筛查,对其中162例HACE疑似病例进行观察随访,总结急进高原1w内的症状、体征变化。结果在这些HACE疑似病例中,有36例最后确诊为HACE。HACE患者早期头痛、呕吐（症状评分≥4）以及呼吸困难、胸闷、咳嗽、紫绀发生率明显高于非HACE组（P〈0．05）,且经休息及对症治疗后无缓解;HACE发病高峰为急性高原暴露24—72h。结论严重头痛、呕吐症状的出现与早期HACE发病密切相关,尤其当这些症状经15—24h单纯卧床、小流量吸氧及对症治疗后无明显缓解时,应警惕早期HACE的发生。     

Altitude illness: update on prevention and treatment

ABSTRACT: Altitude illness is a broad category of disease encompassing acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) that can affect persons who travel to altitude without adequate acclimatization. Initial symptoms of AMS and the more serious HACE or HAPE can be subtle, and it is important that the practitioner be able to recognize and differentiate between these diagnoses because they can progress rapidly and be fatal if untreated. There are well-established criteria and many proven therapies both for prophylaxis and treatment of altitude illness; however, despite intense research efforts, the specific mechanisms of these complex diseases remain elusive. Adequate acclimatization via controlled ascent remains the most important factor in preventing altitude illness, although prophylactic pharmacotherapy also may be useful. Rapid descent remains the most important treatment factor, although treatment at altitude with various therapies is possible for mild cases with adequate resources.     

Evidence for a genetic basis for altitude illness: 2010 update

Altitude illness refers to a group of environmentally mediated pathophysiologies. Many people will suffer acute mountain sickness shortly after rapidly ascending to a moderately hypoxic environment, and an unfortunate few will develop potentially fatal conditions such as high altitude pulmonary edema or high altitude cerebral edema. Some individuals seem to be predisposed to developing altitude illness, suggesting an innate contribution to susceptibility. The implication that there are altitude-sensitive and altitude-tolerant individuals has stimulated much research into the contribution of a genetic background to the efficacy of altitude acclimatization. Although the effect of altitude attained and rate of ascent on the etiology of altitude illness is well known, there are only tantalizing, but rapidly accumulating, clues to the genes that may be involved. In 2006, we reviewed what was then known about the genetics of altitude illness. This article updates that review and attempts to tabulate all the available genetic data pertaining to these conditions. To date, 58 genes have been investigated for a role in altitude illness. Of these, 17 have shown some association with the susceptibility to, or the severity of, these conditions, although in many cases the effect size is small or variable. Caution is recommended when evaluating the genes for which no association was detected, because a number of the investigations reviewed in this article were insufficiently powered to detect small effects. No study has demonstrated a clear-cut altitude illness gene, but the accumulating data are consistent with a polygenic condition with a strong environmental component. The genes that have shown an association affect a variety of biological pathways, suggesting that either multiple systems are involved in altitude pathophysiology or that gene-gene interactions play a role. Although numerous studies have been performed to investigate specific genes, few have looked for evidence of heritability or familial transmission, or for epidemiological patterns that would be consistent with genetically influenced conditions. Future trends, such as genome-wide association studies and epigenetic analysis, should lead to enhanced understanding of the complex interactions within the genome and between the genome and hypoxic environments that contribute to an individual's capacity to acclimatize rapidly and effectively to altitude.     

小鼠高原低氧环境暴露下脑内脂质过氧化损伤与高原脑水肿的关系

目的：观察高原不同海拔梯度下脑内脂质过氧化物的代谢变化,进一步探讨高原脑水肿的发生机理。方法：取三个不同海拔梯度下脑组织匀浆化学法测定脑内超氧化物歧化酶,丙二醛,谷胱甘肽过氧化物酶和谷胱甘肽。结果：小鼠急进高海拔区后,随着海拔升高,ＳＯＤ含量逐渐升高,ＭＤＡ始终不变,但ＧＳＨ－ＰＸ和ＧＳＨ在进入中海拔区后增高,进入高海拔后ＧＳＨ－ＰＸ明显降低,而ＧＳＨ明显增高,差异均非常显著。     

Going high with preexisting neurological conditions

This review presents the potential impact of high altitude exposure on preexisting neurological conditions in patients usually living at low altitude. The neurological conditions include permanent and transient ischemia of the brain, occlusive cerebral artery disease, cerebral venous thrombosis, intracranial hemorrhage and vascular malformations, multiple sclerosis, intracranial space-occupying lesions, dementia, extrapyramidal disorders, migraine and other headaches, and epileptic seizures. New developments in diagnostic work-up and treatment of preexisting neurological conditions are also mentioned where applicable. For each neurological disorder, the authors developed absolute and relative contraindications for a trip to high altitude. These recommendations are not based on the results of controlled randomized trials, but mainly on case reports, pathophysiological considerations, and extrapolations from the low altitude situation.     

Simultaneous presentation of subcortical hemorrhage,subdural hemorrhage,and cerebral infarct in a hemiplegic patient

A 90-year-old, non-hypertensive woman presented gait disturbance followed by falls. She had developed a lacunar infarction in the right frontal lobe 1 month previously that subsequently resulted in subtle motor weakness in the left lower extremity. At presentation, the patient showed motor weakness in the left upper and lower extremities with normal findings on blood test. Cranial computed tomography (CT) revealed a subcortical hemorrhage in the anterior part of the right frontal lobe that was accompanied by perilesional edema. In addition, two small subdural hematomas, apparently in the acute phase, were found. Magnetic resonance imaging performed immediately after the CT revealed hyperacute infarct in the right precentral gyrus adjacent to the previous infarct. It was hyperintense on the diffusion-weighted imaging but indistinct on the fluid-attenuated inversion recovery sequence. In addition, findings suggesting cerebral contusions were not observed. Based on these, we assumed that the patient''s symptoms were mainly derived from the infarct and the subdural hemorrhages had developed in association with falls. However, it was unclear whether the infarct had developed before or after the formation of subcortical hemorrhage. Traumatic and non-traumatic intracranial hemorrhage and cerebral infarcts may present simultaneously. When intracranial hemorrhages appearing on CT do not adequately explain the patient''s neurological findings, undetected cerebral ischemia should be assumed.     

Evidence for a genetic basis for altitude-related illness

Altitude-related illnesses are a family of interrelated pulmonary, cerebral, hematological, and cardiovascular medical conditions associated with the diminished oxygen availability at moderate to high altitudes. The acute forms of these debilitating and potentially fatal conditions, which include acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE), often develop in incompletely acclimatized lowlanders shortly after ascent, whereas, the chronic conditions, such as chronic mountain sickness (CMS) and high altitude pulmonary hypertension (HAPH), usually afflict native or long-term highlanders and may reflect a loss of adaptation. Anecdotal reports of particularly susceptible people or families are frequently cited as evidence that certain individuals have an innate susceptibility (or resistance) to developing these conditions and, in recent decades, there have been a number of studies designed to characterize the physiology of individuals predisposed to these conditions, as well as to identify the specific genetic variants that contribute to this predisposition. This paper reviews the epidemiological evidence for a genetic component to the various forms of altitude-related illness, such as innate susceptibility, familial clustering, and patterns of population susceptibility, as well as the molecular evidence for specific genetic risk factors. While the evidence supports some role for genetic background in the etiology of altitude-related illness, limitations in individual studies and a general lack of corroborating research limit the conclusions that can be drawn about the extent of this contribution and the specific genes or pathways involved. The paper closes with suggestions for future work that could support and expand on previous studies, as well as provide new insights.     

高原胸部火器伤后TXB2和6-keto-PGF1α含量的变化及其意义

目的探讨高原胸部火器伤早期血浆及肺组织血栓素B2（TXB2）和6-酮-前列腺素F1α（6-keto-PGF1α）的变化及其意义。方法 18只体重相近（10～15 kg）的健康杂种犬,随机分成3组（每组6只）：平原伤前组、平原对照组和高原移居组,另外6只高原杂种犬作为高原世居组。平原对照组实验海拔高度为500 m,高原组实验海拔高度为3700 m。实验动物用3%戊巴比妥钠静脉麻醉（30 mg/kg）后,用0.44 g钢珠以400 m/s的初速度从右第6肋间射入,造成右胸贯通伤,伤后立即封闭伤口,安放胸腔闭式引流。各组分别在伤后2、4、6、8、12 h通过中心静脉插管抽取血标本,伤后12 h取双侧肺组织,检测血和肺组织内的TXB2和6-keto-PGF1α含量。结果各组伤后血浆6-keto-PGF1α和TXB2均明显升高,而TXB2和6-keto-PGF1α的比值仅高原移居组在伤后6 h开始有明显升高。各组伤侧肺组织的TXB2/6-keto-PGF1α比值都比平原伤前组明显增高,尤以高原移居组最为明显;但是,健侧肺组织TXB2/6-keto-PGF1α的比值仅高原移居组显著升高,其他组无显著差异。结论高原世居组和平原对照组在胸部火器伤后,肺组织水肿主要局限在伤侧;而高原移居组在胸部火器伤后早期,不论是伤侧还是健侧肺,均存在发生水肿的风险,在伤后应积极预防肺水肿的发生。     

Magnetic resonance imaging findings in chronic carbon monoxide intoxication

Purpose: To define the cranial magnetic resonance imaging (MRI) features of the chronic stage of carbon monoxide (CO) poisoning in patients with and without neuropsychiatric sequelae.

Material and Methods: Eight patients who had neither symptoms nor neurological sequelae and eight patients with neuropsychiatric sequelae were included in the study. Patients aged between 9 to 57 (mean 32.2 years). All patients had been comatose at initial admittance and awoke after normobaric 100% oxygen therapy within 1-7 days. In this study, the patients were being examined with routine cranial MRI between 1 and 10 years (mean 3.4 years) after exposure to CO.

Results: The most common finding was bilateral symmetric hyperintensity of the white matter, which was more significant in the centrum semiovale, with relative sparing of the temporal lobes and anterior parts of the frontal lobes on T2-weighted and FLAIR images in all patients. Cerebral cortical atrophy was seen in 10 patients; mild atrophy of cerebellar hemispheres in 8; and vermian atrophy in 11. Corpus callosum was atrophic in one patient. Bilateral globus pallidus lesions were seen in three patients. The lesions were hypointense on T1-weighted images and hyperintense on T2-weighted and FLAIR images.

Conclusion: Patients with severe CO intoxication may develop persistent cerebral changes independently of their neuropsychiatric findings in the chronic stage. They may present with characteristic MRI findings as described here, even if asymptomatic. The history of CO exposure is therefore helpful for recognizing and interpreting the MRI findings of chronic stage CO intoxication.     

高原脑水肿现场就地急救治疗的效果及影响因素

目的：探讨高原脑水肿就地急救治疗的效果和影响因素。方法：通过对50年住院病例的回顾性调查，分析高原脑水肿高原现场治疗的效果，寻找影响治疗效果的主要因素。结果：328例高原脑水肿患者经过就地治疗，319例治愈，治愈率达到97．3％，平均住院7，1d。影响治疗效果的主要因素是多脏器功能障碍，占67％，其中56％患者伴有肺水肿，41％伴肾功能不全，14％伴心功能不全，3个以上脏器同时受损占12．5％。结论：高原脑水肿就地治疗是提高治愈率的重要措施，高原脑水肿并发多脏器功能障碍是影响治疗效果的主要因素。     

Normal perfusion pressure breakthrough occurring during treatment of carotid and vertebral fistulas

Of the 185 carotid and vertebral fistulas treated by the authors over the past 10 years, five developed neurologic deficits after abrupt closure of their fistulas. The earliest case, treated initially by proximal surgical carotid occlusion, presented 32 years later with cerebral steal symptoms from the large, long-standing carotid cavernous fistula. Upon completion of a surgical trapping procedure, there was immediate massive cerebral edema, brain herniation, and death. In the remaining four patients (three vertebral fistulas and one with carotid cavernous fistula), all treated by transvascular embolization techniques, neurologic deficits occurred coincidentally with the abrupt closure of the fistula and resolved with reestablishment of fistula flow. This indicated that the cerebral vasculature is unable to tolerate the reestablishment of normal cerebral perfusion after abrupt closure of the fistula. All four patients were treated with staged or slow occlusion of their fistulas, which resulted in complete fistula closure without permanent neurologic sequelae. All five patients who developed symptoms consistent with normal perfusion pressure breakthrough had large, long-standing fistulas, ranging in duration from 9 to 32 years. Two of the five patients developed slowly progressive neurologic deficits consistent with cerebral steal prior to treatment. This sign was not observed in the 180 patients who did not develop symptoms during treatment. We conclude that patients with carotid or vertebral fistulas of long duration, particularly those with cerebral steal symptoms, are at risk to develop neurologic deficits related to perfusion breakthrough if their fistulas are abruptly closed. Staged or gradual closure may prevent this potentially devastating complication.     

PRES (posterior reversible encephalopathy syndrome), a rare complication of tacrolimus therapy

With increasing numbers of solid organ and hematopoietic stem cell transplantations being performed, there have been significant increases in the use of immunosuppressive agents such as cyclosporine and tacrolimus. Posterior reversible encephalopathy syndrome (PRES) is a serious complication of immunosuppressive therapy use following solid organ or stem cell transplants. Clinical findings including headache, mental status changes, focal neurological deficits, and/or visual disturbances. Associated with these are characteristic imaging features of subcortical white matter lesions on computed tomography (CT) or magnetic resonance imaging (MRI). The changes in the subcortical white matter are secondary to potentially reversible vasogenic edema, although conversion to irreversible cytotoxic edema has been described. These imaging findings predominate in the territory of the posterior cerebral artery. Many studies have shown that the neurotoxicity associated with tacrolimus may occur at therapeutic levels. In most cases of PRES, the symptom complex is reversible by reducing the dosage or withholding the drug for a few days. While PRES is an uncommon complication, it is associated with significant morbidity and mortality if it is not expeditiously recognized. MRI represents the most sensitive imaging technique for recognizing PRES. This report highlights the value of MRI in prompt recognition of this entity, which offers the best chance of avoiding long-term sequelae.     

高原脑水肿的早期影像学表现探讨

目的探讨高原脑水肿（high altitude cerebral edema,HACE）早期的影像学表现,为HACE的早期诊断寻找更为可靠的检查手段和依据。方法根据高原反应症状评分以及典型症状,对24200例急进高原人员进行筛查,对其中162例HACE疑似病例进行随访观察,进行了脑CT、MRI检查;并对最后确诊为HACE病例的CT及MRI的动态变化进行分析。结果在这些HACE疑似病例中,有36例患者最后确诊为HACE。22例（61.1%）HACE患者在未出现精神、神经症状时,即有MRI异常表现,以脑实质内T1WI低信号和T2WI高信号的斑点状或小片状改变为主,而同时CT仅有1例异常（2.8%）。结论 HACE早期MRI表现以脑实质内T1WI低信号和T2WI高信号的斑点状或小片状改变为主。与CT相比,MRI更有助于HACE的早期诊断。     

EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population:a cross-sectional study

Background:More people ascend to high altitude(HA)for various activities,and some individuals are susceptible to HA illness after rapidly ascending from plains.Acute mountain sickness(AMS)is a general complaint that affects activities of daily living at HA.Although genomic association analyses suggest that single nucleotide polymorphisms(SNPs)are involved in the genesis of AMS,no major gene variants associated with AMS-related symptoms have been identified.Methods:In this cross-sectional study,604 young,healthy Chinese Han men were recruited in June and July of 2012 in Chengdu,and rapidly taken to above 3700 m by plane.Basic demographic parameters were collected at sea level,and heart rate,pulse oxygen saturation(SpO2),systolic and diastolic blood pressure and AMS-related symptoms were determined within 18-24 h after arriving in Lhasa.AMS patients were identified according to the latest Lake Louise scoring system(LLSS).Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders(age,body mass index and smoking status).Results:In total,320 subjects(53.0％)were diagnosed with AMS,with no cases of high-altitude pulmonary edema or high-altitude cerebral edema.SpO2 was significantly lower in the AMS group than that in the non-AMS group(P=0.003).Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction.The rs6756667(EPAS1)was associated with mild gastrointestinal symptoms(P=0.013),while rs3025039(VEGFA)was related to mild headache(P=0.0007).The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS(OR=2.70,P＜0.001).Conclusions:Under the latest LLSS,we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population;this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA.     

关于高原病的命名、临床分型和诊断标准的建议

本文阐述了高原病的定义、命名、临床分型和诊断标准。强调指出高原病的命名和临床分型应根据临床特征并结合病因、病理生理、病理诸因素综合考虑,应力求精简,明确和实用,有利于临床诊断、治疗、预后判断和研究以及疾病统计管理,并对命名、分(?)和诊断标准作了简要讨论。     

不同方法治疗高原脑水肿的疗效及对肾功能的影响

目的探讨不同方法治疗高原脑水肿的疗效及对肾功能的影响,为高原脑水肿的防治提供临床依据。方法选择高原脑水肿患者24例,随机分为A、B、C 3组,每组8例,A组在常规治疗的基础上给予20%甘露醇治疗,B组给予甘油果糖治疗,C组交替给予20%甘露醇和人血白蛋白治疗。统计各组症状缓解时间、CT脑水肿征象消失时间和平均住院时间,以及血清肌酐（Scr）和尿素氮（BUN）水平的变化。结果从症状缓解时间、CT影像上脑水肿征象消失时间及住院时间方面比较,A组和C组显著低于B组（P〈0.01）;治疗前各组Scr、BUN水平无显著差异,治疗3 d后,各组Scr、BUN水平均较治疗前增高,A组显著高于B组和C组（P〈0.01）,B组与C组间无显著差异（P〉0.05）。结论采用交替给予20%甘露醇和人血白蛋白的方法对高原脑水肿的疗效好,且对肾功能影响最小。