慢性疲劳综合征真的是病
疲惫 @J Cruikshank on Unsplash
过去很长一段时间里，慢性疲劳综合征（chronic fatigue syndrome）
都没有得到足够的重视，医生和其他医疗工作者都将其视为一种心理层面的疾病，认为它没有真正的生理学病因。


近年来，研究人员开始更加认真地对待这种疾病了，它目前的正式名称是肌痛性脑脊髓炎/慢性疲劳综合征（myalgic encephalomyelitis/chronic fatigue syndrome，ME/CFS）。尽管有时它简单地被称作慢性疲劳综合征，但许多患者更喜欢称之为肌痛性脑脊髓炎，因为它实际上远不止是疲劳那么简单。
在新冠疫情期间，数百万人患上了一种与 ME/CFS 非常相似的疾病，也就是“长新冠”（long COVID），这引起了科学家对 ME/CFS 的重视。其实在新冠疫情之前，美国国立卫生研究院（NIH）就已经开始研究 ME/CFS 了。当时的 NIH 主任弗朗西斯·柯林斯（Francis Collins）找到了一位名叫阿温德拉·纳特（Avindra Nath）
的科学家，希望他能对 ME/CFS 患者展开深入细致的研究，以期发现导致这令人极度疲惫疾病背后的潜在病因。

除了疲惫，ME/CFS 患者还会面临多种其他症状的困扰。他们经常会遭受脑雾的煎熬、对光线异常敏感，还会出现短期记忆障碍。劳累后不适也是一个普遍存在的问题，简单来说，就是患者进行任何身体活动后症状都会加重。遗憾的是，目前并没有什么有效的治疗方法。


纳特目前担任 NIH 国家神经疾病与中风研究所（National Institute of Neurological Disorders and Stroke）
的临床主任，同时也是神经系统感染科负责人，他和同事从 2016 年开始研究 ME/CFS。由于 ME/CFS 是一系列疾病的统称，研究人员希望找到具有特定病征的患者群体。他们专门招募了在一次感染过后发展出这种疾病的人，并且要求这些患者的身体状况允许他们前往 NIH 参与实验。最后，他们共招募到 17 名 ME/CFS 患者和 21 名健康志愿者。


接下来，研究人员对受试者进行了一次全面检查，他们查了磁共振成像（MRI）
、认知功能，查了腰椎穿刺、各个时间点的血液样本，查了免疫功能、代谢组学，查了肠道微生物组，还查了心率、血压和自主神经功能。


结果发现，ME/CFS 患者体内存在多项异常。首先，ME/CFS 患者的免疫系统被异常激活，似乎免疫系统在长期激活中“精疲力竭”了。此外，免疫激活还存在性别差异，女性患者主要表现为 B 细胞通路激活，而男性主要为 T 细胞通路激活。这一观察结果很重要，它可以告诉我们哪些治疗方法可能对女性起效，哪些可能对男性起效。


相比健康受试者，ME/CFS 患者的大脑和神经系统也存在显著差异，他们的大脑代谢物和神经递质存在大量异常。研究人员采用经颅磁刺激（TMS）和功能性磁共振成像（fMRI）等技术对大脑进行了刺激和测试，以观察大脑在静息状态和活跃状态下的代谢。为了让大脑活跃，受试者进行了一项简单的运动任务。结果表明，患者的运动皮层本身没有问题,，但在颞叶和顶叶的连接处……[查看全文]
Large Study of ME/CFS Patients Reveals Measurable Physical Changes
Josh Fischman: Today, we are delving into the disease originally known as "chronic fatigue syndrome." Now it's called ME/CFS. Recently, a big study looked at people who got the illness after an infection, and it turned up a few clues about what might be causing their debilitating, often lifelong symptoms.
Tanya Lewis: The disease once called chronic fatigue syndrome has historically been dismissed by doctors and other health care professionals as a psychosomatic illness, without any real physiological causes.
But in recent years, researchers have begun to take the disease—whose official full name is now myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS for short —more seriously.
Fischman: That really is a mouthful, and I'm not even going to try it. But Tanya, what does it mean?
Lewis: Well, it comes from myalgia, which means muscle pain, and encephalomyelitis, which is inflammation of the brain and spinal cord due to an infection. And while it's sometimes referred to as just chronic fatigue syndrome, people with ME/CFS prefer to call it ME, because it's really more than just fatigue.
Fischman: And during the COVID pandemic, millions of people developed something that was very, very similar to ME/CFS, and that's long COVID. So, scientists started taking that a lot more seriously. Even before the pandemic, I know the National Institutes of Health was starting to study ME/CFS.
Lewis: Yeah, that's right. So Francis Collins, who was the director of NIH at the time, approached a scientist named Avindra Nath and asked him to launch a comprehensive study of people with ME/CFS to really try to find some clues as to what was causing their exhausting symptoms.
Fischman: Yeah, like you said in addition to fatigue, there's a whole bunch of other very serious problems.
Lewis: People with ME/CFS often experience brain fog, hypersensitivity to light and short-term memory problems. And another really common issue is something called post-exertional malaise—it's basically a worsening of your symptoms after any kind of physical activity. And there aren't really good treatments for it.
Fischman: I've known some people with ME/CFS, and it can be really devastating.
Lewis: Yeah, it really can. So starting in 2016, Avi and his colleagues set out to study this, but since ME/CFS is sort of an umbrella term for a wide array of disease forms, they wanted to find a group of people who fit a very specific patient profile. They specifically recruited people who had developed the disease after an infection, and they also had to be well enough to travel to NIH for the experiments.
They ended up with a total of 17 participants with ME/CFS, and 21 healthy volunteers. Next, they set about putting the participants through a whole series of tests of pretty much every organ system.
Avindra Nath: I'm Avi Nath. I'm the clinical director of the National Institute of Neurological Disorders and Stroke and also the chief of the section of infections of the nervous system.
We did a very thorough investigation, looking at MRI scans, cognitive function. We did spinal taps, lots of blood draws at various time points. We looked at the immune function, metabolomics. We looked at the gut microbiome, we looked at their heart rates and blood pressures and autonomic function.
Fischman: I know that it was a really complete workup. What did they find?
Lewis: A lot of this is described in an online news story by writer Kamal Nahas, which we'll link to in the transcript.
Here's Avi:
Nath: We found that there were multiple systems that were involved. There wasn't a single abnormal observation. We found that there were a number of abnormalities. One, we found that there was activation of the immune system in the ME/CFS patients.
Lewis: It was almost like the immune system was "exhausted" from being chronically activated.
Nath: And, interestingly, we found that there were differences between men and women, such that women had predominantly B cell pathways that were activated, and in men, it was predominantly T cells. And so that in itself is a very important observation because it tells us that what may work for women may not work for men.
Lewis: ME/CFS occurs predominantly in women, but men can obviously get it too, so treatment could look for different for men vs. women.
The researchers also found differences in the brains and nervous systems of people with ME/CFS.
Nath: We found a lot abnormalities in the metabolites and the neurotransmitters. We tested the brain in many different ways by stimulating the brains with transcranial magnetic stimulation and a functional MRI scan, whereby you can look at the metabolism of the brain in a resting state and when you exercise the brain. In order to exercise the brain, we did a simple motor task. We found that the motor cortex itself was fine, but...[full transcript]
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论文信息
Walitt, B., Singh, K., LaMunion, S.R. et al. Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome. Nat Commun 15, 907 (2024).
DOI: 10.1038/s41467-024-45107-3
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