#7 – ME/CFS: Causes, Symptoms and Unanswered Questions

00:00:06: There's still a lot of unknowns about the mechanism, about the root cause.

00:00:11: About what actually causes the disease?

00:00:14: We know that infections can trigger it but we don't if they actually cause and thats problematic.

00:00:46: Hello & welcome to Virological!

00:00:48: This episode was recorded on February first of twenty-twenty six in New York City.

00:00:55: So today we're not going to talk about a virus per se, but we are talking about disease that is likely connected with viral infections.

00:01:04: The details aren't completely clear... ...but I'll try to summarize what's known and the diseases often mostly know by an abbreviation Five letters ME-CFS Another big fan of using abbreviations for diseases because it confuses people and then they don't understand what this actually meant.

00:01:30: And I know these abbreviations are easier to say than the actual words that they stand for, but i think its important to know what is actually means.

00:01:40: So ME stands for Mialgic Encephalomyelitis and CFS is easier which stands for Chronic Fatigue Syndrome.

00:01:51: So what does ME or myalgic and the fellow myelitis mean?

00:01:56: It's actually pretty hard to say, I know for me at least.

00:01:59: Myalgic means basically muscle aches And encephalomyelitis means inflammation of brain and spinal cord.

00:02:08: Chronic fatigue syndrome is really clear.

00:02:11: Basically this a chronic disease that includes the nervous system The immune system energy metabolism and also blood circulation.

00:02:19: So it's complex, there are a number of factors involved And there is lot things that aren't clear yet.

00:02:27: Why did I say the disease is likely connected to viruses in virus infections?

00:02:32: Sixty-to-eighty percent cases start after an infection.

00:02:37: Historically we'll talk about people have tried too connect different viruses.

00:02:46: So basically the symptoms include chronic fatigue to a degree that impacts on daily life muscle weakness and Something, that's called post exergenal malaise or PEM.

00:03:00: And what?

00:03:00: That means is that if you make an effort To do something right it is hard Or may not be that hard for normal person but this heart for somebody who has MEcfs taking a shower.

00:03:12: For example.

00:03:14: then doing that might make the symptoms worse after about twelve to forty-eight hours.

00:03:22: So typically there's activity and then, after that activity... ...there is a worsening of symptoms again usually not right away but typically twelve to fourty eight hours later.

00:03:34: And this worsening can last for hours up two weeks.

00:03:39: And that's kind of this.

00:03:40: PEM is a hallmark signature or hallmark symptom, of ME-CFS.

00:03:47: But there are also number other symptoms associated with it.

00:03:51: One is basically sleep disorders.

00:03:53: people have very unrefreshing sleep.

00:03:57: They wake up, they're still exhausted.

00:03:59: Didn't get any rest even though they slept for four hours.

00:04:03: This can also lead to broken sleep where people just sleep a few hours at the time sometimes Even during that day but they can get full night's sleep and in some cases The REM phase of the sleep cycle is missing.

00:04:17: There are often also cognitive dysfunction Often described as brain fog.

00:04:22: We know this from long Covid.

00:04:25: that can lead to slow reaction times, slower reading speed impact on concentration problems with paying attention for example.

00:04:35: another group of symptoms are pain often higher pain sensitivity and often chronic pain.

00:04:44: And there could also be increased sensitivity to different stimuli including light or sounds.

00:04:52: kind of fine when they're laying down, but if they sit up or stand-up.

00:04:59: They become dizzy.

00:05:00: the disease is classified into basically mild moderate severe and I guess very severe And it's about a quarter people who have the mouth version.

00:05:11: a quarter that has to moderate one approximately maybe a little bit more than a quarter, and the quarter is severe.

00:05:19: The mild form of it means that people can still go to work or take care of themselves.

00:05:25: It impacts on their life quite a bit but they manage in a way to have regular lives.

00:05:32: Moderate means that it already impedes some activities of daily life And its usually hard for them to keep a job and to really take care of themselves.

00:05:45: The severe version, severe form means that people are typically housebound.

00:05:51: they need help They can't perform all their daily activities... ...they might be able do some things like brushing their teeth but not other things like cooking for example.

00:06:00: And the very severe form is basically when patients are bed bound.. ..they cant' really do anything anymore.

00:06:08: The severity change over time.

00:06:10: People can get better but they can also get worse, and the symptoms come in waves.

00:06:15: And there could be quite some fluctuation... ...in terms of the symptoms In terms of diagnosis There are no biomarkers So it's hard to basically diagnose on a biological basis.

00:06:29: But there is clinical criteria.

00:06:32: There're actually bunch different criteria that have been developed Nice Criteria or from National Institute for Health Care Excellence in UK.

00:06:42: The US Institute of Medicine has put criteria together.

00:06:47: There are the ICC or International Consensus Criteria and CCC, Canadian consensus criteria... ...and then there's also criteria from the CDC which is sometimes called Fukuda criteria.

00:07:01: What all of them basically recognize and include is chronic fatigue, functional impairment this post-exertional malaise or BEM.

00:07:12: And sleeping disorders.

00:07:14: some of these definitions are criteria a little bit more loose.

00:07:17: I think the CDC or Fukuda criteria more loose.

00:07:20: that includes more people more cases and other criteria a Little bit more strict.

00:07:26: based on those criteria then there's fewer cases to qualify.

00:07:30: People with ME-CFS have a relatively normal lifespan, but they do have higher suicide rates.

00:07:37: Also it needs to be said that often takes a long time until they are diagnosed.

00:07:42: There's still a lot of stigma, stigmatization involved or associated with the disease.

00:07:49: Often physicians aren't familiar with symptoms Or think this is psychological psychosomatic.

00:07:58: Sometimes you even hear that people are just called lazy, and of course this is very frustrating for the patients.

00:08:06: And there's a long fight already for recognition of ME-CFS to make sure it's diagnosed correctly... ...and that the patients get care they need.

00:08:19: The problem is not much in terms of treatments other than symptom management.

00:08:25: Of course, if people have sleep disorders that can be managed to a certain degree with medication and improvement in terms of the sleep disorders can actually lead to improvements on overall symptoms.

00:08:39: but it's not always the case.

00:08:41: And of course pain also could be managed by medications.

00:08:47: It's problematic because we don't know what the underlying mechanisms are and so it is really hard to actually fight a mechanism, do something about their actual disease can only manage symptoms.

00:09:01: There one medication that has been licensed in one country I believe in Argentina for ME-CFS and that's Rindotolimod which is an innate immune stimulant based on nucleic acids.

00:09:16: that has been shown to be somewhat promising in clinical trials, but it's not completely clear how well it works.

00:09:24: Actually a number of things have been tested in clinical trial but so far there was nothing really like breakthroughs.

00:09:31: The disease itself is not so rare.

00:09:33: depending on the definition used There are two-to nine cases per thousand people So quite few.

00:09:42: One prominent example is the best player of red hot chili peppers, who also has ME-CFS.

00:09:48: And it's interesting.

00:09:51: with long COVID there are pretty strong overlaps so fifteen to fifty percent of the long Covid patients fall under the ME- CFS criteria.

00:10:00: again depending on which criteria you use.

00:10:05: There a higher risk for women And there are two waves of onset for the disease.

00:10:10: One is between ten and nineteen years old age, The second one is between thirty to thirty-nine years of age.

00:10:18: We know that viral infections often trigger the onset of diseases.

00:10:22: Viruses that have been implicated here are the Epstein-Ba virus Human herpesvirus VI chickenpox which also a herpes virus Influenza A viruses SARS coronavirus I SARS Coronavirus II, enteroviruses are in discussion for triggering or causing ME-CFS but also bacterial infections like proselyosis or Q fever.

00:10:49: There's also an association with fungal spore exposure and mycotoxins.

00:10:54: And then stress can also trigger the onset of the disease a drama Or even pregnancy on childbirth.

00:11:02: so These things can trigger the onset of symptoms, but it's not clear if they are the root cause.

00:11:09: And that is a problem here – The mechanism itself isn't clear!

00:11:14: There are hypotheses about its viral persistence causing these symptoms and there are hypotheses on autoimmunity.

00:11:22: Genetic factors are probably involved even though nobody has found a smoking gun in terms one gene might drive this.

00:11:33: Sometimes changes in brain and brain stem activity can be detected with people who have ME-CFS.

00:11:40: In some cases you see lower activity of natural killer cells, D-cells... ...and all the antibodies to certain cellular receptors are identified but again there's nothing really out there yet that qualifies as biomarker.

00:11:57: so it is hard because the mechanism isn't clear enough.

00:12:02: underlying biological cause is not clear.

00:12:05: And this makes it really, really hard to develop medications because if you don't know the mechanism... ...you cannot rationally design drugs and molecules that can counteract it.

00:12:17: You also can not design vaccines against a virus that might cause it.. ..because its not known which virus would be.

00:12:24: A little bit about the history of ME-CFS.

00:12:28: It's actually known for quite some time already or at least diseases that have the same symptoms.

00:12:34: In the nineteenth century, a disease called Neuroastinia was described and also included nerve and muscle weakness which fits well with ME-CFS.

00:12:48: in the nineteen thirties there were epidemics of what people back then call atypical bolium eulitis in LA, Wisconsin.

00:12:58: I think those are someone who describes Switzerland And that's interesting because they're described as epidemics, which means could have been a virus that caused it or at least triggered.

00:13:08: Right?

00:13:12: That is one of the reasons why people look for viral causes for their disease.

00:13:16: In the late nineteen forties there was this disease characterized in Iceland called Akuriri Disease.

00:13:25: There also had about five hundred cases resembling ME-CFS And between nineteen forty nine and nineteen fifty one there were about eight hundred cases in Adelaide, Australia.

00:13:37: that also basically fit the description of ME-CFS.

00:13:42: Nineteen fifty five The Royal Free Hospital In London actually came forth with a name for the disease.

00:13:48: they call it benign mealgic encephalitis.

00:13:54: was put there because they wanted to differentiate my Algaeic Antifolar Myelitis that would be lethal.

00:14:01: The benign wasn't here to say, it's not an issue and not a problematic disease.

00:14:06: And over time this was dropped Because It gave the impression That its Not really a Problematic Disease In the nineteen sixties.

00:14:13: in nineteen seventies There Was also kind of discussion if If the disease could Be just basically mass hysteria Thats Driven by psychology or has psychosomatic reasons.

00:14:27: And that did a lot of damage.

00:14:30: because basically, it's also the reason why nowadays people might think this has psychological reasons and not biological reasons.

00:14:39: but there was a lot pushback from physicians who treated patients with ME-CFS because they clearly saw that this is a real disease, not something... A biological disease isn't something caused by psychological issues.

00:14:53: In the nineteen eighties there was an outbreak in Lake Tahoe and initially it was suspected to be associated or caused with Epstein-Barr virus infections but wasn't the case.

00:15:05: And for that outbreak the term chronic fatigue syndrome was termed.

00:15:10: so basically starting with the disease is known as ME-CFS and in nineteen eighty six, The first diagnostic criteria were published by Melvin Ramsey.

00:15:25: In the nineteen nineties Hilary Koprowski was a famous virologist.

00:15:30: tried to make connection to a human retrovirus.

00:15:34: He thought he had reason to believe that ME-CFS is caused or at least associated with HDLvII, where an HDLVII like virus.

00:15:45: So HDL vII as a human retrovirus can also cause issues in humans.

00:15:50: but it turned out later this was wrong and not the case.

00:15:55: In two thousand six the CDC started a public awareness campaign Also make sure that researches focused on the disease.

00:16:04: And in two thousand nine, there was another paper that linked ME-CFS to a virus.

00:16:11: In this case also retrovirus.

00:16:13: but the mouse retrovirus xenotropic murine leukemia virus or at least the virus would be very close to that virus.

00:16:21: But unfortunately researchers had it wrong and turned out that XMRV wasn't really connected with ME-cfs.

00:16:29: There's still alot of unknowns about the mechanism, about the root cause.

00:16:35: About what actually causes the disease?

00:16:37: We know that infections can trigger it but we don't know if they actually cause or there is another root cause.

00:16:45: and again... ...we do not have a mechanism behind the disease and thats problematic.

00:16:51: There is a lot of research going on right now, there's also a lot awareness about ME-CFS.

00:16:56: I think this is because of Covid and long Covid.

00:17:01: Again, long Covid is very similar to post-viral infection syndrome.

00:17:10: a harder bush to understand what's happening.

00:17:16: There is actually one big study ongoing in the UK right now, Decode ME where they are looking for genetic reasons or underlying genetic causes.

00:17:30: Columbia University also has its own center of solutions for ME-CFS and they're doing very good research there.

00:17:37: Unfortunately, early in twenty-twenty five some of their funding was terminated by the incoming Trump administration.

00:17:44: I think they got some of it back and not a hundred percent sure but i'll share an article about that in the link section here.

00:17:51: And more recently In The End Of Twenty-Twenty Five Germany pledged five hundred million euros for research into post viral syndromes which include MEcfs.

00:18:02: So hopefully there will be more more information out there about the cause of ME-CFS soon with all this research going on and that might also lead to more effective treatments, potentially prevention or a cure for ME CFS.

00:18:20: Certainly very problematic disease that affects quite large number people but as I said currently unfortunately not much can be done.

00:18:36: So, very interesting disease.

00:18:38: Lots of open questions and lots of research to be done!

00:18:41: That was it for today's episode of Virological And as always if you have any comments or question please write an email to virologicle at podcastjoach.com And that is all for the day.

00:18:56: Thanks for listening in Until next time Bye You'll find a link in the show notes.

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