Is myalgic encephalomyelitis/encephalopathy an inappropriate name?

[halcyon]

I don't think anyone has replicated the results from Japan

I don't think so either but I hope someone tries to soon and I hope whoever does has the good sense to also use ME-ICC as selection criteria as the Japanese did.

'Low level' neuroinflammation is a term that I tend to use to describe this type of non encephalitis CNS inflammation

Understood. How would inflammatory/infectious injury to cerebral microvasculature that I mentioned above (re: Richardson's autopsy patients and alluded to by SPECT findings) be classified, still as encephalopathy/encephalomyelitis or something else?

 

[charles shepherd]

Encephalitis associated with ME/CFS need not be acute. In fact, I would imagine it would not be acute, but rather chronic and low grade - persistent but not obtrusive enough to be on conventional radar.

It could be but chronic encephalitis has to start with an acute encephalitis and people with ME/CFS do not normally start with acute encephalitis

And we have not found any convincing evidence in the post mortem studies to say that there was chronic/on-going encephalitis present

I agree it's important to keep an open mind here but I really don't think we are dealing with what neurologists and pathologists would regard as an encephalomyelitis - either clinically or pathologically

Hence the general reluctance/refusal of many doctors to use the term ME

 

[duncan]

I am not convinced chronic encephalitis has to start with raging or pronounced acute encephalitis, but I agree this is likely.

Again, relative to the post-mortems, I would be interested in what metrics were used.

 

[duncan]

Two conditions that relate back to a persistent encephalitis might be tertiary neurosyphilis and late stage neuroborreliosis. Dr. Judith Miklossy has published about brain pathologies in both. There is also a pathologist named Alan MacDonald who has done post-mortems on brains of Lyme patients and I believe has published about abnormalities found in the brain parenchyma.

So there is arguably precedence.

 

[msf]

How about 'Chronic Lyme Disease' then?

I'm joking, I just wanted to highlight the problems with choosing a name before we have a good understanding of the pathophysiology of the disease. Until then, I think ME (in whichever form) does the job.

 

[Sidereal]

Myalgic encephalopathy means "disease of the brain causing muscle pain"

I agree with you @leokitten. I know it's controversial to say this around here but really there isn't a shred of evidence that ME is a neurological illness. It causes brain manifestations in its victims but for an illness that's supposedly primarily neurological in origin, there is really nothing pointing towards that, either in terms of neurological exam, brain imaging, pattern of cognitive dysfunction seen on neuropsych testing, or post-mortem findings in the small number of sporadic cases that have been studied.

Nonspecific neuroinflammation of the kind observed in the Japanese study occurs in all kinds of neuropsychiatric presentations including major depression and autism. The same goes for hypoperfusion findings on SPECT from back in the day when this test was popular, and neuropsych testing showing problems with sensory gating and sustained attention and working memory.

The Japanese study is often cited as evidence that ME is a neurological illness. It proves nothing of the sort. It does, however, show that there is inflammation in the brain and that ME is not a non-disease / false illness belief. I think it's important to get our facts straight in terms of advocacy efforts so we're not dismissed as crazy when we advocate for names like encephalomyelitis.

Where I would disagree is with your statement that myalgic encephalopathy is a bad name. I think it's a good name. Encephalopathy doesn't necessarily mean primarily neurological disease. It's a disease that affects the brain but its origin may be in the periphery as in hepatic encephalopathy or D-lactic acidosis encephalopathy. I think the zombie-like state we call brain fog and balance issues we have are likely caused by something along those lines and mostly reversible once the energy crisis is resolved.

 

[EllenGB]

Re neurological disease, perhaps classic ME is, but CFS, being a broader concept, is not. I've just co-written a paper about the progressive form of ME and if you read it, you'll see a number of symptoms similar to those of MS. Charles Poser also noticed this. Decision expected Monday. Earlier decision was 'acceptance with minor revisions' but I didn't like the title the referee suggested. If they accept and compromise on the title, it will be free online the 9th. I dare say that it will be my last paper.

A recent paper by Jason et al looked at the differences between the different diagnostic categories. They found that only 5% of those who met the CDC 1994 criteria also met the 2009 criteria for ME (Goudsmit, Shepherd et al). These ME criteria are based on Ramsay's description and not polythetic, i.e. where you need fatigue and four others and you don't have to have PEM. There are no optional minor criteria in the ME criteria. Criterion 1 comes across as very neurological. It's not 'fatigue'. It's Ramsay's key symptom.

Keep an eye on the longitudinal studies, following people after diagnosis of an infection. No sign of abnormalities e.g. raised cytokines or psych issues in the first six months. The difference between those who recover and those who don't is the severity of the initial illness. Which means that the abnormalities documented later may be a result of a process, or a genetic effect (source: Lloyd). With a more homogeneous group, the scans will be easier to interpret. If ME, they need to be repeated 24 hours after the first, and after minimal exercise. One test tells us nothing and hence, most abnormalities are not replicated. It's the post-exertional abnormalities that characterise ME. Pleased to see the Americans are coming to the same conclusion.

Intelligent discussion above.

Howes, S and Goudsmit, EM. Progressive Myalgic Encephalomyelitis (ME) or a New Disease? A Case Report. Submitted for publication. 2015.

Jason LA, Sunnquist M, Brown A, Reed J. Defining essential features of myalgic encephalomyelitis and chronic fatigue syndrome. J Hum Beh Soc Environ. 2015; 26(6): 657-674.

Goudsmit EM, Shepherd C, Dancey CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychology Update. 2009; 18(1): 26-33. 2014 updated version, free online available from: http://www.axfordsabode.org.uk/me/mecrit2014.htm

 

[duncan]

Sidereal, I appreciate your point, but for the sake of accuracy:

1) There is evidence that ME/CFS is a neurological disease, but the evidence is probably not enough to prove it.

2) I should think we all have "brain manifestations".

3) On the contrary, there are studies that point to brain imaging (Nakatomi et al), pattern of cognitive dysfunction on neuropsych testing (DeLuca et al), as well as other neurological considerations.

4) Nonspecific neuroinflammation can be seen in serious brain disease such as tertiary syphilis and NB, so although having it doesn't prove a primary brain mechanism behind ME/CFS, it certainly doesn't allows us to dismiss it as a possibility.

5) As I noted, and despite your claim, the Japanese study is evidence that ME is a neurological disease, just not proof enough.

I agree with much of the rest of what you have written.

EllenGB, it's nice to be able to distinguish between ME and CFS, unless one happens to live in the US. US citizens have not been able to indulge in that distinction historically.

 

[EllenGB]

EllenGB, it's nice to be able to distinguish between ME and CFS, unless one happens to live in the US. US citizens have not been able to indulge in that distinction historically.

It's coming. See the trend. Prof. Jason will not let this go. He sees the point of it. Various articles of late. Be patient a little while longer.

Best wishes,

Ellen

 

[msf]

EllenGB, the recent Lipkin study found raised cytokine levels in patients who had been ill for less than 3 years. The Dubbo study, which I believe you are referring to, may have identified a different group, those who take longer to recover from Mono.

 

[Sidereal]

1) There is evidence that ME/CFS is a neurological disease, but the evidence is probably not enough to prove it.

What evidence, specifically? Please also define what you mean by neurological disease because I get the impression you're lumping into that category all sorts of conditions with neurological manifestations which no neurologist would classify as a neurological disease per se.

2) I should think we all have "brain manifestations".

Well, I meant "brain manifestations" of some kind of disease process which normal people clearly don't experience, at least not on a daily basis.

3) On the contrary, there are studies that point to brain imaging (Nakatomi et al), pattern of cognitive dysfunction on neuropsych testing (DeLuca et al), as well as other neurological considerations.

The Nakatomi study shows microglial activation which also occurs in diseases currently classified as "psychiatric".

Various degrees and patterns of impairment in performance on neuropsychological tests occur in all neuropsychiatric disorders. Such deficits don't necessarily prove "organic" brain disease.

4) Nonspecific neuroinflammation can be seen in serious brain disease such as tertiary syphilis and NB, so although having it doesn't prove a primary brain mechanism behind ME/CFS, it certainly doesn't allows us to dismiss it as a possibility.

I didn't say it dismissed it as a possibility. I said it didn't prove it's a primary neurological disorder.

5) As I noted, and despite your claim, the Japanese study is evidence that ME is a neurological disease, just not proof enough.

No, it isn't. Microglial activation / neuroinflammation occurs in "psychiatric" conditions also.

Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

Evidence for activation of microglia in patients with psychiatric illnesses

Immunological aspects in the neurobiology of suicide: Elevated microglial density in schizophrenia and depression is associated with suicide

Etc.

 

[duncan]

Oh no, I'm not going in linguistic circles here.

You said, "...there isn't a shred of evidence ME is a neurological illness." Neurological disorders include the brain.

Logic aside for the moment, please appreciate, @Sidereal , that evidence does not equate to proof. Evidence is an indicator or sign that can be used as proof.

So there is evidence that ME/CFS is rooted in the brain, e.g, the Nakatomi effort, but arguably that evidence can be interpreted differently, or be said to be insufficient.

 

[EllenGB]

EllenGB, the recent Lipkin study found raised cytokine levels in patients who had been ill for less than 3 years. The Dubbo study, which I believe you are referring to, may have identified a different group, those who take longer to recover from Mono.

Like many, I don't recall this study included likely confounders, which means it's hard to interpret the results. I like sound evidence and don't care about the person. Good science is good science. Use good definitions, good measures etc and don't leave out likely influences like stress. Lon term patients might have adjusted to the point that raised cytokines due to stress are no longer there. We know that chronic stress result sin raised cytokines (e.g. Danese et al). Without something like the 14 item perceived stress scale, we haven't got a clue about likely explanations. It needs to be replicated, and the design has to be able to rule out depression and chronic stress.

MS patients make good comparison groups.

ellen

 

[msf]

The second study (on spinal fluid) compared ME, MS and controls, and found cytokine differences once again.

 

[msf]

Oh, and ME isn't caused by stress.

 

[msf]

Or depression.

 

[charles shepherd]

Like many, I don't recall this study included likely confounders, which means it's hard to interpret the results. I like sound evidence and don't care about the person. Good science is good science. Use good definitions, good measures etc and don't leave out likely influences like stress. Lon term patients might have adjusted to the point that raised cytokines due to stress are no longer there. We know that chronic stress result sin raised cytokines (e.g. Danese et al). Without something like the 14 item perceived stress scale, we haven't got a clue about likely explanations. It needs to be replicated, and the design has to be able to rule out depression and chronic stress.

MS patients make good comparison groups.

ellen

Which is why we have added blood samples from a cohort of people with MS to ME Biobank at the Royal Free Hospital……..

 

[EllenGB]

Isn't it a CFS Biobank? No one has ever allowed me to participate. Anyway, if stress has been excluded, then it's time to do a MRI. I'm surprised how few are done. If you read Poser's articles, sadly, I misplaced one, he identifies similarities and differences, so you can see abnormalities in ME and PVFS. Stress can explain raised cytokines but it can't explain some of the MRI results e.g Daugherty, Schwartz et al. I'm very keen on MRI and repeat SPECT. Tirelli et al replicated Costa et al. I think they were on to something. And activity might explain raised cytokines too, come to think of it (despite Lloyd et al's odd results). So you need a test-retest design for that, and then you can interpret the data with more confidence. Don't tell me, my memory has failed me and that's exactly what Lipkin and Hornig did.

I'm getting old.

Ellen

 

[leokitten]

@EllenGB and @charles shepherd I read through some of the listed papers and I have to say I worry sometimes that you are splitting hairs a bit that there are two distinct diseases and that it's black or white. Maybe I'm not processing it well I've crashed since yesterday after a long week of work and I'm in a lot of pain.

Have you two ever met a person who you would diagnose as having full ME but they can, although with a lot of difficulty, work full-time?

There may be a distinction between ME and CFS but it's not a distinction of severity, i.e. you can have full ME and not have a moderate to severe disease. If there are really two distinct diseases then each has a its own spectrum of severity.

 

[EllenGB]

No, it's not a matter of severity. In short, there's more to ME than fatigue. Or a headache. Or a sore throat. Or all the other common symptoms in the CDC criteria. A good scientist nitpicks, to be accurate. Fatigue is subjective. That is perhaps why Powell et al managed to reduce fatigue after CBT lasting three hours. Lots of people suffer form fatigue, headaches, sleep disturbances and sore throats. As you get older, the memory goes, especially if you're also menopausal. So as researchers have already pointed out, you need to get away from the CDC criteria, ergo, the alternatives. The latest are all tending towards the old concept of ME.

Is CFS the same as ME/CFS or ME? Well, ME can occur in epidemics (name me an epidemic of CFS - bit difficult when you can't diagnose it for six months), and is closely linked to enteroviruses. It is also associated with Summer bugs. Can you say the same about CFS, or ME/CFS? At the moment, following the evidence, they are different. They overlap, but are different and that is what Ramsay thought too. And a lot of other doctors.

ME is an acute illness, though has a tendency to become chronic as Ramsay discovered around 1978. (That is his claim to fame. He didn't think up the name but he was the one who showed it tended to be chronic). There are mild forms. People can work, and do. In my studies, I had a few who worked fulltime. It depends on the symptoms and if you can compensate for them. But, as you should know, fatigue is NOT the core symptom of ME. It's less common than CFS (1 per 1000). I've summarised it all in the criteria paper. They are different unless you're a CBT fan who will tell you, they are not. They lump. It's all stress and fatigue.

If you don't define your research sample well, you can introduce confounders and make the results impossible to interpret. Another example, GET works well if you take the course at Barts, but it's not as effective in the USA. Different concept of CFS and ME. In the US, CFS is closer to ME than in the UK. But research HAS to exclude people with chronic stress or you get results like Heim et al etc.