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Immune network analysis of cerebrospinal fluid in ME/CFS with atypical & classical presentations

duncan

Senior Member
Messages
2,240
You have missed the point Duncan. These conditions are considered neuropsychiatry and they are dealt with by neurologists once the mental dysfunction has been correctly attributed to a structural or metabolic cause. So neuropsychiatry is the study of how such causes give rise to mental symptoms. As far as I know the is no such thing as a clinical neuropsychiatrist in the UK. There might be in the US but I doubt it. There are psychiatrists who deal with mental symptoms and neurologists to whom they pass on the neuropsychiatric problems that an MRI or blood test shows has an identifiable cause. There may be researchers who call themselves neuropsychiatrists because they deal with neuropsychiatric problems but I doubt it. I suspect they are either trained psychiatrists or trained neurologists who do neuropsychiatric research. Many happens to have trained in psychiatry but that does not matter. It is probably more pertinent to ME/CFS than training in neurology since ME/CFS has no hard neurological signs but has plenty of symptoms from abnormal higher function

No, I got your point. My point is that at the end of the day we will be dealing with an immune issue or a neuroimmune issue or an endocrine issue or a metobolic issue or a neurological issue or an infectious issue or an autoimmune issue..or a combination of these. Some may give rise to anxiety and depression and, yes, cognitive issues, and some psychiatrists/psychologists may try to claim them as falling within their purview -- but they will be able to help only marginally if at all. Their role will be relegated to employing metrics designed to gauge the extent of symptoms, and as it is now, those tools can be blunt and frequently misleading and sometimes can do more harm than good.

I want the appropriate experts who will figure out how to treat my disease, and in my opinion those who dole out antidepressants and other mood modulators like so much grass seed on a vast plain of soil likely just won't cut it. I have personally seen up close neuroborreliosis and brain cancer and a debilitating potassium channelapathy, and although each generated considerable cognitive problems, not once was a neuropsych consulted since the cause of each problem was beyond their expertise. Now, with a nod to your point, each of these may have generated symptoms that fall within someones definition of neuropsychiatry, but on a practical and real-world level, and with all due respect, I could not care less as it in no way helps. Definitions can by politicized with far too much ease. Definitions can prove to be a gateway to intrangency and dogma. Give me the appropriate experts any day.

So, whereas I admittedly do not know how they practice medicine in the UK, where I live we try to let the appropriate experts treat the disease that falls within their silo. I don't much care about political distinctions. I want experts who will appreciate the biology and not potentially fall back to voodoo dogma. I want my disease out of harm's way, and when I go seeking these individuals I am not going bar-hopping in a dark corner of the French Quarter, if you get MY point.

Accordingly, I remain puzzled by the choice of journal, despite its claim that it is part of the neuroscience cadre.
 

Pendergast

Spain
Messages
82
Location
Spain
Think this answers your question.

Thank you so much @AndyPR . Yes, it does! :)

So I´m the Classical Type. Also, All my life prior to illness and some years after developing it, I had a lot of tonsilitis (one every two months, that was a crazy stuff). But now, 18 years post-illness, I don´t catch even a mild flu (the last one was in 2009)....:confused:
 
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Manganus

Senior Member
Messages
166
Location
Canary islands
So I´m the Classical Type. Also, All my life prior to illness and some years after developing it, I had a lot of tonsilitis (one every two months, that was a crazy stuff). But now, 18 years post-illness, I don´t catch even a mild flu (the last one was in 2009)....:confused:
Yes, your history fits perfectly well with this paper's hypothesis.
;)

The condition with classical onset seemingly end up similar to the condition with atypical onset.
 

TreePerson

Senior Member
Messages
292
Location
U.K.
Do they? Except classical people have lower cytokines and don't get cancer as often? While atypical people continue to have an activated immune system and go on to develop cancer and seizures? I'm completely confused. Does anyone know how many of the long-term atypicals in the study (I believe there were six or seven) developed these conditions? Or did they develop quite quickly after say three years?
 

JES

Senior Member
Messages
1,320
Do they? Except classical people have lower cytokines and don't get cancer as often? While atypical people continue to have an activated immune system and go on to develop cancer and seizures? I'm completely confused. Does anyone know how many of the long-term atypicals in the study (I believe there were six or seven) developed these conditions? Or did they develop quite quickly after say three years?

Yeah that makes no sense to me. Everything I read about immune modulators like LDN suggest they reduce the likelihood of certain cancers, same with AHCC, etc. I have also read that people with a "strong" immune system are more prone to autoimmune diseases and less prone to cancer (women have a higher rate of most autoimmune diseases and CFS, but lower rate of most cancers).

I would probably belong more to the atypical category, but I've caught a cold twice over the last 8 years or so, before that regularly every year.
 

TreePerson

Senior Member
Messages
292
Location
U.K.
Yeah that makes no sense to me. Everything I read about immune modulators like LDN suggest they reduce the likelihood of certain cancers, same with AHCC, etc. I have also read that people with a "strong" immune system are more prone to autoimmune diseases and less prone to cancer (women have a higher rate of most autoimmune diseases and CFS, but lower rate of most cancers).

I would probably belong more to the atypical category, but I've caught a cold twice over the last 8 years or so, before that regularly every year.

I think the atypical up regulated immune system would protect against colds. So that makes sense anyway. The bit I was querying is that ultimately the two groups become very similar because I had understood the opposite.
 
Cort has written an article covering this study for Simmaron - http://simmaronresearch.com/2017/04/petersons-atypical-chronic-fatigue-syndrome-me-cfs/

ETA: Towards the bottom of his article, Cort talks to Mady Hornig about future work, including
What Dr. Hornig wants is “system-biology” work that ties all these systems into a coherent whole. A gut level disturbance could, for instance, end up impacting virtually every system involved in ME/CFS – including the central nervous system.

“Further systems biology-type work will help us delineate how altered gut microbiota might translate into faulty signals – ranging from bacterial or human metabolites, including a range of immunity-modifying and neuroactive molecules, to immune molecules, to autonomic/vagal nerve axis effects – that then access the CNS (perhaps involving damage to the integrity of the blood-brain barrier to allow entrance of these aberrant signaling molecules) and disrupt brain function.”

In fact, Mady Hornig and Ian Lipkin do have most of the samples they need to begin this work. In what must have been one of the stranger NIH grant awards ever, however, the NIH funded the collection of an enormous amount of samples taken at four points over a year in 250 ME/CFS and healthy controls, but has not funded the analysis of these very same samples.

“In the more recent longitudinal NIH study we have no funding at all for laboratory studies, but have a unique banked set of well-characterized samples (oral, fecal and blood).” (bold added)

Having so many samples just sitting there is astonishing, and hopefully the second half of the study will get funded.

When I asked Dr. Hornig about funding the metabolomics and proteomics work she said that the metabolomics and proteomics assays had been run – but only for a subset of patients. The CII, she said had funding:

“Only for analysis of a subset of the Chronic Fatigue Initiative main study cohort samples (and this assay work is completed with analysis in progress) – not for the latest 125+ cases and 125+ controls based on the 1-year, NIH-funded study with 4 serial sample collections.

We don’t have any funding to follow up on candidates identified, including validation, quantitation and correlation with genetic, epigenetic and RNA-based assays.”
Building up the funding for this analysis of all those samples is what the Microbe Discovery Project is working to do, to donate or to read more visit - http://microbediscovery.org/
 
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Manganus

Senior Member
Messages
166
Location
Canary islands
Do they? Except classical people have lower cytokines and don't get cancer as often? While atypical people continue to have an activated immune system and go on to develop cancer and seizures? I'm completely confused. Does anyone know how many of the long-term atypicals in the study (I believe there were six or seven) developed these conditions? Or did they develop quite quickly after say three years?

Sorry, my fault!
I'm not convinced the hypothesis is right.
 

helperofearth123

Senior Member
Messages
202
I'm confused am I typical or atypical? My CFS started a few months after coming down with lyme disease (diagnosed by a professor of infectious diseases) which was probably caught while hiking in America, Virginia, though I live in the UK. I was treated for the lyme with antibiotics but then the fatigue and brain fog returned anyway and have stayed with me for 6 years. Am I typical or atypical can anyone please say? Thank you
 

Snowdrop

Rebel without a biscuit
Messages
2,933
I'm confused am I typical or atypical? My CFS started a few months after coming down with lyme disease (diagnosed by a professor of infectious diseases) which was probably caught while hiking in America, Virginia, though I live in the UK. I was treated for the lyme with antibiotics but then the fatigue and brain fog returned anyway and have stayed with me for 6 years. Am I typical or atypical can anyone please say? Thank you

I don't know if this will clear things up but here is the bit on Atypical from CJ's blog:

What does a typical chronic fatigue syndrome (ME/CFS) patient look like? Something like someone who suddenly comes down with a flu-like illness and never recovers. They may get better or they may get worse, but they don’t come down with cancer, an autoimmune illness, seizures or other significant illnesses.

An atypical patient, on the other hand, might have a history of viral infection (viral encephalitis) or have been exposed to unusual pathogens during foreign travel or had a blood transfusion before becoming ill. They also tended to be more severely cognitively impaired and had more neurological complaints. They tended to suffer from severe diseases as well.

Many of these illnesses appeared long after the ME/CFS diagnosis. In fact, at the time of diagnosis these patients looked like a typical ME/CFS patient. This study suggests, though, that very early on, something different was happening in their central nervous systems.

The Atypical Patients in the Study (the “Peterson Subset”):
  • Atypical multiple sclerosis – 3
  • Other autoimmune/inflammatory disorders – 4
  • Cancer – 8 (brain-3, breast-2, lymphoma -2, pancreatic-1)
  • Infections – 2 (West Nile Virus encephalitis – 1; Unspecified viral encephalitis – 1)
  • Illness during foreign travel – 2
  • Illness after blood transfusion – 1
  • Seizure disorder – 6
  • Gulf War Illness – 1
It didn't really help me but you might fall into Infections category?
 

ash0787

Senior Member
Messages
308
If stanford could send over one of those nano cube things they could check in retrospect that both subgroups produce the impedance effect, I'd like to see a quick transition to more empirical selection criteria, any studies that are just starting now should also use 'the cube'.
 
Messages
2,087
The Atypical Patients in the Study (the “Peterson Subset”):
  • Atypical multiple sclerosis – 3
  • Other autoimmune/inflammatory disorders – 4
  • Cancer – 8 (brain-3, breast-2, lymphoma -2, pancreatic-1)
  • Infections – 2 (West Nile Virus encephalitis – 1; Unspecified viral encephalitis – 1)
  • Illness during foreign travel – 2
  • Illness after blood transfusion – 1
  • Seizure disorder – 6
  • Gulf War Illness – 1

A proportion of patients who meet
diagnostic criteria for ME/CFS at the onset of their illness have
either a remote history of relatively uncommon exposures (viral
encephalitis, illness after foreign travel or blood transfusion, Gulf
War Illness) or develop comorbid immune-mediated6,7 or
neurological8,9 disorders years later.



I have no technical knowledge on this subject so these might be basic questions:


How can they mix comorbidies and exposure type into the same list.

Surely patients should be classified based on one or the other feature but adding these patients up into the same list seems like they are lumping two different features together for no reason.


To classify a patient as atypical ME because they subsequently developed cancer seems odd to me.

Have I missed something obvious?
 
Messages
54
From the paper: "All cases (both classical and atypical) met either the 1994 CDC criteria10 and/or the 2003 Canadian consensus criteria."

How do we know which subjects met which criteria? The "and /or" is very confusing.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I think the issue with which type is empirical. They suspected a different group based on different symptoms, compared the cytokine results, and found an association.

I expect to see big changes in how we assign patients to subgroups as the science evolves. We are in a transition phase, and some of the findings may be misleading. This should be corrected as further, larger and more in-depth studies are done.
 

Alvin2

The good news is patients don't die the bad news..
Messages
2,984
EEK!
I fall under the atypical, had this all my life, but not this bad. This complicates things when it comes to discovering a treatment :(
 
Messages
16
Also confused/scientifically illiterate/worried. Are they saying that every patient that did not exhibit a classical viral onset (e.g. all gradual onset patients, like myself) are 'atypical' and thus predisposed to later comorbidities? The language in the Simmaron piece is vague.