Evidence of Neurological Abnormalities in ME Suppressed in the IOM "ME/CFS" R

[alex3619]

This seems to be confusing, as these symptoms are due to opposite causes.

That is one of the issues of a multisystem disease. Different and sometimes opposite things are going on, and the actual symptoms are a result of the moment to moment balance of maybe a hundred different things.

 

[lazzlazz]

This quote from Neilk:
From the 2012 IC Primer, pages 4-5:
Neurological Abnormalities
Neurocognitive, sleep, autonomic and sensory disturbances, pain, headaches, and paresthesias are prominent neurological signs and symptoms. Cognitive impairments including slow processing of information, poor attention, word finding, and working memory are some of the most functionally disabling symptoms. [1, 73, 74]

(responding to Neilk, above)
If I were to name my most disabling symptom this would be it. It's why I feel frozen out of IOMs disease, whatever they want to call it. ICC is where my illness resides.

I'm a little late to this discussion but I guess I don't understand why one would "feel frozen out of IOMs disease" - the IOM report ("Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness") includes extensive discussion of neurocognitive manifestations in ME/CFS (from page 96 to 107 of the report); autonomic dysfunction is discussed from p 107 - 118; pain is discussed p. 141-147; sleep is discussed p. 86-96; headache is discussed in multiple places (use the search function to go through the PDF) . The report also acknowledges many patients experience pain (they just didn't list pain as a core symptom - Lucinda Bateman discusses this in some of her talks about the criteria; see video linked in this thread http://forums.phoenixrising.me/inde...an-new-webinar-iom-diagnostic-criteria.36945/ ) Since the quote above italicizes the neurocognitive symptoms, I'll quote the report for them.

page 96 says the following:
"Impairments in cognitive functioning are one of the most frequently reported symptoms of ME/CFS. Patients describe these symptoms as debilitating and as affecting function as much as the physical symptoms that accompany this disease. During a survey of ME/CFS patients, descriptions of neurocognitive manifestations included, among others, “brain fog,” “confusion,” disorientation,” “hard to concentrate, can’t focus,” “inability to process information,” “inability to multitask,” and “short-term memory loss” (FDA, 2013). The short-term memory problems of ME/CFS patients include difficulty remembering something they just read. Patients usually report slowed information processing and impaired psychomotor functioning in more general terms as overall mental fatigue or slowed thinking (Constant et al., 2011; Larun and Malterud, 2007). In more severe cases, patients have difficulty completing tasks that require sustained attention and report problems performing even relatively simple activities such as watching television (FDA, 2013). Studies of the exact nature of neurocognitive deficits reported by patients with ME/CFS have shown that some patients meeting various current criteria for ME/CFS have different or more severe impairments than others, but also that self-reported severity of impairments is not always associated with severity based on objective measures (Cockshell and Mathias, 2013)."

 

[Nielk]

I'm a little late to this discussion but I guess I don't understand why one would "feel frozen out of IOMs disease" - the IOM report ("Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness") includes extensive discussion of neurocognitive manifestations in ME/CFS (from page 96 to 107 of the report); autonomic dysfunction is discussed from p 107 - 118; pain is discussed p. 141-147; sleep is discussed p. 86-96; headache is discussed in multiple places (use the search function to go through the PDF) . The report also acknowledges many patients experience pain (they just didn't list pain as a core symptom - Lucinda Bateman discusses this in some of her talks about the criteria; see video linked in this thread http://forums.phoenixrising.me/inde...an-new-webinar-iom-diagnostic-criteria.36945/ ) Since the quote above italicizes the neurocognitive symptoms, I'll quote the report for them.

page 96 says the following:
"Impairments in cognitive functioning are one of the most frequently reported symptoms of ME/CFS. Patients describe these symptoms as debilitating and as affecting function as much as the physical symptoms that accompany this disease. During a survey of ME/CFS patients, descriptions of neurocognitive manifestations included, among others, “brain fog,” “confusion,” disorientation,” “hard to concentrate, can’t focus,” “inability to process information,” “inability to multitask,” and “short-term memory loss” (FDA, 2013). The short-term memory problems of ME/CFS patients include difficulty remembering something they just read. Patients usually report slowed information processing and impaired psychomotor functioning in more general terms as overall mental fatigue or slowed thinking (Constant et al., 2011; Larun and Malterud, 2007). In more severe cases, patients have difficulty completing tasks that require sustained attention and report problems performing even relatively simple activities such as watching television (FDA, 2013). Studies of the exact nature of neurocognitive deficits reported by patients with ME/CFS have shown that some patients meeting various current criteria for ME/CFS have different or more severe impairments than others, but also that self-reported severity of impairments is not always associated with severity based on objective measures (Cockshell and Mathias, 2013)."

I agree that the report itself (without the resulting criteria and name) is pretty extensive and covers a lot.

page 96 says the following:
"Impairments in cognitive functioning are one of the most frequently reported symptoms of ME/CFS. Patients describe these symptoms as debilitating and as affecting function as much as the physical symptoms that accompany this disease. During a survey of ME/CFS patients, descriptions of neurocognitive manifestations included, among others, “brain fog,” “confusion,” disorientation,” “hard to concentrate, can’t focus,” “inability to process information,” “inability to multitask,” and “short-term memory loss” (FDA, 2013).

Yet, when it comes to the criteria itself, cognitive impairment is not even demanded for a diagnoses, it is just a choice.

 

[duncan]

Unfortunate that these IOM quotes reference "patient reports" or patient descriptions about neuro-cognitive issues, as opposed to any references to studies demonstrating such.

Potentially ratchets down the importance of these reports or descriptions, while appearing to address them sincerely, at least imo.

 

[Research 1st]

Abnormal neurological findings, no matter how robust, do not necessarily equate to 'encephalomyelitis'.

Well yes and no.

It's all a matter of semantics at this point. Without a diagnostic test and excluding the severely affected from research
the two combine to hardly be able to find much at all, neurologically (TILT test is still not used to show dysautonomia is wide spread in CFS).

So indeed a classic encephalomyelitis isn't found, but low grade chronic encephalitis is.

If novel is not classic.. is the item in question (low grade) excluded from the same designation? Well no.

ME has neuroinflammation, the dead patients have neuroinflammation, the brain scans show neuroinflammation and the brain can shrunk - a sign of neuroinflammation/oxidative stress.

Thus ME is a reasonably accurate term, far more accurate than SEID or CFS.
Dr Komaroff (Harvard medical school) explained this all in his talk last year, which you may have misse?
I don't know if you missed it, so here is the 'ME' part.

Komaroff was asked if neuro-inflammation was not encephalomyelitis, to which he replied: “Yes. If it were confirmed by multiple other investigators it would, for me, say that there is a low-grade, chronic encephalitis in these patients, that the image we clinicians have of encephalitis as an acute and often dramatic clinical presentation that can even be fatal has – may have – blinded us to the possibility that there may be an entity of long-lasting – many years long – cyclic, chronic, neuro-inflammation and that that underlies the symptoms of this illness”, commenting that it was“entirely plausible and these data are consistent with it”.

Source: http://www.meactionuk.org.uk/Komaroff-Summary-San-Francisco-March-2014.htm

I would agree that to claim CFS = low grade 'ME' is absurd considering the diagnostic criteria is a joke but that doesn't mean that a significant percentage of ME within ME, really won't be ME - all be a newly accepted form of an encephalomyelitis.

 

[Marco]

Thus ME is a reasonably accurate term, far more accurate than SEID or CFS.
Dr Komaroff (Harvard medical school) explained this all in his talk last year, which you may have misse?
I don't know if you missed it, so here is the 'ME' part.

No I didn't miss it - just disagreed.

Do these findings then finally validate the name Myalgic ‘Encephalomyeltis’ thereby consigning ‘chronic fatigue’ to the historical dustbin? My view is that they do not – but they may pave the way to a better and more productive understanding of the underlying pathology of what is likely to be a heterogeneous disorder. The crux of the problem lies in the framing of the historical debate between users of the terms ME and CFS and in the nature of neuroinflammation.

Read more: Neuroinflammation: Putting the ‘itis’ back into Myalgic Encephalomyelitis – Back to the Future For Chronic Fatigue Syndrome? http://www.cortjohnson.org/blog/201...yelitis-back-future-chronic-fatigue-syndrome/

 

[Research 1st]

I'm confused.

You're saying that you don't agree with Tony Komaroff that CFS patients who display the brain abnormalities have a Myalgic Encephalomyelitis that science missed?

As that is what I quoted below regarding the 'ME' in CFS, not my views, but Dr Komaroff's.

Komaroff was asked if neuro-inflammation was not encephalomyelitis, to which he replied: “Yes. If it were confirmed by multiple other investigators it would, for me, say that there is a low-grade, chronic encephalitis in these patients, that the image we clinicians have of encephalitis as an acute and often dramatic clinical presentation that can even be fatal has – may have – blinded us to the possibility that there may be an entity of long-lasting – many years long – cyclic, chronic, neuro-inflammation and that that underlies the symptoms of this illness”, commenting that it was“entirely plausible and these data are consistent with it”.

Can you expand on why you feel Dr Komaroff is incorrect?

 

[Marco]

I'm confused.

You're saying that you don't agree with Tony Komaroff that CFS patients who display the brain abnormalities have a Myalgic Encephalomyelitis that science missed?

Can you expand on why you feel Dr Komaroff is incorrect?

Yes I'm saying that I don't agree with Komaroff's conclusions for the reasons I set out in the article.

To summarise, physicians are fairly clear what they mean when talking about encephalitis (including encephalomyalitis) - an acute inflammation of the brain following some insult (viral, baterial, autoimmune) where swelling/tissue damage or infection is apparent via MRI, EEG, lumbar puncture etc.

What the Japanese study found suggested chronic (by definition in a CFS cohort) activation of brain resident microglia without obvious swelling or tisssue damage which can be loosely described as 'neuroinflammation'. You could argue that any inflammation is an 'itis' but it's clearly not the same thing as encephalitis.

Even the term neuroinflammation is problematic as it is used even by those working in the field to describe processes proposed to be active in a range of conditions from stress and depression (low grade, possibly transitory microglial activation) to Alzheimer's/Parkinson's (more pronounced chronic activation which results in irreversible tissue damage).

We really need to be specific what we are talking about :

We thus propose the use of the terms “increased neurokine signaling” or “increased central immune signaling” to apply to these sub-inflammatory states, and only when there is large-scale damage as a result of immune cell derived neurotoxicity and inflammation should the term “neuroinflammation” be applied in order to reduce confusion within the literature.

http://forums.phoenixrising.me/inde...-central-immune-signalling.39736/#post-638349

It's not just a matter of semantics. Continuing to use the term encephalomyelitis inappropriately has consequences. As I said in the article, the absence of evidence of encephalitis plays into the hands of those who would prefer to deny any physical basis to the illness. Secondly the terms is (was) likely to lead researchers up the garden path looking for the putative causes of encephalitis whether viral, bacterial or whatever. This hasn't been a fruitful line of enquiry to date.

I can appreciate the attraction of wanting to use these findings as support for putting the 'itis' back into ME but much better I think to accept the findings for what they are rather than what we would like them to be.

 

[snowathlete]

Yes I'm saying that I don't agree with Komaroff's conclusions for the reasons I set out in the article.

To summarise, physicians are fairly clear what they mean when talking about encephalitis (including encephalomyalitis) - an acute inflammation of the brain following some insult (viral, baterial, autoimmune) where swelling/tissue damage or infection is apparent via MRI, EEG, lumbar puncture etc.

What the Japanese study found suggested chronic (by definition in a CFS cohort) activation of brain resident microglia without obvious swelling or tisssue damage which can be loosely described as 'neuroinflammation'. You could argue that any inflammation is an 'itis' but it's clearly not the same thing as encephalitis.

Even the term neuroinflammation is problematic as it is used even by those working in the field to describe processes proposed to be active in a range of conditions from stress and depression (low grade, possibly transitory microglial activation) to Alzheimer's/Parkinson's (more pronounced chronic activation which results in irreversible tissue damage).

We really need to be specific what we are talking about :



http://forums.phoenixrising.me/inde...-central-immune-signalling.39736/#post-638349

It's not just a matter of semantics. Continuing to use the term encephalomyelitis inappropriately has consequences. As I said in the article, the absence of evidence of encephalitis plays into the hands of those who would prefer to deny any physical basis to the illness. Secondly the terms is (was) likely to lead researchers up the garden path looking for the putative causes of encephalitis whether viral, bacterial or whatever. This hasn't been a fruitful line of enquiry to date.

I can appreciate the attraction of wanting to use these findings as support for putting the 'itis' back into ME but much better I think to accept the findings for what they are rather than what we would like them to be.

Completely agree with this. It isn't that there isn't any inflammation in the brain or spinal cord necessarily, it is about recognising what encephalomyalitis means to people in medicine. Many diseases show inflammation in the brain but no one would think to name such a disease encephalomyalitis as a result of possible low grade inflammation unless it was to such a degree that the term would be proven appropriate.

The evidence to date is not enough to justify calling our disease encephalomyelitis. I've yet to see anyone put together a compelling case on existing evidence. That doesn't mean there might not be a some out there with a diagnosis of ME or CFS or something else who do have encephalomyelitis (and though I don't believe it - conceivably we all could have). But I have not heard of many proven cases, and without evidence you aren't on solid ground and risk bringing the disease into further disrepute if you try to argue the case for encephalomyalitis too seriously.

Personally I don't think true encephalomyalitis will ever be proven, I don't think it's accurate in our disease and think the ultimate answer to what our disease is, and how to treat it, will be found through research into other areas.

But if I did believe it then rather than trying to argue the point on current evidence (which I consider futile due to a lack of evidence) I'd do what I could to set up studies to find the required evidence of encephalomyelitis - anyone doing something like this? Without the evidence it's not possible to convince medicine/science that the term ME is accurate.

 

[ScottTriGuy]

...

But if I did believe it then rather than trying to argue the point on current evidence (which I consider futile due to a lack of evidence) I'd do what I could to set up studies to find the required evidence of encephalomyelitis - anyone doing something like this? Without the evidence it's not possible to convince medicine/science that the term ME is accurate.

I think the research should be focused on the cause of our symptoms - I feel that 'convincing' encephalomyelitis to medicine/science is a less helpful approach.

 

[Snow Leopard]

I think the research should be focused on the cause of our symptoms - I feel that 'convincing' encephalomyelitis to medicine/science is a less helpful approach.

Exactly. The name is just a placeholder until we have a better understanding of this disease.

 

[Gijs]

Maybe low bloodflow to the brain is causing microglia activation?

 

[Snow Leopard]

Maybe low bloodflow to the brain is causing microglia activation?

Seems rather vague.

 

[Gijs]

Seems rather vague.

Why? Low bloodflow, less oxygen and energy... damaging tissue, white- grey matter, neurons.... microglia try to repair and clean it up.... they are the macrophages of the brain....

 

[Research 1st]

You're correct Gijs.

However, may I suggest I think the low blood flow isn't causing microglial activation, it's a product of it? I can't prove this but I think it's possible also.

As for a reason to the low blood flow? Elevated lactate in the brain can alter blood flow. (We know 'CFS' has multiple high brain lactate studies). The culprit is likely infection, infection mediated autoimmunity leading to this brain cell inflammation (glial cells).

The recent acetylcholine autoantibody research from Norway, demonstrates an an autoimmune autonomic neuropathy. These patients don't have a CFS, they have an brain autoimmune disease. Dr Bell found brain autoimmunity years ago, as did a Japanese study (acetylcholine autoantibodies in 'CFS' patients). Muscaranic
or Nicotinic receptor, I forget.

So what does this lead to?

Well, as Fukuda CFS is based on unexplained chronic fatigue, then these brain autoimmunity patients are more likely ME patients in my opinion. For the sake of argument in this reply, I will call them ME, so I can link to the following:

In ME:
Something is screwing up the mitochondrial metabolism of the body, so the brain has no energy as it requires
huge amounts of ATP to function correctly. ME sufferers report they feel dreamy or drunk at rest with poor cognitive function. (This doesn't just affect our brains it affects our muscles, such as our hearts). However, I'll just debate neuroinflammation with you all so we keep on topic.

In ME:
When we then actively use our exhausted at rest brains by thinking (intellectually is the worst) we develop visible signs of neurological dysfunction (rather than symptoms) that are clearly a central nervous system reaction and cannot be simulated - which psychiatrists would like to suggest and have done in the past with MS - MS was called 'Hysterical Paralysis'.

In ME:
The post exertional relapse in ME is not a ''malaise'' as in Fukuda CFS. A malaise is a feeling.
In ME these are neurological signs that can be witnessed by a doctor to be recorded as 'real'. Signs are what differentiates CFS from ME, but signs of ME are not required to be diagnosed with CFS, CFS/ME, or CFS CCC.

Here are some classic post exertional neurological signs (not symptoms, signs) from extensive brain use in ME.
I've removed cardiac/breathing to stay on topic. I get these a lot using this forum, and it takes me a long while to think and I am always 'out smarted' by people on here, as I struggle to 'think' and spend hours sometimes formulating a reply as the more I think, the more symptoms I get.

Weakness in fingers/hands if doing manual work such as typing, sewing (fine motor dysfunction).
Involuntary twitching of fingers, or other body parts, such as the face.
Sensory neuropathy worsening (biting sensation on skin, burning, etc).
Onset of worsening photophobia
Onset of worsening hyperacusis
Onset of Facial Palor
Vertigo/Dizzyness
Eyelid Twitching
Eyeball involuntary movement
Sluggish pupils
Stammer
Confusion/Sudden onset short term memory loss.
Feeling overly hot or cold.
Itching.

NB: None of the above Post Exertional Signs of ME are DETECTED or REQUIRED in CFS, CFS/ME, CFS CCC, & SEID. Lack of neurological signs are very important to remember when Dr Lipkin/Dr Hornig cannot find infection in CFS (which they call ME/CFS!), and cannot find Cytokine inflammation either after 3 years. Yet Dr Montoya and others can (e.g. Dr De Meirleir, Dr Klimas, Dr Peterson, Dr Kogelnik etc) and patients who test privately can too.

So what if people said by black bold text is hysterical and the ME patients are somehow making their neurotic fear of 'thinking' make their bodies react adversely to neurological exertion? I would respond that Parkinson's patients also neurologically burn out, as in ME, by 'thinking', by using their ATP.

This study is thus of interest, that shows that a brain area had low CO-Q10 in Parkinson's. Other research
has also pointed to Parkinson's disease being a problem with Mitochondria.

Hargreaves IP, Lane A, Sleiman PM. The coenzyme Q10 status of the brain regions of Parkinson's disease patients. Neurosci Lett. 2008 December 5;447(1):17-9.
Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, UK.
Abstract: http://www.ncbi.nlm.nih.gov/pubmed/18840506
Paywall: http://www.sciencedirect.com/science/article/pii/S0304394008013426

So the idea of an exhausted brain that 'works', then is affected by exertion (classic sign of ME) it's not a whack idea or belief of ours (that needs CBT GET), it's happening to us and its real, we just don't know why yet.

It seems possible a lack of brain nerve cell cellular energy increases inflammation (and/or is impaired already by inflammation), as we recover, if we rest,it reduces.

How long this takes, depends on how affected you are at the time, and how severe your disease is. The 'payback' can also fluctuate massively, irrespective of pacing yourself. That is the nature of the beast unfortunately.

In ME: using our brains battery cells, causes a central nervous system effect patients can demonstrate.
In CFS, this is not required to be shown, or to be experienced. All that is required is self report of 'FATIGUE'.
FATIGUE cohorts, stymie inflammatory ME research. Hence the British love it and SEID allows for it.

 

[Sing]

I am very slow too Research 1st just as you described how you are too with intellectual work. I have the neurological signs and symptoms, also a lot of dysautonomic ones.

What frustrates me most about the research that is being proposed or getting done is how little of it is neurological. The illness I have--ME--is primarily neurological. I think so much progress could be made if the money went to neurological studies for awhile instead of just more projects looking for viruses, genes or the hypothetical original causes--the old line of attack-- or else whatever the latest fad is in the new form of attack. Why can't researchers just get a grip and keep pursuing the study of our brains and neurological systems? I wish they would because like a lot of people here, I have had this for a long time, and with aging, the downhill slide is picking up speed (the only thing fast about me these days).

The only thing that cheers me now is the idea that our situation would make a good Off Broadway show--a bunch of interesting, varied people who have waited all their lives for medical research to help--in an era of tremendous technological innovation and scientific discovery--yet here we still are on the sidelines still waiting. Our stories and conversations are so interesting and valuable even if "the world" outside continues on oblivious. I think this show ought to be named, "Oblivion", in case we have any Broadway producers and playwrights reading.

 

[perrier]

I am very slow too Research 1st just as you described how you are too with intellectual work. I have the neurological signs and symptoms, also a lot of dysautonomic ones.

What frustrates me most about the research that is being proposed or getting done is how little of it is neurological. The illness I have--ME--is primarily neurological. I think so much progress could be made if the money went to neurological studies for awhile instead of just more projects looking for viruses, genes or the hypothetical original causes--the old line of attack-- or else whatever the latest fad is in the new form of attack. Why can't researchers just get a grip and keep pursuing the study of our brains and neurological systems? I wish they would because like a lot of people here, I have had this for a long time, and with aging, the downhill slide is picking up speed (the only thing fast about me these days).

The only thing that cheers me now is the idea that our situation would make a good Off Broadway show--a bunch of interesting, varied people who have waited all their lives for medical research to help--in an era of tremendous technological innovation and scientific discovery--yet here we still are on the sidelines still waiting. Our stories and conversations are so interesting and valuable even if "the world" outside continues on oblivious. I think this show ought to be named, "Oblivion", in case we have any Broadway producers and playwrights reading.

Yesterday a doctor told me this was all psychosomatic. I'm just devastated again.

 

[ScottTriGuy]

Sorry you are being traumatized again by the medical system.

I 'out' these charlatans on this Rate my Doctor site:
https://www.ratemds.com/

Others should be aware of the harm that doctor does to patients through ignorance and arrogance.

 

[SOC]

Yesterday a doctor told me this was all psychosomatic. I'm just devastated again.

I'm tempted, the next time some doctor pulls that one on me, to leap up pointing an indignant finger and scream, "Gaslighting!" S/he already thinks I'm nuts, so no harm done to me , the doc might be embarrassed, and it might be cathartic.

 

[alex3619]

Without the evidence it's not possible to convince medicine/science that the term ME is accurate.

This is the crux of the issue. It will never be accepted on current evidence. It would require much stronger evidence to be demonstrated that encephalomyelitis is accurate.

The world of medicine, today, seems to be largely dominated by tickbox evidence based methodology. While provisions exist within EBM to address these issues they are notable in their absence in nearly all studies.

ME is still the best label, largely because of the diagnostic criteria and not the word "encephalomyelitis" itself.

On autopsy data, not every ME patient, if I recall correctly, shows neuroinflammation. I think it was one in four? There is better data in the one animal study, but sadly all such studies are tiny ... they will be automatically rejected in today's scientific climate.

One of the big banes of ME research is a half century lack of funding. Many comparable diseases, in terms of societal impact, get more funding per year then has ever been given to ME. We might have more and better data, to confirm or refute the encephalomyelitis label, if there had actually been adequate research done.

More to the point, with large well designed studies we would have better data, and probably move beyond an ME label in time. At some point it would probably be replaced by something more appropriate.

Whether SEID is that something is extremely debatable, and I think at best its merely another throwaway label. At worst it, and the diagnostic criteria, will be misapplied and lead to misinterpreting the evidence. To be fair though, with the current state of medical education on this topic I think most doctors would misinterpret and misapply every definition we have, including the ME ones, should they get around to using a stronger diagnostic definition.