NIH intramural research program update

[Sasha]

A few quick notes about the CDC Grand Rounds event today:

--Great to reconnect with Drs. Lapp and Komaroff again, as well as Wilhelmina Jenkins, after first meeting them while filming.

--Event was much better attended than the last CDC CFS-related event I attended which was across the street at Emory University's Rollins School of Public Health...This was partly because the event offered CEU's and was part of the established Grand Rounds system...nonetheless, many reflected on how simply getting this disease into Grand Rounds was a big success and reflected greater attention for ME/CFS.

--Our team had e-mailed CDC ahead of time to give them information about the film. They circulated the e-mail among the organizers, and CDC staffers approached me saying they had watched the trailer and were interested to hear more.

--Was able to give Forgotten Plague DVDs to all four presenters (Nath, Komaroff, Lapp, and Unger). Also gave one to CDC Grand Rounds organizers. All were very gracious.

--got to speak with Dr. Unger just briefly about the activities of the Blue Ribbon Fellowship program we've set up with Klimas and Kogelnik as well as getting CME course credits around Forgotten Plague (the film is approved already for nursing and social worker CEUs).

--Dr. Nath, the newcomer to the field, seems a man of integrity and industrial-strength intellect. His comments about listening to patients instead of textbooks were well-received. Listening to patients is an idea championed by renowned scholar William Osler in the 19th century, and which is gaining more credence again in the 21st century. He seems particularly open to hearing from patients and said he'd be happy to have me at NIH to show what they're doing.

--My previous ME/CFS event with CDC had dismal attendance and had lifted up some of the older bad research that had been conducted in previous decades. I had left depressed. Today was much different. Grand Rounds attracted a crowd. There was a sense that real science is going on, and I left with positive feelings.

https://www.facebook.com/CFSDocumen...661299431396/1093285210702333/?type=3&theater

 

[Sean]

Simon Wessely is indeed quoted extensively, from his article Old wine in new bottles: neurasthenia and “M. E.”. Psychol. Med. 20, 35–53 (1990).

That would be the same article and lecture, IIRC, that he conveniently forgot about when recently asked on Twitter if he had ever said ME was just a mental construction, nothing more than the idea of ME, (or words to that effect). IOW, a purely psychosocial construction.

 

[luludji]

I am sorry, but I have the feeling that the proposed research is only touching the surface and misses the real nature of ME. I may be wrong, and my worries may be caused by language problems and lack of medical knowledge.

For example I would have liked to see a bigger focus on the immune system and autoimmunity, and not on the part of virus hunting.

But especially on the area of the brain I miss insight in the presumed pathology.
"Our hypothesis is that Post infectious ME/CFS is triggered by a viral illness that results in immune-mediated brain dysfunction..."
Well, do we have brain dysfunction? Which maybe gives the wrong signals of being tired? I don't think so. I rather think there is brain pathology. We have a form of inflammation of the brain, activated microglia and astrocytes (or whatever). And which causes real damage to the brain. Dysfunction is a result of pathology. Or do I misunderstand the concept of dysfunction?

"Aim two of the study is to define the physiological basis of fatigue using functional MRI scan of the brain to define the brain circuits that are involved."
Again, why looking at the physiological basis of fatigue where one should look at the pathophysiology of ME? Nakatomi did.
After establishing the illness one can look at the dysfunction it causes, not the other way round. It seems to me that this kind of research will not lead to curing the illness, but merely to influence the symptoms.
Or is it medical semantics where I go wrong?

 

[roller]

After establishing the illness one can look at the dysfunction it causes, not the other way round. It seems to me that this kind of research will not lead to curing the illness, but merely to influence the symptoms.

exactly.
and their patient treatment is accordingly, but even this is just based on rough guesses: meds for hormones, neurotransmitters.. instead of looking for the cause.

medicine seems a parallel world, which works inverted to all logic.
ignoring nature and the world we actually live in.

 

[Scarecrow]

Brian Walitt video: Fibromyalgia doesn't fit the disease model (9 minutes)

http://www.familypracticenews.com/s...e-model/e913134880916685f3005dac5459ab88.html

 

[MeSci]

I don't think there's a mouse model.

They will inject cerebrospinal fluid and antibodies into normal and humanized mice, to see if they become sick.

My understanding is that the humanized mice are obtained by essentially transplanting the immune system from patients into mice.

Non-human animals will never be sufficiently humanised to respond or behave in the same way as humans, as many researchers acknowledge. Findings from such research simply lead down blind alleys, delay progress and harm patients (and sometimes trial volunteers).

The animal 'model' paradigm persists because it has become the norm, and funders accept and require it. Maybe if they used elephants the irony would become clearer.

 

[Valentijn]

Other papers from Dr Brian Walitt:

• Increased Brain White Matter Axial Diffusivity Associated with Fatigue, Pain and Hyperalgesia in Gulf War Illness - Brain abnormalities found in GWS/CFS patients, used to explain pain, fatigue, etc.

  Central sensitization mechanisms that alter the spinal cord dorsal horn gating of pain transmission lead to increased perceptions of pain after an aversive, physical stimulus such as cutaneous pressure (hyperalgesia) or an innocuous stimulus such as light touch (allodynia) [21], [22]. These molecular events may sensitize prefrontal regions of the brain’s “pain matrix” leading to structural and functional reorganization associated with chronic symptom complaints [23].

• What Is Fibromyalgia, How Is It Diagnosed, and What Does It Really Mean? - They seem to endorse the Per Fink theory of bodily distress disorder, with FM, CFS, IBS, etc all being the same disorder and cite to him:

  Not a clearly defined entity? So how should we think about fibromyalgia? In the rheumatology literature, fibromyalgia has often been characterized as a specific pain disorder. But it is not seen that way in the broader medical community and literature, where it is looked upon as a type of functional somatic syndrome. Danish investigators characterize fibromyalgia as a bodily distress syndrome, along with chronic fatigue syndrome, irritable bowel syndrome, and similar disorders, because they share a common set of symptoms ([6]).

  And more symptoms = more severe presumed psychosomatic disorder:

  Using a PHQ-15 “moderate” cutoff of 10, a level suggested as consistent with a somatoform disorder ([9]), 89% of 2010 criteria–positive patients had scores ≥10 (moderate or severe somatic symptom severity) ([10]).

  Results on brain scans are probably just reflecting the psychosomatic illness:

  Studies using functional magnetic resonance imaging and similar tools that purport to give insights about fibromyalgia may be tapping into the wider domain of functional and psychological disorders ([12]). Central sensitization, hailed as a biologic marker of fibromyalgia, turned out to be found in almost all painful conditions ([13-15]).

  And finally:

  Most fibromyalgia patients meet criteria for other functional somatic syndromes and psychological disorders ([16]),

• Gene expression profiles of fatigued fibromyalgia patients with different categories of pain and catastrophizing - Honestly, the title says it all. Genes don't cause symptoms, they cause you to think you have symptoms! But anyway:

  The symptom experience of individuals with FM is thought to be influenced by both physiological and psychological factors.

• Chemobrain: A critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy - Exploring why people apparently incorrectly believe they have neurocognitive dysfunction after chemo:

  Repeated studies on the effects of chemotherapy have been unable to demonstrate cognitive impairment after treatment [12–20]. Studies that have shown cognitive impairment, both cross-sectional [21–24] and longitudinal [25–28], demonstrate that the impairment is modest, of unclear clinical significance, and correlates poorly with the severity of the subjective experience of chemobrain.

  Could it be that the wrong tests are being used, and those positive results being dismissed are relevant after all? Of course not :

  However, it seems likely that the discordance between subjective dyscognition and objective impairment is a defining observation of the nature of chemobrain rather than simply being a measurement artifact.

  So what is causing their subjective symptoms? Ooooh, must be psychosomatic:

  Another important feature of chemobrain is its common, but not mandatory, relationship to several somatoform symptoms, in particular anxiety, depression and fatigue, and overall health-related decline [33]. The clinical picture of chemobrain is that of a patient developing a distressing and often disabling alteration in their subjective cognitive abilities that is difficult to objectively demonstrate and is temporally related to both the biological and psychological consequences of cancer chemotherapy.

  Bit of a side note, but interesting that in 2015 he still doesn't acknowledge the prospective studies confirming an infectious cause of ME/CFS:

  Both of these illnesses have disputed causal triggers, such as trauma in fibromyalgia and infection in chronic fatigue syndrome, whose validity is also not answered by the scientific literature to date.

  And here's the smoking gun for @viggster and/or anyone who still thinks this guy isn't a full-blown psychobabbler ready and eager to wreak havoc upon ME/CFS:

  The discordance between the severity of subjective experience and that of objective impairment is the hallmark of somatoform illnesses, such as fibromyalgia and chronic fatigue syndrome.

  But it's all okay, because:

  We emphasize that viewing chemobrain as a somatoform illness does not undermine its clinical legitimacy or trivialize the patient suffering that comes with it. All human experiences are psychosomatic ones whose existence is dependent on discoverable physiological mechanisms that are potentially susceptible to therapeutic manipulation.

• PTSD and Fibromyalgia Syndrome: Focus on Prevalence, Mechanisms, and Impact - A biopsychosocial (BPS) paper, which starts with this lovely and oddly familiar chart clarifying that there is only psychological reasons for FM symptoms to continue:
  

These are just from the 8 studies which mentioned CFS. I'm sure there's plenty of other bad stuff. Searching on Google Scholar for "author:brian walitt" and "neurasthenia" might also bring up something of interest.

But it's clear that he strongly believes in psychosomatic disorders, approves of the BPS model, suggests that many (all?) of these disorders are basically the same thing, and that any biological results are probably the result of the psychosomatic disorder (not the cause) or that they contribute to a psychosomatic disorder, never a biomedical one. The major difference between Walitt and the typical ME/CFS psychobabblers is that Walitt's musings regarding treatments are largely or entirely biological.

He should not be involved in any ME/CFS study, especially in a lead position. I also want to know who put him there, and why.

 

[Valentijn]

That would be the same article and lecture, IIRC, that he conveniently forgot about when recently asked on Twitter if he had ever said ME was just a mental construction, nothing more than the idea of ME, (or words to that effect). IOW, a purely psychosocial construction.

I don't think I'd seen it before, so I downloaded a copy (probably from sci-hub) to take a closer look. Not really relevant to this thread though

 

[Cheshire]

A few slides and extract from the video @Scarecrow provided a link to. Very telling.

about what narrative is to be told to the patient:

The problem is that language is so heavily charged. People are not willing to accept the idea that our emotions affect our sensations, the idea that mind itself is able to create these things and that all experiences are psychosomatic experiences.

Fibromyalgia appears to be a way that people experience suffering in their body both from the way that their bodies are interpreting problems of the body as well as the problems in their lives as well as how society tells us how to experience things. All that come together to create a unique experience in different points and times [...] Is it a disease or a normal way that we handle and are supposed to work is still to be determined. But it's just possible that tricky way that the brain works is that we may create symptoms as part of the way we are supposed to operate as opposed to a person representing the system breaking down.

cc 8.00

 

[Bob]

Hi everyone-
We just put up a transcript of the talk along with @Kati's screenshots at http://www.meaction.net/2016/02/16/transcripts-and-slides-from-dr-naths-talk-on-nih-study/. Please let me know if you see any issues. Thanks to @Kati for the screenshots and @mango for making an audio recording which I did not have the foresight to do!

Wow! That's great! Thanks for organising this, searcher.

Also, thanks for sorting the sides, @Kati.

And thanks, @mango, for the audio.

And thanks to anyone else who contributed.

A great team effort!

Edit: found it at the end of the Q&A and will add it in

Does anyone remember where the 1500 lysates/analytes came up? I remember it but I don't think it was during the main talk. Was it during q&a? Do you remember @Forbin?

I noticed yesterday that there was some interesting info in the Q&As. Worth listening to those as well as the main presentations.

 

[Cheshire]

Surprisingly, Dr Walitt's critique of the central sensitization theory is worth reading...

Proponents of the popular central sensitization analogy have put forward five types of evidence – psychophysical, neuroimaging, genetic, neurotransmitters, and treatments – to support their view, but Dr. Walitt said that the evidence is weak, doesn’t prove anything, or seem legitimate. For instance, none of the treatments for fibromyalgia are particularly effective, at best giving a minimally clinically important difference that does not change patient outcomes.

Another issue with the analogy is that it is not possible to disprove the hypothesis. Any central nervous system measurements that correlate with differences in subjective pain reports can be presented as “mounting evidence” but not definite proof, he said. If the idea was changed from amplification of pain signals to distortion, the same data could be used to prove that, too. “Distortion is also bogus. It’s just another idea, another way of talking about it that shows that whatever you pick you can find ways to make a story that fits all the data,” Dr. Walitt said. However, analogies can be powerful, particularly if they wash away the complexity and difficulty in understanding neuroscience.

http://www.rheumatologynews.com/spe...analogy/1ef25b80b204de77f900184dbfa3ff79.html

If only he could apply his scepticism to his own theory...

It's very worrisome, I agree with @Valentijn this guy shouldn't be involved.

 

[Bob]

I am sorry, but I have the feeling that the proposed research is only touching the surface and misses the real nature of ME. I may be wrong, and my worries may be caused by language problems and lack of medical knowledge.

For example I would have liked to see a bigger focus on the immune system and autoimmunity, and not on the part of virus hunting.

But especially on the area of the brain I miss insight in the presumed pathology.
"Our hypothesis is that Post infectious ME/CFS is triggered by a viral illness that results in immune-mediated brain dysfunction..."
Well, do we have brain dysfunction? Which maybe gives the wrong signals of being tired? I don't think so. I rather think there is brain pathology. We have a form of inflammation of the brain, activated microglia and astrocytes (or whatever). And which causes real damage to the brain. Dysfunction is a result of pathology. Or do I misunderstand the concept of dysfunction?

"Aim two of the study is to define the physiological basis of fatigue using functional MRI scan of the brain to define the brain circuits that are involved."
Again, why looking at the physiological basis of fatigue where one should look at the pathophysiology of ME? Nakatomi did.
After establishing the illness one can look at the dysfunction it causes, not the other way round. It seems to me that this kind of research will not lead to curing the illness, but merely to influence the symptoms.
Or is it medical semantics where I go wrong?

I think you raise some interesting questions, but my understanding is that there is a heavy immune-focus in this study. They seem very interested in the neurologic aspects of the illness, but I don't think we should complain about that. MRI scans have previously demonstrated abnormalities. The hypothesis that you highlighted: "immune-mediated brain dysfunction", covers both immunology and neurology, which seems like a sensible comprehensive approach, covering both angles. I've always thought that ME is more immunological than neurological, but I don't object to them looking for brain abnormalities. ME is categorised as neurological by the ICD-10, and plenty of patients complain of neurological issues, and the study is being led by NINDS. But there is also a very heavy focus on looking for immune abnormalities, using a sophisticated technology, which I'm very happy about.

If you look at the "Aim 3" slide, it covers a huge and comprehensive immunological investigation. The abbreviated/shortened descriptions of the methodology make it look less impressive than it is, but when it's explained in full, I think it should look very impressive.

 

[ScottTriGuy]

Brian Walitt video: Fibromyalgia doesn't fit the disease model (9 minutes)

http://www.familypracticenews.com/s...e-model/e913134880916685f3005dac5459ab88.html

I had to stop watching that video of Walitt. There is only so much psychobabble bullshit I can handle.

My confidence in the NIH study just took another big hit.

 

[duncan]

Walitt isn't the only one, I fear.

It may be a good exercise to look a little closely at each of the Associate Investigators.

 

[Valentijn]

Walitt isn't the only one, I fear.

It may be a good exercise to look a little closely at each of the Associate Investigators.

Yeah, but my brain's fried after just doing a bit of Walitt. Maybe people can say who they're looking into (one at a time) so we don't up being redundant and burning out before getting to the end of the list.

I took a preliminary look at Nath himself a few days ago, and he didn't look dodgy.

 

[TiredSam]

Surprisingly, Dr Walitt's critique of the central sensitization theory is worth reading...


http://www.rheumatologynews.com/spe...analogy/1ef25b80b204de77f900184dbfa3ff79.html

If only he could apply his scepticism to his own theory...

It's very worrisome, I agree with @Valentijn this guy shouldn't be involved.

x3.

Interesting to note that despite my anxiety about a potential catastrophe, I'm having a fairly symptom-free day.

 

[Yogi]

Let's crowdsource it and systematically go through them.

We know Ian Lipkin is good as gold- no need there.

We should all probably have a look at Avi Nath and Brian Walitt given importance.

Unger is already known about it.

As @Valentijn says Walit is a concern. Fred Gill is also a big concern.

There are 28 names. If we all take two each then we need 14 volunteers.

I will take Acevedo and Cohen.

Anyone else up for it. We can then report back if there are any serious concerns that need to be fed back.

 

[Cheshire]

Carine Mauder:

Neurologist. Involved in a few research projects in neurology. https://www.doximity.com/pub/carine-maurer-md
Two seem interesting for us:
- Neurobiology of Psychogenic Movement Disorder and Non-Epileptic Seizures currently recruiting participants. (project dates back 2007) https://clinicaltrials.gov/ct2/show/NCT00500994
- A biological measure of stress levels in patients with functional movement disorders http://www.prd-journal.com/article/S1353-8020(15)00267-9/fulltext

Introduction
While the presence of co-existing psychological stressors has historically been used as a supportive factor in the diagnosis of functional neurological disorders, many patients with functional neurological disorders deny the presence of these stressors. The stress response circuitry in these patients remains largely unexplored.

Results
Patients with functional movement disorders did not differ from matched controls with respect to levels of circulating cortisol.

Conclusion
We demonstrate that current stress levels are not altered in patients with functional movement disorders. Our results warrant careful review of current management of patients with functional neurological symptoms, and suggest that the insistence on heightened stress levels in these patients is unjustified.

 

[duncan]

I will cover Marques.

@Valentijn , I didn't mean to suggest you should look up the others. I think everyone will agree you and @Cheshire and @Snow Leopard researched Walitt in a beautifully thorough fashion.

 

[Bob]

I've just read the transcript and the NIH's ambitions for this study are much larger and broader in scope than I realised. Dr Nath's presentation only covered phase I of the study, and there are three phases. I think this may be a $15 to $20 million project. Ultimately, for phase iii of the study, they aim to test biological treatments in a full scale medical trial. I recommend, to everyone who's interested in this, that you should read the transcript. And it helps to read it carefully, because there's a lot of detail in it. It's a short transcript. http://www.meaction.net/2016/02/16/transcripts-and-slides-from-dr-naths-talk-on-nih-study/