Jen Brea: My ME is in remission

[JenB]

Hi @Michiel Tack. Thanks for posting this.

I guess I’d just say that we’re not textbooks. Think of how inaccurate or incomplete so many of our own criteria have been over the years. IIH is also idiopathic, which means the causes and symptom complex can vary. It may come alone or as part of a more complex cluster of symptoms and diagnoses.

The ICC includes headaches as one of the symptoms of ME and defines it as follow:

Headaches:e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; migraine; tension headaches

This might certainly “pick up” people with intracranial hypertension or craniocervical instability (whether or not we categorize those folks as having “true ME”). The former is associated with aching of eyes/behind the eyes, CCI with headaches in the back of the head (and cervical muscle tension).

For a better understanding of what these clinicians are arguing, there are four references in the Medium post (three of which are on the MEpedia page linked to in the post, one of which is at the bottom of the page). You might try pulling out and critically analyzing those publications.

What clinicians in the EDS space have noted for some time and what these clinicians looking at “CFS” are noting is that their patients who also present with pressure headache seem to have something that ranges from classic IIH to subclinical IIH. Anecdotally, ME/CFS docs in the US and EDS docs have been using Diamox for years with these patients. The Higgins studies are the first that I know of to try to characterize an ME/CFS patient cohort and report the results of venous stenting in those that met the classic IIH criteria.

This talk is about EDS but is also relevant:

Several of those papers specifically deal with the question of whether it’s possible to have IIH w/ lower opening pressures and without papillodema, but in presence of TSS, which is highly correlated with IIH.

I hate to give away Pt II but to save at least some consternation, I did ultimately have high pressure (as defined by standard guidelines) measured when I had an intracranial pressure bolt test, but more on that in the next article.

Lastly, none of us are expert in any of this. What I’d love to see is some of these folks invited to present at our conferences in future so that they can directly present their work and answer their colleagues’ questions.

 

[ME/CFS Skeptic]

Hi Jennifer (@JenB)

I'm looking at the MEpedia references right now. I have some concerns about the clinicians in the United Kingdom you referenced (Higgens and colleagues) . In this paper from 2017, they speculate that chronic fatigue syndrome is merely the "most common and least severe" manifestation of the same disorder of intracranial pressure, of which IIH is the least common and most extreme manifestation.

Their 2013 study of the same group found an increased prevalence (4/20) of IIH in ME/CFS patients with severe headaches. But the problem seems to be that clinicians could choose on which patients they wanted to test IIH with a lumbar puncture and there's no indication how large the sample of CFS patients was from which they selected those 20 patients (they also give no response rate). The article mentions this:

we are looking at a highly selected group of patients. This is a product of the particular approach used in this work, in which the clinician was effectively given licence to choose for further investigation those patients in whom he thought it was not unreasonable to look for raised intracranial pressure.

I suspect this was the reason the article has been rejected by three other journals. It's hard to tell what it actually says.

I couldn't find the other article about a case report - the reference on MEpedia leads me to article on a different subject: Takanaka et al. (2014). "Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance"

 

[JenB]

All I can say is that these diagnoses were accurate for me. I don’t know how generalizable my case is or isn’t. Fortunately, we have the technology to examine every case that presents with the symptoms I presented with in Unrest. We just rarely do.

Oh that must be a typo on the MEpedia page. Thanks for noticing that. There are three articles (including the case report) that all have Higgins as the lead author. The review article is by a different research group. I believe you guys have already discussed that elsewhere.

 

[ScottTriGuy]

Fwiw, I have an empty sella - and a 2 mm adenoma on my pituitary - it would not surprise me to ultimately find out that my spinal fluid squishing my pituitary is implicated in at least some of my symptoms (hypothyroid, and near hyper-testosterone).

 

[ME/CFS Skeptic]

What clinicians in the EDS space have noted for some time and what these clinicians looking at “CFS” are noting is that their patients who also present with pressure headache seem to have something that ranges from classic IIH to subclinical IIH.

I do not quite understand what subclinical IIH is. If patients, for example, do not have an elevated lumbar puncture opening pressure (⩾250 mm CSF in adults) or papilloedema then why would one think that common symptoms such as (severe) headache and vision problems are caused by this rare disorder?

 

[Gecko]

Fwiw, I have an empty sella - and a 2 mm adenoma on my pituitary - it would not surprise me to ultimately find out that my spinal fluid squishing my pituitary is implicated in at least some of my symptoms (hypothyroid, and near hyper-testosterone).

Have either you @ScottTriGuy or @JenB had the Short Synacthen Test done, looking at adrenal insufficiency?
Only ask as I've just had this come back abnormal a few days ago, and wonder whether the pituitary gland could be implicated - more investigation to be done.

 

[ScottTriGuy]

Short Synacthen Test

Nope, never heard of it so had to google it - my cortisol is all over the place so I think I'll ask my doc for this, thanks for sharing.

 

[Seven]

@Hip I am struggling w EDS like things, I am getting bones pop out like at least once a month, not fluro antibiotics for me but I do struggle w coaxsxie b2.
I also feel pressure on the head and pain behind the eye. I do
Not get headaches ( except pressure) and I do not think I have cci. I am getting MRIs of
Spine and back next. Doctor found hyper mobile joints ( he can see it) so not sure what all this mean. I am still digging

 

[Dx Revision Watch]

anyone have access to the tweets that this was replying to?

eta:
one of the '3 others' was the OMF

eta2: I know they are on a break at the moment but it would be nice to have some kind of official statement from #MEAction.

The accounts that Tweet was replying to (or tagged in) are:

@tweetingmole

@OpenMedF
@JanetDafoe
@MEAssociation

But it appears to be a stand alone Tweet into which four accounts have been tagged (ie, it does not appear to be in response to one of these accounts as part of an existing thread). It is located on MEAction's timeline two Tweets before this one:

 

[Trish]

Moderator note:
A discussion of EDS that started on this thread has been moved to a new thread here:
EDS, hypermobility, and the link, if any, to ME/CFS

 

[Guest 2176]

I have crashed pretty hard to the extent that I can no longer get into detailed back-and-Forth arguments on each point. But I had forgotten one thing:
In my personal experience as a pwME, as a form of protection against false hope while still trying to have just the right amount of hope and curiosity toward new findings, I try and have criteria for evaluating the plausibility of recovery or remission anecdotes. I consider recovery or remission anecdotes important sources of information because of the lack of clinical trials or even fundamental ideas of etiology in this illness, so despite the fact that anecdotal evidence is different than evidence validated by peer review, I still weigh that against the relative lack of good evidence in this field in general.
One of my criteria for a remission or recovery story is to wonder how robust their diagnosis of this illness was to start with and how severely ill they were. Jeff and Jen both met fairly strict ME criteria and were severely ill. Some recovery stories from psychological methods etc have moderately ill people with ill defined fatigue symptoms.

Another criteria in evaluating the story is just whether it seems likely to be true based on this person having either given lots of details of their time with ME or having a past record of having been in the community. Jeff ans Jen both fulfill this criteria. Many of the recovery stories on the Recovery Norge site that that BPS guy Henrik Vogt runs won’t even use their full names, supposedly for fear of harassment, but the stories aren’t detailed at all and there’s no record they were ever in the community at all.

A third criteria is that of some improvement on an objective criteria as well as subjective ones. Probably the best one is sustained increased activity. I think that it’s possible for a placebo effect to induce increased activity, short term, and then inevitably this is not sustained , because a core aspect of this illness is exercise intolerance. Jeff and Jen included detail about their increase in mental and physical activity. A full case report with labs before and after would be even better , but this is what we have now.

All in all, those criteria may not be perfectly scientific, but I think they are sound. Perhaps not good enough for peer review lol but good enough to wade through the noise to pick out promising anecdotes to investigate further.


There is an extent to which I regret my earlier comments, not because they were incorrect (I stand by what I said totally) but because ultimately this issue will not be decided by discussion on a forum. It seems we all want the same thing, more research. Except this is slow to come for reasons that generally have more to do with political economy than with any personal fault of researchers or lack of will among the people who have shared their stories.

 

[Esther12]

Many of the recovery stories on the Recovery Norge site that that BPS guy Henrik Vogt runs

But maybe he thinks he has some special criteria which means that the anecdotes he likes should be given particular prominence?

I get the impression that as humans we tend to like stories, and to imagine that our stories help us make sense of things (this is my story to help me make sense of humanity).

Peoples' symptoms can improve, get worse, stay stable, etc. Patients will sometimes be sure that some particular intervention made them better, or worse, or kept them the same (for good or ill), but it could always be that they're just completely wrong. It's worth thinking 'is there a plausible mechanism here, and if so how can I test it', but I don't think that an individual's unblinded experiences can be much of a test, and we've seen how often the promotion of anecdotes leads to other patients wasting their time and money on interventions that do more harm than good.

This is a problem for lots of health conditions, but I think that the problems caused are often worse for ME, where there are likely to be people with many different sorts of health problems given the diagnosis, symptoms can naturally fluctuate, there's lack of good quality research showing and genuinely useful interventions and there's a huge social pressure to 'try' different quacky things in order to get better.

Whenever someone's health improves, for whatever the reason, that's a great thing. While celebrating that I think that it's always worth trying to constantly remind each other that stories about these sorts of improvements will often be misleading because we do not know exactly what happened and why. We can't presume that an anecdote about recovery following a surgical procedure and any more likely to be revealing than one about LP. I hope this doesn't seem rude to Jen or anyone else... some LP advocates claim that these sorts of comments are hostile abuse, but I'm really just trying to remind people how difficult it is to know anything. There's a long history of misleading anecdotes in medicine leading people astray, and the politics around ME mean that we need to be particularly wary of this imo.

 

[Guest 2176]

I get the impression that as humans we tend to like stories, and to imagine that our stories help us make sense of things (this is my story to help me make sense of humanity).

Yes, and this is also no less true of scientists who have particular theories about ME and whatnot. The extent to which theories differ from stories could be hotly debated but any time someone arranges facts into a sequence and starts to infer causality and meaning, it’s sort of narrativizing. And yet it’s essential for us to make sense of things and some stories will have more value than others.

Peoples' symptoms can improve, get worse, stay stable, etc. Patients will sometimes be sure that some particular intervention made them better, or worse, or kept them the same (for good or ill), but it could always be that they're just completely wrong. It's worth thinking 'is there a plausible mechanism here, and if so how can I test it', but I don't think that an individual's unblinded experiences can be much of a test, and we've seen how often the promotion of anecdotes leads to other patients wasting their time and money on interventions that do more harm than good.

Ahh, this reminds me of the other thing I meant to say. People keep talking about how remission could just be spontaneous. Frankly I haven’t heard of many full spontaneous remissions from severe ME, at least ones that were sustained as soon as the person started to exercise. Usually even when there’s a remission as soon as the person starts pushing themselves they crash again. I’d love to see data on this but I’m afraid we probably have none. However I am definitely skeptical of the idea that spontaneous remission is common enough to explain this, although of course I could be being fooled by randomness.

I don’t claim that anecdotes are the same value as peer reviewed evidence. But often to even get peer reviewed evidence you have to start with picking through anecdotal evidence to see what’s worth following up on. And I explained my process for doing so.

I also think that the cost/benefit of telling a story like Jens or Jeff’s, especially with a procedure that is as difficult to access as surgery, is likely to cause more benefit than harm. The surgeons involved will not tell anybody that this procedure will cure their ME, and they will not operate on anybody that doesn’t have cci. The part of the debate that involves personal judgments of Jen and Jeff’s character or actions has gotten quite contentious, both on this board and off. But I personally think, as someone with severe ME, that we can make our own decisions, even though our cognition is damaged. The particular kind of cognitive defects in this illness have to do with memory and executive functioning, but tend to not be dementia level/irreversible, which means that I think no matter how slow we think, the decision-making part of the person is still intact.

With rituximab, you had people offering it as a cure for ME with no evidence that anyone had autoimmunity, or any extra B cells or whatever. Whereas with this surgery, whether or not the idea that it could cure ME is believed, it will only be offered to people who have evidence of cci. So I think the concern about the dangers involved is a little overblown to say the least.

 

[Guest 2176]

And again, the only thing that can really settle this is more research, and the only thing that can change that is more funding, and most likely the only thing that can change the funding situation is aggressive advocacy. So we are back to square one in terms of what is important.

 

[Jonathan Edwards]

I’d love to see data on this but I’m afraid we probably have none.

I have chosen a slide of the results from the open label extension rituximab study for my PACE presentation to my old academic unit on Wednesday. The more I look at it the more I realise that if you want a placebo effect (which Knoop and White said is how CBT works) then rituximab is a darn sight better than CBT. And the phase 3 study shows that plain water is pretty good. What is remarkable is that for a period of three years without let up a good proportion of patients go to zero score on fatigue (the score is actually maximum on the scale but presumably means 'no fatigue').

This is actually pretty surprising and thought provoking. It seems that if you sell your treatment right you can get a substantial proportion of PWME to get well and stay well for three years with no active ingredient.

The surgeons involved will not tell anybody that this procedure will cure their ME, and they will not operate on anybody that doesn’t have cci.

The problem we have at the moment is that the definition of CCI seems to be very subjective. From what I can gather from the consensus statement the imaging thresholds are not considered diagnositic. They are suggestive in the presence of appropriate clinical signs. So far we have not heard of any PWME having any physical signs. So I am not very reassured by the idea that they only operate where there is CCI.

I absolutely agree that PWME are not impaired in terms of decision making. They seem very on the ball to me. But children are not in a position to decide and children are being sent for this imaging. With potentially sixty or more years to develop secondary complications from cervical fusion a child does not want ill advised cervical surgery. And if Jen is right to say that the surgeons don't really know anything about ME symptoms and it's just another busy day at the office for them I think I have reason to worry.

Mod note. The section of this post on Rituximab has been copied to a new thread and posts discussing it move to that thread:
Rituximab and placebo response

 

[Esther12]

Yes, and this is also no less true of scientists who have particular theories about ME and whatnot. The extent to which theories differ from stories could be hotly debated but any time someone arranges facts into a sequence and starts to infer causality and meaning, it’s sort of narrativizing. And yet it’s essential for us to make sense of things and some stories will have more value than others.

I would say a lot of scientists theories about ME are no more that a prejudiced reading of anecdotes and junk-science! So I'm setting higher standards for us than there are for peer-reviewed research papers (partly because I've seen the harm done by poor quality peer-reviewed papers.)

Things like double-blinded randomized trials, results from blinded assessment of patient and control samples... these sorts of things do provide more meaningful evidence for letting us make sense of things. I think it's useful to avoid stories until we have good quality evidence, particularly given the current state of the politics around ME and the danger of harming advocacy efforts with premature speculation.

Ahh, this reminds me of the other thing I meant to say. People keep talking about how remission could just be spontaneous. Frankly I haven’t heard of many full spontaneous remissions from severe ME, at least ones that were sustained as soon as the person started to exercise. Usually even when there’s a remission as soon as the person starts pushing themselves they crash again. I’d love to see data on this but I’m afraid we probably have none. However I am definitely skeptical of the idea that spontaneous remission is common enough to explain this, although of course I could be being fooled by randomness.

I've not looked into the current CCI stories, partly because I think anecdotes are so often misleading, but I have seen lots of other people report remission and often tied to to something or other they were doing at the time. Sometimes these interventions will be for things that can be of no plausible value beyond ritual (homeopathy), sometimes treatments for other health conditions that seem entirely unrelated to ME, sometimes interventions that may seem plausible but that go on to be shown to be of no net value as a treatment of ME. It seems like the percentage of patients who have an experience like this is low (there's the 5% recovery rate from a meta-analysis that has many of its own problems), but there are millions of patients around the world so a low percentage can still lead to more remission anecdotes than anyone would have time to look through. Sometimes the people who thought that they found the answer for their own health can still end up ill again, without really knowing why.

When there's so much uncertainty I'm wary of reading much into a handful of case reports about anything.

I also think that the cost/benefit of telling a story like Jens or Jeff’s, especially with a procedure that is as difficult to access as surgery, is likely to cause more benefit than harm. The surgeons involved will not tell anybody that this procedure will cure their ME, and they will not operate on anybody that doesn’t have cci. The part of the debate that involves personal judgments of Jen and Jeff’s character or actions has gotten quite contentious, both on this board and off. But I personally think, as someone with severe ME, that we can make our own decisions, even though our cognition is damaged. The particular kind of cognitive defects in this illness have to do with memory and executive functioning, but tend to not be dementia level/irreversible, which means that I think no matter how slow we think, the decision-making part of the person is still intact.

I definitely wasn't arguing against Jen, Jeff or anyone else telling their story. I just think it's worth us all encouraging one another to make clear how difficult it is to know what causes what, and the danger of reading too much into medical anecdotes.

I don't know much about CCI, but there have been other cases of dodgy surgical practice and people receiving unnecessary operations. I wouldn't trust surgeons any more than anyone else, and it's always worth trying to make sure that they have good evidence for their claims, and are not just getting prematurely caught up in their own stories.

I realise that for Jen and Jeff this is going to seem like a very personal debate, and it's worth everyone being understanding of that (I know I can tend to be quite blunt). At the same time, for me this is really not personal, and these are the things I'd say in response to any remission anecdote. I've got no reason to be critical of Jen or Jeff's character or actions, and so much as possible would like to avoid tying my concerns about the the way some people can respond to hopeful anecdotes to individual cases. [edit: This is not a new thing for me to express concern about and I've now said similar things to many, many people.] I do feel that I've seen things with some similarity to this a number of times over the decades though, and it's worth trying to avoid some of the problems that have occurred previously by trying to limit our human enthusiasm for a positive story.

 

[JES]

Peoples' symptoms can improve, get worse, stay stable, etc. Patients will sometimes be sure that some particular intervention made them better, or worse, or kept them the same (for good or ill), but it could always be that they're just completely wrong. It's worth thinking 'is there a plausible mechanism here, and if so how can I test it', but I don't think that an individual's unblinded experiences can be much of a test, and we've seen how often the promotion of anecdotes leads to other patients wasting their time and money on interventions that do more harm than good.

This is a problem for lots of health conditions, but I think that the problems caused are often worse for ME, where there are likely to be people with many different sorts of health problems given the diagnosis, symptoms can naturally fluctuate, there's lack of good quality research showing and genuinely useful interventions and there's a huge social pressure to 'try' different quacky things in order to get better.

I agree in principle with most of what you said. The fact that ME/CFS can remit spontaneously is indeed always a possibility and there could be a number unknown factors involved, which affected the end result. But there are aspects of these stories, like the part below I quoted from the web site of Jeff, which are so obviously linked to the therapy/treatment that it makes other mechanisms not seem plausible, especially the quoted part where he measures his heart rate with and without traction. It is still anecdotal and it's still a "story", but the symptom observed can hardly get much more objective than what was described:

For the past four years, ever since the onset of my severe ME and POTS, my standing heart rate was usually in the 130’s or higher. But, with maximum halo lift, this suddenly didn’t seem to be the case. I felt so different—I suddenly felt… kind of healthy? I grabbed my pulse ox and measured. Sure enough, my standing heart rate was 86! I couldn’t believe it. This seemed too good to be true, and I couldn’t accept this so easily. I had to verify this was actually happening. So I let go of the halo, and my skull sank downward. My heart rate measured 127. I lifted the halo again with maximal traction, and my heart rate was now 82.

I repeated this lifting and dropping maneuver for several days. My heart rate responded consistently, every time. Though I knew this was very significant, I was still guarded about getting my hopes up. During my years with ME, I had experienced several periods of mild, though noticeable, improvement. These improvements never lasted. And so, I had learned over time to continually temper my expectations for recovery. Avoiding false hope was necessary for self-preservation.

 

[Esther12]

And again, the only thing that can really settle this is more research, and the only thing that can change that is more funding, and most likely the only thing that can change the funding situation is aggressive advocacy. So we are back to square one in terms of what is important.

Yes, although I think that it's important that advocacy is not unduly influenced by these sorts of hopeful anecdotes. In the past it has caused problems when patients start pretending that we know more than we do, or arguing that we really need research into x or y on the basis of a recovery story. If independent researchers then look at x or y and they seem like implausible stories lacking any real evidence of value then it can leave advocacy efforts looking silly. At the moment I think that we need to be more rigorous than many researchers are.

I agree in principle with most of what you said. The fact that ME/CFS can remit spontaneously is indeed always a possibility and there could be a number unknown factors involved, which affected the end result. But there are aspects of these stories, like the part below I quoted from the web site of Jeff, which are so obviously linked to the therapy/treatment that it makes other mechanisms not seem plausible, especially the quoted part where he measures his heart rate with and without traction. It is still anecdotal and it's still a "story", but the symptom observed can hardly get much more objective than what was described:

I've really not been reading much about the specifics here, partly because I feel as if I've seen anecdotes that seems important and specific and reliable like this popping up over the years and never leading to anything (including for conditions other than ME). That's not to say that I'm sure these won't be different, but I do think that it's worth staying cautious until we've got something much more solid to go on.

It could be that I've now developed an unreasonable cynicism, and that I'm missing out on some justified excitement... but I don't think that's much of a loss. If we get some solid research that indicates CCI stuff is likely to be of important to a subgroup of those with ME then I can be pleased about that then. For now, I think I'm just going to be happy for the individual patients reporting improved health, while not assuming that we know what caused it or whether it might have wider implications for others with ME.

PS: I've been keeping my comments on all this very general and really have not been reading a lot of what Jen and Jeff have been putting out (I've not even been keeping up with PACE news recently, and I love PACE news). I hope that this is not being interpreted as back-handed insults on either of them, or any sort of straw-manning. A lot of my concerns about all this stem from having seen other patients responding to this on social media, rather than what Jen or Jeff have written themselves (I'm not sure I've even read anything from Jeff on this). Maybe things have calmed down a bit now, or I just saw a few over-excited posts, but I did see a few examples of people jumping to assuming that this CCI stuff was likely to be important for ME.

 

[Jonathan Edwards]

But there are aspects of these stories, like the part below I quoted from the web site of Jeff, which are so obviously linked to the therapy/treatment that it makes other mechanisms not seem plausible,

This account was actually what made me think there must be a different explanation.

My memory of all the details is incomplete, having now been ten years retired, but this is my understanding:

The main purpose of traction for CCI is not usually to lift the brainstem but to prevent the nodding forward movement that brings the odontoid peg of C2 into contact with the brainstem.

If the problem is purely ligamentous laxity in a forward/back direction (i.e. there is nothing to see on an ordinary plain x-ray) then I would not expect traction to 'lift the brainstem' more than perhaps a millimetre if at all. Actual lifting of the skull off the cervical spine is only likely to occur if the peg of C2 has migrated up through C1 to enter the foramen magnum and the ligaments are still lax enough for it to be drawn back down. I was never sure this was possible in our RA cases. Upward migration of the peg only occurs if the transverse ligament of C1 is actually ruptures or there is marked bone loss. I have never heard of these occurring outside the context of violent trauma, RA or maybe a developmental disorder with bony deformity.

The fusion operation, which I assume fuses base-occiput to C1 and C1 to C2, or just one of those, will not lift the brainstem up at all as far as I can see. It will just prevent forward nodding and/or rotation. One of the problems in the old days was that surgery left the patient with permanent pressure on the brainstem rather than just intermittent.

Which all makes me think that traction/surgery is much more likely to have an effect on ME by removing sensory input from interceptive signals from the neck and vestibular apparatus rather than relieving brainstem pressure from CCI.

 

[Sly Saint]

Is there anything in the procedure that might affect/ improve blood flow to the brain?