Understanding jugular venous outflow disturbance, 2018, Zhou et al.

I just wanted to share an article that was recently posted to our Facebook group on ME/CFS and structural diagnoses. A woman in it who meets ME/CFS criteria was recently diagnosed with bilateral internal jugular vein stenosis (IJVS). This is considered a congenital condition, however she never had symptoms before contracting Dengue Fever. Her doctor hypothesizes that since Dengue Fever can thicken the blood, her infection took a previously asymptomatic congenital condition and made it symptomatic. This hypothesis is supported by the fact that a drug called Stugeron, a vasodilator, improves her symptoms.

IJVS, as this article describes, can cause symptoms that “mimic” intracranial hypertension including altered CSF flow and cerebral hypoperfusion:
https://onlinelibrary.wiley.com/doi/full/10.1111/cns.12859

This pings for me given the conversation in another thread about how there might be a range of diagnoses that can cause intracranial hypertension and/or cerebral hypoperfusion, resulting in ME/CFS symptoms.

It also pings for me as it is an example of a concept I keep encountering: that there are patients who have a congenital, anatomical abnormality that prior to an infection, is completely or largely asymptomatic, and that only becomes apparent after a major inflammatory event. That was the case for me with tethered cord syndrome and, apparently, in this patient with IJVS.

(*posted with permission.)

 

Which ME/CFS symptoms? That meet which criterion? Just because someone had an infection that brought forth a congenital diagnosis that resulted in ME/CFS symptoms does not mean this person has ME/CFS. This is the whole problem. Apparently other conditions can meet symptoms of ME/CFS and not be ME/CFS. Diseases can sometimes have the same biomarkers which would necessitate further testing for biomarkers that will lead to an accurate diagnosis.

Once again my point is that there are multiple conditions that can be misdiagnosed using criterion. All the ME/CFS criterion were developed with a specific diagnosis in mind, not to sweep in other conditions that lead to a misdiagnosis of ME/CFS. But clearly, this is happening.

For Lewy Body Disease, the first symptom is a sleep disorder. Specifically one that involves REM and body movement. This can start 20 years before the clear onset of dementia symptoms. However, that does not mean you will develop LBD because there are lots of conditions that have these specific sleep disorders. For now, all they know is to review family history for dementia, especially LBD, have a cognitive assessment every five years, and a brain MRI reviewed by an LBD expert. And to steer clear of certain OTCs, drugs, and some anesthetics.

 

We have no idea how to tell if someone has ME/CFS, other than clinicians judging whether they have the disease based on the patient’s history and a set of criteria. That is the situation we are in.

I don’t have this person’s full clinical history or anything close to it, but pretty much everyone I am talking about has PEM, meets CCC/ICC criteria. Many have been diagnosed by expert clinicians who have written criteria.

Is it a misdiagnosis if a pathology is found? Is it a correct diagnosis only if no pathology is found? Is ME/CFS, then, a diagnosis of exclusion?

Or is it more like POTS, a syndrome that can have many causes?

 

Jen, we have already discussed and agreed that if you have a venue such as a specialist clinic or a Facebook site known to have an interest in an association between A and B that venue will rapidly get filled up with people who happen to have, or think they have, A and B. If, as for Facebook, the catchment is about a billion people then it is of no surprise that one or two will report having A and B.

This is precisely the problem that has given rise to the 'hEDS/ME' story and the MCAS/ME story and so on. There are plenty of medical practitioners out there only too ready to take advantage of this.

So far I have not seen any clear evidence that anyone with ME has a structural neurological problem, other than some standard cervical spine stenosis which is everywhere. IJVS looks to be another obscure diagnosis with no very clear diagnostic requirements and a vague 'just about anything' clinical presentation.

The key thing about science is that it involves setting things up so that you might find what you are not predicting. Venues designed for people with A and B are unlikely to fulfil that need.

 

Social Media Representation of Chronic Cerebrospinal Venous Insufficiency Intervention for Multiple Sclerosis

https://www.ncbi.nlm.nih.gov/pubmed/27134577

https://www.statnews.com/2017/11/28/multiple-sclerosis-paolo-zamboni/

A number of neurologists and scientists expressed the opinion that the decision to conduct a trial on CCSVI in the absence of valid scientific evidence was unethical and a waste of resources.28 However, we believe that the best way to provide useful information to patients (and regulatory authorities) on the benefit and safety of venous PTA was to conduct a randomized trial—as also recommended by NICE7—that assessed outcomes directly relevant to patients.29 Venous PTA has proven to be a safe but ineffective technique in treating CCSVI in about half of patients. The procedure cannot be recommended for treatment of patients with MS; no further double-blinded clinical studies are needed. The delayed effect of venous PTA 6 months after the procedure on the magnetic resonance biomarker suggests a possibility that PTA may produce benefit for a subgroup of patients with MS. This should be further analyzed and investigated.

 

On the face of it this seems totally unethical without some theoretical basis that makes a grain of sense. It is also very peculiar at the end of the abstract:

So what further investigation other than a double-blinded clinical study is being suggested - maybe some more operations on paying patients?

 

The vascular surgeon was moved to look for the cause of MS because his wife suffers from the disease. In 2009, Zamboni published a paper suggesting the neurological damage the condition causes was triggered by pooling of blood in the brain that was the result of inadequate drainage.

He called the condition — which he said was common among MS patients — “chronic cerebrospinal venous insufficiency,” or CCSVI.

Zamboni further suggested inserting stents — which are designed to hold open arteries — into veins in the neck would increase blood drainage and improve symptoms.

His 2009 study appeared to show it worked, though skeptics were quick to note major flaws. There were no controls — a group that didn’t get the treatment to use as comparators — and both the patients and the doctors knew everyone was treated. A study of this kind is open to the placebo effect and to researcher bias — both of which can result in individuals seeing something they hoped to see.

Surprise surprise.

 

This has an all too familiar ring:

Social Media Representation of Chronic Cerebrospinal Venous Insufficiency Intervention for Multiple Sclerosis.
Ghahari S1, Forwell SJ1.
Author information
1
School of Rehabilitation Therapy, Queen's University, Kingston, ON, Canada (SG); Department of Occupational Therapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran (SG); and Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, BC, Canada (SJF).
Abstract
BACKGROUND:
We conducted a rigorous review of videos related to multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) treatment posted by people with MS on one social media website (YouTube) that describe symptoms before and after the surgical procedure, as well as videos presented by health-care professionals (HCPs).

METHODS:
All relevant videos posted from December 2009 to July 2011 were downloaded, viewed, and systematically organized. Categorical data were classified, and dominant messages were gleaned.

RESULTS:
A total of 1789 videos were extracted. A total of 621 videos by people with MS and 238 by HCPs were included. Eighty-six percent of people with MS anecdotally reported experiencing some improvement in at least one symptom. The most common message was that "CCSVI is not a miracle but worth trying." Most HCPs posting videos recommended the procedure but called for continued research.

CONCLUSIONS:
Social media are conveying an anecdotal favorable message about CCSVI treatment for MS. The relative absence of videos offering a negative or more balanced perspective is a concern. Social persuasion through these videos creates a strong positive impression of CCSVI treatment, but the videos do not acknowledge the lack of supporting scientific evidence and the possible role of the placebo effect. Given the strong influence of social media on health-care decision making, researchers and clinicians should actively use social media to reach out to people with MS and describe the state of the evidence for MS treatments, both positive and negative.

 

How about this. CCI has neurological symptoms. If one has a diagnosis of CCI, that patient's neurological symptoms now have an explanation. Having POTS does not mean a CCI patient has ME/CFS. It means they have another Dx. PEM occurs in other diseases and is reported in EDS patients. I suspect a number of illnesses, such as EDS and CCI, are being misdiagnosed as ME/CFS.

I am thinking more and more that yes, ME/CFS should be a Dx of exclusion. Rule out neurological and congenital diseases that would explain symptoms. Even with IOM and CCC, which I believe are good criterion, there should be full neurological and congenital disease work ups that could explain symptoms especially when there is no infectious event that a patient could point to as the definitive beginning of their symptoms. Can one have another illness along with ME/CFS? Of course. But it is becoming very clear that a number of patients have received an ME, ME/cfs, or CFS Dx that should not have. It especially worries me that MS patients have mistakenly received an ME Dx. Or my wonderful neighbor, who has had diabetes since I met her in 2003, now has a CFS Dx where at age 64 had to leave her job as a university professor due to "CFS".

I am also starting to believe that if a person had an enterovirus and now have ME/CFS symptoms, they most likely don't have ME/CFS but symptoms that result from such an infection.

Thinking of the many that have an ME, ME/CFS, or CFS Dx that are severely neurologically impacted, I now believe they have an incorrect Dx or perhaps an additional Dx that would explain their neurological symptoms. That's a shame. I think the ICC a very bad criterion impeding a correct Dx of other neurological and congenital diseases.

 

Sorry, but this seems to me to be unrelated to what is being discussed here. Nobody in these threads has never mentioned undergoing PTA treatment to cure any disease. It has been described a situation where a patient who was originally diagnosed with ME/CFS was later found to also meet the criterion for CCSVI, defined by Prof. Zamboni, the Vascular Surgeon who first described this vascular pathology.

The fact that clinical trials have demonstrated that the PTA is not an effective treatment for preventing MS progression doesn't mean that CCSVI isn't a pathology on its own with its own clinical manifestation (described in the article that Jen has linked). In fact, a) clinical trials so far have only ever had the intent to verify whether CCSVI could be considered a causative factor in the onset and progression of MS. Although there is at least an article about its correlation with Meniere's disease: https://www.ncbi.nlm.nih.gov/m/pubmed/24594584/?i=2&from=Bavera. They haven't so far tried to establish the efficacy of PTA to improve CCSVI clinical manifestation. B) PTA has been found ineffective because veins are essentially elastic and they tend to on average re-stenose after some time. The ideal treatment would be stenting, but Zamboni has always made it very clear that this is not possible to do at present, as there are no existing compliant stents for the jugular veins yet. The majority of news about CCSVI are (as far as I can see) written in Italian, so you probably don't know that a team from the University of Catania and Ferrara in Italy has been working on a new stent designed specifically for the jugular veins. This project was funded by the Italian Ministry of Health. They nicknamed the stent "petalo" (petal) and clinical trials to study its effectiveness should start in 2020.
Here's a link about it, and it says it was presented at "International Society of Neurovascolar Disease" http://fondazioneodmcatania.it/sten...c7VDqkP1l8kFRvzw-LjeTCwrEqjTz8DoSfjtdSAz2OLw8.

So that article really doesn't mean that CCSVI cannot be considered a pathology on its own, where effective treatment is still being researched.

 

From the article here https://onlinelibrary.wiley.com/doi/full/10.1111/cns.12859
"4 CLINICAL MANIFESTATIONS
There is strong evidence showing that venous outflow abnormalities can contribute to the development of intracranial hypertension. The degree of clinical presentations of IJV outflow disturbance may vary from none to severe based on individual variation and compensatory capability. Broadly speaking, these characteristics such as headache, pulsatile tinnitus, visual impairment, sleep disturbance, and neck discomfort or pain may mimic, at least partially, those of idiopathic intracranial hypertension and chronic cerebral circulation insufficiency.2, 7, 53

Constant or intermittent head noises, known as intracerebral noise and unilateral or bilateral tinnitus, are specific features of the disease that are highly indicative of altered blood flow patterns in the IJV lumen. Some of other prevalent symptoms include headache, heavy‐headedness, dizziness, sleep disturbance, neck discomfort, and back pain. Ophthalmological discomforts such as eye soreness and eye dryness, dysmorphopsia, diplopia, blurred vision, and even visual loss are frequently complained in a certain amount of patients. Patients may also have decreased cognitive function and behavioral changes, which can be mistaken for psychiatric issues. Physical findings are of limited localizing value. Abducens nerve weakness and neck stiffness, although not usual, may sometimes be detected in this condition. Notably, abnormalities identified in the ophthalmic examination such as impaired visual acuity, visual field defects, and papilledema should raise urgent suspicion."

 

Equally we have no reason to think CCSVI is a real pathology.

Please be aware that reviews like this much of the time are marketing for research programmes with no valid evidential basis. Science is full of stuff like this now.

I think this case is extremely relevant to the discussion about ME cases because it highlights the problem that neurosurgery is not regulated the way medicine is and operating without sound theoretical or evidence base is commonplace.

Why take these surgeons any more seriously than the psychiatrists? Both branches of medicine are poorly regulated.
If one lot of doctors is capable of promoting meaningless treatments, why not another?

 

I really don't understand why you keep referring to surgical treatments here. As I explained in my previous post, Jen has never said that the patient is going to have PTA treatment or any other surgical treatment for the IJVS issue. And as I said, Zamboni admitted that PTA is not an effective treatment and research is still ongoing to find an effective one. CCSVI has been linked to many other diseases, such as Meniere's and migraines. Zamboni has always ever worked as a researcher and has never himself offered the operation privately. Actually, he's always discouraged patients to pay for the operation, because it was already being offered free by the Italian National Health System to patients with MS as an experimental procedure in the years around 2012-13, when the first studies came out. So even though there are some doctors that offer this procedure privately, your portrayal of unregulated surgeons hungry for money doesn't stick to the reality of the CCSVI research field, I'm afraid. The only real obstacle to research in this field is that Italians' organisation skills are terrible (and I can say that as an Italian) and unfortunately that's why they haven't been able to get much done over the past 10 years of research.

The focal point of Jen's post should be that this patient's symptoms improved while being on a medication called Stugeron, which acts in the same way as Pentoxifylline. They are both drugs that make the blood more fluid and less viscous. This kind of drugs is sometimes prescribed by CCSVI specialists to patients with CCSVI to relieve symptoms.

Research for IJVS issues or otherwise called CCSVI is still in its infancy, but is ongoing and the fact that a balloon angioplasty doesn't resolve symptoms doesn't mean that the whole idea of vascular abnormalities impacting in some measure neurological conditions is rubbish.

And by the way, CCSVI testing (echo doppler ultrasound) is also available on the Italian National Health System, so the patient might have even got the diagnoses for free.

 

I think the real obstacle is that this is pseudo-physiology. I am pretty sure this condition does not exist - at least in the context proposed, and certainly has nothing to do with MS.

It may be that Dr Zamboni does not charge for operations but I think we would be naive to think this is not driven by attracting business - which is widespread within government-run health care systems. The alternative is that there is some sort of missionary zeal to cure people without knowing what one is doing and in many ways that is just as bad.

I don't think that the use of Stugeron was the only issue of interest in the original post but I would just point out.

1. Stugeron is not primarily a vasodilator. If at all it is an extremely weak vasodilator and the effect is not even noticeable clinically. It belongs to a group of drugs with all sorts of action including sedation and anti-emesis. If it has an beneficial effect it is inherently very unlikely that the effect is from vasodilation.

2. The problem that has been diagnosed (bilateral internal jugular vein stenosis) would not be expected to respond to a vasodilator anyway, since it is a stenosis, not a state of contraction.

3. The doctors suggestion that the problem was thickening of the blood due to Dengue is groundless and would not be an indication for a vasodilator. Pentoxifylline is mentioned having an effect on viscosity. This again would be of little or no relevance to venous stenosis - it is used to improve flow in micro vessels where rheology is important.

The whole story is pseudo physiological. Surgeons tend to go in for this sort of pseudo physiology. Physicians can be as bad, I admit.

I cannot see a reason to think there is a grain of sense in any of this. What makes you think their might be?

 

Back in late 1990's/early 2000, hypercoagulation (thick blood) was a theory going around in the ME community. Blood thickening due to pathogens. A few of us here had our blood sent to the US (HEMEX labs) for testing, there were a handful of doctors treating their patients based on the theory, one including Dr. Carol Ann Ryser who later lost her license for misdiagnosing and overcharging for unnecessary treatments for Lyme.
My Functional doctor attended a workshop in Arizona to learn more and was astonished at how these handful of doctors were convinced that my test results were due to an 'underlying pathogen' from thicken blood and yet he could not get the support from doctors here (Virologist and Head Haematologist) because they said it was nonsense.

Follow the money.

 

I think that you're still reading lines in between paragraphs that are not there. Have I ever mentioned vasodilator properties? No. I said that both stugeron and Pentoxifylline have the property of reducing blood viscosity, making the blood more "fluid". If the blood is more fluid, it will flow much more easily through blood vessels, in fact as you say "it is used to improve flow in micro vessels". So if a person with jugular stenosis takes stugeron or Pentoxifylline, the blood will pass through the narrowing much more easily, improving the overall drainage from the brain to the heart. So it's not about the vasodilating properties, it's about the hemorrheologic properties of these drugs.

Also, I might have to rectify Jen by saying that the thing with Dengue is not so much the fact that it changes blood thickness (even though it does during the acute phase of the illness, as it's known to attacks platelets), but the fact that being an hemorrhagic fever it directly affect vascular structures. So in this case, the congenital defect that this patient had was likely triggered by the Dengue considering the way this virus affects blood and blood vessels.

Prof. Edwards, I'm not making this up, the effects of Stugeron/Pentoxifylline on the jugular venous system was explained to me by an Italian vascular surgeon that has been part of the CCSVI research and has been studying this for the past 10 years.

 

I didn't know how to multi quote, but please see my reply to Prof. Edwards above.

Again, reading lines in between paragraphs that are not there. Nobody said that Dengue is still active in this patient, like these doctors you've mentioned say. It's only been suggested Dengue as a trigger.
Edit: also, I've never said that there is a problem with blood thickness in ME patients or patients with IJVS.

 

The symptoms you mentioned are also classical symptoms of Meniere's disease. Stugeron is also known to be prescribed for Meniere's disease. Here's an interesting study correlating Meniere's and CCSVI:
https://www.ncbi.nlm.nih.gov/m/pubmed/28034701/?i=2&from=/24594584/related
"CCSVI was diagnosed in 175 (87.5%) patients with MD. Venography was performed in 69 patients to confirm the diagnosis of CCSVI. In 80% of these patients, PTA of the IJV and/or AV was effective for treating signs and symptoms of MD. In the healthy cohort, CCSVI was observed in only 12% of subjects.

CONCLUSIONS: These results suggest a possible etiologic relationship between CCSVI and MD that warrants further investigation."

Just a coincidence you say?