Could Ehlers-Danlos syndrome cause ME/CFS-like symptoms as a result of a Chiari malformation?

Hip

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It is well known that there is an overlap in the symptoms of hypermobile Ehlers-Danlos syndrome (EDS) and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). 1 This type of EDS is often misdiagnosed as ME/CFS.

This post examines the idea that a Chiari malformation might cause the ME/CFS-like symptoms in hypermobile EDS patients.



Chiari malformation is a condition that can occur with hypermobile EDS (ie, hypermobile EDS patients are at higher risk of Chiari). 1

A Chiari malformation is where brain tissue is pushed into the spinal canal, due to a skull which is too small or misshapen and thus squeezes the brain and forces it downwards. Chiari is usually a congenital condition, but asymptomatic congenital Chiari can be worsened by a physical trauma such that symptoms may then appear. 1

Now since a Chiari malformation can mimic the symptoms of ME/CFS, fibromyalgia or multiple sclerosis (MS), I was wondering whether when hypermobile EDS patients who have ME/CFS-like, fibromyalgia-like or MS-like symptoms, these symptoms might actually be a result of a Chiari malformation.

In other words: hypermobile EDS ➤ Chiari malformation ➤ ME/CFS, fibromyalgia or MS symptoms



The symptoms of Chiari malformation vary a lot from one person to another. Some people may not have any symptoms (asymptomatic); others have serious manifestations.

The general symptoms of a Chiari malformation include:
Occipital headaches (felt near the base of the skull and may radiate to cause pain in the neck and shoulders).

Abnormalities affecting the eyes including: double vision (diplopia), abnormal sensitivity to light (photophobia), blurred vision, involuntary eye movements (nystagmus) and pain behind the eyes.

Vertigo, dizziness, ringing in the ears (tinnitus) and bilateral hearing impairment can also develop.

Additional symptoms associated with a Chiari malformation may include poor coordination and balance problems, muscle weakness, difficulties swallowing (dysphagia) or speaking (dysarthria), palpitations, fainting episodes (syncope) and tingling or burning sensations in the fingers, toes or lips (paresthesias).

Sleep disorders, especially sleep apnea and chronic fatigue, have also been described in individuals with Chiari malformations.
Source: here.



Chiari malformation will not show up on a standard brain MRI, according to @jeff_w in this post. It requires an upright flexion-extension MRI to see a Chiari malformation.

Patients with Chiari malformation may also have craniocervical instability. This is a structural instability of the bones that join the head and neck which can also lead to ME/CFS-like symptoms. It can be caused by physical trauma, or can be congenital.

A story of a patient diagnosed with ME/CFS who was cured after corrective surgery for craniocervical instability is found here.



Types of EDS include: hypermobile EDS (the same or very similar to joint hypermobility syndrome) which involves joint hypermobility; classical EDS which involves stretchy skin; vascular EDS which affects blood vessels and internal organs; kyphoscoliotic EDS which involves curvature of the spine and fragile eyes. 1
 
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Rlman

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i think Chiari can show up on standard supine MRI, but sometimes only shows on the upright. CCI more often needs an upright MRI for diagnosis though i believe in really bad cases like jeff_w's it was visible even on supine.
 

Wonkmonk

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I don't have EDS or Marfan syndrome (a similar disorder linked to CFS), but I have some degree of hypermobility (fingers, hand wrist etc.). People are sometimes shocked when they see what I can do with my fingers, which they would never be able to do.

I am wondering if hypermobility could be a risk factor for CFS or if what causes hypermobility makes people more prone to get CFS.
 
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@Hip I think Chiari 1 malformation is increasingly recognized as a syndrome, i.e. secondary to an underlying cause. Cranial constriction can cause CM1, but it’s not always the case (especially not in people with EDS). Other possible causes are intracranial hypertension, occipito-atlanto-axial instability, cranial settling, tethered cord, intraspinal hypotension, lesions. This up-to-date doctoral thesis on CM1 has a good literature review: https://www.duo.uio.no/bitstream/handle/10852/59387/PhD-Fric-DUO.pdf?sequence=1


My supine and upright MRI photos show almost equal degree of tonsil herniation. Most people get diagnosed with supine MRI. Photos in neutral position are required (not flexion/extension). The tonsils should be evaluated in different planes and with different slices.

However, the degree of herniation on its own is not a good measure of the severity (csf flow obstruction and pressure on the brain stem) of CM1. It’s important to look at the craniocervical junction as well, evaluate flow and intracranial pressure.
 

Moof

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Interesting thoughts. My ME symptoms have gone into full remission more than once, then reappeared when I went back to doing a bit more; they also fluctuate quite a lot when I'm not in remission. That probably suggests the EDS isn't the cause of the ME symptoms.

I also have two relatives with EDS who developed ME as mature adults – one at about age 35, the other in his late 50s – but recovered from it completely after a few years. They continued to have EDS-related problems such as subluxations until the natural stiffening of the joints that comes with old age eventually gave them more stability. (That's started to happen to me, thank heavens, I haven't had a hip subluxation now for over two years.)

It's still an important point, though, and I guess it's well worth following up for people whose pattern of ME symptoms is more stable?
 

Hip

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I am wondering if hypermobility could be a risk factor for CFS or if what causes hypermobility makes people more prone to get CFS.
That's what I am getting at in this thread: there have been other discussions on this forum on the idea that the hypermobility of Ehlers-Danlos syndrome might be a risk factor for ME/CFS, or at least a risk factor for an ME/CFS-like illness.

One would normally think in terms of molecular mechanisms creating this risk factor: ie, that there might be some biochemical or immunological factors present in EDS that predispose to getting an ME/CFS-like illness.

But what I am suggesting in this thread is that conceivably it could be a structural mechanism rather than a molecular mechanism that creates the risk: namely that hypermobile EDS results in a propensity to Chiari malformation, and this Chiari malformation might then be the cause of the ME/CFS-like symptoms that are known to sometimes appear in hypermobile EDS.



It's actually very interesting that there are a number of cervical spinal abnormalities or injuries that can lead to ME/CFS-like symptoms:
Cervical spinal stenosis — where the spinal canal becomes too narrow, which can put pressure on the nerves, leading to ME/CFS-like symptoms. Cervical spinal stenosis can be caused by a physical trauma to the spine (or just caused by general wear and tear). Surgical treatment of cervical spinal stenosis can lead to resolution of ME/CFS symptoms.1

Syringomyelia — a fluid-filled cyst which appears within the spinal cord, and compresses the spinal nerves, which may result in ME/CFS-like symptoms.1 A trauma to the spine can sometimes cause a syringomyelia to form some time later. Syringomyelia can be treated surgically.

Chiari malformation — where brain tissue is pushed into the spinal canal, due to a skull which is too small or misshapen and thus squeezes the brain and forces it downwards. This may cause ME/CFS-like symptoms, as well as multiple sclerosis-like or fibromyalgia-like symptom. Chiari is usually a congenital condition, but asymptomatic congenital Chiari can be worsened by a physical trauma such that symptoms may then appear.1 Chiari malformation will not show up on a standard brain MRI. It requires an upright flexion-extension MRI to see it.1 Patients with Chiari malformation may also have craniocervical instability. Chiari malformation is sometimes found in Ehlers-Danlos syndrome.

Tethered cord — where spinal cord is "stuck" to a structure within the spine, such as dura, scar tissue from a previous operation, a bony spicule or even a tumor. This condition may cause ME/CFS-like symptoms. Tethered cord can be caused by physical trauma, or can be congenital. Tethered cord is often found in those with chiari malformation.

Craniocervical instability — this is a structural instability of the bones that join the head and neck that may lead to deformation or compression of the brainstem, upper spinal cord, and cerebellum, which can then lead to ME/CFS-like symptoms. It can be caused by physical trauma, or can be congenital. A story of an ME/CFS patient who was cured after corrective surgery for craniocervical instability is found here. Patients with craniocervical instability may also have Chiari malformation.
Source: Roadmap of Chronic Fatigue Syndrome Testing and Treatment

Even though these cervical spinal abnormalities or injuries are quite rare, and almost certainly not the cause of most people's ME/CFS, I find it intriguing that damage or abnormalities in this particular part of the spine will often produce ME/CFS-like symptoms.
 
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Sidny

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@Hip Could infections in and of themselves precede/precipitate cervical spinal abnormalities? (As in the sole or primary factor that causes them) possibly trough connective tissue degeneration, mutations to collagen complexes, or protein metabolism as a result of the infections downstream effects?

I ask because in a previous post you mentioned elevated MMPs due to enterovirus infection. It makes me wonder if they stay elevated for long enough, if that in itself can wear down supportive structures/tissues to the point where "chiari" for example is the final result.
 

Hip

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@Hip Could infections in and of themselves precede/precipitate cervical spinal abnormalities?
I have not come across infections causing these cervical spinal abnormalities, but since these abnormalities can cause ME/CFS-like symptoms, I wonder if there may be some common pathways (eg, both triggering the sickness behavior response).
 

Iritu1021

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I was told that my CFS and POTS were due to Ehlers Danlos by the POTS specialist who claimed that he was the first one to make the connection between the two.

He was completely wrong in my case. I ended up having a bunch of treatments and unnecessary procedures that only made me worse. I then found an EDS specializing surgeon who was willing to operate on my spine in the absence of any indications, with the high risk of death and permanent disability. Thank God I changed my mind.

The whole hypermobility hype is just another popular "theory du jour" and I'm pretty sure that it will be discredited in a few years from now. There are some genuine cases of EDS but most of the hypermobility observed in CFS patients is probably just a normal phenotypical variant. The estimate is that about 10% of patients are hypermobile, and it seems that these days one doesn't even need to have hypermobility to qualify for EDS diagnosis. So in the absence of genetic markers and hypermobility, I really don't understand what this diagnosis is hinged on rather than the desperate need to provide the patient with some explanation.
 
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Strawberry

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My supine and upright MRI photos show almost equal degree of tonsil herniation. Most people get diagnosed with supine MRI. Photos in neutral position are required (not flexion/extension). The tonsils should be evaluated in different planes and with different slices.
Oh man, you guys are really making me think more that this is more the direction of my illness. I had my tonsils out at approximately age 32-35, and I felt great for a year. After a year and a half I was back to pre tonsillectomy illness.....

Thank you Hip and everyone, I will definitely follow all of these threads closer. I found a local doc that does flexion extension, now I just need to get the exam.
 

lafarfelue

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Oh man, you guys are really making me think more that this is more the direction of my illness. I had my tonsils out at approximately age 32-35, and I felt great for a year. After a year and a half I was back to pre tonsillectomy illness.....
Be aware that this refers to brain tonsils (not throat tonsils that can be commonly removed via surgery)! Like in this image: http://1.bp.blogspot.com/-eBLETCd2-Uc/T43f7u6osPI/AAAAAAAAANw/L6iThQ1wRz0/s1600/Mayfield Clinic Pic.jpg

*edited* to make the distinction between types of tonsils
 
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I have not come across infections causing these cervical spinal abnormalities, but since these abnormalities can cause ME/CFS-like symptoms, I wonder if there may be some common pathways (eg, both triggering the sickness behavior response).
Infection can cause instability (through tissue damage).

See for instance this article by Henderson: “Atlantoaxial instability (AAI) occurs as a result of trauma, congenital conditions such as os odontoideum, neoplasm, infection and degenerative connective tissue disorders such as rheumatoid arthritis, genetic conditions such as HOX-D3 and Down syndrome, and heritable connective tissue disorders, emblematic of which are the Ehlers Danlos syndromes (EDS)”
https://www.omicsonline.org/open-ac...n-2165-7939-1000364.php?aid=87993&view=mobile
 

Sidny

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I have not come across infections causing these cervical spinal abnormalities, but since these abnormalities can cause ME/CFS-like symptoms, I wonder if there may be some common pathways (eg, both triggering the sickness behavior response).
I would think both could trigger the sickness behavior response (as structural abnormalities and infections seem like things that could cause central nervous system inflammation) but what I also find intriguing is whether two proposed factors in ME/CFS-like illnesses (infections and cervical spinal abnormalities) might be on the same continuum as one potentiates the other and/or one precedes the other

Interestingly a quick google search reveals both infections and toxic exposures as possible causes of acquired chiari malformation.

In my case I had rather solid structural stability before falling ill. Within a few weeks of catching my infection and developing ME I began to notice changes to supportive structures like skin, collagen, and general connective tissue degeneration throughout my body but very notably in my neck and jaw region.

Although I have no dx of cervical spinal abnormalities I could see that happening downstream of the connective tissue degeneration I'm currently experiencing. (That I believe was precipitated by the infectious processes and subsequent damage to tissues rather than EDS being the precursor) but who knows maybe I've lived with an unidentified form of EDS?

I still believe however, infection is playing a role in my structural instability probably at least through MMP activation as one mechanism
 
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Hip

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I also find intriguing is whether two proposed factors in ME/CFS-like illnesses (infections and cervical spinal abnormalities) might be on the same continuum as one potentiates the other and/or one precedes the other
Yes, I guess that there is a possibility that a pre-existing cervical spinal abnormality might be a predisposing factor that makes it more likely for ME/CFS to appear as a result of an infection with an ME/CFS-associated viruses like enteroviruses or herpesviruses.



It's also worth noting that dysfunction of the brainstem area of the brain has been implicated in ME/CFS, most recently in this 2018 study.

The brainstem is where the top part of spinal cord connects to the brain. In the MRI image below, the brainstem is colored green. So it's interesting that a disruption to the brainstem or the top part of spinal cord seems to be involved in ME/CFS or ME/CFS-like symptoms.

MRI of brain and spinal cord, with brainstem colored green
hd09.jpg

It's also worth pointing out that 2 brain autopsies of ME/CFS patients have found enterovirus infection in the brainstem, as well as in other brain areas.



A Chiari malformation impinges on the brainstem area, perhaps squeezing the brainstem and spinal cord.
Chiari malformation = where part of the brain
gets pushed into the spinal canal

chiari-illustration.gif
 
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debored13

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I was told that my CFS and POTS were due to Ehlers Danlos by the POTS specialist who claimed that he was the first one to make the connection between the two.

He was completely wrong in my case. I ended up having a bunch of treatments and unnecessary procedures that only made me worse. I then found an EDS specializing surgeon who was willing to operate on my spine in the absence of any indications, with the high risk of death and permanent disability. Thank God I changed my mind.

The whole hypermobility hype is just another popular "theory du jour" and I'm pretty sure that it will be discredited in a few years from now. There are some genuine cases of EDS but most of the hypermobility observed in CFS patients is probably just a normal phenotypical variant. The estimate is that about 10% of patients are hypermobile, and it seems that these days one doesn't even need to have hypermobility to qualify for EDS diagnosis. So in the absence of genetic markers and hypermobility, I really don't understand what this diagnosis is hinged on rather than the desperate need to provide the patient with some explanation.
I think this is unnecessarily dismissive. Everyone has pet theories but I rate anecdotal evidence high if fits a certain standard of plausibility. Jeff and Jen had standard diagnoses of ME through specialists that are highly regarded in the community. They also fit all of the ICC criteria. And yet they were both diagnosed with CCI, which explains all of the symptoms of ME/ POTS, and Jeff has made a full recovery since surgery. Neither of them had hypermobility or EDS diagnoses. CCI could be caused by a virus or bacteria that produces collagenases. Brainstem compression couldnexplain many of the findings in ME/CFS.
More than 10 Me/CFS patients since Jeff’s story came out have been diagnosed with this. It’s not a clinical diagnosis and there’s no way to simulate it, it’s not social contagion or a bandwagon. It’s clear cut given the proper imaging and a good neurosurgeon to review the imaging.

There was one large study on fibromyalgia patients that showed about 70% of them having either spinal stenosis or chiari. There is also recent published research of a couple cases of ME/CFS patients recovering after surgery for spinal stenosis. These all seem like possibly small anecdotes until you realize how few people with this have been screened properly for chiari/CCI/etc.

Either it’s a possible cause of ME/CFS or it can be so similar that it can mimic the symptoms enough to fool ME/Cfs specialists. I don’t care which is true, it’s a semantic argument at this point. Either way there’s literally no harm in a thorough differential diagnosis that includes this imaging, and it could quite possibly save a lot of people.

Chiari, btw, is treated a lot differently than CCi and it seems like would be a lot more difficult to treat, the surgery seems to be way less likely to be successful. Regardless these are serious conditions and people should know if they have them. diagnostic procedures ade probably the worst part of the healthcare system to have rationing in

It sounds like your experience was shaped a lot by an encounter with someone who was probably or possibly a quack. This doesn’t mean that all doctors who diagnose and treat this are quacks. I don’t think bolognese et al are and many patients are satisified with them.