The first large study examines spinal issues in chronic fatigue syndrome (ME/CFS).
A couple of years ago, there was hardly any discussion of spinal issues in ME/CFS. It’s become clear, though, that spinal issues are present in some patients and can even, in some instances, produce virtually all the symptoms found in this disease. From cerebral spinal fluid leaks, to spinal stenosis, to intracranial hypertension, to craniocervical instability, the spine is now of intense interest.
Now comes the first large study – from Sweden – to assess spinal issues in ME/CFS.
Signs of Intracranial Hypertension, Hypermobility and Craniocervical Obstructions in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Björn Bragée1,3*, Anastasios Michos3, Brandon Drum1,3, Mikael Fahlgren2,3, Robert Szulkin3, Bo C Bertilson1,2,3*
This study was notable for a couple of things. For one, it appears that Sweden is moving rapidly on
ME/CFS. Not only has a large collaborative effort formed around the Open Medicine Foundation’s Uppsala Collaborative ME/CFS Research Center, but a newly formed – apparently quite busy – ME/CFS clinic (Bragee Clinic) has shown up in Stockholm. (That makes two ME/CFS clinics in Stockholm, now.)
Bjorn Bragee, the creator of the clinic, talked about it:
“We need quality research and a better understanding available in public health care regarding this diagnosis. At our clinic we will be working from a biomedical perspective and staying updated on new available treatments. So far, there is no treatment that works for everyone. “Many are bedridden at home and their quality of life is alarmingly low.”
Created in 2017, the clinic worked quickly to gather what may be the largest array of MRIs collected for ME/CFS. These 200- plus MRIs were used to produce easily the biggest assessment of spinal issues in ME/CFS. The group used the MRIs and a clinical examination to assess intracranial hypertension, joint hypermobility, Ehlers Danlos Syndrome, various conditions that can obstruct spinal fluid flows, spinal issues and craniocervical instability.
Nobody expected Sweden or anywhere else to so quickly focus on spinal issues but Bragee jumped on this issue quickly, and here we are with a quite large ME/CFS spinal study.
The Conditions Assessed
Joint hypermobility – When the joints become too flexible, they can produce pain and stiffness, clicking joints, easily dislocatable joints, recurring muscle/joint injuries, constipation and irritable bowel syndrome (IBS), fatigue, dizziness and fainting, thin or stretchy skin.
Intracranial hypertension occurs when high cerebral spinal fluid pressure is present. Its symptoms are similar to those produced by a brain tumor and include frequent headaches, blurry or double vision, poor peripheral vision, dizziness, nausea and/or vomiting, stiff neck, gait and coordination problems, tinnitus (ringing in the ears), forgetfulness and depression.
Ehlers Danlos Syndrome refers to a highly heterogenous groups of connective tissue disorders characterized by hypermobile joints, a high degree of skin extensibility, and fragile tissues. Thirteen subtypes are believed to exist including classic, hypermobile and vascular EDS.
- Classic EDS is characterized by symptoms such as loose joints, elastic, velvety and fragile skin, easy bruising, extra skin folds over the eyes, muscle pain and fatigue and heart valve problems.
- Hypermobile EDS is characterized by loose joints, easy bruising, muscle pain and fatigue, early onset arthritis, degenerative joint disease, heart valve problems and chronic pain.
- Vascular EDS is characterized by thin, transparent looking skin, fragile blood vessels, thin nose and lips, sunken cheeks and small chin, protruding eyes, collapsed lungs and heart valve problems.
Craniocervical Instability refers to a condition where lax ligaments which hold the head up over the body allow the brain to impinge upon the brainstem, spinal cord or nerve roots. Symptoms can be diverse but generally include headache, neck pain, numbness, heavy feeling head, “bobble-head”, dizziness, vertigo, gait and coordination problems, muscle weakness, problems with sleep and visual disturbances. Jeff, Jen Brea and others diagnosed with ME/CFS were found to have CCI. Jeff and Jen Brea made full recoveries from severe cases of ME/CFS after surgery.
Chiari malformation occurs when the cerebellum dips down into the spinal column cutting impeding spinal fluid flows. Its associated pain (especially headaches aggravated by coughing/straining), weakness – especially in the hands, neck, and arm – and leg pain, numbness, temperature insensitivity, unsteadiness, double vision, slurred speech, trouble swallowing, vomiting and tinnitus (ringing in the ears).
A major downside to this study concerns its mode of publication. Instead of being published in a peer-reviewed medical journal, it was published on a non-peer reviewed “open access site“. That will greatly limit access to the study and blunt its impact.
The authors didn’t say how they determined severity but reported that the study examined a severely ill patient group.
- The group used the 2017 International Classification of the Ehlers-Danlos Syndromes to assess the incidence of Ehlers-Danlos Syndrome.
- The Beighton Score (> or = to 4) was used to assess the degree of hypermobility. (The Beighton score, it should be noted, does not assess all types of hypermobility.) While hypermobility is associated with EDS, most people who are hypermobile do not have EDS.
- Interestingly, the group bypassed the new criteria for FM and used the 1990 criteria.
Assessments of Intracranial Hypertension (IH)
The authors used well-established non-invasive means of assessing IH including:
- The Eyeball Transverse Diameter (ETD)
- The Optic Nerve Sheath Diameter (ONSD) – CSF fluid percolates through the nerve sheath that wraps the optic nerve. Normal ONSD = 4.8-5.8; >5.8 believed to correspond with elevated CSF pressure (>25 mm Hg)
- ONSD/ETD – normal = 0.19+/- 0.02; > 0.25 = IH with severe symptoms
Spinal issues that could disrupt spinal fluid flow
The group also looked for structural problems which could result in reduced spinal fluid flows and IH. They included:
- Lowered foramen magnum – The foramen magnum is a large hole at the base of the skull through which several arteries, membranes and ligaments and a nerve passes.
- Lowered position of cerebellar tonsils – the bottom half of the cerebellum can dip down into the upper spinal canal – cutting off spinal fluid flows. In more severe cases, this is called Chiari malformation.
The authors used something called the clivo-axial angle (CXA) to assess craniocervical instability (CCI). Experts agreed in the 2013 Consensus Statement on Craniocervical Instability that four tests can be used to assess craniocervical instability. The Consensus states that a clivo-axial angle (CXA) 135º or less is possibly pathological, and that, in some circumstances, stress the brainstem and spinal cord. It is not a definitive test of CCI, but indicates that further investigation is warranted.
Cervical Spine MRIs
In the cervical spine MRIs, the researchers assessed a number of factors which could impact spinal cord functioning including:
- spondylolisthesis (forward or backward slippage of the vertebrae)
- osteophytes (boney projections that can impede nerves)
- spinal cyst(s) or syringomyelia
- bulging or herniated discs.
An astonishing 96% of patients fulfilled the criteria for fibromyalgia. That number is quite high and may reflect the more severely ill group of ME/CFS patients the authors stated made up the study. A 1000 person ME/CFS Spain study found that 54% had fibromyalgia.
The Swedes found joint hypermobility (Beighton score >4) in a remarkable 49% of ME/CFS patients. Most of those (41% of total) fulfilled the hypermobility criteria (Beighton score >5) for hypermobile Ehlers Danlos Syndrome (hEDS). Twenty percent of ME/CFS patients met the full criteria for EDS (including hyper-elastic, extensible skin/fragile tissues).
Only a few studies have assessed hypermobility in ME/CFS. The 2002 Barron/Rowe study found that no less than 60% of children with ME/CFS had a Beighton score indicative of hypermobility. Four years later, Nijs et. Al. found 22% of the 69 ME/CFS patients had a Beighton score >4.
Why the focus on joint hypermobility? Because connective tissue and lax ligament problems also underlie many of the spinal problems the authors looked at. Lax ligaments, for instance, are responsible for craniocervical instability. Connective tissue problems can contribute to a lowered cerebellum, foramen magnum, as well. (EDS is not the only “lax ligament disorder. Others include: Loeys Dietz Syndome, Stickler Syndrome, Marfan Syndrome, Cleidocranial Dysostosis, Morquio Syndrome, Down syndrome, etc..)
While more studies are needed, hypermobility and therefore connective tissue problems appear to be common in ME/CFS. We will surely learn more about the incidence of hypermobility and EDS incidence from the CDC’s multisite study.
- Take the Beighton Test – note, though, that the Beighton test does not assess hypermobility in all parts of the body
Signs of intracranial hypertension (IH) were common with 55% having high ODNS ( >5.8 mm) and 83% having an ODNS/EDS ratio of greater than .25. The author reported that an ODNS/EDS ratio >.25 was associated with IH with severe symptoms.
Drooping Cerebrellar Tonsils – Fifty-six percent of patients (as opposed to a general population prevalence of 25%) had evidence of drooping cerebrellar tonsils which could be obstructing spinal fluid flows. Seventeen percent had evidence of the more severe Chiari malformation.
The authors reported that only a fraction (11%) of the patients had what is considered a normal position of the cerebellar tonsils.
The authors did not break out bulging discs from herniated discs. Bulging discs are quite common and often do not cause problems. Herniated discs on the other hand are rare and almost always cause problems. The authors reported that eighty percent of the patients had one or more obstructions in the cervical spine. More than one vertebral segment from the neck to the lumbar region was obstructed in 64% of participants.
A Clivo-axial angle (CXA) angle of less than 150 degrees was found in 114 of the patients (56%). Normal CXAs are reported to range from 150-170 degrees. Henderson reported that “the CXA has a normal range of 145° to 160° in the neutral position”. One study reported a mean CXA 148° for the healthy controls – which was identical to that found in this study.
While Van Gilder (somewhere – I couldn’t find the citation) reported that a CXA of less than 150° was associated with neurological changes, most authors and the CCI Consensus Statement report that only a much smaller CXA angle (135 degrees) is considered possibly “pathological” and indicative of craniocervical instability (CCI). The authors of this paper did not report how many patients met the more restrictive criteria.
A very high incidence of fibromyalgia comorbidity and the almost 50% incidence of hypermobility suggested that this patient population was indeed severely ill. The incidence of Ehlers Danlos Syndrome (EDS) appeared to be quite high (20%) as well.
- A large spinal study involving over 200 MRIs found:
- High rates of fibromyalgia (96%), joint hypermobility (49%) and Ehlers Danlos Syndrome (EDS) (20%) in ME/CFS
- High rates of increased spinal fluid pressure (intracranial hypertension) (55-80?) – a condition which can produce many symptoms associated with ME/CFS
- Apparently normal rates of spondylolisthesis, osteophytes and spinal cysts
- Possibly high rates of bulging or herniated discs (which could interfer with spinal flows)
- Most normal clivo-axial angles – suggesting that cranialcervical instability may not be common in ME/CFS
- The fact that the study was not published in a medical journal severely limits its impact.
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It was not easy to assess the incidence of spinal issues but they appeared in line with those found in the general population. Eighty percent of the participants tested, however, had either bulging or herniated discs.
Craniocervical instability (CCI) was assessed by Clivo-axial angle. Most sources suggest that the mean CXA in ME/CFS (148 degrees), was low normal or borderline (normal = 150-170 degrees). (CXAs of 135 degrees or less are likely pathological and may be indicative of CCI). Because the authors only provided a mean for the group, it’s not clear how many patients had lowered CXAs, but some clearly did. As a whole, though, the group’s CXA – and therefore, one would assume the rate of CCI – did not appear strikingly abnormal.
The big news was the very high rates of intracranial hypertension found. Depending on which measure was being assessed, estimates ranged from a whopping 55% to over 80% of the group. Plus, the study suggested that a strikingly high percentage of patients (17%) relative to the general population (<1%) may have Chiari malformation.
It seems the more ME/CFS is studied, the more possibilities turn up. Since IH can produce or contribute many symptoms found in ME/CFS, this study, while unpublished, will hopefully incentivize others to assess spinal issues in ME/CFS. Hopefully, the CDC’s multi-site study will shed more light on the spine. Avindra Nath is also assessing spinal issues in the intramural study.
Unfortunately, the study was not published in a peer-reviewed scientific journal and therefore will not get much traction in the medical community. Doctors will need studies published in medical journals to begin to assess and diagnose spinal issues present in ME/CFS. Hopefully, the CDC’s multisite study will address these issues.
Check out a deeper dive in intracranial hypertension
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