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The title, “Provocation of brachial plexus and systemic symptoms during the elevated arm stress test in individuals with myalgic encephalomyelitis/ chronic fatigue syndrome or idiopathic chronic fatigue“, doesn’t exactly roll off the tongue trippingly. It’s getting at something potentially important, though. The brachial plexus refers to an area where the nerves and blood vessels that run from the neck, shoulder, arm, and hand that run to the spine get bundled together and have to pass, yes, through a small opening.

Brachial plexus dysfunction—also referred to as thoracic outlet syndrome—results when the nerves, veins, or arteries get compressed as they pass through the thoracic outlets. The thoracic outlets are narrow passageways between the collarbone and the rib at the top of the rib cage. Because many nerves and blood vessels flow through that area, TOS can cause a wide variety of symptoms and often takes some time to be diagnosed.

Thoracic outlet syndrome

The thoracic outlet – another narrow passage for the nerves and blood vessels to get through…(Image by Nicholas Zaorsky, MD – from Wikimedia Commons)

Most TOS patients have “neurogenic TOS” where the nerves get compressed, resulting in pain, numbness, tingling in the neck, upper chest, shoulder, and arm that may worsen when the arms are moved. TOS can also produce chest pain similar to that found in angina. (The key difference is that the pain does not get worse when you walk, nor do people with TOS experience the classic symptoms of shortness of breath, stomach discomfort, sweating, and a feeling of impending doom that sometimes show up during a heart attack.)

Dr. Kamran Aghayev, a Turkish TOS specialist, wrote, “Pain is typically triggered by raising the hands or arms overhead (washing/combing hair, for instance), and headache typically starts at the base of the neck, spreads to the back of the head, then to the top of the head, and sometimes to the forehead and temples. Migraines are common, TMJ may be affected.”

If the classic symptoms of pain, numbness, fatigue, cyanosis (blue discoloration) of the arm, hand, and fingers, swelling, and visible veins in the arm were all there was to the TOS in ME/CFS, I wonder if Rowe would have done this study. Rowe, however, looked for signs that simple movements that put stress on the thoracic outlet were causing ME/CFS symptoms as well.

Aghayev has found them. He reports that exercise-induced symptoms are quite typical and that cognitive problems, lack of concentration, blurred vision, dizziness, chronic fatigue, ear pressure, tinnitus, sinus pressure, facial spasms, fainting, and facial flushing may also result.

He also writes, though, that pain, cyanosis (blue discoloration) of the arm, hand, and fingers, swelling, and visible veins are typically seen in the affected arms of TOS patients, and it’s not clear how often that is seen in ME/CFS/FM.

THE GIST

  • Thoracic outlet syndrome results when the nerves, veins, or arteries from the hands, arms, and shoulders are compressed as they pass through the narrow thoracic passageways to the spine.
  • Most TOS patients have “neurogenic TOS,” where the nerves get compressed, resulting in pain, numbness, and tingling in the neck, upper chest, shoulder, and arm that may worsen when the arms are raised. In Peter Rowe’s recent study, though, a substantial number of ME/CFS patients with TOS also experienced increased ME/CFS symptoms.
  • Forty-two percent of the 154 patients seen with chronic fatigue or ME/CFS and orthostatic intolerance over several years experienced pain when holding their arms over their head. Of that group, virtually everyone developed local symptoms, suggesting that TOS was present. In 41% of that group, TOS exacerbated their ME/CFS symptoms (lightheadedness, overall fatigue, racing heart, cognitive fogginess, and nausea) during a 1-minute EAST test. as well.
  • A Turkish TOS expert, Dr. Aghajev, believes that insufficient blood supply to the brainstem, cerebellum, and back part of the brain could be causing symptoms like dizziness, tinnitus, visual disturbances, and gait problems.
  • When asked by Dr. Rowe, though, why he thought TOS produced ME/CFS symptoms, he said nobody knows. It’s possible that the compression could impair blood flows to parts of the brain, and/or increased strain on the sympathetic nerves could also activate the sympathetic nervous system.
  • With regard to treatment, Peter Rowe’s first step with his ME/CFS/FM/TOS patients is physical therapy (PT). If that doesn’t work, botox injections to allow the nerves to pass through with less compression can provide 2-3 months of symptom improvement. For the occasional patients who have more severe symptoms, such as grip strength loss or chronic arm pain, first rib resection is the usual surgical approach.
  • Because stress can increase muscle tension in the neck, shoulders, and upper back, tightening the muscles around the thoracic outlet and compressing the nerves and blood vessels, several websites suggest that improving posture may also help.
  • Kjetal Larsen at MSK Neurology believes that stress, which causes the patient to become very tense, “clench,” and hyperventilate, can, over time, impair the function of the muscles in this area. People who “pec clench” (i.e., tighten their chest muscles when stressed) can exacerbate TOS.
  • Various stretching and strengthening exercises may help.
  • Kjetal Larsen also recommends “raising the shoulders slightly in posture (and staying there) to decompress the thoracic outlet and optimizing diaphragmatic breathing to strengthen the scalene muscles. On that note, a recent review paper highlighted the importance of diaphragmatic (gut) breathing in FM.
  • Thoracic outlet syndrome joins other anatomical + disorders such as craniocervical instability, spinal stenosis, and cervical myopathy that can produce or exacerbate ME/CFS/FM symptoms that are not typically associated with them. Treating these disorders can, at times, even remove the ME/CFS/FM symptoms entirely.
  • These anatomical areas where nerves and blood vessels bundle together and become vulnerable to compression and irritation are showing up more and more in these diseases. The complex architecture in the neck, in particular, through which the nerves to the brain flow, has become a key focus with doctors (if not yet with researchers).
  • Neuromuscular strain, brachial plexus, craniocervical instability, spinal stenosis, high intracranial pressure, cerebral spinal fluid leaks, and other spinal findings all involve nerves, blood vessels, and the spinal canal that are either in the wrong place—perhaps because of connective tissue failure—or have become damaged enough for movements – sometimes quite small – to cause pain, fatigue, etc.
  • Much of this could be due to mast cell activation damaging the connective tissues. An overview of the Mast Cell Masterminds Conference is coming up

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Tests

Rowe used two tests to assess the likelihood that TOS was present.

The Modified East Test

The Modified East test Rowe used:

  • The patient sits with both arms at 90 degrees and elbows at 90 degrees forming a “goalpost” or hands up position.
  • The patient then repeatedly opened and closed their hands slowly for 1 minute.
  • A normal response is mild forearm fatigue and minimal discomfort.
  • A positive local test resulted when the participant experienced pain, fatigue, heaviness, tingling, warmth or tremulousness in the upper limb, shoulder, neck, head or upper back.
  • A positive systemic test resulted when the participant experienced overall fatigue, cognitive fogginess, lightheadedness, racing heart, diaphoresis, dyspnea, overall warmth, and/or nausea.

The study also assessed whether orthostatic intolerance and/or joint hypermobility/Ehlers-Danlos syndrome (Beighton) test was present.

 Upper Limb Neurodynamic or Tension Test 1 (ULNT1)

They also did an upper limb neurodynamic or tension test 1 (ULNT1).

Results

The study found that many people diagnosed with chronic fatigue or ME/CFS and orthostatic intolerance also appear to have thoracic outlet syndrome (TOS). If I’m reading this right 42% of the 154 patients seen at the Johns Hopkins clinic with chronic fatigue or ME/CFS and orthostatic intolerance over several years experienced pain when holding their arms over their head. Of that group, virtually everyone developed local symptoms suggesting that TOS was present, and in 41% of that group, TOS exacerbated their ME/CFS symptoms (lightheadedness, overall fatigue, racing heart, cognitive fogginess, and nausea) during a 1-minute EAST test. as well. Almost 60% of the TOS group had evidence of joint hypermobility.

The high incidence of local symptoms (pain, numbness, arm fatigue) was noteworthy, but even more so was the approximately 40% of patients with TOS who experienced things like lightheadedness, cognitive problems, nausea, etc., during the quickie 1-minute EAST test. How could simply raising one’s arms in a goalpost position and squeezing one’s hands for one minute produce symptoms like dizziness and cognitive problems?

Brachial plexus

Another look at the tight junctions in the brachial plexus area. (Image_Gray_Retouched_-Rafael-Di-Marco-Barros_Wikimedia_Commons)

Aghajev believes that insufficient blood supply to the brainstem, cerebellum, and back part of the brain could be causing symptoms like dizziness, tinnitus, visual disturbances, and gait problems.

When asked Dr. Rowe, though, why he thought TOS produced ME/CFS symptoms he said nobody knows. It’s possible that compression of the subclavian artery could impair blood flows to parts of the brain. Because the nerves in the brachial plexus are connected to the sympathetic ganglia, increased strain on those nerves could also activate the sympathetic nervous system.

I also found some suggestions that compression of cervical lymphatic vessels could theoreticlly impair the glymphatic drainage of toxins from the brain.

Note that most explanations of TOS, including the video below, do not mention the systemic symptoms, such as dizziness and problems with cognition, that Rowe found in his ME/CFS group with TOS.

In what’s called the “hyperperfusion paradox”, compression of the subclavian artery can also divert more blood flows to the head causing excessive blood flows (cerebral hyperperfusion), producing headaches, migraines and neurological symptoms.

Treatment

Recognition of this problem introduces another avenue for treatment of those with ME/CFS and the related conditions we have studied. The authors

The first step for Peter Rowe with his ME/CFS/FM/TOS patients is physical therapy (PT). If that doesn’t work, botox injections to reduce the volume of the scalene muscles and allow the nerves to pass through with less compression can provide 2-3 months of symptom improvement. For the occasional patients who have more severe symptoms, such as grip strength loss or chronic arm pain, first rib resection is the usual surgical approach.

The stellate ganglia in the neck near the first rib provide sympathetic nerves to the brachial plexus. Stellate ganglia blocks can sometimes help with TOS pain, but don’t help with the underlying problem—the compressed nerves.

Stress and Posture

Posture

Postural problems and muscle tension can contribute to TOS.

Stress can increase muscle tension in the neck, shoulders, and upper back, tightening the muscles around the thoracic outlet, compressing the nerves and blood vessels, and leading to poor posture, a known risk factor for TOS, which one study suggested is commonly found in FM. Kjetal Larsen at MSK Neurology believes that stress, which causes the patient to become very tense, “clench,” and hyperventilate, can, over time, impair the function of the muscles in this area. People who “pec clench” (i.e., tighten their chest muscles when stressed) can exacerbate TOS.

While it’s unclear what’s happening, one study suggested that upper body muscle tension could produce or enhance a flattening of the cervical spine. In a recent study, fifty percent of FM patients showed a “complete loss of lordosis,” i.e., the normal curve of the spine at the neck, which was associated with an increased FM headache risk.

While various stretching and strengthening exercises are recommended, it’s probably best to work with a physical therapist (PT) who can determine the appropriate interventions.

Kjetal Larsen at MSK Neurology, who appears to be an outlier, does not like stretching what he believes are already weak muscles. He uses manual muscle testing, palpation, and strengthening exercises. He wrote that “raising the shoulders slightly in posture (and staying there) to decompress the thoracic outlet and optimizing diaphragmatic breathing helps to strengthen the scalene muscles”. On that note, a recent review paper highlighted the importance of diaphragmatic (gut) breathing in FM.

The Anatomical Plus Problems

Welcome to a new anatomical + problem in ME/CFS/FM! These are anatomical plus problems because, besides the normal symptoms they’re associated with, they can produce ME/CFS/FM symptoms in some people

We’ve seen these “anatomical plus” problems in these diseases for some time. A 2007 Chicago FM study assessing cervical myopathy (spinal cord compression) in FM reported, “that many of the patients’ complaints are not commonly associated with cervical myelopathy, e.g., fatigue, cognitive disturbance, depression, irritable bowel syndrome, nausea, and intolerance to cold”.

They found, though, that surgery to treat cervical myopathy (spinal compression) produced “a striking and statistically significant improvement in all symptoms attributed to the fibromyalgia syndrome” a year later. This is despite the fact that the FM patients were specifically told that the surgery was not being done to treat their FM symptoms. The authors recommended “detailed neurological and neuroradiological evaluation of patients with fibromyalgia in order to exclude compressive cervical myelopathy, a potentially treatable condition.”

In 2008, Holman reported that 71% of fibromyalgia patients and 85% of people with chronic widespread pain met the criteria for spinal cord compression and called for “dynamic” MRI imaging (i.e., imaging done with the neck flexed or extended).

In 2015, Holman was back with a conference presentation, which for whatever reason never got published. His blinded study found that almost 60% of FM patients met the criteria for positional spinal cord compression (PCS), which was triggering sympathetic nervous system activation. Although the abstract stated, “Further investigation will to sort out the role of PC3 in the diagnostic conundrum of FM, its pathogenesis and its treatment algorithms“, Holman never published on FM again.

In 2018, Rowe showed that relieving spinal stenosis can relieve ME/CFS/FM symptoms and, in some cases, even remove them entirely. He attributed the symptoms to spinal cord compression.

These spinal problems aren’t the only place where these mysterious “plus” diseases, where systemic symptoms like widespread pain, fatigue, etc., get added onto more localized symptoms. People with rheumatoid or osteoarthritis, lupus, primary muscle dysphonia, and other chronic pain diseases are also at increased risk of coming down with fibromyalgia, i.e., nociplastic pain problems. How a condition like spinal stenosis, TOS, or other diseases moves from producing more localized symptoms to system-wide symptoms is unclear. One would think, though, that the brain must be involved.

Vulnerable Areas

These anatomical areas, where nerves and blood vessels bundle together and become vulnerable to compression and irritation, keep showing up in ME/CFS/FM. The complex architecture in the neck, in particular, where the nerves to the brain have to maneuver, has become a key focus with doctors (if not yet with researchers!).

Neuromuscular strain, brachial plexus, craniocervical instability, spinal stenosis, high intracranial pressure, cerebral spinal fluid leaks, and other spinal findings all seem to involve nerves, blood vessels, and the spinal canal that are in the wrong place, perhaps because of connective tissue failure.

Central sensitization in the brain and spinal cord is a complicating factor. Could the overaimplification of pain signals associated with that be the reason that the overt symptoms of TOS—the blue hands, the bulging veins in the arms, the numbness—don’t show up so much in these diseases? Is central sensitization making an anatomical issue worse or is a connective tissue failure (driven by mast cells) the main culprit? The high rate of joint hypermobility found in the TOS patients suggests that connective tissue damage certainly plays a role.

The stage for this study was seemingly set years ago when Peter Rowe’s neuromuscular strain studies found that small movements could cause symptoms such as fatigue and pain. Rowe discovered that the inability of nerves and soft tissues to elongate properly produced tension in the nerves, at times causing pain and other symptoms. Rowe postulated a number of factors (connective tissue laxity, poor posture, anatomical problems, etc.) that could be causing the movement restrictions he found, but his findings have never been properly explored.

Getting Unrestrained: Dr. Peter Rowe on Neuromuscular Strain in Chronic Fatigue Syndrome (ME/CFS)

Recent fibromyalgia studies, which found reduced tissue elasticity/muscle stiffness in fibromyalgia patients’ trapezius muscles associated with increased pain and migraine, perhaps underscored Rowe’s finding. The study’s authors pointed to a now-familiar possible culprit: connective tissue problems.

Mast cell activation could explain a lot of this.

  • Coming up – a blog on what may be a surprisingly effective drug for mast cell activation, plus an overview of the recent Mast Cell Masterminds Conference.

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