Within the last year, there have been some very good comprehensive studies published on Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) pertaining to the how and why of such a mysterious illness. It continues to be an enormous endeavor for researchers to piece together this illness and related illnesses like it. The kaleidoscope of research points to multilayered neurological, immune, and gut inflammation involving numerous pathways. The current hypotheses and findings allow validation, insight and management for those who struggle with CFS/ME and similar complex disorders like fibromyalgia, postural orthostatic tachycardia syndrome, chronic Lyme’s disease, and others.

Chronic Fatigue Syndrome Triggers

The consensus amongst the latest CFS/ME and fibromyalgia research is that there is usually some trigger that ignites the disease process. Depending on what journal is reviewed, different triggers are cited. Triggering events may include an immune challenge such as an infection, severe stress, trauma or musculoskeletal injury, gut dysbiosis, or a combination of the events.

A genetic predisposition may also be present. Statistics show higher risk of developing CFS/ME if an immediate family member also has the disease. Genetics may also influence the progression and severity of the immune inflammation.

Common Thread: Glial Cell Over-activation and Neuroinflammation

The overall common thread in CFS/ME relates to glial cell over-activation and brain inflammation. Researchers hypothesize that one or all of these triggers listed above lead to glial cell activation. Glial cells are the brain’s immune cells and workhorse. They take care of daily housekeeping, but they work best when not under constant stimulus and strain. If the trigger is substantial enough or cannot be adequately managed, glial cells become chronically activated. This creates a significant amount of oxidative and nitrosative/nitric oxide distress.

The consequence of the oxidative and nitrosative stress is neuroinflammation. This impact creates a collective ripple effect that deregulates and exhausts the endocrine system, immune system, mitochondria, and leads to neurodegeneration, autoimmunity, and central sensitization with chronic fatigue, chronic pain, and cognitive dysfunction. Chronic glial cell activation also leads to the brain atrophy identified in Chronic Fatigue Syndrome and fibromyalgia.

In response to overstimulation and chronic activation, glial cells release calcium, glutamate and histamine, TNF-a, nitric oxide, and other inflammatory chemicals. These compounds lead to further irritation, like a nervous system that is sunburned and becomes even more sensitive to toxins and electromagnetic fields (EMF), electromagnetic radiation, autoimmune dysfunction, and aging. This gives rise to brain fog, brain fatigue, immune-induced fatigue, poor physical energy production, and host of other symptoms. It also leads to chronic pain and “wind up”, sensory overload, headaches, and poor blood flow to the brain.

Neuroinflammation Alters Neurotransmitters and Creates Systemic Effect

Neurotransmitters are affected by the glial cell inflammation and neuroimmune dysfunction. This alters serotonin, dopamine, norepinephrine, epinephrine, glutamate, and GABA, and even affects how adrenal steroid hormones work. Neurological inflammation also affects the heart and blood pressure regulation. It is seen as smaller heart size, lower blood pressure, and decreased oxygenation of brain tissues from decreased circulation. Diminished blood flow in the brain may ultimately impact the pH in blood and muscle tissues, which leads to increased lactic acid.

Trigger: Posture and Musculoskeletal Stress

One trigger seen but not often discussed in CFS/ME literature pertains to posture changes which stress the spinal column and in turn affect the spinal nerves and brain. Postural changes seen with forward head position, commonly seen with “text neck” from the use of today’s technology, desk work, driving, and whiplash injuries and loss of the normal curve in the low back creates significant strain to tissues. This contributes to tension and dysfunction within spinal nerves and ultimately the brain’s glial cells.

Loss of healthy posture and chronic strain to the spine leads to neuroinflammation and increased inflammatory cytokines. In some cases, it is thought to become a self-perpetuating cycle if the dysfunctional musculoskeletal patterns remain. As a result of the chronic postural strain, increased levels of glutamate and non-beneficial nitric oxide are released and either contributes “wind-up” and central sensitization.

Trigger: Infections and Autoimmunity

More recent research from February 2018 expands on the hypothesis of glial cell activation and neuroinflammation as it relates it to infections and autoimmunity. In this article, Infection Elicited Autoimmunity and ME/CFS: An Explanatory Model, researchers refine the immune-infection connection and gut dysbiosis hypothesis. In individuals who are genetically susceptible, there is an interplay and autoreactivity or a “hit and run response” with the infectious agent like mononucleosis or other illness, genetics, and the gut microflora, which creates autoantibodies. There might be a coexisting history of irritable bowel syndrome, dysbiosis and likely increased intestinal permeability or “leaky gut syndrome”.

Autoantibodies, likely from B cells, occur and depending on what tissues are affected, may lead to problems with energy metabolism and exercise intolerance (CFS/ME), fibromyalgia (FM), postural orthostatic tachycardia syndrome (POTS), autoimmune thyroiditis and hypothyroidism, or others. The process leads to increased levels of cytokines and inflammation, loss of energy production, and impaired cognitive function.

Trigger: Epstein Barr Virus as a Culprit?

Infectious agents that are suspect in triggering these autoantibodies and autoimmune reactivity vary across the scale. These include Epstein Barr virus, Q fever, giardiasis, and others. Much focus continues on the Epstein Barr virus (EBV) as it is seen as a frequent trigger. Essentially, the virus activates and fools the immune system into attacking the body and more inflammation ensues.

In a different publication, researchers discuss cutting-edge information on how Epstein Barr virus triggers, spreads, and leads to glial cell inflammation. The theory suggests that the first step is where lymphatic-like tissue comes together near or in nerve cell bodies in the spinal column or other sites as the result of some type of infection. The second step is that certain white blood cells which are already infected with the Epstein Barr virus transfer or deposit themselves where the lymphatic tissue has congregated in the nerve tissue.

Then, the EBV infected cell within the lymphatic tissue provokes inflammation in the surrounding nerve tissue. The local inflammation that is triggered kicks off a ripple effect or chain reaction that leads to glial cell inflammation within the brain and peripheral nerves. If the immune system is exhausted, then the glial cell inflammation expands and disease follows.

Trigger and Result: HPA Axis Hypoactivity and CFS/ME

Another dimension of triggers causing dysfunction relates to the hypothalamic-pituitary-adrenal axis (HPA axis) The HPA axis is found to be hypoactive or underactive in CFS/ME. This will look like adrenal fatigue, but it’s not an adrenal problem. The HPA axis, or relay structures and mechanisms that manage adrenal steroid hormone signals, are not working correctly. Why the HPA axis is underactive is still under investigation. However, it is likely that chronic inflammation and oxidative stress triggered by the immune system causes the diminished activity. It may also perpetuate itself as a negative feedback mechanism. Learn more about the HPA axis in a previous article, Stress and Adrenals: Restoring the HPA Axis.

Trigger and Result: Gut Dysbiosis, Lactic Acid and CFS/ME

There has been recent considerable research on gut bacteria found imbalanced with CFS/ME. Several studies have uncovered a common focus of gut dysbiosis and gut bacteria that produce toxic compounds to the brain and cellular energy production. Toxins from the dysbiosis and changes with intestinal permeability stimulate the immune system and lead to inflammation throughout the body and brain. Metabolic by-products from the gut flora may lead to toxic metabolites of D-lactic acid and ammonia, which contribute to lactic acid, fatigue, brain fog, other cognitive challenges and additional neurotoxicity.

Gut bacteria also produce hormones and neurotransmitters and talk to the brain via the vagus nerve or cranial nerve ten. If the gut is dysbiotic, it negatively impacts the neurotransmitters and even disrupts the HPA axis affecting fundamental processes like sleep-wake rhythms, energy production, and simple stress tolerance.

Does Lactic Acid and EBV Effects Extend Further?

Lactic acid has been implicated over the years with CFS/ME and fibromyalgia in various settings. New research published in the Journal of Virology February 2018 provides some valuable insight into lactic acid production and Epstein Barr virus. The study identified that elevated lactic acid helps B cells that are infected by EBV grow and adhere to tissues.

This is considered a strong risk factor for cancer cell growth because cancer cells prefer an acidic environment for growth and development. Is the gut dysbiosis lactic acid with underlying EBV trigger contributing to the incidence of cancer in this population? It is too early to correlate but research shows that some CFS/ME patients have an increased incidence of cancer and mortality potentially related with EBV and lymphoma. Small studies show patients with CFS/ME also have an earlier mortality rate due to heart problems and suicide. Recently noted, is the finding of CFS/ME patients with shortened telomeres which reflects accelerated aging. No matter how one looks at CFS/ME, there is a war going on many different battlefronts throughout the body and it takes a toll.

It is also recommended that individuals with the complex neuroautoimmune disorder avoid or reduce factors that contribute to the total body burden. These include heavy metals, chemical pesticides, like glyphosate/Roundup, mold toxins, low frequency and high frequency electromagnetic field/ EMF, psychological stress, dehydration, and exhaustion.

Disorders that are as complex as CFS/ME and fibromyalgia require many, many different tools. But it can be boiled down to the gut, brain, immune system inter-relationships and how inflammation reverberates or is managed throughout the body. The triggers from trauma, stress, and musculoskeletal injury, viral or infectious insults must be appropriately addressed.

There is not a simple path back to recovery with just one thing, but improvement and recovery can occur. The understanding of CFS/ME is like the story of the ten blind men trying to identify different parts of the elephant. Each part explored provides more clues to the identification and knowing what it is. Considerable knowledge is now available and can be utilized to help restore vitality and health over time.