CFS and other fatigue syndromes

To correctly estimate the exact incidence of CFS is problematic, because the diagnosis is very often made late or not at all. The disease is simply not diagnosed.

In the USA it is assumed that 1.7 to 3.3 million people are affected and a rate of 857 per 100,000 inhabitants.

Transferred to Germany this would mean about 600,000 patients with CFS. For comparison: That would be 50% more than sufferers of multiple sclerosis. Thus CFS would not be a rare disease.

But these figures are not undisputed. Otherauthors assume significantly lower frequencies.

Gender ratio

As always with functional disorders, women are more often affected than men. In the USA, however, 35-40% were also men.

However, there are errors here. Physicians apparently tend to diagnose such disorders more in women.

Source

The fatigue is often hard to describe for those affected: "When I get up in the morning, I feel as if a steamroller had run over me during the night," reports one young man. "I then try to struggle out of bed and only after ages do I then come out and need 2, 3 hours until I can keep my eyes open to some extent.

After 2 hours, when I have expended just a little energy, I am then so exhausted again that I have to lie down again, although I have done almost nothing. I can't run my household, can't concentrate, can't do any physical work. I just shuttle between bed and armchair and can't get myself up to do anything."

The exhaustion increases thereby above all with physical in addition, with mental exertion, and/or after infections clearly.

Investigations showed that despite the complained forgetfulness, the intelligence is completely preserved. However, the mental performance was reduced in CFS patients. Above all, the speed with which certain tasks could be solved was lower than in healthy people.

Besides fatigue, muscle pain is a major symptom (about 75% are affected). This is similar to sore muscles or as during a viral infection. One feels "flu-like" all the time.

Muscle fasciculations, the twitching of individual muscle bundles, is also a common symptom that can be very irritating for those affected.

See Muscle fasciculations

The discomfort worsens with any form of physical exertion. This fact is significant, as it makes the frequently recommended sport practically impossible.

The pain is similar to that of fibromyalgia.

See Fibromyalgia

In medicine, there is a tendency to associate numerous diseases with the usual suspect life circumstances (alcohol, smoking, obesity). But in the case of CFS, things look quite different. ADutch studyeven comes to a contrary conclusion: the affected people live significantly healthier!

"Compared to the general Dutch population, significantly fewer CFS patients were overweight. Significantly more female CFS patients abstained from alcohol, and fewer male CFS patients smoked. Unhealthy lifestyle factors were not significantly associated with fatigue severity or functional impairment."

Many patients report a stressful, hectic time before the onset of the disease. This is described as particularly stressful if other complaints such as infections, pain or stressful events such as separations or illness in the environment are added.

Another indication of the importance of chronic stress is the fact that natural disasters, violent events or severe emotional stress increase the chance of developing exhaustion.

The soul probably plays a greater role in the development of fibromyalgia syndrome. In 50-80% of patients, there is a history of a more or less pronounced mental illness.

Especially depressive disorders are frequently present. A distinction between depression and CFS is therefore sometimes difficult, since depression is associated with exhaustion. Strictly speaking, depression is an exclusion criterion for CFS if it was already present before.

ADutch study investigated the so-called "disease attribution", i.e. to which causes the symptoms are attributed. It was found that patients who suspected external causes had more complaints. Possible explanation: They felt more helpless, more like victims.

Quote: CFS patients attributed their fatigue more often to external causes, reported poorer physical functioning, more doctor visits, and lower employment rates. Results of a regression analysis showed that patients who believe their fatigue is associated with more severe consequences, that their fatigue lasts longer, and is responsible for more additional symptoms are more likely to be classified as CFS, while patients who are more physically active and have higher levels of "all-or-nothing" behavior are less likely to be classified as CFS.

Corticotropin (CRH) is the central stress hormone and ensures the body's readiness reaction for flight and fight. Via the intermediate station of the pituitary gland (production of ACTH), cortisone is increasingly produced. This then ensures readiness.

However, permanent stress and permanent pain change the way the system reacts. Patients suffering from chronic fatigue appear to have lower blood cortisol levels and altered responsiveness of the CRH-ACTH-cortisone axis.

Growth hormone: Many studies suggest that low levels of growth hormone (GH) are both a consequence of the disease (lower production in sleep disorders) and play a role in causing the disease.

Melatonin: There are different results here, ranging from no difference to healthy individuals to increased melatonin production at night.

Sleep disorders are an essential part of CFS. In this case, those affected suffer from "hypersomnia," or an abnormal need for sleep. "I could sleep 24 hours a day without being well-rested, said one patient.

The hallmark is disturbed deep sleep, which is described as non-restorative sleep.

Anobjectification of the sleep disturbancesdoes not succeed however also in the Polysomnographie (sleep laboratory) usually. The sleep architecture is usually normal. Therefore, this lack of recovery is often interpreted as a misinterpretation of sleep.

Recently, we are increasingly studying the influence of carbon dioxide on sleep quality in CFS. This metric is usually not monitored in the sleep laboratory. It may play a major role regarding the restfulness of sleep.

Very many sufferers complain of a constant feeling of dizziness. They feel as if their head is wrapped in absorbent cotton or they have drunk too much. Not infrequently, they complain of a feeling of derealization, as if they were standing behind a glass wall and were not "really there".

This symptomatology is very similar to PPD, "vertigo without findings" or brainfog, which is explained in detail elsewhere.

Even though very many affected persons report a severe infection as the beginning of the symptomatology, the role of chronic viral infections in the further course is unclear.

Frequently, EBV infection is referred to as a possible cause. But it must be taken into account that the infectivity in the population is95%and the rate of CFS is less than 1%.

• Some subsets of white blood cells (B- CD19- lymphocytes) are increased, others (T- CD4- cells, T- CD8- cells) are decreased.
• The ratio between certain parts of lymphocytes is altered (T-CD4/T-CD8 ratio decreased).
• The number of killer cells is increased.
• Immunoglobulins show no clear findings (increase/decrease).
• Partial ANA (antinuclear antibodies) and autoantibodies are elevated.

Numerous viruses have been blamed for CFS. In CFS, signs of an infection that has passed through were indeed found to be disproportionately frequent. Whether this was actually the cause of the disease or just one of many triggers remains open. Personally, I tend to the latter view.

• Paroviruses: No clear connection
• Herpes Simplex Virus: No clear connection
• Cytomegalovirus: No clear connection, since most people had a contact anyway.
• Epstein-Barr virus (EBV): 90% of all adults have had contact with the virus. Certainly no "chronic EBV infection" is present.
• Human herpes viruses 6- 8: No clear connection
• Influenza viruses (flu): No clear association

However, the significance of these findings is open. Onereview concludes:

"Currently available data on the role of chronic viral infection in ME/CFS remain controversial; at least for a subset of ME/CFS patients, they show potential viral involvement."

We consider immunological disorders to be very significant: Especially after physical or mental stress, there is a general feeling of illness or "flu feeling" with swelling of the lymph nodes or increased temperature.

Inflammatory factors in CFS have been reliably proven. Areview showed that patients with CFS had significantly elevated tumor necrosis factor, interleukin-2, interleukin-4, transforming growth factor, and C-reactive protein. Likewise, impaired T-cell metabolism wasfound, as was a reduction inco-enzyme Q10.

In aNorwegian study, CFS was treated with rituximab, which is otherwise used in cancer therapy and suppresses the immune system. After initial hope, further studies showed that this hope was premature. The side-effect-rich and expensive drug showed no improvement in symptoms within 24 months. On the contrary, the placebo group showed a better response (36%) than those treated with rituximab (26%).

It is unclear whether immunological changes are the actual cause or only the consequence of the symptoms (e.g. overstimulation of the immune system after a severe infection).

Mitochondria are often referred to as the "power plants" of cells. They are the site for the citrate cycle and the respiratory chain. Therefore, more of these cell organelles are found in cells with a high energy turnover, e.g. muscle cells, sensory cells or nerve cells.

So could it be that the perceived lack of energy in CFS is due to a disturbance of these energy supplying cells? At least, this assumption does not seem unreasonable at first glance.

Mitochondriopathy: Diseases of the mitochondria(mitochondriopathy) are rare (about 12/100,000) and usually occur in childhood or early adulthood. There are several dozen known disorders. Diagnosis (usually muscle biopsy) should be done at aspecialized facility. Currently, there is no causative therapy and no cure. Various vitamins are used, but the effect is uncertain. Endurance training below maximum load, on the other hand, is recommended.

Pseudoscientific definition: The so-called "mitochondrial medicine" must be sharply distinguished from these serious diseases. It is a non-scientific model of thinking that associates countless disorders and diseases with a presumed disorder of the mitochondria. Therapeutically, a variety of vitamins and minerals are usually recommended.

CFS and changes in mitochondria: There are a number of scientific studies investigating the link between CFS and changes in mitochondria. The assumption that changes in energy production are responsible for the perceived exhaustibility is in some ways obvious.

However, such studies are by no means trivial, as the small power plants have a complex structure and numerous functions. The results of investigations are contradictory. Sometimes changes are found, sometimes not. However, the quality of the studies is highly variable. Was there a comparison group? Was age taken into account? How many people are included? How is the disease defined?

In 2020, acomprehensive comparative studyhas now beenpublished, highlighting 19 high-quality studies from the plethora of publications. Here is the authors' conclusion:

"Detection of potentially disrupted mitochondrial pathways is difficult to establish with certainty because of the use of different sampling methods. There is consistent genomic research suggesting that ME/CFS/SEID is not a primary mitochondrial disorder, but mitochondrial damage could occur due to secondary effects of other disrupted pathways. In addition, the findings were inconsistent across studies. Because the population samples were small, these findings should be interpreted with caution. The cause of ME/CFS/SEID remains unknown, and future studies using the same diagnostic criteria and analytical methods for ME/CFS/SEID are needed to determine the mitochondrial contribution to the pathomechanisms of ME/CFS/SEID."

CONCLUSION: There is a preponderance of evidence that the cause of CFS is not due to mitochondrial damage. This is also supported by the fact that corresponding therapeutic approaches with vitamins and enzymes usually do not show a pervasive and stable effect.

A positron emission tomography (PET)scan found evidence of inflammatory processes in the brain that correlated with symptom severity.

From our point of view, very significant arestudies on shortness of breath in CFS, which are in line with our own observations. In one study, 54% of CFS patients but only 3% of controls showed relevant dyspnea. In contrast, lung function itself was not different.

This substantial difference suggests the importance of functional breathing disorders in CFS.

More in the presentations infunctional breathing disordersand their influence on cerebral blood flow.

There is a great deal of evidence, both in our patients with CFS and in theliterature, of impairedcirculatory regulation in CFS. Many of those affected fulfill the criterion ofpostural tachycardia (POTS), which, like CFS, is often accompanied by massive exhaustion.