Term – What is Fatigue?

Fatigue has been on everyone’s lips since the Corona virus outbreak. The publications with the latest figures on the high proportion of fatigue symptoms (20-60% depending on the study) in the so-called LongCovid Syndrome. LongCovid stands for persistent symptoms beyond the actual period of illness, even in people who had a mild course.

Here the similarity to CFS becomes clear. A viral disease (usually EBV) is also observed in CFS as a trigger for the fatigue symptoms.

Now what is fatigue?

Colloquially, the term exhaustion stands for a physical and/or mental state that is described as being tired, drained or powerless.

However, there is a form of tiredness and exhaustion that differs significantly from normal levels. This particularly pronounced form is referred to in medical jargon as fatigue. Such fatigue of medical disease value is characterized by extreme tiredness, lack of energy reserves or a massively increased need for rest, which cannot be alleviated by sleep and which is absolutely disproportionate to previous activities.

CFS patients have often completed an odyssey of visits to the doctor to get to the bottom of this phenomenon of profound and unresponsive fatigue that goes beyond normal levels of fatigue. Here they immediately find themselves in a tautological vicious circle when they meet a doctor who does not know this clinical picture or who, prejudiced against it, “does not believe” that it exists.

Unfortunately, due to ignorance of the disease, many colleagues in this country largely equate the chronic fatigue syndrome with neurasthenia ICD10, F48.0, a depressive syndrome F 32.1 or a “somatization disorder” or “somatoform pain disorder”.

The renowned US institute “National Academy of Medicine” also comes to the conclusion with the group of experts specially set up for this topic that misunderstandings and disbelief in the medical community mean that 84% to 91% of patients are not diagnosed and the patients ” undergo treatment strategies that worsen their symptoms (National Institute of Medicine 2015).

In this respect, the clinical picture with its misinterpretations is similar to the clinical picture of multiple sclerosis (MS). In the 1950s, these patients were also classified as hysteriform or mentally ill, until the development of computed tomography and laboratory findings from the liquor allowed the characteristic disorders to be identified. This is the stage of CFS disease, but now there are investigative findings that clearly identify an underlying somatic disorder.

What does it look like in everyday practice?

People who suffer from fatigue syndrome often have a hard time getting their condition recognized as a real illness. In my everyday practice, I hear again and again that the complaints of my patients are not taken seriously in the professional environment and among friends. A change in thinking is only taking place very slowly. Affected people have often had numerous visits to the doctor who were unable to diagnose CFS or rather ME. Accordingly, have not initiated any treatment that cures the disease. This is because CFS is very difficult to diagnose.

Frequently observed symptoms of CFS or rather ME
  • An exhaustion that cannot be changed by rest
  • Drastic collapse of the forces to only 20-30% of the original capacity
  • Other physically fluctuating ailments
  • The individual symptoms are often subject to extreme fluctuations within a very short time
  • Phases of exhaustion from e.g. T. more than 24 hours, depending on the effort several days

Toxic exposures, viral diseases and massive long-term overloads are discussed as the cause. This leads to a dysregulation of the information system within the body on a neuronal, hormonal and immunological level.

Cancer-related fatigue (CRF), which often breaks out in many patients after chemotherapy and radiotherapy, is also related to this. The well-known “exhaustion” after the interventional therapies does not go away and there are symptoms that are similar to the clinical picture of chronic fatigue syndrome.


In 1988, the clinical picture “chronic fatigue syndrome, CFS” was first defined by an international group of authors on behalf of the US Department of Health’s Centers for Disease Control and Prevention (CDC) in Atlanta/USA and published in the Annals of Internal Medicine. Transferred to Germany, CDC publications correspond to the reports of the Robert Koch Institute (RKI) or the Federal Institute for Risk Assessment (BfR) in terms of seriousness and relevance.
In 1994, the definition criteria were revised by the “International CFS Study Group” at the renewed initiative of the CDC and published in the current form. In 2000, the North Rhine Medical Association recommended in a position paper to use the criteria according to Fukuda et al for the diagnosis of CFS.
In January 2002, a comprehensive overview of the problem, including all available international sources, was published as a report by a CFS working group to the British government.
The severity classification contained in this publication into the groups “mild”, “moderate”, “severe” and “very severe” identifies CFS as a clinical picture that, even in its mild form, has serious effects on the lives of those affected. Patients from the “severe” group are substantially limited in their mobility and all activities of daily living, suffer from strong fluctuations in symptoms and serious cognitive problems, no longer work, need frequent rest breaks. Even minor stress leads to massive deterioration in well-being that lasts longer than 24 hours.

The scientific starting point of the CFS definition

The scientific starting point today, as well as at the time of the first CFS definition, is characterized by the fact that the existing knowledge in all medical fields, including psychiatric, does not offer satisfactory access to the disorder that has been observed frequently since the early 1980s. In medical practice, the diagnostic and treating physicians are confronted with the problem that with seriously ill patients, who often “feel like AIDS patients two months before they die” (quote Prof. Mark O. Loveless before US Congressmen 1995) regularly no corresponding findings can be objectified. As a result, patients find themselves in a hopeless situation of justification and evidence, which leads to many ultimately frustrating visits to the doctor in a desperate attempt to find an explanation for the symptoms of exhaustion. The costs add up.

The CDC stated in 2006:

“There are a few other factors that add to the complexity of CFS diagnostics:

  1. There is no diagnostic laboratory test or biomarker for CFS.(here’s the news)
  2. Fatigue and other CFS symptoms are common to many illnesses.
  3. Many people with CFS don’t look ill despite their profound disability.
  4. The type, number, and severity of symptoms vary from patient to patient.
  5. Symptoms may change in individual patients over time.

These factors have contributed to a worryingly low diagnosis rate.”

Problems with the appraisal

The discrepancy between observation and laboratory tests

The discrepancy between the observation of the most severe states of exhaustion with a wide range of accompanying symptoms and the fact that pathognomonic proof of what is happening in CFS with laboratory or other examinations has not been possible up to now reflects the core problem of the specialist discussion to this day. With the current state of medical knowledge, it is by no means a question of selecting highly differentiated test procedures to provide evidence of the disease and indications of the disabilities caused by it, in particular of professional performance or earning capacity. As defined in the CDC definition criteria for CFS according to Fukuda et al. 1994, no objectifiable findings are explicitly secured as definitive proof of the clinical picture. This also corresponds to the current recommendations of the DEGAM guideline “Fatigue.
The agency responsible for the Old Age, Survivors, and Disability Insurance (OASDI) of the US state pension system, the Social Security Administration (SSA) clearly states in guideline SSR 99-2P that CFS can cause disability. In the context of the SSA instructions for the clarification of a CFS, however, it is pointed out that the sole individual declaration of complaints is not sufficient to justify a corresponding entitlement to benefits.
In order to prove the diagnosis of CFS, its severity and the duration of the resulting disability, documentation that is as comprehensive as possible with a thorough anamnesis, detailed recording of all findings including laboratory and technical examinations as well as long-term recordings are required.
It is emphasized that CFS is to be regarded as a medically relevant disability with a corresponding entitlement to benefits if, in addition to the patient’s information, there are other medical examination results and laboratory findings that are consistent with the patient’s medical history.

The problem at the moment is that the expert examination, including the checks by the MDK or insurance experts, is usually carried out purely as a cross-sectional examination or only by viewing the preliminary findings. As a result, no trend-setting findings can be found. The neuropsychological tests usually yield average to slightly below-average ratings. From these facts it is then concluded that the subjects actually have to be able to perform at least up to more than 3 hours a day. If at all, they are granted an impairment for psychological reasons.

In these assessments without prior knowledge of the clinical picture of CFS/ME, it is overlooked that the usual static definitions of the resilience of the situation of the person concerned cannot do justice. The condition typical of the disease, that the individual symptoms are often subject to extreme fluctuations within a very short period of time, is of decisive importance for an appropriate assessment of the performance of CFS patients. These are performance limits which, on the one hand, do not take into account the environment in which the person acts and, on the other hand, are unsuitable for defining adequate limitations for symptom complexes that fluctuate strongly in the short term without any recognizable cause.

The basic dilemma in the case of chronic fatigue syndrome / myelite encephalomyelitis (CFS/ME) is that the subjects are able to perform at almost normal levels for short periods of time. Through the retrieval of performance, both cognitive and physical/muscular, the system resources are so exhausted that a sustained phase of exhaustion of sometimes more than 24 hours, depending on the effort also several days, occurs in which the previous performances are no longer available are available.

These functional impairments and performance losses cannot be systematically perceived or recorded in the usual cross-sectional assessment of CFS/ME sufferers. Expert opinions that do not explicitly take this fact into account therefore lead to systematically incorrect results.

The reason for this is that the many complaints from the preliminary findings are misinterpreted in such a way that the symptoms are more likely to be assigned to a somatization disorder or depressive illness, both of which do not exhibit this phenomenon of sustained exhaustion after exertion and thus the lack of regular access to services. In the case of these two psychological differential diagnoses, an expert rightly concludes from the impression in the expert’s situation that the patient is able to perform in everyday life. In the case of CFS sufferers, it is not possible to draw conclusions about everyday performance from the cross-sectional assessment. If experts are not informed about the clinical picture and its specific abnormalities, it is repeatedly argued that the test persons either aggravate the complaints or deliberately don’t make enough effort in the examination tasks. The most sweeping criticism is then the assertion that the clinical picture of CFS has not been scientifically proven and is an outsider’s opinion. This only speaks for ignorance or a lack of examination of the predominantly international scientific literature.

Since 1994 (Fukuda) diagnostic guidelines have been developed and further adapted to the development of research findings. The disease was consequently included in the International Classification of Diagnoses (ICED 10) under the rubric “Neurological diseases” G 93.3.

In Germany, too, the German Society for General Medicine and Family Medicine is now stating in its current DEGAM guidelines No. 2 “Fatigue” that the strictly defined chronic fatigue syndrome (CFS) or chronic fatigue syndrome is a rare consultation result, laboratory tests and imaging procedures only served to exclude other diseases, since a definitive diagnostic test does not exist, so that, apart from the detection of comorbidities, corresponding examinations could not provide any information on the cause or therapy of the clinical picture CFS.

The DEGAM guidelines refer to two definitions that are internationally important for clinical care practice: The definition of the British National Institute for Health and Clinical Excellence (NICE) and the definition of a Canadian consensus document, which was mainly formulated by clinicians and is much narrower be taken as the NICE definition. In both documents, CFS is not only described as a residual category after other diseases have been ruled out, but as a disorder in which there must also be several symptoms from several organ systems.

As already stated in the CDC definition criteria for CFS according to Fukuda et al. 1994, no objectifiable findings are explicitly secured as definitive proof of the clinical picture. This also corresponds to the current recommendations of the DEGAM guideline “Fatigue”. With the current state of medical knowledge, it is by no means a question of selecting highly differentiated test procedures to provide evidence of the disease and indications of the disabilities it causes, especially in terms of professional performance or earning capacity, but the diagnosis is based on the scientifically prepared interviews and the plausibility check of the descriptions of the course of the disease.

If there is a suspicion of a CFS/ME disease, this phenomenon of sustained exhaustion and the lack of availability and thus the ability to plan services, which is the main symptom of the diagnosis, must be taken into account.

As such, a certain preconception of the assessor as to the existence or medical credibility of the CFS/ME condition determines their assessment outcome.

Suspected diagnosis of depression or somatization disorder

In the search for an explanation, CFS patients are then referred to psychiatrists by their somatic colleagues with the suspected diagnosis of depression or somatization disorder.
Portions of this can certainly often be identified, but more in the sense of a secondary event as a reaction to the massive exhaustion that usually occurs suddenly, which entails a significant decline in everyday activities. It is therefore primarily a somatic illness, i.e. anxiety and depression are not the cause, but rather the result of a dramatic loss of physical strength, and are often further aggravated by the lack of recognition and helplessness of the medical system in Germany. In most cases, this even results in complete disability.

Unfortunately, this clinical picture is still largely unknown in Germany and has a stigma among doctors that is scientifically incomprehensible. This then leads to the frustration repeatedly reported by patients of not knowing what they are suffering from. The usual resource-activating therapy recommendations, which are then based on the assumption that it is a question of masked depression, such as increasing activity, sport and overcoming stress limits, are highly counterproductive for CFS patients and even exacerbate the course of the disease. In contrast, CFS sufferers must very carefully explore and learn to respect their limits of resilience.

Diagnostic procedure

Chronic exhaustion that does not subside with recovery, accompanied by other fluctuating somatic symptoms, suggests the suspected diagnosis of chronic fatigue syndrome. In order to confirm this suspected diagnosis of “chronic fatigue syndrome” (CFS), this first requires a comprehensive somatic diagnosis to exclude possible individual somatic causes of the complained symptoms such as thyroid, liver, metabolic, neurological and brain diseases or condition after tumor diseases. If none of these diseases could be diagnosed, the complained symptom complex is recorded with a complex symptom list. Various diagnostic interviews were developed for this purpose. We refer to the latest, the Canadian CFS criteria. A collapse of the pituitary-adrenal cortex stress axis is currently seen as the lowest common denominator of the researched hypotheses as the cause of the CFS disease, with the resulting diverse functional disorders in the somatic functional areas.

According to the currently valid international scientific guidelines, the semi-structured diagnostic interview for CFS, the “Canadian criteria”, is to be carried out for diagnosis.

Diagnostic medical interview according to the Canadian consensus criteria

CFS Diagnose, Kanadisches InterviewPlease note: ME/CFS usually has an acute onset, but it can also be insidious. A preliminary diagnosis can be made in the early stages. The disorders generally form groups of symptoms that are often characteristic of the individual patient. The manifestations of the disease can vary and change over time.

It is always important to make a comparison with how you felt before the collapse began. The symptoms are typical of the massive regulatory disorder of the autonomic nervous system with overemphasis on the sympathetic and underemphasis on the parasympathetic and thus the disturbance in the complex internal information and control system.

Test yourself online in 7 Minutes for CFS with the “Canadian Interview”»

A commission set up by the top American health authority (CDC Centers for Disease Control and Prevention) was commissioned to review the diagnosis and the specificity of the disease in contrast to mental and neurological diseases. This commission came to the conclusion that CFS is not an original mental disorder, and it also finds the term myalgic encephalomyelitis misleading, since the term encephalomyelitis is an inflammation of the meninges that cannot be detected with the usual methods of CCT and MRI head, and the term Myalgia (muscle pain) is present but not the core symptom. Rather, after examining all the research findings on this subject, the panel comes to the conclusion that the core symptoms complained about indicate a failure of the signal transmission structures, whether nervous, hormonal and immunological. This is the only way to explain the massive limitation in performance and especially in repeatability and permanently available performance. This overload of the body’s “information system” physically, cognitively and emotionally affects the affected person in all organ systems (a basis of diagnosis) and in all aspects of their lives. The Commission is therefore proposing a new name that is more appropriate to current scientific knowledge: Systemic exertion intolerance disease (SEID Systemic exertion intolerance disease).

Considerations on Etiology

How does this stress intolerance, the constant stress on our system, come about? Chronic stimulation of the warning function of the amygdala (danger warning sensor) in the limbic system (emotional processing center) leads to a chronic provision of stimulation of the autonomic nervous system via the pituitary-adrenal stress axis. The result is a chronic imbalance of the sympathetic and parasympathetic to the detriment of the recovery function via the parasympathetic. This leads to changes in the chronobiological structures. Normal cortisol secretion changes. The daily rhythm of the cortisol level levels out at a high level. This leads to the lack of the evening dip, which is necessary for recovery and REM sleep, with the effect of sleep disorders that are soon perceived. In addition, the high cortisol level leads to an acceleration of the metabolic system with the consequences of thermal overheating, which is perceived more drastically at night, e.g. as inexplicable sweating. The result is increased permanent tension in the muscular system. If the chronic overload persists, the chronobiological rhythm changes, with the cortisol release leveling off at a low level during the day, but remaining at a higher level in the evening.

The advancing processes in the sense of a vicious circle lead neurobiologically to an encapsulation of the amygdala from the regulatory systems – hippocampus (movement) and frontal lobe (reason) – in the sense of a retreat to flight or fight mechanisms.

This sets in motion autonomous processes and mechanisms. These are no longer subject to the control of the frontal lobe. Psychologically, this process is perceived as diffuse fears and feelings of paralysis of the intentional willingness to perform, somatically as heart tightness, toning of the muscular system with the consequences of tension and diffuse pain. Further consequences can be found in the respiratory parameters, a system that has to adjust to supposedly dangerous situations, as the amygdala pretends, needs more oxygen. This leads to an increased VO2 Max requirement, the tidal volume increases due to increased respiratory rate. Shortness of breath develops, the pulse increases.

An indication of a systemically disturbed oxygen processing can be seen in the spiroergometry examination. If these tests are repeated every 24 hours, CFS patients show a performance reduction of 15% compared to healthy people.

The balance disturbance of the autonomic nervous system is measurable. We use the measurement of the basic body tension with the SAM device (developed and researched on high-performance athletes at the Sport University and the Olympic Center Hamburg by Dr. C. Ziaja) and the heart rate variability measurement (HRV) with change of position and long-term measurement in the relaxation phase. A chronic regulatory disorder shows up in the disproportion of the frequencies of the sympathetic tone compared to the parasympathetic. The first publications on this are in preparation.

The encapsulation of the amygdala can be found according to the latest research from Stanford University.

Functional MRI scans in CFS patients found disturbances in the pathways between the limbic system and the cerebral cortex (Zeineh et al. 2015). This would fit with the fluctuating cognitive information processing disorders that CFS patients also refer to as brain fog. The authors even suggest that these findings could serve as biomarkers for CFS in the future.

Zeineh MM, Kang J, Atlas SC, Raman MM, Reiss AL, Norris JL, Valencia I, Montoya JG: Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome. Radiology: Volume 274: No 2, 2015

Therapeutic Approaches

There are now initial indications of effective treatment methods for CFS at the research level.

The persistent pain, which is also partially resistant to analgesics, and the massive exhaustion lead to a deficit structure and reduction of the daily range of movement and training as well as a widespread avoidance of fast movement sequences with the consequences that the natural regulatory ability of the autonomic nervous system to the detriment of the parasympathetic system decreases. The sympathetic innervation increases, also due to the psychological effect of the negative assessment of the life situation perceived by the patient and the symptoms, which according to the literature must be interpreted as an existential physical threat. The patients are unable to call up their usual services and are confronted with a large number of somatic complaints for which the consulted doctors have no well-founded explanation and no therapeutic approach. The then usually deportation to the psycho drawer is a more far-reaching stigmatization. That’s scary.

This is where the first pillar of therapy has to start, psychotherapy graded according to the clinical picture with the aim of giving the patient back confidence and the ability to act by providing a coherent explanatory model (psychoeducation). A longer-term monitoring of this process in the order of approx. 50 hours of cognitive behavioral therapy would be necessary. This also corresponds to the recommendations of the international therapy guidelines.

The second pillar aims to regain the ability of the autonomic nervous system to regulate itself.

The regulatory disorder shows in the measurement of heart rate variability (HRV) – in the USA the gold standard of stress measurement – in the postural measurement with a change in position from lying to sitting a constant high frequency component of the sympathetic tone and an absence of parasympathetic frequencies. This speaks for a “frozen” system that does not even react to changes in position or even to a relaxed state in the long-term measurement while lying down.

Here, physical therapy exercises developed on the basis of sports science show clear successes, which are also reflected in the measurement results. In this way, the progress of therapy can be checked.