an autodidact meets a dilettante…

‘Rise above yourself and grasp the world’ Archimedes – attribution

exploring chronic fatigue syndrome, myalgic encephalomyelitis, etc

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published in 1991

Canto: What do you know about chronic fatigue syndrome (CFS)?

Jacinta: Not much. I read somewhere recently that it’s a term not so much used now. Maybe because the term ‘syndrome’, I think, is a kind of ‘placeholder’, like a collection of symptoms – adding up to a regular feeling of fatigue for no clear reason, or without an established cause, or set of causes. And now maybe they’ve established some causes, and the ‘syndrome’ has been divided up into a few more clearly understood disorders.

Canto: Well, that may be so, but I know that, some twenty years ago or so, there seemed to be a spate of people coming down with what they called CFS – sports people, entertainers, people in the limelight for one reason or another – but I don’t hear so much about it now. So I’m wondering – can a person have this syndrome, or one of its instantiations, on and off for, say, 27 years?

Jacinta: I’ve no idea? Why do you ask?

Canto: Well, I know of someone who still attributes her aches and pains – at least some of them – to chronic fatigue, some twenty-odd years after getting that diagnosis, and it bothers me… I know that there’s an issue out there about women’s health, and women not being believed, particularly by male doctors, and I’m male…

Jacinta: Well recently what they call ‘long Covid’ has cropped up, and it seems to be similar. I know from experience that you can have a serious illness, I mean an infection, one that really puts you on your back and takes a long time to recover from, and it really changes your life in a ‘before and after’ sense. That’s to say, after that illness you never feel quite the same again, as if your immune system has been permanently compromised, damaged in some way. That seems to be happening with long Covid, and maybe it’s an issue for CFS. Maybe CFS starts with an infection that more or less compromises the immune system. Of course I’m no expert on matters medical…

Canto: So some research is required. As I recall, another name for CFS is myalgic encephalomyelitis (ME), which at least sounds like a right proper disease, one to scare the bejazus out of people – especially the ‘encephalo’ part. Clearly it eats your brain.

Jacinta: The ‘myalgic’ term has to do with muscles, tendons, ligaments and stuff. And muscle etc pain, or myalgia, can have an astronomical number of causes. The ‘encephalomyelitis’ term can be broken into two parts. The ‘myelitis’ part refers to myelin, the white-coloured material that sheaths our neural circuitry. ‘Encephalo’, as you say, refers to the brain in general. Encephalomyelitis is defined as ‘inflammation of the brain and spinal cord’, of which there are many types. For instance, Encephalomyelitis disseminata is another name for multiple sclerosis. So ME, if this is just another name for CFS, involves the muscles and associated tissue, and the nerves leading to and from them.

Canto: Okay, that’s all useful, but I’m just wondering whether, if you come down with CFS, or ME, it might be with you, like, forever.

Jacinta: It’s interesting that ME suggests there is evidence of damage to myelin in this condition. That needs to be explored further. I’ve accessed a book published in 1990 called The disease of a thousand names, by Dr David Bell, a pioneer in exploring this syndrome. The name he gives to it is Chronic Fatigue/Immune Dysfunction Syndrome (CFIDS), and on the cover he gives no less than 37 alternative names, some of them, such as Yuppie Flu and Yuppy plague, less serious, or more dismissive, than others. In the foreword he presents the hope that the book will be a starting point for further study, and makes his view of the disease/syndrome/condition clear:

I freely admit to bias in writing this book. I fully believe that CFIDS is a specific, organic illness, caused by a specific agent or agents. I make no claims to be impartial in the argument of whether the illness is real or not. It is interesting that of those researchers directly involved in epidemics of CFIDS, there is no discussion of this question. Personal experience has made the issue irrelevant and even insulting.

Canto: So that’s over 30 years ago, and now I’m watching a disturbing DW documentary from just under a year ago, telling the story of three German sufferers from this condition – and they’re suffering very badly, without a doubt. It also focuses on the doctors, neurologists and researchers trying to get a handle on it. One of them, Dr Carmen Scheibenbogen, an immunologist and oncologist, points out that still, after 30 years, we’ve made little progress, and that very few scientists are working on the disease (which for convenience, let’s call CFS), especially compared to the number of sufferers. They estimate that 17 to 24 million people have it worldwide, with women outnumbering men. They also estimate that only half of sufferers have been diagnosed – but whether that means they think the number may be as much as 50 million or that only 8 to 12 million have been diagnosed isn’t made clear.

Jacinta: Well Dr Bell’s intro ends optimistically:

It is my hope that by the time this book is published, much of the speculation presented here will have been confirmed. If so, the absurd argument of whether this illness is ‘real’ will have ended, an unnecessary argument that has caused so much pain and added so greatly to the burden of those ill with chronic fatigue/immune dysfunction syndrome.

I’d guess he’d be sadly disappointed if he’s still around today. As he notes in the first chapter, the number of names given to the illness is a testament to ignorance more than anything else. And the term CFS arguably downplays the seriousness and debilitating nature of the symptoms, and suggests nothing about damage to the immune system, for example.

Canto: Hearing the stories of the sufferers, and watching them actually and obviously suffering, is itself painful. They seem in a sense like the disappeared. Their illness causes them to disappear from the workplace, from civic or social activity, from any circle wider than immediate family. And all of them seem lost in the mystery of their condition. The term ME is suggestive of inflammation, but often there’s no detectable inflammation. The symptom most common to all sufferers according to Dr Scheibenbogen is a very low tolerance of exertion.

Jacinta: I note that Dr Bell writes of the difficulty of defining a precise set of symptoms, which ‘has surrounded the illness for the past 20 years’, which dates the illness back to 1970 or before. He mentions recent recognition by the CDC, as ‘an illness characterised by months or years of severe pain and exhaustion nearly everywhere’. He also expresses his view, and hope, that ‘it is most likely caused by a single specific agent’. From my laywoman’s perspective, I’m very doubtful about that.

Canto: One of the subjects in the documentary, a teenager, contracted mononucleosis two years before, and hasn’t been the same since. Mononucleosis, often called the kissing disease, is carried by the Epstein-Barr virus (EBV), and so no doubt this virus and/or its relatives have been focused on as possible sources of the illness. Listening to her describing the problem as like a faulty battery which doesn’t recharge properly suddenly made me think of a far more horrific illness, encephalitis lethargica, which killed hundreds of thousands of Europeans from when it first appeared there in 1916. In their case, the battery often ceased to function, leaving them in a state something like total paralysis – but with some mental processes intact. In her book of the epidemic, Asleep, Molly Caldwell Crosby describes a very young woman struck down by the disease, visited by a physician, who rather unprofessionally told her family at the bedside that there was no hope. Her eyes welled with tears. She died shortly afterwards. The image it brings to life still haunts me. No cure or cause of the disease has ever been found.

Jacinta: So, as we explore this current ‘disease of a thousand names’ it does certainly seem that some manifestations can be lifelong. However, because they tend not to be life-threatening, and because causes can’t be found via biopsies, blood tests and the like, it’s generally seen as a ‘diagnosis by exclusion’. And of course it’s likely believed to be psychosomatic by many more than care to admit…

Canto: And yet the WHO recognised it as a neurological disease back in 1969. Perhaps that designation doesn’t help, because it’s often seen as a ‘mind’ disease, something like depression. But getting back to mononucleosis, which has been seen as a stepping-stone or trigger in some cases, it does seem likely that CFS starts with infection, particularly viral infection (SARS, enteroviruses), though again, not in all cases. It does seem to be a case of excessive immune reaction, which can perhaps also be triggered by injury or surgery. EBV is very common – more than 90% of humans catch it, usually in childhood, when it’s more often than not asymptomatic. But in can re-appear as mononucleosis later, usually in early adult life, according to the documentary, though it’s not clear whether that means reinfection, or a virus that lies dormant for a period. In any case, the symptoms are swollen lymph nodes, fatigue, sore throat and a high temperature.

Jacinta: I’ve heard of it, but I thought it was some exotic virus, nothing that I’d ever catch. Sounds like I’ve already been infected…

Canto: Perhaps, but not reinfected – and there can be much more serious, even life-threatening complications, such as spleen damage, low blood cell count and respiratory disease. And CFS.

Jacinta: Well it seems to me that the great mystery of encephalitis lethargica is an object lesson as to how little we know about the ailments and infections our bodies are prey to. It seems that they’re prone to over-reaction, as is the case with allergies, and the ‘cytokine storm’ in Covid-19. But the problem with CFS is that, quite often, no previous infection can be pinpointed.

Canto: Well, this may tell us something new about viruses, and about the immune system, as, to some extent, Covid-19 has. Mononucleosis, for example, is generally seen as a mild illness, but not always, and in some cases it can be life-threatening, or it can somehow stuff up the immune system, leaving sufferers prey to a range of ailments. Some of these are clearly described from symptoms rather than causative agents – for example post-exertional malaise (PEM). Without a clearly defined cause, one can only treat symptoms. And because the symptoms are mostly not life-threatening in any obvious way, it can easily be seen as ‘psychosomatic’, and it doesn’t attract funding. And even with encephalitis lethargica, a killing disease, no causative agent has been found. We just hope it has permanently disappeared, which isn’t very satisfactory. Also, with CFS there are generally no visible symptoms, so physicians must rely on reported symptoms, which actually takes the power out of the hands of the ‘expert’. So, the condition has this difficult status – difficult to attract funding, and virtually impossible to insure against.

Jacinta: Yes, so the hunt is really on for causal factors. It seems to be all about the immune system being ‘overactive and/or misdirected’ as Dr Scheibenbogen puts it. The argument some are putting forward is that it interferes with the autonomic nervous system, taking over much of its function. The autonomic nervous system controls our breathing, our heartbeat, our digestion, and our blood flow. Without effective blood flow, there will be muscle problems, dizziness, poor concentration and general feelings of weakness. Oxygenating the blood helps to energise our whole system. Key to all this is our beta 2 receptors. Here’s something about them from a NIH article:

Beta 2 receptors are predominantly present in airway smooth muscles. They also exist on cardiac muscles, uterine muscles, alveolar type II cells, mast cells, mucous glands, epithelial cells, vascular endothelium, eosinophils, lymphocytes, and skeletal muscles.

Canto: So, beta 2 receptors, something to be researched and kept in mind. The documentary presents a CFS sufferer whose autoimmune neurotransmitters are considerably elevated – whatever that means. They’re also described as ‘antibodies’. Dr Scheibenbogen suggests that CFS is disrupting their functionality. Muscles are not being properly supplied with blood, leading to pain and exhaustion. And all this has something to do with a dysfunctional immune system, and a possible problem with the normal dilation of the blood vessels, which carry oxygen to all the body’s muscles and organs. Which takes us back to the beta 2 receptors, located on the blood vessels in muscles. They’re controlled by adrenalin, released during exertion, and antibodies. These antibodies have been found to be dysfunctional in CFS sufferers, resulting in problems with oxygen supply. Dr Scheibenbogen describes one patient’s results:

We know the patient has antibodies against the beta 2 receptor. What we want to know is, which part of the receptor. We’ve divided up the beta 2 receptor into 15 small pieces and stuck each piece onto a different little bead. They glow in slightly different colours, and then we can see…We can compare these reactions to those of healthy subjects. This will help us understand the disruptive receptor pattern better. If there are distinct differences, a clear pattern, we could use this as a diagnostic test.

Samples from different patients are sent to the Julius Maximilians University in Wurzburg, where a team led by Dr Bhupesh Prusty, a microbiologist and virologist, are trying to find infectious agents that might be responsible for or contributory to the disease. Dr Prusty has been studying the role of viruses for many years and was the first to discover the link between EBV and CFS. Here’s what he had to say:

‘What we have found is that herpes viruses, particularly human herpes virus type 6 (HHV6), and Epstein-Barr virus, are the most interesting candidates which can contribute to the development of the disease. We have found that HHV6 produces a small RNA, and that this small RNA can directly target mitochondria to fragment, and it’s already known that in EBV infection mitochondria is also fragmented, so we believe that this virus-induced mitochondrial fragmentation is one of the most important steps in the development of CFS’.

So the documentary turns to mitochondria, the energy organelles in all our somatic cells.

Jacinta: So we turn to ATP and all that. Fragmented mitochondria aren’t going to bode well for our energy levels.

Canto: Dr Prusty’s team have injected antibodies from the blood of CFS patients into healthy cell cultures to see if a factor in the serum of those patients affects the healthy mitochondria. The experiment resulted in mitochondrial fragmentation, which would result in a weakened immune response in the event of future infections, and a generally slower metabolism. Tests of this kind could be used in the diagnosis of CFS – an enormous advance (I’m quoting or paraphrasing the documentary of course). Dr Prusty says the test works for seriously ill CFS patients, but much less so for milder cases. So it would be diagnostic in some cases and it also points towards something causal, though the precise mechanisms would have to be worked out. And there are funding problems hampering further research.

Jacinta: Dr Bell was writing about the lack of funding in his 1990 book, so nothing has changed. And as with the documentary, case histories are presented, of people cut down by this illness, unable to work, unable to obtain insurance or compensation, unable to find solutions, and suspicious or aware that health authorities, family members and others feel that they’re exaggerating or malingering. Often diagnoses cite depression, and of course depression does set in after a long period of incapacity.

Canto: The doco presents a graph that is, well, graphic, in comparing USA funding for multiple sclerosis and HIV compared to CFS (HIV outscores both of the others by a vast amount). Grassroots funding groups are struggling to make a difference, to amplify the issue and combat stigmatisation. Pharmaceutical companies have shown no interest, no doubt because the symptoms seem vague and lacking in ‘acuteness’, and there are no biological markers to provide focus for a cure or a clear form of relief. Meanwhile, the sufferers themselves feel a sense of being useless or having ‘disappeared’ from active social life. A possible drug for treating CFS, Rituximab, was recently trialed in Norway, based on the hypothesis that it is an auto-immune disease, ‘with a role for auto-antibodies and  B-lymphocytes’, according to Dr Oystein Fluge, who led the trial. The documentary explains:

B cells are important immune cells in our body that produce antibodies that destroy viruses and bacteria. Unfortunately this process sometimes goes awry, and the B cells produce antibodies that don’t work properly, or actually attack the body itself. This occurs in many auto-immune diseases, like lupus or myasthenia gravis [a chronic autoimmune, neuromuscular disease that causes weakness in the skeletal muscles]. Scientists believe that ME/CFS is one such auto-immune disease. Rituximab is a medication which temporarily destroys B cells, preventing them from producing antibodies to attack a person’s own body.

Three small trials showed considerable promise, so a ‘phase 3’ randomised, double blind trial, involving 152 patients, was next conducted. One of the major hopes was that a diagnosis could be made based on defective antibodies, and ‘whether a marker could be found in the blood that could simplify the diagnosis’. Could they have been previously infected with EBV? There is apparently a diagnostic test for this, and this has been found in some CFS sufferers, but more proof, through larger-scale testing, is needed. Meanwhile, the SARS-Cov-2 pandemic has left many people with CFS-like symptoms, and while this is in one sense disastrous, it could be a wake-up call for trying to better understand auto-immune diseases – of which CFS is likely one. So far, we have associations rather than proven causes, but the association of a CFS-like illness such as ‘long Covid’ with a disease that clearly plays havoc with our immune system is, to say the least, extremely suggestive. As one researcher points out, being able to establish a cause will encourage people to seek treatment earlier, reducing the damage that time brings about.

Jacinta: Yes, people suffering from ‘long covid’, as it’s called, are of course making the connection with CFS and highlighting the lack of progress re this presumably auto-immune disease.

Canto: Yes, Dr Scheibenbogen is concerned that an after-effect of the pandemic will be a spike in long-term CFS sufferers, which we may already be seeing. The silver lining, though, may be an increased focus on, and increased funding for, solving its current mysteries. Dr Prusty is still of the view that latent herpes viruses are reactivated after covid and perhaps other autoimmune infections. It just isn’t known whether long covid and CFS are essentially the same condition. Meanwhile as Dr Uta Behrends, another frontline researcher in CFS, points out, sufferers need to have a diagnosis made as soon as possible so that they can be supported, so that they don’t feel isolated and become depressed, as so often happens.

Jacinta: Supported, but how can they be treated, when there’s no clear cause?

Canto: Indeed. The Norway trial returned a negative result. This may have been because the Rituximab dosage was low due to lack of funding. Still, the researchers have collected a sizeable bank of blood samples to test with other drugs or enhanced versions of Rituximab. There is also a problem with correct diagnosis of CFS, and perhaps a reluctance to diagnose such a condition in the absence of clear biomarkers. Meanwhile the suffering continues, and an untold number of people remain in limbo…


Dr David Bell, The disease of a thousand names, 1991

Written by stewart henderson

March 27, 2023 at 9:43 pm

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