case study – American ME and CFS Society

A Woman With Multiple Neuropathic Symptoms, Hypersensitivity to Heat, Peppers, and Alcohol, With a Variant in the TRPV1 Capsaicin Receptor Gene: Possible Implications to ME/CFS

Abstract:

Transient receptor potential vanilloid 1 (TRPV1) is a ligand and heat-gated ion channel expressed on nociceptors that plays a central role in thermal and chemical pain signaling. Loss-of-function variants in TRPV1 have been associated with reduced nociception. We report a 65-year-old woman with disabling polyneurofunctional/neuropathic symptomatology including migraine, functional gastrointestinal disorders, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Diagnostic evaluation revealed sensory polyneuropathy and autonomic instability. Whole genome sequencing reanalysis identified a heterozygous TRPV1 c.2174A > T (p.Lys725Met) Likely Pathogenic variant that is very rare and highly conserved.

Our patient reports consistent, longstanding, marked hypersensitivity to heat, capsaicin, and alcohol, all of which are known TRPV1 agonists, supporting a gain-of-function mechanism for this variant. Furthermore, prior studies have implicated TRPV1 hyperactivity in migraine, nociceptive sensitization, and ME/CFS. Despite the excellent clinical correlation, causality of the variant cannot be definitively established without functional studies.

This case expands the potential phenotypic spectrum associated with TRPV1, and highlights a possible role for TRPV1-mediated channelopathies in complex neurofunctional disorders including ME/CFS.

Source: Zimmermann PM, Boles RG. A Woman With Multiple Neuropathic Symptoms, Hypersensitivity to Heat, Peppers, and Alcohol, With a Variant in the TRPV1 Capsaicin Receptor Gene: Possible Implications to ME/CFS. Case Rep Genet. 2026 Nov 3;2026:1920171. doi: 10.1155/crig/1920171. PMID: 42979319; PMCID: PMC13729082. https://pmc.ncbi.nlm.nih.gov/articles/PMC13729082/ (Full text)

“The Prisoner”

Case Histories of ME/CFS: “The Prisoner”
ProHealth.com
by David S Bell, MD, FAAP
April 4, 2012

This is the case history of a man whose fear of relapse 4 years after sudden onset of ME/CFS nearly robbed him of recovery. It is excerpted from Dr. Bells free e-book Faces of CFS – Case Histories of Chronic Fatigue Syndrome, published in August, 2000 ( David S Bell, MD, 2000).

Reprinted with the kind permission of ProHealth: 4/4/12

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THE PRISONER

It is so ironic that while most doctors see CFS as hypochondriasis, I feel that hypochondriasis may be the result of the combination of CFS and the physician ignorance. Patients must sail these waters without guidance, forcing them to make it on their own.

Those of us in good health rarely appreciate our good fortune. We live our lives ravenously, devouring the minutes of the day with work, play, love – ever eager for the next course. We charge ahead, assuming life will go on as always.

In order to accomplish this, we allow ourselves to be oblivious to the suffering of others. We push their pain to the deep recesses of our subconscious, and remain blind to the fact that around the corner may lie an event that will change the foundation of our lives with similar finality.

Gary Burns was just like the rest of us. There was nothing malevolent about his view of life; he harbored no evil intentions. Yet, he was as unaware of the suffering of others as the rest of the world was about to be of his own suffering.

Like most patients, Gary’s ordeal began with a bout of what he assumed must be flu. He was 37, robust and active, a husband and a father.

This flu announced itself to Gary one day in October of 1986. The course of Gary’s illness, and the eventual dissolution of everything that he had once taken for granted, was typical for an adult who experiences what we doctors call sudden onset of chronic fatigue syndrome (ME/CFS).

Initially, he was offered a months sick leave by his company, a nearby factory. He tried to go back to work when his sick leave ended, but often he felt in a state of collapse by noon, and had to leave the jobsite.

He took an extended leave of absence, hoping for recovery. If he could just catch up on his sleep, he kept telling himself and others, all would be well. Gary had moments during the day when he found the strength to shower, wander through his house, and ponder the possibility of returning to his job. But, soon enough, it would return, and he would tumble onto the sofa and sleep the day away.

Gary still had no idea what it was, and his doctor hadnt a clue, either. Gary had been ill for six months when his doctor announced that he had been unable to discover a medical explanation for Gary’s symptoms.

He advised Gary to snap out of it, to get more exercise, and to see a psychiatrist.

Like a lot of people, Gary trusted his doctor and believed what his doctor had told him. With some embarrassment, and worry over the expense, Gary arranged an appointment with a psychiatrist. After all, he was desperate, and willing to try anything. The psychiatrist probed for information about Gary’s life, and Gary answered the psychiatrists questions honestly.

He said he was in the process of being fired, and that he was going broke.

He confessed he had been unusually irritable, chastising his kids for creating noise and havoc in the house, and sulking whenever his wife tried to comfort him.

In a revelation that was somewhat difficult for him, Gary admitted he was depressed.

The doctor prescribed an antidepressant, and invited Gary to continue therapy in order to resolve emotional conflicts – conflicts that the psychiatrist suggested were the cause of Gary’s disabling illness.

The following day, however, when Gary took the first pill, he rapidly deteriorated, feeling as if he had been hit full force by a freight train.

He slept for two days, and when he was finally able to stay awake, he felt hung over, as if he had drunk a case of liquor the night before. Perhaps not surprisingly, Gary decided to cancel his next appointment.

The psychiatrists secretary insisted the antidepressant could not possibly have caused Gary’s severe reaction. She also advised him he would be charged for the appointment, whether he showed up or not. So much for psychiatry, Gary thought, and never returned. By then, Gary felt as if he was riding a wild and powerful horse, but the reins had slipped from his hands.

Desperation was a daily staple, and as he lay in a helpless mound on his bed, or the sofa, he searched his mind frantically for solutions.

His mother, whom he had frequently accused of being a health nut, owned a health food store. Gary decided to sample the assorted vitamins and nostrums available in his mothers shop. He began eating organic food and taking vitamins for the first time in his life, although he noticed no immediate improvement.

On his worst days, he wondered if he had a terminal illness, especially cancer, that his doctor had missed. He decided to read everything he could about cancer; if the doctors were incapable of discovering the cause of his symptoms, he would become a doctor himself.

In the course of his reading journey, Gary came upon an article that described CFS.

The stories of the patients in this article resonated with his own experience of the disease: sudden onset; a long, chronic course, exhaustion, headaches, pain; sensitivity to light, night sweats, the sensation – if not the reality – of high fever.

He was stunned when he read that patients with CFS are exquisitely sensitive to many drugs, including anti-depressants such as the one he had taken. He felt as if he was reading his own biography. In fact, he was so persuaded that the long-standing mystery of the last year was resolved, he felt incredulous that his doctor had missed the obvious signs, which now seemed so obvious.

There was just one small detail of the disease, as CFS was described in the article, that didnt seem to fit: Gary had never really thought of himself as a Yuppie [with Yuppie Flu].

Certain of his diagnosis, nonetheless, Gary plunged headlong into health nut-ism, with his mothers encouragement and guidance. He eliminated fat from his diet and took handfuls of vitamins. He waded through lengthy discussions of echinacea, germanium, and zinc. Still, he remained unable to work.

Even though previous attempts to exercise had ended in disaster, Gary next decided workouts might be the solution to his nightmare.

He committed himself to pushing past the sore throats and exacerbated fatigue that had followed on the heels of vigorous activity on other occasions. In fact, he gave it everything he had, beginning with a brisk, one-mile walk each day.

On day four, however, when he tried to jog, he felt so suddenly weak at a juncture in the road not far from his house, he wondered whether he would be able to make his way back on two feet. He was completely bedridden for the next two weeks.

Gary felt hopeless.

He had been fired, and most of his friends had dropped him, seeming to have forgotten about everything they had once shared in common.

The medical profession seemed utterly ignorant of his condition.br />

A day rarely passed when he failed to ponder suicide, but the notion of leaving such a traumatic legacy for his children always pulled him up short.

Now, he became exceedingly cautious with his body.

He cloistered himself from the noise and activity of his family.

He woke at nine, downed his vitamins, and showered, and then he rested.

At noon, he ate a health nut lunch of fruits and grains, and then he rested.

In the late afternoons, he attempted a few chores and stretched his muscles in the quiet of his living room. His children stayed with neighbors after school until his wife returned from work.

Together, the family ate a nutritious dinner. Afterward, Gary rested.

At ten, he went to bed, where he lay quietly until he fell asleep at midnight.

Two years of Gary’s life passed in this way.

Most of what was important to him before the onset of CFS had dissolved in those two years. His children became used to their new father, the one who could not play baseball or take them to the county fair. They began to forget their old father.

And then something wonderful happened: Gary started to get better.

The severity of his daily headache lessened, as did the crushing fatigue; he was able to be more active. Gary felt confident that his improvement was due to his adherence to his rigid schedule of the previous two years.

In the third year of his illness he told me he felt he was functioning at about 70% of his pre-CFS activity level.

Still, he planned his days with great care, taking a short walk just twice a week, playing catch with his children each day. He told me proudly that he could ride the lawn mower and cut the entire lawn without stopping to rest in the middle of the job.

It was apparent that he had finally accepted his new life; his despair was gone.

By the fourth year Gary complained only of persistent fatigue, muscle aching, and the fractured, disturbed sleep patterns that are common to virtually all CFS patients, and, in fact, are one of the most pervasive hallmarks of the disease.

Although Gary’s symptoms were less severe than they had been in the past however, he continued his rigid adherence to a reduced level of activity. He believed that his careful attention to what he ate and his meager exercise regime was responsible for his improvement; that he had finally regained control of his destiny.

I became worried – not about the illness, but about Gary’s nearly obsessive concern with over-exerting himself. He had become his own prisoner, caught up in self-imposed rules and regulations that severely limited his experience of the world. One day, I voiced my concerns. I told him that he was both his own jailer and inmate.

I told him he needed to take some risks. I suggested exercise.

His mouth nearly fell open, recalling his own disaster with exercise two years before. Most CFS patients have learned through bitter experience that efforts to surmount their disability and engage in the kind of exercise activities they routinely performed before they fell ill is unlikely to have a good result.

But the problem is not exercise, it is the assumption that exercise will by definition change the course of the illness.

For patients with severe illness, exercise does not change the course and may lead to worsened symptoms.

But if CFS is getting better, exercise is great and may speed the recovery.

I suspected Gary was no longer in the severe illness category. In fact, I was uncertain whether his reduced activity level, which continued to hover around 70% of what was normal for him, was due to CFS, or due to physical de-conditioning as a result of his fear of exertion.

After all, he had been monitoring himself like an organism under a microscope for three years. Granted, he had learned the brutal limits of his disease through suffering, but it seemed to me that he was becoming almost hypochondriacal in his attention to his body.

Of course, the only way to find out was to ask Gary to exercise, and he and I both knew the proposition was risky.

Which is better: to exist safely in a compulsively rigid way of life? Or try for a full-out, 100% return to normalcy – at the risk of initiating a relapse that might turn the clock back for Gary by months or even years?

Gary reminded me that it was his life I was risking by making such a request, not my own. Good point. I was asking him to throw away his fear of the pain and suffering of the past years, all the while courting its return. Did I have that right? I had come to know Gary well by then. My observations and intuition led me to believe that Gary was going to be one of the lucky ones; he was going to beat the illness.

All signs pointed to continued improvement.

If my suspicions were in error, I thought, Gary would have a relapse, but he would likely recover from it within a month.

And, more importantly, at least we would have our answer. He would still be a prisoner, but he would be prisoner of the disease, not his own fear.

After a great deal of discussion, Gary finally agreed to try.

We planned an exercise program that was extremely gentle.

Most healthy people wouldnt have considered it an exercise program at all.

We planned stretching exercises, then slow walking, then brisk walking – depending upon the progress, if any.

When Gary joked that he was dedicating his body to science, his wife frowned. In the beginning, Gary experienced significant anxiety, and increased muscle aching, as well. But, over a period of weeks, the quality of his sleep began to improve, along with a decrease in the muscle pain.

In fact, at the end of two months, it was clear to Gary and to me that he was better.

And when his fear began to diminish, he became more willing to venture out into the world of the living. After three months, he had even more energy, and felt confident and enthusiastic about life to a degree he had not experienced for years.

This is not to say his fatigue evaporated. He was tired, sometimes very tired. But, as Gary pointed out, it was good tiredness, not a CFS tiredness.

In the complicated realm of CFS, where there remain so many unanswered questions, I am not sure what recovery actually means.

I often wonder whether the illness vanishes completely, leaving the patient the same as before,

Or if it simply recedes in the background, becoming mild enough that the patient learns to ignore its nagging distractions.

Both probably occur.

In a study Mary Robinson did of our patients, 20% remained disabled after 15 years. Of the remaining 80%, half persisted with symptoms although they were able to lead relatively normal lives.

Several years have passed for Gary and we continue to stay in touch. He has clearly entered that privileged circle of CFS patients who actually recover fully from the disease. I do not think that his continued recovery can be attributed to exercise, or even the vitamins, but who knows?

I do feel that if Gary had not tried the exercise, he would have stayed in his prison for the rest of his life. Gary recovered for reasons that are mysterious, but he needed to take a leap of faith in order to demonstrate the recovery to himself.

Gary doesnt really think about these issues very much anymore. He is working again, and engaged once more in the lives of his spouse and children. Nevertheless, he has been changed profoundly by his experience. He left his prison of four years, but as a different man. He carries with him an appreciation of his incredible good luck. His suffering now is confined to feeling the suffering of others who are in pain.

When he watches the news on television, and there is a story about AIDS or multiple sclerosis or cancer or CFS, he does not rush to change the channel as he once might have done.

Instead, his eyes fill with tears.

– David S Bell, MD, Aug 15, 2000

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Note: This information represents the experience and opinions of Dr. David Bell. It is generic and for general information purposes only. ME/CFS/FM is an extremely complex illness, and such general information may not be appropriate for an individual with this illness. Therefore, should you be interested in the ideas presented here, please discuss them with your personal physician.

“The Poison Ivy Treatment” – An Intriguing CFS Case Study by Dr. Bell

by Dr. David S Bell, MD, FAAP*
February 2, 2011

This ME/CFS patient case history is one of 10 that Dr. David Bell included in his book Faces of CFS – Case Histories of Chronic Fatigue Syndrome, published in August, 2000.* Each case illustrates a different aspect of the illness that he observed in managing patients affected by the ‘Lyndonville Outbreak’ in New York, and none remains more fresh or intriguing than this one.

Reprinted with the kind permission of ProHealth: 2/2/11

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“This minor test is one of hundreds that prove to me that CFS is real and can be studied.” – David S Bell

I had been treating patients in my Lyndonville clinic for 10 years when, one day, I happened to pick up the chart of a patient whose name was unfamiliar to me. He was awaiting me in my examining room.

I quickly learned that Edwin Maxwell was the man who owned the beautiful farm on the Stillwell road. I had admired this farm every time I passed it on my way to the nearby hospital. The old barns were always maintained with care. I had come to expect an orderly procession of snowdrops, tulips and lilies on tended patches of lawn every spring and summer. I could see that a lovely stream ran through the rear of the property, which looked like a European forest – tidy, but natural, as wonderfully wild as anything could be and still be called a farm.

I also knew whoever tended this farm had a certain mysterious wisdom. If hay had just been cut on the Maxwell farm on a summer day, you could count on three sunny days to follow. Even the weather seemed to respect this farmer; his sixth sense was more reliable than any TV forecast.

I observed, as well, that there was no rush, no great urgency, to this farmer’s life. He tended his fields with patience, as if he knew that the earth would unfold its crops the way life unfolds its secrets – all in due time.

I liked the 45-year-old Edwin Maxwell immediately. He began our conversation by letting me know he was Dr. Wilson’s patient and would remain Dr. Wilson’s patient. He wanted to talk to me about this new disease I was studying, however, because he knew something about it.

He allowed as how he had every intention of paying for his visit, but he wanted me to understand that he was there to tell me something about CFS, not to be treated.

I settled back in my chair and waited. By then – the autumn of 1988 – there had been so much publicity about CFS that literally hundreds of people, some of them writing to me or calling me from the four corners of the earth, had already offered me their theories about what was causing CFS.

These theories of causation ranged from discarded plutonium at the nearby West Valley nuclear processing plant, to PCB’s in the salmon of Lake Ontario, to yeast in the intestinal tracts of sufferers. Then, as now, I listened to every one of these ideas with honest interest.

I continue to believe that, someday, someone would come up with the correct answer. Nevertheless, even then, these theories were growing pretty thin, sometimes bordering on the weird.

Edwin continued by stating that he, too, suffered from the disease I was studying. He was not looking for confirmation from me; in fact, his expression brooked no argument. He explained that he had been comparing notes on his symptoms with a number of his friends and neighbors who had CFS and were my patients.

I confess I was surprised: Most people with CFS show up in my clinic in a state of perplexed misery, wondering if I can tell them what is causing their joint pain and headaches and exhaustion. Edwin, in contrast, seemed to have a rare intellectual grasp on the disease.

When I tentatively asked him to tell me about his symptoms, he explained that the fatigue was the worst.

Three years before, he said, he could lift six, maybe seven, wagons of hay bales if he had to, and feed them onto the conveyor belt to the barn loft. He could plow and roll 17 acres of land in one day. Had for years – until three years ago. He added that he suffered from scratchy, sore throats. He had muscle pain, but he also pointed out that there was no reason, at his age, to have muscle pain. Hell, his father was still baling hay at 70.

He reported with obvious chagrin that he needed to wear sunglasses while he worked, even though he had always disliked sun glasses; they were something city people took to the beach.

So Edwin Maxwell could have CFS, I mused. Okay – now what? I waited.

“This spring,” Edwin said, “I had a lot of fields to plant in a short time.” He was choosing his words carefully. “The winters are okay, because it’s easy to cut the days down and get the extra rest. But not in the spring. There is so much to be done after the geese leave.”

Lyndonville happens to be on the migration pathway of Canadian geese. These great birds descend on the land for four to six weeks in the early spring, and when the fields begin to dry out from the winter snow, the geese head across the lake toward Canada. It is a time of great excitement in Lyndonville. The days begin lengthening in earnest now, and the geese are incredibly noisy.
You don’t even mind being woken at five in the morning by two thousand geese in the back cornfield. They leave when the ground begins to dry, the beginning of the plowing season.

“I remembered that the spring before,” Edwin continued, “I got poison ivy on my arm while cutting some brush in the back of the house. The poison ivy was nasty, but I noticed that the fatigue was better.

“I didn’t think much more about it. Then, this spring, just before plowing, I decided to pull up some poison ivy roots and rub them on my arms. Afterward, the itching was horrible, but my fatigue got better for about two full weeks. I could work just like before I got this disease, and I got all my planting done in time. But I noticed that as the poison ivy wore off, the fatigue came back.”

Edwin Maxwell was a careful observer of not only nature, but of himself, I realized. He asked for nothing in return. He was imparting some information to me, in case I was interested.

I was interested. New concepts about CFS either fit, or they did not fit, based on the selective “principles” I have developed over years of observation, principles framed by my experience. I realized immediately I had just heard a new “principle.”

Edwin’s revelation meant that the fatigue in CFS was not fixed; it could be variable. It could come and go, and was just a symptom; perhaps not even a necessary symptom. Theoretically, you could have CFS without being tired!

Consider the implications: if you were shot, or had a broken bone, little would be changed if you also acquired poison ivy; neither would exposure to the weed impact on your tuberculosis or your depression or your radiation sickness.

Poison ivy was an allergic response generated by the immune system, and localized at the point of exposure. Edwin was suggesting that this immune response – a sharp blip in the day to day functioning of the immune system, resulting from exposure to an allergen – might somehow diminish the fatigue in so-called “chronic fatigue syndrome.”

I had already discovered that among my CFS patients who were children, particularly, at least half had early childhood histories of either asthma, or allergies to various common substances.

I knew that there were a number of papers already published in the medical literature connecting CFS to medical histories of “atopic” illness, also known as allergies. A history of allergies appeared to be a risk factor for acquiring CFS. In fact, it was one of my established “principles” of the disease that a complex, if poorly understood, relationship existed between having CFS and allergies.

Yet, Edwin was telling me that if you applied an allergen to a small patch of an arm – if you localized an allergic response, in other words – you could make the fatigue in CFS go away while the allergic response lasted.

It didn’t really matter to me whether this held true for anyone else in the world. If it was true for one person with CFS, then it provided an hypothesis that could be tested in other CFS patients. The key was to learn whether this phenomenon represented a fundamental physiologic mechanism of the disease, or was just an interesting fluke.

If consistently true of all CFS sufferers, then any theory of the cause of CFS would have to hold an explanation as to why a poison ivy attack gave Edwin Maxwell an energy boost.

Sometimes when you think a great deal about something, you get so used to your own thoughts that they begin to seem dull. It takes someone else’s ideas to wake you up again. Edwin watched me as I struggled mentally to fit these new pieces of the puzzle together. He could see that I was taking his comments seriously.

I was ready to accept that fatigue need not be present for someone to have CFS.

I knew several people who lived in families where one member or more was thoroughly debilitated with full-blown CFS, and who suffered from severe intellectual problems along with other symptoms highly suggestive of CFS, even though they lacked the accompanying exhaustion. In fact, they had no more
than ordinary fatigue.

Could you jettison fatigue from the definition of the disease? I think you could, although this view would be unlikely to be published in a medical journal, especially since, even today, members of the scientific establishment are unwilling to agree that any of the symptoms of CFS are “real” and not psychiatric in origin. To persuade this same community that you can have what they call “chronic fatigue syndrome” without having “fatigue” would be next to impossible.

Nevertheless, the variability of fatigue – the idea that some people could have the disease without being tired – had become for me a defining principle. In truth, if this principle proved true, then the margins of CFS would begin to blur with the margins of attention deficit disorder (ADD), and other learning disabilities, especially in children. That was the population in which I most commonly saw patients with all the symptoms of CFS, minus one: fatigue.

Edwin Maxwell’s story got me thinking more intensively about the cause of the fatigue in CFS. I was intrigued that a natural substance, one manufactured by the body, called interleukin, might be the culprit.

While it may seem naive to look for a single substance responsible for fatigue, it did not seem a hopeless task. Scientists have been experimenting with one type of interleukin, interleukin-2 (or IL-2), as a therapy for several kinds of cancer. What researchers inevitably find, however, is that it doesn’t take very much IL-2 to induce symptoms in cancer patients that are almost as bad as the cancer.

Amidst the numerous side effects that include confusion and mood changes, IL-2 also causes profound fatigue when it is administered as a drug therapy.

Some months before Edwin Maxwell’s visit to my clinic, I had published a scientific paper with a collaborator, internal medicine specialist Paul Cheney, in which we reported that children and adults with CFS had startlingly high levels of the receptor molecule for IL-2. These levels were so high that it implied that the chemical IL-2 could be causing the fatigue and other symptoms of the disease.(1)

I realized that Edwin – if he was willing – could help me test my nascent theory that measuring IL-2 levels might be a way to quantitate the fatigue in CFS in a laboratory. He was willing.

I told him we would take blood samples from him when he was exhausted and measure IL-2 receptor. Then, we would apply poison ivy to his arm and wait until the fatigue improved. When the poison ivy kicked in and the fatigue went away, we would draw more blood. I suggested we do this three times, to be sure of our results.

Edwin liked my idea. It made sense to him. One sunny afternoon at the end of July that summer, I drew blood from Edwin’s arm during a “normal” period when the farmer’s exhaustion was pretty severe. I asked him to maintain a kind of symptom severity journal, as well, which required him to rate the severity of fatigue and 11 other symptoms on a scale of one to ten, with ten being the worst.

After I drew his blood, Edwin himself rubbed poison ivy on his arm. A week later I met him in the emergency room where they kept a camera and photographed the rash on his arms. A few days later, Edwin’s fatigue had subsided substantially, and I drew another sample of blood. We waited for the good effects of the poison ivy to wear off. Then we repeated the entire process.

We did not get to the third trial because by then Edwin had begun to dread the effects of the poison ivy as much as he had grown to dread the fatigue. He begged off, and I respectfully complied with his wishes. I already thought him very brave to offer himself up to medical science as he had done.

Also, the emergency ward staff was beginning to look at me in a funny way because I kept photographing the poison ivy someone was giving himself. Ah, science……

Ours was never anything more than an informal experiment, one that ended somewhat prematurely, but its results were provocative.

Just as Edwin had reported, his fatigue, as well as his other symptoms, were diminished when he was suffering from acute poison ivy. Somehow, this classic allergic response mitigated his most debilitating symptoms: fatigue, compromised intellectual capabilities, and physical pain.

However, the results failed to confirm beyond all doubt my theory about the relationship between IL-2 levels in the blood and fatigue. The results did suggest that fatigue severity was not just a coincidence, the normal ups and downs of CFS symptoms. It was intriguing to speculate that this relationship could even be someday turned into an effective treatment of the symptoms.

Unfortunately, the options are not that good. Edwin preferred the regular CFS symptoms to severe poison ivy symptoms. Maybe it’s not such a great treatment.

Medical science is cumbersome. Hints, such as the hints produced by this experiment, cannot be published in medical journals without real proof. And to conduct a proper experiment takes a great deal of time, money and paperwork, all of which are in short supply for the clinician. But the most frustrating part is the inability of clinicians to communicate to those able to do real experiments that CFS is real and must be taken seriously.

Two weeks ago I attended a neurology conference and CFS was dismissed by the lecturer as a minor psychosomatic nuisance for which there were no tests. The real problem is that academics and governmental public health personnel refuse to put aside their biases and look for the proofs. They seem content to criticize experiments like Edwin’s as incomplete. And of course they are correct.

But Edwin’s poison ivy treatment was over 10 years ago [now more than 20], and still nothing has come from it. This minor test is one of hundreds that prove to me that CFS is real and can be studied. From a scientific perspective, the relationship between the debilitating symptoms of CFS and allergic response is fascinating. I have been naive to think that it would be fascinating for others.

The misperception that CFS is psychosomatic comes only from scientists’ inability to look beyond their psychosomatic biases and look for the proofs.

Edwin doesn’t care, and in this respect he is unique. He gets on with his life, tends the springtime garden with care, manages to get the hay in every summer. He is able to accept the presence of symptoms as he accepts hail which damages the apple crop. And he is lucky, his symptoms are relatively mild and he can ration his time. If he worked in a factory assembly line with rigid hours, he would not be as lucky.

I rarely see Edwin now. Sometimes, while driving by his beautiful farm on the Stillwell road on my way to the hospital, I wave to him in the flower bed, or when he is putting the tractor into the barn. He is busy getting on with the business at hand, he doesn’t have time to feel sick.

– Dr. David S Bell, MD, Lyndonville, New York, August 15, 2000
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1. Citation: “Interleukin-2 and the Chronic Fatigue Syndrome,” Annals of Internal Medicine, Feb 15, 1989, by Paul R. Cheney, MD, PhD; Susan E. Dorman; David S. Bell, MD.

* This article is excerpted with kind permission from Dr. Bell’s classic book Faces of CFS – Case Histories of Chronic Fatigue Syndrome; © David S Bell, MD, 2000.

“The November Factor”: Dr. Bell on ME/CFS & the Flu that Isn’t Flu

by Dr. David S Bell, MD, FAAP*
March 30, 2011

This ME/CFS patient case history is excerpted from Dr. Bell’s book Faces of CFS – Case Histories of Chronic Fatigue Syndrome, published in August, 2000. Each case illustrates a different aspect of the illness that he has studied in patients affected by the ‘Lyndonville Outbreak’ over the years.

Reprinted with the kind permission of ProHealth: 3/30/11

THE NOVEMBER FACTOR

If robbery is taking without permission, CFS could be the greatest thief of all.

Certainly much has been stolen – the energy to go to work, to play with your children; the ability to enjoy reading a book; the luxury of a refreshing sleep. And, like true, great crimes, the victim sometimes does not even realize that a robbery has been committed.

It is as if the thief in a department store steals the surveillance camera along with the jewelry. The thief of CFS steals not only energy, it may rob the victim of the ability to perceive loss. And the mechanism is simple: Energy is quietly replaced with guilt.

Because the victim feels guilty about experiencing fatigue, the robbery goes unreported. Is it any wonder that this is a controversial illness?

The gift of human nature is the perception of who and what we are. We see ourselves either accurately or inaccurately dependent upon personality and the myriad of factors we call life. We see and feel, relating these experiences to our image of who we think we are. Because fatigue is something to be ashamed of in our society, it may go unreported.

The thief makes off with the priceless essence of our life and replaces it with a plaster statue of guilt. CFS becomes a thief of identity as well as activity. It is possible to say “I am an athlete,” or “’I am a devoted parent.”

When CFS has crept out the back door with energy and hope in a burlap sack, these statements are no longer possible.

It makes no difference whether they were accurate to start with. Even if a fantasy, they were a real fantasy for us. With CFS, even fantasies and dreams are stolen. It is like the movie The Dark Crystal, where the small victims are placed in an evil machine that sucks out their ‘vital essence’. CFS is the thief of the ‘vital essence’.

CFS will do to medicine what quantum mechanics has done to physics. The laws, once considered inviolable, are turned on their head.

Just as we were comfortable with the simplistic notions of physics before relativity, doctors are comfortable with the simple notions of medicine now. It really makes little difference that these notions are incorrect, except to those who are not helped by modern medicine.

When CFS becomes accepted and understood, the simplistic mechanisms will be replaced by theories that are able to explain what is now considered subtle. And, of course, with this understanding will come effective treatments – not just those to improve the symptoms of CFS – but those that will revolutionize medicine.

An example of an illness assumed to be straightforward but is, in fact, bewildering, is the ‘flu.’

A person will say, “I was well until a year ago February when I got the flu.” Or “In the months before I got sick I kept getting the flu.” Or “My immunity must be low because I have had the flu three times this winter.” And of course, when the doctor has no idea of what may be causing your symptoms, comes the standard, “I think it is the flu.”

The longer I study medicine the less I understand about the flu.

Jason Ewing was in his mid-thirties, and apart from being a little overweight, appeared like many up-and-coming executives who trooped into the company offices in the morning, brief case swinging at his right side. He had a promising career until two years ago when he developed a typical case of the flu. Actually, as with many persons with CFS, there was one minor difference. This flu had more-than-usual exhaustion associated with it.

It is a detail frequently overlooked, and it has always been difficult to tell whether there really was more exhaustion with this first flu or whether now, two years later, the fatigue is remembered more prominently.

But at the time Jason took time from work and returned, still not feeling well, a week later. He had not even bothered to see his doctor during the illness because ‘it was just the flu.’ Two weeks later he had crept almost to the point of recovery, and paid it little attention. He was at work when the flu came back a second time.

Jason noted with clarity that this second flu episode was identical to the first.

Not just a similar illness, but the same illness. And now we are getting into strange territory. If a person gets a cold, we assume runny nose, cough, sore throat. But, like ice cream, colds come in many varieties – hundreds in fact – and they are all slightly different.

For example, one cold starts off with a scratchy throat, swollen glands, a little nausea and intense sneezing which lasts a day. But this cold is not the same as that of the neighbor down the street, sore throat and headache but no sneezing. We can call them both colds, but the pattern of symptoms is slightly different, and indeed with viral studies we can see that the initiating virus is also different. But what Jason noticed was that whatever the first virus had been, the second one felt exactly the same.

It would be hard to describe the specific combination of 20 symptoms that made up this particular ‘flu’. It would be like trying to describe an unknown ice cream flavor. In the ice cream store drooling Mocha Vanilla from the corner of your mouth, you say, “that’s it.” And it was a second one. It was separate from the first because he had recovered, implying that his body’s immune mechanism had conquered the first invader. He had returned to work and nearly forgotten about the flu three weeks before.

He went to the doctor and described the course and symptoms, and the exact similarity of the second course to the first. His doctor said that he could not get the same ‘flu’ twice, and that it must be a coincidence that the two were similar.

Jason nodded agreement; they had just made a pact to accept a statement, clothed in the language of science, that was obviously wrong.

There are many viruses that cause the illness we call the common cold. In fact the viruses that cause colds are of several different groups. Flu viruses are a little different, but sometimes it is difficult to say by the symptoms if something is a cold or the flu, because they overlap so much.

In general a cold is mild, one or two days of feeling crummy, and the flu is a week. The flu can be dangerous to older people because they develop secondary infections. And there is a vaccine to cover many of the strains of flu that appear during a given winter. There is the ‘Warsaw’ flu, the ‘Beijing’ flu, the ‘Moscow’ flu. It always seemed to me as a medical student that the different strains of flu were named for communist cities as if they were deliberate attempts at biologic warfare.

Each flu strain is distinct. If you had the ‘Hong Kong’ flu once, you would develop antibodies to this particular viral strain and recover. Then, because of blood cells called memory T-cells, you would remember this strain and not get it again, except in the rare instance after decades when the memory T cells become a little senile. That is why, in general, we get chicken pox or measles once in childhood and then do not get these illnesses again when our children have them.

It is difficult to measure or determine the specific strain of virus during an infection. The government will look for new strains in order to include them into the flu vaccine, but because they take several weeks and are costly they are not routinely done during a flu infection. You go to the doctor and he or she says “You have the flu. Please pay at the front desk.” (As an aside, have you ever noticed that the first ten visits for CFS are said to be due to a virus, and the next ten are said to be due to depression?)

So therefore it is not likely that Jason had the same flu twice in a row. And all of this would not have made any difference if everything got better and resolved.

Jason didn’t care much about T-cells and strain variation. Unfortunately, as he was recovering from this second bout he had a third, again with identical symptoms. There was a very particular set of discomforts that made up this flu and a particular malaise, and it came back full force.

He was treated with antibiotics – maybe it was a sinus infection – and again recovered, only to get it again a fourth time.

Over the next six months the process kept repeating with one significant trend. The episodes of this “flu” began coming closer and closer together and the recovery period shortened.

Six months after the initial episode, they were no longer separate bouts, but a constant illness with the symptoms of abdominal pain, flu-like aching, sore throat, joint pain, headache, blurry vision, trouble concentrating, and, of course, exhaustion.

Instead of being 35 and playing piggy-back with his children, Jason had CFS.

Jason’s six-month onset was not the most common for CFS, but then, again, there are many types of onset in this illness.

Jason’s particular onset, however, raises several important questions:

• Is the illness due to a flu-like virus?

• Is CFS due to an unusual virus that plays hide and seek for the first six months?

• Or does CFS have nothing to do with a virus at all?

Can flu-like symptoms be due to something other than an infection with a tiny microbe? The first time this question ever occurred to me was while I was an intern, working 36-hour shifts in the intensive care nursery. After being up all night and struggling to remember where I parked my car, I would notice that my lymph gland felt swollen and that I was coming down with the ‘flu.’ But after a coma-like sleep I would be recovered and ready to hit the next 36-hour shift.

Another of life’s ironies: They have now made it illegal for interns to work those hours because they would prescribe the wrong medications, put IV fluids in the wrong patients, and make other mistakes due to fatigue. But when a person is disabled with CFS and is constantly in that exhausted state, no one believes them, particularly the former interns.

The most common type of onset in CFS is the “acute onset” flu-like illness that does not resolve.

Yet even in this more frequent type, there are parallels with Jason’s flu. In the acute onset, there is a flu-like event, which after five days or so begins to resolve, just as one would expect with the flu. But after the initial resolution, almost to good health, the symptoms come crashing back and do not disappear again.

This implies that the illness is a little uncertain, it wavers a little at the beginning as if trying to make up its mind. “Shall I come down on Mrs. Peterson or not?” If this is so, it had a really hard time deciding about Jason.

A second unusual detail common to the onset of CFS is the severity of the fatigue during the initial episode of the apparent flu. Again, difficult to differentiate in retrospect, but in the initial illness, the fatigue seemed to be more severe than usual.

When I observed the outbreak in Lyndonville, I felt that this was one detail which set this flu apart from all the others. In fact I felt that you could even guess which people were destined to not get better – although I never hinted that at the time.

The belief I held was that there was a unique infection which caused CFS.

What is it about the flu that causes the symptoms that everyone knows only too well? The conventional explanation is that with an infection, viral or otherwise, chemical mediators designed to fight the infection are released into the blood stream. And it is the presence of these immune substances that actually cause the symptoms.

Part of the evidence for this is that when these substances are infused into healthy people they feel rotten, as if they had the flu. The flu virus and many other viral, and bacterial agents stimulate the production of these normal chemicals, which causes the symptoms. When the body’s immune mechanism destroys the infecting virus or bacteria the production of these immune mediators shuts down with a return to good health.

With Jason, the onset had begun as a typical viral infection followed by repeat episodes or relapses until a continuous illness developed. His course of CFS was then typical: There were good days and bad days, but no days without exhaustion, brain fog, and muscle and joint pain.

There were the usual problems with diagnosis, many specialists consulted, tests run. After 15 months the
diagnosis of CFS was made.

The time when the flu-like events coalesced into a continuous illness was around March of 1995. By summertime the symptoms followed a daily ritual that varied little.

• He would have four or five hours of up-and-around activity, headaches every other day, and so on.

• When he had a bad week, his activity would drop down to two to three hours a day and he would feel more ill.

• On a good week, sometimes coinciding with sunshine and a warm breeze off the lake, the activity could go as high as six good hours a day.

Summer eased on into fall, and into November.

Jason had a severe relapse in November, and felt the same as at the onset of his illness. Exactly the same.

His symptoms worsened to the degree that he was confined to bed for two weeks. He saw his physician who, predictably enough, said he had a virus and to take plenty of fluids and aspirin. On the next visit he was given an antibiotic just to be on the safe side. The flavor of this virus was the same flavor that had started his illness nearly two years earlier.

In this detail, Jason is not unique. CFS is an illness of relapses and remissions, and when patients describe relapses, they describe very similar events to those which occurred in their onset. It is not uncommon to hear, “It was like it was beginning all over again.”

It is because of this observation that the theory of a persistent infection, one that does not resolve, has been a steady thread through the tapestry documenting the history of CFS.

Viral and bacterial candidates come and go, but the proof has been hard to come by.

A second characteristic of Jason’s relapse that seems typical of CFS was its occurrence in November. In our office we call it the “November Factor.” For some reason, people with CFS get sick or sicker in late fall, and our telephone rings off the hook. I believe there is some connection between the unusual onset type and the worsening which occurs in November.

One possible explanation is that the patient has caught another bug. Kids are back in school, a perfect breeding ground for bugs of all sizes. They bring these bugs home, particularly this year’s variety and share them with their parents. The relapse is due to a worsening caused by an intercurrent infection, probably viral. This explanation implies that the relapses, and possibly the onset, are random, due to any old virus.

A second possible explanation is that summer is over and winter is setting in. Many persons with CFS feel better in the summer, perhaps because there is less stress, and more time sitting around on the porch in the warm August air. For young persons and schoolteachers, summer is a time of unsustained activity. That is, instead of eight straight hours of work, school or study, it is an hour here, a couple of hours there with rest in between. Therefore starting back to a day with eight straight hours of work or school can precipitate a relapse.

In this theory, the November factor is the resumption of sustained upright activity after a stress-free, relaxing summer. This possibility implies that a critical amount of sustained activity initiates a relapse, a common experience for persons with CFS.

A third possibility has to do with sunlight. Upstate New York, next to Lake Ontario, undergoes a change in November. The days become short with sunset at 4:45 PM by mid December. Worse yet, water vapor from the lake creates a perpetual cloud bank that drifts over Lyndonville and lingers for the next four months. Mid day is gray, bleak and cold, and all sensible adults have left for Florida.

Perhaps the lack of sunlight alters the brain’s melatonin and the addition of seasonal affective disorder is the November factor. Nearly everyone around here is depressed all winter, a fact that the chamber of commerce leaves out of the brochures. Our great joy in winter is a good nor’easter storm which blows the clouds up to Toronto and gives us several wonderful days of sunlight in which we can shovel snow. My lack of enthusiasm for winter here is more than compensated for by the arrival of the geese in the spring and the following months of cherry and apple blossoms that blanket the county.

There are other possibilities. With the coming of cold and bleak weather in November, people go into their homes, shut the windows, add plastic sheeting to help insulate the windows and begin breathing more carbon monoxide. Carbon monoxide, despite being a deadly poison, is very interesting. It can cause a flu-like illness and prolonged neurologic symptoms very similar to CFS.

Oxygen makes many persons with CFS feel better, at least temporarily. Experiments with hyperbaric chamber treatments, where oxygen is pushed into tissues at high concentrations, have shown improvement in patients with CFS. High altitude sickness also shares many of the symptoms of CFS, again due to decreased oxygen availability to brain cells.

Could it be that the flu-like event is not due to an elusive virus at all, but instead to decreased oxygen availability to the cells? [Note: In 2007, Dr. Bell published Cellular Hypoxia in Neuro-Immune Fatigue – a book laying out his hypothesis that ME/CFS and FM may involve a dysregulation of cellular metabolism leading to the inability of the cells’ mitochondria to utilize oxygen normally.]

Medical science is amazing. The technological advances are astounding. We can rescue one pound preemie babies and transplant hearts, livers, and fingers. We can diagnose retroviruses and have made great strides in treating AIDS. Few pediatricians can boast of seeing measles epidemics, and chicken pox will not be seen by the next generation of doctors. But try to explain something as simple as the flu.

Jason did well for the most part. The one time he got really sick was when I tried to treat him with fludrocortisone.

He got the same flavor flu-like event, initiating the relapse. It was not as severe this time, and it was not in November. He has been the only person treated with this medication who has had a relapse, but it again raises the question of whether the flu-like symptoms are due to infection or an entirely different mechanism. We stopped the medication, left him alone for two weeks and the relapse ended, albeit slowly.

It has now been almost five years since Jason began his journey, and he has improved slowly and steadily. He is up to eight hours of daily activity, and while the symptoms persist, Jason feels grateful that the crushing flu-like malaise has passed.

– Dr. David S Bell, MD, Lyndonville, New York, August 15, 2000

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This article is excerpted with kind permission from Dr. Bell’s classic book Faces of CFS – Case Histories of Chronic Fatigue Syndrome; © David S Bell, MD, 2000.

“The Fruitcake Factor”: Dr. Bell on the Neurologic Nature of ME/CFS

by Dr. David S Bell, MD, FAAP*

This ME/CFS patient case history is one of 10 that Dr. David Bell included in his book Faces of CFS – Case Histories of Chronic Fatigue Syndrome, published in August, 2000. Each case illustrates a different aspect of the illness that he has studied in patients affected by the ‘Lyndonville Outbreak’ over the years.

Reprinted with the kind permission of Prohealth: 3/2/11

____________

THE FRUITCAKE FACTOR

“Neurologic symptoms appear to me to be the most direct window into the heart of this illness; they both define and explain CFS.” – David S Bell

When I was a child, I lay in a field one sunny day, puzzling over something that was brand new. Staring at the sky, I noticed what seemed to be an object of unknown identity hovering in my left field of vision. When I turned my head in its direction, however, it seemed to slide away and disappear. I realized I could also see a similar strange shape in my right field of vision. If I directed my gaze ever so slightly away, it might remain still for a moment, delicately balanced, but it slid away, too, when I turned my head to focus on it. They were shy, transparent objects, and they were not really in the sky. I studied the problem for an hour or so, then I fell asleep.

During my medical training, I learned that these curious objects are called “floaters” by neurologists and eye specialists. They are white cells that have collected in the anterior chamber of the eye. Almost everyone will notice them from time to time.

I have decided that floaters are very like CFS since, whenever you try to look directly at them, they skitter off to the periphery and then disappear. If you pretend not to really look at them, they may hold still just long enough for you to get some sense of their shape and size. Certainly, the illness I study in Lyndonville is like that. The harder you look at a specific aspect of CFS, the more whole disease slides off to one periphery or another, hiding itself just beyond your line of sight.

Let me give you an example. Nearly 80% of people suffering from CFS will have joint pain at some point in their disease, and many will have it as a chronic symptom. Yet, this pain is by no means a true arthritis.

When these painful joints are subjected to X-rays, the image looks normal; there is no joint damage or deterioration. I am able to rule out rheumatoid arthritis, a more severe disease than the common osteoarthritis, in CFS patients, as well, because the blood tests used to diagnose rheumatoid arthritis are negative.

I have noticed that the typical rheumatologist seeing a CFS patient may end up – as I did once as a child studying curious objects in the sky – falling asleep before the patient even comes to the end of his symptom list. Whatever the root cause of CFS, joint pain is some distance away from it.

Still, there are a few symptoms a doctor notices in CFS sufferers that I believe are crucial to understanding the disease.

Amanda Lewis was nearly 40 when I first saw her, and she had been ill with CFS for years. She had all the typical symptoms: unending fatigue, joint and muscle aches, headaches, trouble concentrating.

As her years of illness wore on, she had learned ways to cope with these unpleasant sensations, but there were a whole category of symptoms, which came under the heading of “neurologic,” from which she rarely found relief or escape, nor could she hide them from others.

• Lights hurt her eyes, and certain high pitched noises caused her to experience pain just behind her ears.

• Sometimes her fingers hurt when she touched objects.

• Amanda also described a burning sensation in her arms, as if they were in flames, and occasional episodes of either numbness, or tingling, in her arms.

• On occasion, she would also experience tremors in her upper arms, which would shake and begin to rise involuntarily. If Amanda had lost consciousness at such times, one could say she was suffering a seizure, but these were not true seizures because she was fully conscious throughout the ordeal.

• Amanda discovered, too, that on occasion her arm and hand muscles were so weak objects like empty coffee cups would just slip out of her hand.

Most distressing to her, Amanda’s intellectual capabilities seemed to have been shattered.

Sometimes she got lost – in her house. When she cooked, she sat by the oven until her food was ready in order to make sure she remembered to turn off the burners. She was utterly helpless when it came to managing two simple tasks simultaneously; she simply lacked the ability to concentrate.

She felt her brain’s gears had gone rusty.

I was hardly the first doctor Amanda had consulted. Among those few doctors who took her complaints seriously, a few had suggested her intellectual difficulties were the natural result of aging, a worrisome suggestion, as she was young.

In addition, although all the symptoms she described to these doctors could be huddled together under the umbrella of neurologic disease, they had been unable to find evidence of muscle wasting or atrophy, nor had they been able to measure any abnormal degree of weakness, using standard neurological tests. (They did detect a slight tremor in her arms and hands, however.)

In addition, Amanda failed what’s known in medicine as the Romberg test, named after its inventor. When she stood in a relaxed stance with her arms outstretched, she wobbled and usually fell backward and to the right.

When Amanda came to see me and described these problems, I decided to test her reflexes.

Everyone who has ever had a physical exam remembers the doctor tapping a rubber hammer on their knee, and watching their lower leg jerk forward. That’s a normal reflex.

When doctors test reflexes, they are checking a “reflex arc,” a nerve circuit or pathway that travels from a tendon in the leg to the spinal cord and back to the leg muscles. Diseases that interfere with the nerves of the leg will suppress that reflex to kick your doctor in the groin.

I was startled when I tapped Amanda’s kneecap tendon. She didn’t kick me – her whole body shook.- In fact, she almost jumped off the table. I then tested her vibratory sense with a tuning fork, the ability of her leg nerves to detect vibration. Her reaction was more muted, but similar to the first response by being exaggerated. It seemed to me as if Amanda was very much like a set mousetrap that was ready to trip given the tiniest nudge. I think this was the first time I was worried about hurting someone by tapping a tendon with a rubber hammer.

• I sent Amanda to a specialist, a neurologist. His diagnosis: Huntington’s chorea, a fatal disease of the central nervous system. Amanda was hardly cheered by the news, and I was dubious because her tremor was unlike the jerking motions of “chorea.”

• I arranged for another neurologist to see her in an effort to get a second opinion. The second neurologist suggested that Amanda might have multiple sclerosis, but seemed unwilling to test his own hypothesis by conducting the standard diagnostic tests for the disease.

• A third neurologist insisted that all of Amanda’s symptoms could be ascribed to depression. He prescribed antidepressants.

When I asked him, in a telephone conversation afterward, about Amanda’s remarkable response to tendon tapping, he assured me that her response was phony. Nobody jumps off the table when you tap their reflexes, he noted with a degree of confidence I found chilling.

I realized he was telegraphing to me some basic information he believed I needed to know: Amanda was a fruitcake. Amanda’s exaggerated reflex response became “the fruitcake factor.”

Neurologic symptoms appear to me to be the most direct window into the heart of this illness; they both define and explain CFS.

The reluctance of neurologists to be interested in CFS mystifies me. Perhaps it is too difficult; perhaps it is because they prefer the classic symptoms of seizure, isolated headache, and the shaking of Parkinson’s disease.

CFS is a unique blend of numerous neurologic symptoms, none of which are well understood today.

• The fatigue (not tiredness) must be generated somewhere in the primitive midbrain;

• The sleep center is nearby and clearly does not work correctly.

• Cognitive problems, pain, and headache are clearly neurologic.

• Even the immune system problems of CFS may be neurologic as we know that brain injured patients display immune system abnormalities.

But right now it is too complicated. Physicians can be very interested and scientific when it regards any other organ of the body, but the thing that sits atop the shoulders remains the “black box” of medicine and is largely ignored.

I have no problem with not understanding the exact mechanism of the symptoms of CFS. I was never good in the two week neuroanatomy class in medical school. I do have a problem with the lack of respect given patients with poorly understood neurologic disease.

Science has created a false aura of mastery, and if there is an area where mastery does not apply, it is an area to be disregarded, ignored, and even ridiculed. And this injury by the medical profession and society hurt almost as much as the symptoms of CFS.

I routinely see patients with CFS who are disappointed when an MRI scan does not find a nice big brain tumor. At least that is real. Ultimately, the neurologic symptoms of CFS will gain a foothold in the thinking of neurologists and garner respect. The brain is the Rodney Dangerfield of medicine.

It was a colleague who first described to me a possible mechanism for the fruitcake factor in CFS. Paradoxically, this symptom is prominent in only a small minority CFS sufferers, always the most severely ill; it may even be the medical marker for the degree of severity.

When I look for it, however, I can see traces of it, or at least very subtle myoclonus, in up to half of all patients.

And here I will reveal my hunch: The fruitcake factor not only represents a fundamental process of the disease, it probably exists in every patient to some degree, however minor, and expresses itself as pain.

Amanda’s violent reaction to tendon tapping was a manifestation of what doctors call “myoclonus.” Neurologists define myoclonus as a sudden and generalized jerking contraction of the muscles. You may have noticed your sleeping partner in the early stages of sleep either jump or jerk, sometimes kicking you quite fiercely without once offering an admission of guilt or regret.

So called “sleep myoclonus” is sometimes violent enough to wake you just as you’re falling asleep. Sleep myoclonus is perfectly normal, but – with few exceptions – it is the only kind of myoclonus that is normal.

Sadly, although myoclonus is a markedly abnormal finding, it is also the ultimate humiliation for the patient with CFS. Although this finding may be one of the most important signs of neurologic disease during any clinical exam, doctors most typically dismiss it as “hysterical” when they are examining CFS sufferers. What they mean by this is that the patient is going for dramatic effect.

In my view, this is like calling an epileptic patient a drama queen when he has a seizure.

Epilepsy is not due to “evil humors,” as seventeenth century healers once decreed, and the fruitcake factor – myoclonus – is not hypochondria.

Of course, muscle tension can cause the tendon reflex to be increased, and anxiety certainly increases muscle tension. But an abnormal reflex due to mere muscle tension would never cause someone to jump off the examining table.

This response is due to the fact that the reflex travels up the spinal cord, not just the isolated arc back down the leg.

Anxiety could not possibly explain Amanda’s reaction. Some experts on the subject consider myoclonus to be a form of epilepsy, because it originates in the brain. But whether myoclonus is a seizure or not, in a sane world, the neurologists Amanda visited should have recognized her abnormal response to their sensory stimulation for what it was: a highly abnormal neurologic sign.

Amanda had seen three neurologists over a one month period. She has been told:

• That she will either die soon, maybe in a while,

• And that she was a fruitcake and will probably never die.

She is in a bit of a dilemma; and I, as her doctor, am also in a bit of a spot. As primary care physicians, we suggest specialty examinations to offer patients the “real doctors”, who will solve their problem, perhaps verifying an opinion to instill confidence. However, as a first line clinician, one who sees the patients who walk off the street, I am now in a bad spot. I admit to bafflement at this juncture.

My patient was diagnosed with Huntington’s chorea, but if the neurologist who announced that dramatic news had really believed his own diagnosis, he should have conducted additional tests to confirm the diagnosis, as well as offered genetic counseling, since the disease is passed from generation to generation within families.

My patient was then diagnosed with multiple sclerosis, but if the neurologist who rendered that diagnosis had really believed Amanda had MS, he should have offered to perform the standard tests that MS experts use to confirm the presence of the disease, and told Amanda about some of the new MS drugs on the market, which are considered most effective when prescribed early in the disease.

My patient was then diagnosed as an hysteric, but if that doctor really believed his diagnosis, he should have written me a collegial letter explaining his theory about Amanda’s myoclonus response.

I guess few self-respecting neurologists, especially if they thought she was seriously ill, would call Amanda’s disease by its absurdly trivial and unscientific name: ‘chronic fatigue syndrome’.

As it turns out, this name not only debases the patient who suffers from it, this name also seems to chip away at the self-esteem of the doctor, especially if he is a highly paid specialist with a reputation to protect. I suspect that’s why people suffering from CFS are showered with myriad vaguely outlined diagnoses, or no diagnosis at all, despite having prominent abnormalities during examinations and on a number of lab tests.

Very few medical schools teach young doctors about this illness, and as medical students move into specialty training, their opportunities to learn about CFS from senior doctors who have actually studied the disease become even more rare. Publishing scientific papers about CFS has become so difficult in the last decade, a group of researchers decided in 1995 to establish a journal specifically for the disease, one that would afford clinicians and scientists a forum in which to report on developments in the field. [The Journal of Chronic Fatigue Syndrome, now discontinued, but succeeded by the Bulletin of the IACFS/ME.]

I sat down with Amanda in my office soon after the third specialist rendered his opinion. We had been offered a less than appealing choice by these men, all of whom were well respected: Either Amanda was going to die, or she was a great actress.

I suggested to Amanda that rather than arbitrarily choosing one of these diagnoses out of a hat, or choosing the one we liked best, that we throw them all out.

• I told her that her central nervous system symptoms were part of a disease that none of these highly regarded specialists really knew anything about.

• I told her she had CFS.

Over the next few years, that diagnosis has proven correct. Her symptoms abated somewhat except for a marked worsening when we tried a mild stimulant drug because of the fatigue. At that time the myoclonus became worse, but, fortunately quieted down when the drug was stopped.

She has not gone on to develop Huntington’s chorea nor has she developed the typical findings of MS. The symptoms persist; she has good years and bad years. So that means that she has either CFS or is a consistent fruitcake.

How do you go about diagnosing someone as a fruitcake; what, exactly, are the diagnostic markers?

Actually, while I know that many of my colleagues consider my patients fruitcakes, I am not really sure what a fruitcake is, exactly. It is a sweet pastry filled with nuts. Neurosis was defined by Carl Sandberg as the denial of legitimate suffering, and therefore most of my patients are surely neurotic as hell. But fruitcakes?

It turns out there is a diagnostic test for the diagnosis of fruitcake: time.

I have now known Amanda for several years. I have seen her during crises and during relatively good times, and the symptoms and signs persist. I have shared her sadness and anger – normal, healthy emotions that anyone should have. And as time passed I have come to admire her courage to get by despite the illness and the society’s contempt. And I respect her wishes not to be referred for further neurologic opinions.

– Dr. David S Bell, MD, Lyndonville, New York, August 15, 2000
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This article is excerpted with kind permission from Dr. Bell’s classic book Faces of CFS – Case Histories of Chronic Fatigue Syndrome; © David S Bell, MD, 2000,

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined.

Methods: We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12 weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted.

Results: The patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n = 8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy.

Conclusion: Brain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.

Source: Kim DY, Youn J, Kang N, Cho SI, Ha IH. Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review. J Transl Med. 2026 Feb 10. doi: 10.1186/s12967-026-07807-w. Epub ahead of print. PMID: 41668172. https://link.springer.com/article/10.1186/s12967-026-07807-w (Full text available as PDF file)

A Case of Psoriasis Concurrently Complicated by Sacroiliitis and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a systemic chronic disorder characterized by persistent and unexplained severe fatigue. Recent population-based studies have revealed that patients with chronic inflammatory skin dermatoses, including psoriasis, are more likely to develop ME/CFS.

Here, we report a case of psoriasis, whose exacerbation occurred concurrently with the development of sacroiliitis and the onset of ME/CFS. The pathogenesis of ME/CFS has not yet been fully elucidated, while inflammatory cytokines are involved in dysregulated interactions among the nervous, immune, and endocrine systems in the disease.

We discussed the shared immunological abnormalities of psoriasis and ME/CFS based on previous literature. Our case contributes to the understanding of the association between psoriasis and ME/CFS.

Source: Iijima M, Miyagaki T, Nakajima K, Kadono T, Watabe H. A Case of Psoriasis Concurrently Complicated by Sacroiliitis and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Cureus. 2025 Sep 16;17(9):e92435. doi: 10.7759/cureus.92435. PMID: 41111852; PMCID: PMC12529862. https://pmc.ncbi.nlm.nih.gov/articles/PMC12529862/ (Full text)

Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report

Abstract:

Background: The COVID-19 pandemic has led to an increase in post-acute sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), potentially mediated by dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. Corticosteroids are occasionally administered to ameliorate fatigue symptoms in ME/CFS; however, their psychiatric adverse effects, particularly in individuals with preexisting mood disorders, necessitate careful consideration.

Case presentation: We report the case of a 32-year-old woman with bipolar disorder who developed ME/CFS following COVID-19 infection. Initial corticosteroid therapy with betamethasone and prednisolone, agents with potent glucocorticoid receptor (GR) activity, resulted in a manic episode with psychotic features, necessitating psychiatric hospitalization. Although mood stabilization was achieved with olanzapine and valproate, corticosteroid withdrawal subsequently led to metabolic alkalosis and hypoxemia, secondary to hypothalamic hypoadrenalism. Following a comprehensive endocrinological assessment, physiological replacement therapy with hydrocortisone, characterized by relatively higher mineralocorticoid receptor (MR) activity and lower GR potency, was initiated, resulting in the resolution of physical symptoms without destabilization of psychiatric status.

Conclusion: The clinical course suggests that GR-dominant corticosteroids may exacerbate psychiatric instability in patients with mood disorders. Simultaneously, MR-favoring agents, such as hydrocortisone, may offer a safer therapeutic alternative for managing HPA axis dysfunction. This case underscores the critical role of receptor selectivity in corticosteroid therapy, particularly in patients with comorbid psychiatric conditions, and highlights the necessity for individualized treatment strategies that integrate both endocrine and neuropsychiatric considerations.

Source: Nakajima K, Ayani N, Matsuoka T, Kasahara K, Nakajima Y, Ikawa H, Kitaoka R, Akimoto T, Narumoto J. Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report. PCN Rep. 2025 Oct 12;4(4):e70222. doi: 10.1002/pcn5.70222. PMID: 41089430; PMCID: PMC12515714.

Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome

Abstract:

Thoracic outlet syndrome (TOS) is characterized by compression of nerves or blood vessels as they pass through the scalene triangle and the costoclavicular space, and under the pectoralis minor. Common symptoms include arm fatigue and heaviness, paresthesias, and neck and upper back pain, provoked by arm extension or elevation.

We have recently reported that some myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients report symptoms suggestive of TOS, specifically with respect to overhead activity, but there is uncertainty whether this overlap in symptoms is more related to ME/CFS itself or a direct contribution by TOS. This case report describes an ME/CFS patient diagnosed with TOS, who experienced major decreases in many expected and unexpected symptoms after bilateral TOS surgery.

A 19-year-old female patient with ME/CFS and the hypermobile Ehlers-Danlos syndrome (hEDS) developed progressive symptoms of numbness and tingling in the upper limbs, which did not improve after two months of physical therapy. The patient elected to undergo the rib resection with neurolysis and scalenectomy surgery on her left side. Due to the success in the reduction of symptoms, she elected to undergo the same procedure on the right side three months later.

By eight weeks after the second surgery, the patient had experienced an expected complete resolution of upper limb numbness and tingling. She also reported a complete resolution of migraines, occipital neuralgia, vertigo, and visual disturbances, along with a marked improvement in cognitive fogginess and lightheadedness.

This case report highlights the potential for marked improvements in clinical function after recognition and surgical treatment of TOS in a patient with comorbid hEDS and ME/CFS. In addition to expected improvement in upper limb symptoms and the resolution of occipital headaches, our patient noted improvement in systemic symptoms of lightheadedness, cognitive dysfunction, and visual disturbances.

This experience suggests that those with hEDS and ME/CFS should be more carefully screened for brachial plexus dysfunction. Conversely, ascertainment of systemic symptoms may enhance the diagnosis of TOS and the items assessed in surgical treatment outcome studies.

Source: Christoforou ME, Lum YW, Sroge SC, Azola AM, Rowe PC. Improvement in Upper Limb and Systemic Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptoms After Surgical Treatment of Neurogenic Thoracic Outlet Syndrome. Cureus. 2025 Aug 19;17(8):e90494. doi: 10.7759/cureus.90494. PMID: 40978926; PMCID: PMC12445393. https://pmc.ncbi.nlm.nih.gov/articles/PMC12445393/ (Full text)

HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab

Abstract:

This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments.

Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient’s blood supportive of an altered immune system.

Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.

Source: Martín-Martínez E, Gil-Perotin S, Giménez-Orenga K, Barea-Moya L, Oltra E. HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab. Int J Mol Sci. 2025 May 20;26(10):4885. doi: 10.3390/ijms26104885. PMID: 40430026; PMCID: PMC12111851. https://pmc.ncbi.nlm.nih.gov/articles/PMC12111851/ (Full text)