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“Anna’s Identity”: When Nobody Believes You’re Really Ill

This is the case history of a woman who suffered CFS symptoms since childhood but was never believed – until at age 35 doctors decided something ‘real’ was wrong. It is excerpted from Dr. Bell’s free e-book Faces of CFS – Case Histories of Chronic Fatigue Syndrome,* published in August, 2000. “Anna’s Identity” illustrates one aspect of cases he has followed since the mid-1980’s. 

Reprinted with the kind permission of ProHealth: 9/14/11

ANNA’S IDENTITY

Where does self end and illness begin? When we are ill for years, or for a lifetime, what part of our personality is really our own, and what part has been shaped or even created by disease?

These questions are probably nowhere more pressing than in the realm of brain disease, in which the foundation of the personality – the physical brain itself – is under siege.

CFS, of course, presents a particularly difficult challenge to its sufferers because, unlike many brain diseases, CFS leaves the brain intact enough to sense its own difficulties. As a result, people who have CFS are forced to cope not only with unceasing physical pain and exhaustion, but with sorting out their real selves from the demon that has attacked their faculties as well as their body.

Adults have an advantage over children with CFS.

Adults have accrued years of personal history; they have a sense of who they are, a personality, against which they may compare their new, unwell selves. Everyone around them may be snickering and laughing, but the adult with CFS knows he or she is unwell, and that what is happening is anything but normal. Children, on the other hand, lack the requisite life experience and sense of self against which to measure a sudden development like CFS.

I am a pediatrician by training, and I have learned to see the world through the eyes of my youngest patients; I also frequently look into their eyes and see the adult world reflected there. I do not believe I am being disproportionate to state that, for children, CFS is among the very most difficult, if not the most difficult, disease to survive into adulthood.

Perhaps the greatest tragedy of CFS in children is that poorly informed adults ascribe a false identity to the child, and that false perception of self is carried by the child into adulthood.

CFS has robbed far too many children of their identities, or more precisely, has robbed them of the chance to develop an identity – to grow into themselves. In the case of at least one patient I know, however, a true perception of self has emerged, despite the odds, but it took 35 years.

I am speaking of Anna, who became ill with CFS when she was probably four or five years old.

We often remember of our childhood that which was wonderful and beautiful, but when there has been little joy, memories are dimmer. Anna’s memories are cloudy, but she recalls that by the time she was six or seven, she was unable to keep up with her playmates.

• She could not skip rope because her balance was poor and the slightest exertion left her breathless.

• The bright sunlight that poured onto the playground left her feeling blinded.

• She found herself on the sidelines, inexplicably exhausted. Other children seemed to shy away from her.

Anna went to school every day, but she felt sick all the time.

She found it difficult to learn skills like reading and math. It was humiliating. She couldn’t remember her multiplication tables. Everyone else could, but Anna couldn’t. Anna began to devise tricks to help her remember, tricks so complicated she could not have explained them to anyone. For example: eight times seven. Add a zero to a seven, subtract seven, then subtract another seven.

For Anna, visualization was easier than memorizing. She could see numbers in her mind, for instance, and in order to solve the problem, she would look at them. She knew she did not think like other children. The world was a very confusing place.

She had trouble following directions. Her teachers were harsh with her; they believed she was either deliberately ignoring them, or preoccupied with private thoughts. But Anna was simply puzzled and tired.

The simple noise of the classroom distracted and perplexed her. It made her ears hurt, too. She had trouble finding words to describe how she felt. She once told her teacher that her brain seemed to “ache” because of the noise, and her teacher dismissed it with a wave of her arm.

“Pooh,” she said, “everything seems to bother you.”

Perhaps Anna’s greatest humiliation was the way her one of her legs would jump without warning, hitting the desk, or even kicking toward the child sitting next to her. Her classmates would burst into laughter, and her teacher would inevitably become angry, scolding her for being disruptive. Anna had no control over these muscle spasms, but her teacher never believed that.

Eventually, Anna learned that if she rested the legs of her desk on top of her feet during class, the weight of the furniture would diminish the force of her jerking legs. The desk was heavy, and hurt her feet, but the technique worked.

Anna wondered why her muscles behaved unlike anyone else’s muscles, and why she was unable to memorize facts, and unable to remember what the
teacher said to the class from day to day. She wondered why she lacked the energy to run or play games. She struggled to hide these aspects of herself, her deficiencies, from the girls in her class, because like any child she desperately wanted friends.

Yet, even though Anna privately wondered every day what was wrong with her, no one believed Anna was sick.

She recalls that during her early adolescence, she was stricken with a remarkable number of sore throats, fevers, stomach aches, swollen glands, and headaches. As time passed, and she went from child to teenager, her doctor began voicing his opinion that Anna’s “illnesses” were an obvious cry for attention.

Occasionally, she was hospitalized while a teenager, but the tests ordered by her doctor rarely showed any abnormalities. Her doctor, and eventually, her own parents, began to exhibit increasing frustration.

By the time she was 15, no one believed Anna was sick.

• Her parents’ frustration turned to anger. They were poor people, and the medical bills caused by Anna’s frequent trips to the doctor were beginning to overwhelm their resources.

• Eventually, the doctor her parents took her to simply patted her on her head and told her she had a headache every day because she felt badly about doing poorly in school. The doctor told Anna she needed to stop “playing those games.”

Anna’s response to the anger and disbelief was hardly surprising: she learned not to complain.

She recognized that articulation of her sensations of illness only increased her isolation and actually invited ridicule. She vowed she would hide her symptoms and her feelings however she could from her family, her friends, and her teachers. She even learned to hide these things from herself.

In time, there were two Annas: the one who was sick, and the one who cleaned her room, performed her chores, and attended school every day just like everyone else her age.

• The first Anna would look at the second with a kind of astonishment; the second Anna was ashamed of the first.

• Neither of the Annas found any comfort at school or at home, but they got by.

By the time she became an adult, Anna had hidden her secrets for so long that she barely acknowledged them herself. In fact, by then, she had persuaded herself that her doctors had been right all along: if she had some dreadful illness, she reasoned, her doctors would have identified it, or she would have died.

She embraced fully what she had been told throughout her adolescence: She had made up her symptoms, although her reasons for having done so continued to remain mysterious to herself.

Anna finished high school, married, and began working as an aid in a nursing home. She also had four children. Most of the time, she could keep her secrets hidden, from her husband and children, and even from herself. She was not even being dishonest, because she was in agreement that all the sensations she felt – the weakness, the fatigue, the mental cloudiness – signified nothing at all. There really wasn’t anything wrong.

By then, the years of denial had worked their effect; her identity, her sense of herself, had been formed by the opinions of others. The part of her that felt and experienced was shut away from the part that reasoned. She was, she would tell herself, perfectly healthy, but in fact her identity was built on a foundation of silt, and had little to do with Anna’s true experience, the reality she lived day-to-day.

By the time she was in her early 30’s, Anna skills of self-deception and general deception were finely honed. She had become a master of covering up embarrassing intellectual gaffes with warm, genuine smiles that would put those around her at ease. No one could be expected to see through her smile to the memory loss, or the peculiar lapses in her speech, lapses in which she would jumble the order of her words in a sentence, or make bizarre mistakes in her choice of words.

She had learned to work despite her daily exhaustion and painful headaches. In fact, she felt weak all the time.

But if she had to help lift a patient at the nursing home, she found the strength, proving to herself and the other aids that she was as strong as any of them.

• Though she often experienced double vision, she never said a word about it to her co-workers.

• When she stood rapidly, she got lightheaded, and her hands and feet went numb.

• She developed a painful stomach condition – probably an ulcer, she decided. A doctor she consulted prescribed a drug for ulcers, but the pills did nothing to end the pain and Anna quit taking them.

She was disappointed in neither her doctor nor the drugs. Whatever the cause of this particular ailment, she reasoned, it was outside the doctor’s reach because, as she knew already, there was really nothing wrong with her. She could get by, she reasoned, just as she had always gotten by.

Of course, she never discussed these problems with her fellow workers in the nursing home, and no one around her ever suspected them.

One harsh, upstate New York winter after another passed. Anna acknowledged to herself a certain loneliness, familiar to her from earliest childhood. She had never quite rid herself of that. But her routines were well-established, her coping mechanisms firmly in place, her secrets tucked so deep inside that she barely thought of them.

Anna’s identity was a fragile construct, however, and vulnerable. One bitter day in March of 1988, it began to break up.

She suffered a seizure while working at the nursing home, an event witnessed by several people. She was taken to a local hospital. When the doctor informed Anna afterward that she had experienced a seizure, she found it extremely difficult to believe, despite the bite on her lip and the deep gash in her tongue.

In fact, she did not believe it – not really. After all, after a lifetime of feeling sick, this was the first doctor who had ever told her with any conviction that she actually was sick.

And so she fell back on the opinion of her condition that had been voiced by doctor after doctor from her earliest memories: she was just suffering from a little stress.

When the doctor prescribed medications for seizures, Anna nodded, as if accepting the diagnosis and the treatment. But she did not take the medication. Why should she? She knew there was nothing wrong. There never had been anything wrong.

For three decades, Anna had been able to secret away the ill woman she had been nearly all her life.

But things were starting to change. She continued to avoid the prescribed anti-seizure medication, and both her doctor and her husband insisted that she was having convulsions. Anna found their claims hard to believe. She was unconscious when these so-called seizures were reported to occur; how did she know they were really occurring?

It had been a life-long struggle, but Anna had achieved the ability to believe the medical profession, her parents, and her teachers, that nothing was wrong with her. Now her doctors and family were insisting something was wrong. In fact, her doctor arranged for her driver’s license to be revoked. Anna couldn’t even get to work.

The seizures were exposing the sick side of Anna to herself. They could not be hidden away or covered up with a charming smile and a little joke. The turmoil in her mind was like a hurricane. If she accepted that the seizures were real, she risked opening the long-hidden conflicts about everything concerning her poor health.

In short, if the seizures were real, maybe everything else – the exhaustion, the mental fogginess, the numbness in her hands and feet, the pain, the forgetfulness, the endless headache – were real, too.

The bedrock foundations of her assumed identity began to erode. For the first time in years, Anna began to allow herself to acknowledge her physical sensations of fatigue and pain. She realized that she felt awful. But experiencing the pain and exhaustion somehow seemed better than pretending it wasn’t there. She answered one question that most people are unable to: Is it better to feel suffering than to feel nothing at all?

One day Anna saw a segment on television about CFS. Her mouth hung open as she heard about daily exhaustion, headaches, pain that no one would believe. It was Anna, not a doctor, who recognized at last that her symptoms were characteristic with CFS. In fact, with the exception of seizures, she was picture perfect for the symptom complex that defines the illness.

Anna read everything she could find on the subject. She felt as if she was waking up after lifetime spent cut off from her own feelings and perceptions.

She began to remember painful incidents from her childhood – how she had felt, and how she had learned to deny those sensations not only to those around her but to herself. They were disturbing memories, but Anna, by then 35, was at last beginning to experience her own reality and to recognize herself as she had always been. She was not the healthy, energetic woman she had pretended to be for so long; she was sick.

I met Anna during this period. We talked a lot about these matters in my clinic, and we talked over coffee sometimes in the Tiger’s Den Cafe down the street. We both recognized that her identity was in crisis, because she was having trouble distinguishing real illness from false illness.

After so many years of believing herself to be “falsely” ill, how could she turn around and be herself? In this, she had no experience.

The perception of pain and illness is very simple from a physiologic standpoint. Primitive animals feel pain in their nerve endings, and struggle to avoid it. Electric probes of one-celled creatures like amoebae show that even these tiniest of organisms feel pain. But advanced creatures, specifically human beings, have learned mechanisms for denying some of the basics of biology.

Nevertheless, our denial hardly changes the mechanical impulses of our nervous systems; our nerve endings continue to be stimulated, and send messages to our brain that are registered as pain or discomfort. Our denial merely creates an emotionally confused response to the pain, or health identity confusion.

Anna’s biggest problem, at 35, was her confusion over her health identity. Her confusion had logical origins, but her management of it – to deny her symptoms -put her at risk. She had lost what healthy people would call common sense. Her confusion had cost her the right to drive, and subsequently, her job. She could have controlled her seizures with medication, if only she had been able to believe they were real.

But because she had denied her illness for most of her life, she probably would have been hard pressed to believe she was injured if she had been run over by a truck.

As the years passed, Anna gradually began to learn how to feel. She said it was better to feel pain than to feel nothing at all. It was better to experience the reality of her life, in all its facets, than to deny all of its reality. After decades of pretending, she began to acknowledge to herself the truth of her own experiences, and the place of her identity within those experiences.

I marvel at Anna’s courage. She has been one of my teachers in life. And I wonder if I will ever find the same courage to explore the hidden parts of my own soul.

– David S Bell, MD, Aug 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. This information has not been evaluated by the FDA. It is general information only and is not meant to prevent, diagnose treat or cure any condition, illness or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and reviewing it in collaboration with your professional healthcare team.

“Andrea’s Revolver”: When ME/CFS Includes Pain

This case history of a CFS patient whose symptoms include chronic pain is excerpted from Dr. Bell’s book Faces of CFS – Case Histories of Chronic Fatigue Syndrome, published in August, 2000. “Andrea’s Revolver” illustrates one aspect of cases he has followed since the mid-1980s. 

Reprinted here with the kind permission of ProHealth: 1/21/11

ANDREA’S REVOLVER

Pain is a common problem in CFS, but it is also symbolic of the enormous challenge this illness presents to doctors and to patients. Patients can’t prove it, and doctors usually fail to treat it.

Despite the fact that pain occupies nearly all of their working day, doctors have a very poor understanding of it. Although we now have in our arsenal good medicines to relieve pain, we nevertheless try to avoid prescribing them.

• When a person who has just shoveled the snow off a long driveway complains of back pain, his doctor is likely to prescribe the same pain medications you can readily buy at your local Seven-11.

• If the snow shoveler’s back pain doesn’t abate in a few weeks, then the doctor realizes the problem might be worse than suspected. He refers the patient to a back specialist, which gets rid of the problem – for the doctor.

Most practitioners tell patients who have unexplained pain to seek help elsewhere.

Doctors are, as a rule, genuinely concerned about doing harm to the patient. This concern merges with another worry: losing one’s medical license by prescribing too many narcotics.

By law in New York state, doctors are required to write prescriptions in triplicate for narcotics and other potentially addictive drugs, a category of pharmaceuticals that just happen to be the most effective drugs for pain. These triplicate prescriptions help insure that powerful drugs won’t be over-prescribed, but the law is both time consuming and expensive – a nuisance for busy doctors.

More importantly, we doctors secretly suspect that someone spends their days counting the number of prescriptions we write, and worry that we could lose our medical licenses if there are too many carbons in our waste bins.

Aspirin presents none of these anxieties for us.

We never get into trouble from state regulators for offering aspirin to our patients in pain. The great irony is that aspirin may be more likely to kill the patient by causing a bleeding ulcer. But, ignoring that, we urge our patients to try aspirin or acetaminophen or ibuprofen. And if all of these fail, we usually suggest another mild medication, preferably one that the patient has never heard of.

Cancer pain, of course, is dire, and it is hardly surprising that oncologists (doctors who care exclusively for cancer patients) tend to have the most sophisticated understanding of, and compassion for, pain. They also do the best job of treating pain. When a cancer patient complains of pain, for the most part, the doctor opens his medical chest and says, in effect, take what you need to help with your pain.

Three weeks ago I had a toothache.

Like most men, I find this difficult to confess: My toothache hurt. By Friday, two days after it began, my toothache really hurt. On Saturday, it was unbearable. As I hobbled around my house holding my jaw, I found myself thinking, as if silently reciting a mantra: So this is pain…. so this is pain.

A friend gave me some serious pain medication, the kind that requires a prescription written in triplicate, and I was able to fall asleep at last. Even with the narcotic, however, the weekend was horrible. On Monday, I underwent the most wonderful root canal and my pain vanished.

The experience was an important lesson for me. I was reminded of the vast gulf between the subjective complaints of the patient and the objective doctor who listens to these complaints, the difference between hearing about someone else’s pain, their toothache, and my own.

Most important, I was reminded of the gulf many CFS patients must navigate every day.

I was able to see the end of my pain, even when the pain was at its height. I knew that on Monday my dentist would help me, not only because I can afford a dentist and have always paid my bills on time, but because my dentist understood completely that my particular condition was a painful one, and he had been nicely trained to alleviate it.

I see patients with pain every day in my practice. Pain steals in under many guises: the twisted ankle, the stomach ulcer, the spread of a malignant tumor. I try to respond given my best estimation of the severity of the pain.

I have studied CFS for years, and I still am unsure precisely where CFS fits along the spectrum of pain.

• Some of my colleagues accept as bona fide the pain that often accompanies the disease, and try their best to relieve it with medication.

• Sadly, most of them tell their patients that CFS is a minor illness; they advise them to get used to the pain until either the pain or the illness goes away. They may suggest aspirin.

Despite the fact that pain can be a prominent and even disabling aspect of CFS, it is the rare CFS sufferer who receives adequate treatment for it.

Andrea Thompson had pain, pain that surpassed virtually anything that I had seen before in my practice.

By the time Andrea walked into my clinic, she had already seen over 30 doctors. Her story was typical of most of the CFS patients who end up in the village of Lyndonville: Each of the doctors she had consulted over the long years of her illness were mystified when she recounted her symptoms, inexcusable now that CFS has been studied in this country for so many years.

Some of them performed studies and offered a multitude of conflicting diagnoses, from the common thyroid disease, which causes fatigue, to the more arcane reflex sympathetic dystrophy, an extremely rare and famously painful nerve disease. All of these diagnoses were wrong, since Andrea had the other symptoms as well: sore throat, headache, numbness and tingling in her legs and arms, as well as a kind of intellectual fogginess that made her feel perpetually “out of it.”

As months turned into years, and her doctors found it increasingly difficult to support their original diagnoses given Andrea’s wide array of symptoms, several of them began to suspect Andrea was a junkie who wanted pain medication to get high.

Talking to Andrea for ten minutes displayed the absurdity of these suspicions. Con artists have a certain talent, but Andrea was hardly a con artist. She was in pain.

Andrea was 37 when I saw her for the first time. Before falling ill in 1988, she had worked as an executive in a brokerage firm in New York state. Her education had been top-notch, and she had a Masters degree in business administration. She was married, had three children, and a nice house in the suburbs. Andrea and her family had been living the American dream – even if they didn’t have a Beamer.

Two years after her symptoms began, Andrea’s husband was promoted and transferred to Boston. Andrea was looking forward to taking a few months off work to rest, and to settle into her new home in Boston, after which she planned to look for a new job.

Once the move was complete, however, Andrea seemed to fall apart completely. In the beginning, at a loss to explain the problem, she and her husband blamed her rapid decline on stress. Yet, the move had been relatively stress-free; her husband’s company paid for the packing and unpacking of their possessions, for example.

Andrea’s dominant and most crippling symptom was pain, though she was hard pressed to pin-point its source.

Pain seemed to migrate through her limbs and even her face. But there were other symptoms, too.

• She had migraine headaches that were impervious to medication.

• She became hypersensitive to light, and took to wearing sunglasses even when she was inside her house.

• Curiously, odors of any kind made her feel nauseous.

• Mere sound, too, was often too much to bear. Andrea was an avid R & B fan and had a large library of recordings dating to the 1940s, but she could barely tolerate even the softest music.

It was as if every sense she possessed was too finely wired for life on planet earth.

Her first encounter with a Boston doctor ended as badly as her numerous encounters with doctors in New York. Andrea hadn’t expected a miracle – she just wanted something to take away the pain. Wearing sunglasses and asking for pain medication at the same time apparently made a poor impression.

She downplayed her pain when she met with a second doctor, with the result that he gave her a complete physical exam, ordered several laboratory tests and an MRI scan of her brain and neck, and performed nerve conduction studies. The lab tests were normal, and he prescribed mild pain medications and suggested meditation

The drugs didn’t touch the pain she felt, however, and Andrea was unable to meditate while in so much pain. She soon gave up trying.

She found some relief when a dentist prescribed codeine after she complained of facial pain, but he denied her additional prescriptions for the drug on the grounds that she might develop an addiction to it.

Doctors at a famous Boston pain clinic prescribed exercise and antidepressants, two therapies that simply ended up causing more pain. After two agonizing weeks, Andrea checked out of the clinic.

She had always been an attractive woman, but now Andrea looked ragged. She pleaded with several Boston doctors for more powerful pain killers, but her need for pain relief was proportionate to the degree of skepticism she encountered.

In fact, by now, no one she consulted believed she was in pain at all.

Her life was little more than misery compounded by the skepticism of the medical establishment and her friends. Not surprisingly, she began to doubt her own sanity.

• She became disheveled; her weight plummeted to 89 pounds. She had begun to look like a junkie, even to herself.

• She felt as if she barely knew her children anymore; they spent much of their time in day-care facilities.

• Her once-loyal husband began to display frustration and skepticism about her condition.

And always the pain – pain that doctors refused to treat. Worst of all, pain with no end in sight.

One day, Andrea loaded her husband’s revolver and put it in her mouth.

To this day, she has no explanation for why she didn’t simply pull the trigger.

The following day, she entered a psychiatric unit of a Boston hospital, where she remained for three weeks. The psychiatrists talked to her about “relocation stress,” childhood traumas, and “displaced” anger.

Andrea felt she was the only person who saw the problem clearly: Get rid of the pain, she kept telling the psychiatrists, and she would be okay.

Finally, her pleas were heard.

The psychiatrists prescribed methadone, a synthetic form of morphine that is used to manage morphine addiction, but has the same pain-deadening effects as morphine. The drug worked. Slowly, Andrea began to reconstruct her life.

What was causing Andrea Thompson’s extraordinary pain?

Usually, pain is associated with tissue damage from injury. The pain sensation serves as a warning, preventing further damage to the victim. This sensation travels on nerve pathways from the injured tissue to the brain.

Sometimes, pain is due to damage in the pain receiving areas of the brain itself. In this case, the disease is to the actual pain processing centers, even though the body mistakenly interprets the sensation of pain as if it were coming from somewhere else.

Malignancies involving the thalamus, a part of the brain that helps to process sensory impulses, can cause this kind of pain. But Andrea Thompson had no malignancies, and the MRI scan I ordered of her brain proved to be normal.

A third cause of pain is known as “sympathetically mediated” pain – pain that derives from damage to the autonomic nervous system. The autonomic nervous system controls our breathing, body temperature, blood flow, and heart rate – all those functions we can’t control by sheer will; body functions we barely even notice.

One of the diseases associated with this kind of pain, “reflex sympathetic dystrophy,” was the nerve ailment proposed by at least one doctor as the cause of Andrea’s pain.

Usually, “RSD” is the a result of an injury to a leg or an arm, or even a single nerve in that extremity. What is most curious about RSD is that the pain may be delayed for months or years, long after the specific injury had healed.

RSD is often accompanied by changes in blood flow, sweating, and, curiously, atrophy of the fingers. In 1988, I heard Dr. Paul Cheney, who had studied CFS among Nevada patients, describe what he called the “disappearing fingerprints” of CFS sufferers. The surface of his patient’s fingertips had grown completely smooth, entirely lacking the normal, distinctive whorls.

Dr. Cheney, a true disease detective, even remanded a few of these patients to a police station to find out whether they could be fingerprinted, but their fingerprints left no distinctive pattern.

When I heard about this bizarre discovery, I wondered whether it was possible to experience RSD as a body-wide disease instead of one confined to an extremity.

Though it remains controversial, some doctors believe that sympathetically mediated pain can be eliminated by blocking the nerve pathways, or even severing the nerve itself. In truth, doctors argue about the causes – and the treatment – of sympathetically mediated pain every day. Some of my colleagues believe it to be a psychological condition, although new research suggests otherwise.

I began to learn about the relationship between CFS and another puzzling condition called orthostatic hypotension, a failure of the body to adequately pump blood while standing in the upright position, from Dr. Peter Rowe and colleagues at Johns Hopkins.

Soon afterward I began working with Dr. David Streeten, an endocrinologist who had worked extensively with “orthostatic intolerance” – the inability of the body to tolerate the upright position.

There are only a few truly great doctors who stand out from the thousands of ordinary ones; they are the true masters of medicine. [The late] David Streeten was one of these masters. He had both a brilliant scientific mind and the perception and intuition of a superb clinician. If I were 30 years younger and fresh from medical school, I would have become his intern and really learned medicine.

But working with a master has its drawbacks. When I sent my CFS patients to see him for a consultation, they returned to my clinic with the news that he was much nicer to them than I ever was.

I met Dr. Streeten for the first time in February 1994 when I accompanied Andrea Thompson to his offices in order to observe his evaluation of her first hand. Until this experience, I was under the mistaken perception that I understood CFS. Dr. Streeten proceeded to teach me some of the basics that I had overlooked for 15 years.

I had always viewed chronic fatigue as the result of the chemicals released by a viral infection, and had concentrated solely upon looking for the infection that might have caused the condition.

Now I was seeing what could be the mechanism, regardless of cause, which might be causing the symptoms to persist.

The myriad of symptoms revolving around exhaustion, weakness, lightheadedness, and inability to concentrate were likely due to the inability of the body to circulate blood to the brain when standing, or sometimes even sitting.

When the CFS patient is lying down, the symptoms are improved, although not gone entirely. The disability of CFS has to do with the fact that we spend our non-sleeping lives in the upright position.

Dr. Streeten utilized MAST trousers in his experiments. The acronym stands for Military AntiShock Trousers. These inflatable pants can be blown up like an inner tube in order to create a veritable body cast from the toes all the way to the mid-chest. When paramedics need to transfer trauma patients suffering from fractured legs, MAST trousers are very handy because they become an instant cast and compress the lower body.

Dr. Streeten performed a deceptively simple experiment with his patients.

He bid them don deflated MAST trousers, then asked them to stand next to a wall of his examining room. As they stood upright in these somewhat peculiar circumstances, he monitored the patient’s blood pressure and pulse. When the CFS patient would become ill during standing, he would inflate their MAST trousers.

Upon meeting Andrea, Dr. Streeten measured the amount of blood in circulating in Andrea’s body and discovered that the level was strikingly low. Next, he tested Andrea’s blood pressure and pulse for 10 minutes while she was lying down, and they were normal. Blood tests drawn at that time for adrenaline and other “catecholamines” were drawn and later shown to be normal.

Then Andrea stood quietly with the plastic MAST trousers around her body but not inflated. Then the problems began. Within minutes she began to feel ill, her pulse began to climb, and the pain began to grow. By 10 minutes of standing her speech was slurred and she appeared a little drunk, swaying back and forth and her feet began to look purple. Her blood pressure dropped and heart rate increased.

Then the pain really kicked in.

She was confused. All she could do was to say over and over, “The pain…the pain…” While still standing, a second sample of blood was drawn from the line in her arm, again tested for adrenaline.

At that point, while Andrea was still standing, Dr. Streeten inflated the MAST trousers, causing symmetrical pressure around her legs, thighs and abdomen. I had often seen Andrea in this state before, a state where she looked as if she had been on a binge for days. But my teeth nearly fell out when seven seconds later she straightened up and looked around and said with a clear voice, “What happened? The pain is gone.”

I was as astonished as Andrea. Even Dr. Streeten was surprised by the magnitude of this response. He hypothesized that the pressure on Andrea’s legs and abdomen by the MAST trousers had forced a more vigorous blood flow through Andrea’s brain, and that this increased blood flow stopped the pain.

Andrea wanted to buy a pair of MAST trousers for home use. (Later on we actually tried this, but it turns out to be impossible to walk around with these things on which sort of cancels out the purpose.)

Dr. Streeten was suitably impressed by Andrea’s case. He submitted his MAST trouser experiment on Andrea and about 20 other CFS patients to a scientific journal. The editors rejected the paper, initially, because the patient was not sufficiently “blinded” in this experiment. In the world of science, of course, it is optimum for patients in experiments to be ignorant of the researcher’s modus operandi.

My question to the journal editors is this: How could we sneak Andrea into a pair of MAST trousers without her finding out about it? I can think of only one way: Render her unconscious with a general anesthetic. The problem with that, of course, is that it is very difficult for people to describe their pain, or lack of it, while unconscious. Sometimes modern medicine is bewildering.

The temporary stoppage of Andrea’s pain in Dr. Streeten’s office that day offers up no simple explanations or conclusions, just theories.

One simplistic theory is that because Andrea had too little blood circulating in her body, her blood pressure dropped dramatically when she was forced to stand for any length of time. When her blood pressure dropped, so did the flow of blood to her brain, which houses the mechanism that mediates both the sensation of pain and blood flow: the autonomic nervous system.

By inflating Andrea’s MAST trousers, Streeten was able to rescue, so to speak, blood that was trapped in her legs, and send more to her brain.

Still, the theory has by no means been proven. In the time that has elapsed since Andrea’s visit with Dr. Streeten, however, it has become apparent to me and to other doctors who study CFS that problems with blood flow to the brain, and the regulator of that flow – the autonomic nervous system – is responsible for both the exhaustion and the migrating pain of the disease.

Of course, myriad questions remain. Might the cause of pain in CFS be a result of a decreased blood flow through the thalamus? Is there an inherent abnormality of the blood vessels that causes the decreased blood flow through the brain?

A different theory of CFS pain centers on hormones. Studies have demonstrated that a number of different hormones are in insufficient supply in CFS patients. One of these is called growth hormone. The pituitary gland of the brain produces this particular hormone, and besides its primary job of making children grow, it has numerous functions in the body.

Scientists have discovered that there is also a second hormone, called vasopressin, that is deficient in CFS patients.

This hormone is essential to regulate the concentration of water in the body, as well as to regulate the size, or diameter, of the blood vessels. I had already determined that Andrea had levels of vasopressin that were much too low to be considered normal. A deficiency of vasopressin could predictably cause excessive thirst as well as an insufficient supply of circulating blood in the body.

As things have turned out, many patients with CFS experience both of these problems.

And this is where the trail leads us to endorphins, hormones produced by healthy people that act as the natural pain killers for the body. Interestingly, vasopressin is a substance that reflects the production of the natural pain-killing endorphins.

Could it be that CFS patients have low levels of the endorphins, explaining in part, why they experience so much pain?

The fact remains: Regardless of why it exists, or what causes it, pain that is both intense and chronic is a daily fact of life for a great many patients who suffer from CFS.

I began testing CFS patients in my office for changes in pulse and blood pressure when they stand quietly, and found that the vast majority have abnormalities. This is the reason that people with CFS may look healthy to outsiders, but they are unable to stand at the check-out counter of the grocery store. In fact, on occasion, some of them faint, or come very close to fainting, presumably because they cannot maintain good blood flow to the brain.

One day, I showed the blood pressure graphs to one of my best friends, David Lieberman, a substance abuse counselor. I pointed out to him that in addition to their blood pressure abnormalities, these patients often experience a racing pulse. David made the observation that these physiological signs are picture identical to the body’s reaction during withdrawal from narcotics.

Could it be that CFS sufferers are in a constant state of ‘narcotic withdrawal’ because they fail to produce enough of the body’s natural pain killers, the endorphins?

I remember a patient with CFS that I had seen almost 15 years ago. This woman had taken doses of codeine three times a day, every day, for nearly 20 years. She told me it boosted her energy, and provided relief from her symptoms of muscle and joint pain, headache, and trouble thinking. Although she had never increased her dose, I privately suspected she was addicted to codeine.

To see if she was addicted, I asked her to stop taking codeine for a period of two months, and for reasons I will never understand, she actually agreed to do so upon my request. During those two months, her symptoms of pain and fatigue were prominent and troublesome, but she bravely stuck it out.

What fascinates me, in retrospect, is that after 20 years of taking codeine, this particular patient displayed absolutely no signs of withdrawal or even a craving for the drug. She never developed tolerance to codeine, where it would become ineffective without increasing the dose.

Could it be that for these 20 years she was replacing her own body’s deficient endorphins with daily codeine?

Many scientists would tend to dismiss this particular observation. The skeptics among them would probably assume that the woman was sneaking codeine on the side without my knowledge, and, frankly, I would be unable to prove otherwise, since I did not perform regular tests on this woman for the presence of codeine in her system. But, after years of practice, I believe that there is one factor in clinical medicine to which scientists rarely give credence: the bond of trust between doctor and patient. I tend to believe what my patients tell me. I may just be gullible.

Andrea has been taking methadone for four years now, and the synthetic morphine provides her with relief from her pain.

Curiously, she, too, has not required any increase in her dose, which typically occurs when people take drugs like morphine and methadone over the long haul. David Lieberman and I often talk about the possibility that CFS patients require narcotic drugs the way a diabetic needs insulin. The myriad symptoms of diabetes are caused, after all, by a deficiency of insulin, a natural substance that healthy people produce in adequate amounts.

I have wondered, as well, if blood volumes that are far too low are a clue to the cause of the major symptoms of CFS, particularly pain.

I frankly consider it embarrassing that so little research has been done on blood volume, blood flow, endorphins and other brain hormones in patients with CFS. If one tenth of the money that has been applied to psychological studies of people suffering from CFS had been used to study endorphins instead, we would have seen some progress in understanding this terrible disease.

One problem, of course, is that CFS continues to be so controversial throughout medicine that earnest investigators eager to study it are often stymied by the failure of government granting agencies to help.

This phenomenon is particularly unfortunate when one considers how many CFS patients are in pain each day. According to some researchers, more people in this country have CFS than all the people with AIDS, lung and breast cancer combined.

Currently, the disease is approximately 15 times more prevalent than paralytic polio was at the height of the polio epidemic of the late 1940s.

Research barriers have not only impeded my colleagues from understanding the disease, these barriers have prevented doctors from taking a hard look at the pain CFS patients experience, and from treating that pain appropriately.

Eventually, some patients just give up. The foundation of the Hippocratic oath is, “First, do no harm.”

By failing to treat her pain, doctors caused Andrea Thompson to spend half an hour with a loaded revolver in her mouth.

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

* 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. This information has not been evaluated by the FDA. It is general information only and is not meant to prevent, diagnose treat or cure any condition, illness or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and reviewing it in collaboration with your professional healthcare team.

 

The Pall Protocol for Treating CFS/ME

Dr. Martin Pall’s NO/ONOO– (“No! Oh, no!”) hypothesis is probably the most comprehensive explanation of cellular dysregulation in CFS and other oxidative stress illnesses. His model proposes that the chronic stage of CFS is driven by a vicious cycle of oxidative stress, in which the basic mechanisms that are meant to control pathogens don’t turn off. The result is oxidants run amok, creating havoc in the cell’s energy cycles, and increasing inflammation.

The protocol described here was originally put together by Dr. Pall and by Dr. Grace Ziem. It is based on antioxidant treatments which break the vicious cycle of oxidative stress as well as other agents that act to lower other parts of the cycle, such as lowering inflammatory responses, improving mitochondrial function and lowering excessive NMDA activity. However, taking large quantities of single antioxidants can actually increase oxidative stress. Once antioxidants such as tocopherols (vitamin E), vitamin C, and flavonoids react with free radicals, these antioxidants are themselves converted into free radicals. Other antioxidants are then needed to neutralize those newly formed free radicals. Therefore, a wide variety of antioxidants is optimal.

PLEASE NOTE: Dr. Pall emphasizes that he is a Ph.D., not an M.D., and none of these therapies should be viewed as medical advice.

Below is a list of Dr. Pall’s therapies. More detailed information follows.

  1. Nebulized reduced glutathione
  2. Nebulized inhaled hydroxocobalamin
  3. Mixed natural tocopherols
  4. Buffered C
  5. Magnesium, as malate
  6. Four flavonoids: gingko, cranberry extract, silymarin and bilberry
  7. Selenium, as selenium-grown yeast
  8. CoQ10
  9. Folic acid
  10. Carotenoids including lycopene, lutein and B carotene
  11. Alpha lipoic acid
  12. Zinc (modest dose), manganese (low dose), copper (low dose)
  13. Vitamin B6, as pyridoxal phosphate
  14. Riboflavin 5′-phosphate
  15. Betaine (trimethylglycine)
  16. Acetyl-carnitine
  17. Taurine

Detailed antioxidant protocol:

Vitamin C. Pall suggests doses on the order of 500 to 1000 mg/day, taken several times per day. Vitamin C can act to regenerate tetrahydrobiopterin (BH4) and, therefore, may act to lower nitric oxide synthase (NOS) uncoupling, and high doses of vitamin C can be useful in scavenging peroxynitrite (ONOO–), the most central element in his NO/ONOO– cycle hypothesis.

CoQ10. CoQ10 has been used in a number of diseases to improve mitochondrial function. It scavenges free radicals, protects against loss of mitochondrial respiratory function, increases energy metabolism, and down regulates NMDA activity. Take early in the day.

Magnesium. This mineral lowers NMDA activity, reducing excitotoxicity. Dr. Pall believes that “magnesium is one of the most promising agents for treatment of multisystem diseases, but, like other such agents, it produces modest responses and may best be used in a complex, combination therapy.”

Selenium. Selenium is considered an antioxidant because certain proteins that contain selenium have antioxidant properties. Selenium occurs in glutathione peroxidases, enzymes that eliminate peroxide in cells. Selenium is also essential in making T3, the most active form of thyroid hormone. The best form of selenium is selenomethionine, which is a selenium-grown yeast. (For those who are yeast-sensitive, there are non-yeast forms.)

Carotenoids. These are plant pigments which are quite active in scavenging free radicals. Lycopene is more active than beta-carotene as a peroxynitrite scavenger. Lutein and zeaxanthin, two carotenoids, may also have special roles as antioxidants because of the way they insert into biological membranes.

Flavonoids. Anthocyanidins, which are found in purple plants, lower inflammatory activity, act as potent chain-breaking antioxidants, and regenerate other chain-breaking antioxidants after they have been converted to free radicals. Flavonoids also act as chelators for free iron, protecting cells from oxidative damage. Many flavonoids are soluble in both water and lipids. Flavonoids from green tea, citrus, grape seed extract, gingko, soy, olive, hawthorn, blueberry, and purple rice are effective antioxidants. Silymarin scavenges peroxynitrite, and increases the synthesis of SOD (superoxide dismutase), which makes it especially important. Flavonoids are rapidly absorbed in foods, and are quickly excreted through the kidneys, so they need to be eaten (or taken) throughout the day.

Acetyl-L-carnitine. Carnitine transports fatty acids into mitochondria, and is therefore essential for providing cellular energy. Acetyl-L-carnitine is more effective than L-carnitine because most oral L-carnitine ends up being excreted by the kidneys before it can be transported through the blood-brain barrier. Acetyl-L-carnitine is transported more efficiently. Recently, it has been shown that acetyl-L-carnitine lowers excessive NMDA activity and this may well be more important than the effects on mitochondrial function for lowering the NO/ONOO– cycle.

Reductive Stress Agents. Reductive stress causes oxidative stress. Methyl groups – SAMe, betaine, and carnitine – act as protective agents. Dr. Pall’s preference for a methylated compound is betaine (TMG.) It is cheaper and more stable than SAMe.

Hydroxocobalamin form of B12. B12 is a potent nitric oxide scavenger, but it is difficult to absorb. Oral absorption of B12 is limited by intrinsic factor. [Independent of intrinsic factor, the absorption rate of B12 is less than 1% of the total amount ingested.] Hydroxocobalamin taken as a nasal spray or injection is more effective.

Folate (folic acid). Reduced folate decreases uncoupling of NOS activity. Reduced folate in the form of 5-methyltetrahydrofolate (5-MTHF) is a potent scavenger of peroxynitrite and may well turn out to be among the most useful agents for lowering the NO/ONOO– cycle. Optimal dosage may well vary among different individuals but, in general, it should be taken along with quite a bit of vitamin C (at least 500 mg and preferably perhaps twice this amount). The reaction between peroxynitrite and 5-MTHF is important not only because it can be used to lower peroxynitrite levels. It is also important because in NO/ONOO– diseases, elevated peroxynitrite will act to lower the levels of 5-MTHF, lowering methylation cycle activity, and will also act to lower all reduced folates in the body. In this way, lowered methylation activity may be caused by the NO/ONOO– cycle.

B6, as P5P. B6 minimizes neurotoxicity. The best form is pyridoxine phosphate (P5P).

Riboflavin. Riboflavin is important for the production of reduced glutathione. It is also useful in the treatment of migraine.

Alpha Lipoic Acid (ALA) scavenges free radicals. As an added benefit, it can regenerate other antioxidants by reducing oxidized and free radical forms of glutathione, tocopherols, vitamin C and flavonoids. It can maintain glutathione pools by turning oxidized glutathione into its active form, reduced glutathione. ALA can cross the blood-brain barrier, making it an effective tool for reducing damage due to oxidative stress in the brain.

Zinc, Manganese and Copper. These minerals are components of superoxide dismutases (SOD), the enzymes that convert the oxidant superoxide into hydrogen peroxide and oxygen. Zinc, copper and manganese deficiencies can produce oxidative stress, part of which may be due to the lowered ability to produce SODs. Doses of these metals can be tricky. Excessive levels of copper and manganese can themselves produce oxidative stress. Excessive zinc lowers copper levels. Dr. Pall suggests “modest levels.”

Taurine is an unusual amino acid, because it is an antioxidant as well as a neurotransmitter. Taurine acts to stimulate the synthesis of GABA, and is transported easily across the blood-brain barrier, allowing it to work in the brain. Taurine stimulates several inhibitory receptors, leading to lowered NMDA activity. It also acts to lower intracellular calcium levels, thus lowering NO synthesis.

Long-chain omega-3 fatty acids. Polyunsaturated fatty acids (PUFAs) are more susceptible to lipid peroxidation than are other fatty acids, and consequently they tend to be depleted whenever there is oxidative stress. Fish oil, borage oil and flaxseed oil are sources of long-chain omega-3 fatty acids.

Curcumin, honokiol (from magnolia), cat’s claw, vinpocetine and feverfew all reduce inflammation by lowering NF-kappaB activity, as do a number of conventional pharmaceuticals.

Vitamin E should not be taken as synthetic alpha-tocopherol, which is the most commonly taken form, Pall argues. Rather, it should be taken as relatively high doses of gamma-tocopherol and tocotrienols with modest amounts of natural alpha-tocopherol. These other forms of vitamin E have important functions, such as lowering inflammation, scavenging an important breakdown product of peroxynitrite, lowering excessive NMDA activity and improving mitochondrial function, all important for lowering NO/ONOO– cycle diseases.

Algal supplements. Both chlorella and blue-green algae are rich in antioxidants. Blue-green algae contain phycocyanin, which is a potent free radical scavenger.

FURTHER READING:

Pall, Martin. Explaining “Unexplained Illnesses”: Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post-Traumatic Stress Disorder, Gulf War Syndrome and Others. New York: Harrington Park Press, trade division of Haworth Press, Inc. 2007.

This book is technical, but well worth reading. Dr. Pall has made a remarkable contribution to the study of “unexplained illnesses.”

“How Can We Cure NO/ONOO– Cycle Diseases: Approaches to Curing Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Fibromyalgia, Multiple Chemical Sensitivity, Gulf War Syndrome and Possibly Many Others.” Martin Pall. Townsend Letter. Feb/March 2010.

Excellent paper by Martin Pall on agents that lower parts of the NO/ONOO? cycle. Contains detailed information on protocols and potential therapeutic agents. 

Martin Pall – MEPedia’s comprehensive page on Dr. Pall includes publications, talks, interviews, papers, and more.

Antioxidant Suggestions from Dr. Martin Pall, Ph.D.  Tables of supplements recommended by Dr. Pall, along with mechanisms and comments.

Identification of SGK1 as a candidate regulator associated with myeloid cell senescence in ME/CFS: An integrative transcriptomic and experimental study

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex illness lacking objective diagnostic biomarkers and clear pathophysiological understanding. Patients exhibit immune dysregulation and chronic inflammation reminiscent of aging phenotypes, yet the role of myeloid cell senescence in this disease remains unexplored.

Methods: A stepwise integrative transcriptomic and computational strategy was employed. Differentially expressed genes were identified from the bulk transcriptomic dataset GSE14577. Weighted gene co-expression network analysis was performed to identify key modules correlated with the ME/CFS phenotype. Candidate genes were obtained by intersecting these modules with aging-related genes from the GenAge database. Core hub genes were further selected using LASSO regression and random forest machine learning algorithms. Cell type-specific expression was mapped using single-cell RNA sequencing data GSE214283, and functional validation was conducted via siRNA knockdown in a THP-1 cell senescence model.

Results: Integrative analysis identified HMGCR and SGK1 as core hub genes. Functional enrichment analysis revealed that candidate genes were enriched in pathways related to cellular senescence and inflammation. Single-cell transcriptomics analysis suggested that SGK1 expression was enriched in myeloid cell populations, including monocytes and neutrophils, in individuals with ME/CFS, whereas HMGCR showed a broader expression pattern. Single-gene GSEA indicated that SGK1 was associated with autophagy and lysosomal function. In vitro experiments showed that SGK1 expression was significantly upregulated in D-galactose-induced senescent THP-1 cells, and SGK1 knockdown markedly reduced the mRNA expression levels of senescence markers p16, p21, and p53.

Conclusion: This study identifies SGK1 as a candidate molecule associated with myeloid cell senescence-related alterations in ME/CFS. Integrated transcriptomic, single-cell, and experimental analyses suggest a potential link between SGK1 expression and aging-associated immune alterations. However, further validation in primary ME/CFS-derived immune cells and clinical cohorts is required to determine the biological significance and clinical relevance of SGK1.

Source: Jin Y, Qin R, Li W, Liu J, Chen X. Identification of SGK1 as a candidate regulator associated with myeloid cell senescence in ME/CFS: An integrative transcriptomic and experimental study. PLoS One. 2026 Oct 16;21(10):e0359082. doi: 10.1371/journal.pone.0359082. PMID: 42886747. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359082 (Full text)

An insight into the long/post COVID care situation in Germany-a rapid scoping review

Abstract:

in English, German

Background: Long/post COVID and related conditions such as myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome and post-vaccination syndrome are associated with persistent functional impairments and are met with care structures in Germany that are difficult to navigate.

Objective: The rapid scoping review offers an insight into care structures, capacities, access, care pathways and gaps in care for these patient groups in the German healthcare system. It also takes into account patient and care provider perspectives.

Methods: The study follows the recommendations of the Joanna Briggs Institute and the PRISMA ScR checklist for conducting (rapid) scoping reviews. A MEDLINE search was conducted from 2020 onwards with predefined inclusion and exclusion criteria for evidence sources related to care in Germany.

Results: 44 evidence sources were included. General practitioners and paediatricians act as the first point of contact. Specialised outpatient clinics and rehabilitation facilities take on complex diagnostics and patient treatment. Care networks are rare. Navigating the healthcare system is characteris ed by information gaps, unclear responsibilities and long waiting times, so that those affected often organise their own care. Some report stigmatisation, misdiagnoses and stressful activation recommendations despite the risk of post exertional malaise.

Conclusion: Care is unevenly accessible, poorly coordinated and only limitedly evidence based. Shared knowledge and case databases, training, better diagnostic tools and robust efficacy studies are needed to improve access, management and safety of long/post COVID care.

Source: Ebster M, Gscheidle S, Lange S, Weijburg T, Arnold M. Ein Einblick in die Long/Post COVID-Versorgungslage in Deutschland – ein Rapid Scoping Review [An insight into the long/post COVID care situation in Germany-a rapid scoping review]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2026 Oct 16. German. doi: 10.1007/s00103-026-04313-8. Epub ahead of print. PMID: 42886231. https://link.springer.com/article/10.1007/s00103-026-04313-8 (Full text in German)

Post-acute sequelae of COVID-19 (PASC) are associated with distinct clinical phenotypes two years after SARS-CoV-2 infection: A data-driven approach

Abstract:

It is important to determine whether the persistent cognitive and fatigue complaints, as part of post-acute sequelae of COVID-19 (PASC), are associated with underlying patterns and specific symptoms clusters. Therefore, the aim of the present study was to investigate symptom clusters and clinical phenotypes in PASC.

We included n = 153 individuals (53 years old, 66% female, 2 years post SARS-CoV-2 infection) categorized into groups with (n = 88) and without (n = 65) PASC, defined by severe fatigue and concentration problems using validated cut-offs. Symptom clusters (i.e., component loadings and component scores) were identified using principal component analyses (PCA, eigenvalue[EV]>1.0), using clinical, somatic, coping and sleep factors, symptom severity, neuropsychological and physical tests (totalling 19 tests and questionnaires). We then used logistic regression techniques on (participant-level) component scores (standardized) to investigate associations with PASC. Finally, K-means clustering methods to identify clinical phenotypes. Analyses were adjusted for age, sex, education, nationality and time since infection.

PCA identified 5 components, explaining 70% of the variance. We labelled these components as follows: (1) PEM, ME/CFS and sleep symptoms, coping factors (EV = 7.0, 36.9% variance), (2) information-processing speed (EV = 2.5, 13.3%), (3) executive functioning (EV = 1.5, 8.0%, (4) physical performance (EV = 1.2, 6.5%), (5) somatic comorbidities and hospital admission (EV = 1.0, 5.5%). Logistic regression showed that only the first component scores (Odds ratio [95% confidence interval] = 97.1 [16.5-570.3], p < 0.001,), and none of the others (all p > 0.05), associated with PASC.

Cluster analysis revealed two distinct clinical phenotypes among individuals with severe chronic fatigue: one marked by physical impairment and the other by diminished cognitive performance. Consistent with existing literature, we confirmed that PASC is a heterogeneous syndrome marked by extensive, interrelated symptoms. Notably, we identified specific cognitive and physical clinical phenotypes. These findings are important for future targeted diagnosis and treatment.

Source: Verfaillie SCJ, Verveen A, Visser D, Nieuwkerk P, Appelman B, Boellaard R, van Heugten CM, Horn J, Hulst HE, de Jong MD, Kuut TA, Maaden TV, van Os YMG, Prins M, Visser-Meily JMA, van Vugt M, van den Wijngaard CC, van Berckel BNM, Bosch JA, Tolboom N, Knoop H. Post-acute sequelae of COVID-19 (PASC) are associated with distinct clinical phenotypes two years after SARS-CoV-2 infection: A data-driven approach. PLoS One. 2026 Oct 15;21(10):e0359844. doi: 10.1371/journal.pone.0359844. PMID: 42879454; PMCID: PMC13671525. https://pmc.ncbi.nlm.nih.gov/articles/PMC13671525/ (Full text)

Measures of Overall Illness Severity and Burden for ME/CFS: A Scoping Review

Abstract:

Background and objectives: Consensus has not been established on measures of illness severity and burden for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), which is characterized by a wide range of symptoms including post-exertional malaise, unrefreshing sleep, and cognitive impairment. A scoping review was conducted to systematically evaluate the measurement of illness severity and burden in individuals with ME/CFS.

Methods: A literature search was conducted following PRISMA-ScR guidelines across five academic databases and one patient-organization-led website (with no restrictions on publication date; restricted to English language studies, and excluding review articles). Records were imported into Covidence, a systematic and scoping review data management tool, with studies retained if they evaluated an ME/CFS population and explicitly measured illness severity or illness burden. Information from each source was extracted and relevant measures were evaluated.

Results: From the reviewed literature, 190 full-text articles met the final inclusion criteria and were retained for analysis. The most frequently utilized tools for evaluating illness severity and burden in individuals with ME/CFS were the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Sickness Impact Profile (SIP). Additional prominent instruments identified across the literature include disease-specific measures such as the DePaul Symptom Questionnaire (DSQ) and generic health-related quality of life indices like the EuroQoL 5-Dimension (EQ-5D-5L).

Conclusions: Significant discrepancies persist in how illness severity and illness burden are operationalized in ME/CFS research. The reliance on generic instruments often obscures core symptom domains like post-exertional malaise (PEM), while inconsistent standards limit cross-comparability. Establishing standardized, disease-specifici illness metrics is critical to accurately capturing the true burden of illness and advancing rigorous clinical research.

Source: Cripe J, Ravichandran S, Deditz S, Jason LA. Measures of Overall Illness Severity and Burden for ME/CFS: A Scoping Review. Patient. 2026 Oct 15. doi: 10.1007/s40271-026-00849-8. Epub ahead of print. PMID: 42879116. https://pubmed.ncbi.nlm.nih.gov/42879116/

Myalgic Encephalomyelitis/chronic fatigue syndrome: a critical narrative review of modern concepts and unani perspectives

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, disabling, multisystem illness characterized by persistent fatigue, post-exertional malaise/post-exertional symptom exacerbation (PEM/PESE), unrefreshing sleep, and cognitive impairment. Classical Unani medicine does not recognize ME/CFS as a distinct disease entity. However, its descriptions of fatigue (I’yā), particularly I’yā Dhātī (spontaneous fatigue), provide a basis for examining parallels with ME/CFS.

Objective: To examine I’yā Dhātī (spontaneous fatigue) and its three simple subtypes (I’yā Qarūḥī, I’yā Tamaddudī, and I’yā Waramī) and compare them qualitatively with contemporary ME/CFS, including areas of similarity and discordance.

Methods: This critical narrative review used structured searches of PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science. Eight primary Unani sources were examined: Al-Qānūn fi al-Ṭibb, Kulliyāt al-Qānūn, Kitāb al-Ḥāwī, Kitāb al-Murshid, Kitāb al-Manṣūrī, Dhakhīrah-i Khwārazm Shāhī, Kitāb al-Kulliyāt, and Al-Mukhtārāt fi al-Ṭibb. The three subtypes were compared using predefined qualitative domains based on contemporary ME/CFS features and classical descriptions.

Results: I’yā Tamaddudī (distensive fatigue) showed the greatest phenomenological overlap with ME/CFS, particularly spontaneous fatigue, generalized heaviness, sleep disturbances, mental dullness, reduced functional capacity, and diffuse somatic manifestations. However, no clearly documented classical equivalent of delayed PEM/PESE was identified, representing a major area of discordance.

Conclusion: I’yā Tamaddudī (distensive fatigue) showed the greatest phenomenological/conceptual overlap with ME/CFS among the subtypes examined. This represents a historical and interpretative correspondence, not biological, diagnostic, or therapeutic equivalence. Independent operationalization and prospective evaluation are required before its clinical or biological relevance can be established.

Keywords: Chronic fatigue syndrome; Integrative medicine; I‘yā; I‘yā dhātī; I‘yā tamaddudī; Myalgic encephalomyelitis; Narrative review; Unani medicine.

Source: Israr IM, Eram F, Ahmed MM. Myalgic Encephalomyelitis/chronic fatigue syndrome: a critical narrative review of modern concepts and unani perspectives. Explore (NY). 2026 Oct 10;22(6):103545. doi: 10.1016/j.explore.2026.103545. Epub ahead of print. PMID: 42874496. https://pubmed.ncbi.nlm.nih.gov/42874496/

Which needs do children, adolescents, and young adults with ME/CFS and their parents express and feel? – Qualitative study in Germany

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-system disease that significantly deteriorates the quality of life for those affected. There is no established effective treatment, and a lack of research on what is needed by severely affected young people with ME/CFS and their caring parents to cope with the disease. The aim of this study was to investigate the needs of young people affected and their parents in order to subsequently build a tailored treatment model for this age group upon this basis.

Methods: Needs were explored using topic-guided focus groups and an adapted diary method. Patients participated either in an online focus group with five sessions discussing needs related to five topics (sports/physical activity/mobility, self-care, mental activity, social contacts, and school/vocational training/study/profession) or in the adaptive diary approach, receiving and answering the same stimuli and questions in the format of voice and text messages. Additionally, focus groups with parents comprised two sessions each, targeting needs of their children and themselves, respectively. Data were analysed by reflexive thematic analysis.

Results: We included 14 young people with ME/CFS (aged 12 to 25 years), of whom five participated in a focus group and nine in the adaptive diary approach. Eighteen parents took part in three focus groups, including three couples. In the patient sample, four themes of unmet needs were identified: (i) not being left alone with the disease, (ii) flexibility and understanding of healthcare providers and authorities, (iii) having to explain oneself less to others, and (iv) appreciation of the family filling part of the healthcare gap. Among parents, the following four themes were revealed: (i) not being left alone with the disease, (ii) health care adapted to ME/CFS, (iii) knowledge, understanding, and acceptance of ME/CFS, and (iv) confidence in dealing with ME/CFS.

Conclusions: The needs of young people with ME/CFS and their parents, respectively, overlap clearly and demonstrate the importance of a needs-based adaptation of healthcare services.

Source: Kircher A, Mayer-Huber S, Eberhartinger M, Mihatsch L, Apfelbacher C, Stojanov S, Behrends U. Which needs do children, adolescents, and young adults with ME/CFS and their parents express and feel? – Qualitative study in Germany. BMC Public Health. 2026 Sep 29;26(1):2942. doi: 10.1186/s12889-026-29549-6. PMID: 42864639; PMCID: PMC13656452. https://pmc.ncbi.nlm.nih.gov/articles/PMC13656452/ (Full text)

searchMECFS: An online, interactive platform to facilitate secondary use of biospecimens and associated research data from myalgic encephalomyelitis studies

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disease affecting multiple body systems, with no established biomarkers for diagnosis or treatment. This publication introduces searchMECFS, a free, interactive online platform developed by the Data Management and Coordinating Center (DMCC) of the ME/CFS Research Network, with funding from the National Institutes of Health. The platform’s purpose is to facilitate the secondary use of biospecimens and associated research data from ME/CFS clinical studies by improving accessibility, visibility, and sharing of these resources.

Currently, searchMECFS facilitates access to biospecimens and associated data from two studies: The Chronic Fatigue Initiative (CFI) study funded by the Hutchins Family Foundation and the Multi-Site Clinical Assessment of ME/CFS study (MCAM) funded by the Centers for Disease Control and Prevention. Users can query participant demographics and clinical information and request available biospecimens through an application process. Eight specimen types are currently available, although availability varies by study.

The results highlight a case where a researcher used the searchMECFS platform to identify 40 serum samples, which contributed to published research on circadian rhythm disruption in ME/CFS. searchMECFS aims to accelerate scientific discovery within the ME/CFS research community by improving biospecimen utilization, fostering data sharing, and supporting collaboration.

Source: Barnette Q, LeGrow K, Ham M, Illei D, Giamberardino SN, Carnes MU, Brown LM. searchMECFS: An online, interactive platform to facilitate secondary use of biospecimens and associated research data from myalgic encephalomyelitis studies. Methods Rep RTI Press. 2026 Sep;2026. doi: 10.3768/rtipress.2026.mr.0058.2609. PMID: 42857848; PMCID: PMC13652500. https://pmc.ncbi.nlm.nih.gov/articles/PMC13652500/ (Full text)