Wednesday, May 31, 2006

Recent Fibromyalgia Findings: An abnormality in the central nervous system in which pain sensations are amplified - A chronic, neurologic disease

Thanks to Jim Carney for his blog entry Recent Fibromyalgia Findings - via 03-08-2006 Source: The Science & Research of CFS, The CFIDS Chronicle Special Issue, 2005-2006.

Although there are some immunological aberrations in FM, including a decreased number of natural killer cells, most researchers now believe that the illness is not an immune system disorder. "Essentially, there is nothing specifically immunological in fibromyalgia - and if there is, whatever little there is, I think it is secondary to the central nervous system problem that fibromyalgia patients have," says Dr. Muhammad Yunas. "It's a chronic, neurologic disease."

Numerous research studies have found biologic abnormalities in FM patients, and it's increasingly uncommon to hear physicians suggest the illness is all in your head. "There was a time when we thought fibromyalgia was psychosomatic. We now understand the pain in fibromyalgia is caused by an abnormality in the central nervous system in which pain sensations are amplified," explains Dr Robert Bennett, an FM expert at Oregon Health Sciences University.

This "central sensitization theory" is described in detail in the August 2005 issue of the Journal of Rheumatology. Basically, the theory is that fibromyalgia results from miscommunication among nerve impulses in the central nervous system - the brain and spinal cord - causing FM patients to feel intense pain when they should only feel mild discomfort or fatigue.

Recent investigations found multiple triggers for this amped-up response to pain. For instance, FM patients have three to four times higher levels than normal of substance P, a central nervous system neurotransmitter involved in pain processing. Researchers also found lower levels of substances that diminish pain sensation, such as serotonin, norepinephrine and dopamine.

Dr Daniel Clauw, the director of the Center for the Advancement of Clinical Research at the University of Michigan, says, "The pain of fibromyalgia is not occurring because of some injury or inflammation of the muscles or joints. There is something wrong with the way the central nervous system is processing pain from the peripheral tissues. It's overamplifying the pain."

Pharmaceutical companies are now interested in developing drug treatments base on the new research.

Reprinted with kind permission of the CFIDS Association of America, that nation's largest non-profit organization dedicated to Chronic Fatigue Syndrome. Online at

Saturday, May 27, 2006

Chronic Fatigue's Genetic Component Study Clarifies Predispositon to Syndrome

Here is a copy of an excellent article in The Washington Post by WP Staff Writer Rick Weiss April 21, 2006 [via Shropshire & Wrekin ME Support Group, England UK, newsletter May 2006 Issue 85]:

An intense battery of medical and psychological tests of people with chronic fatigue syndrome has strengthened the idea that the mysterious ailment is actually a collection of five or more conditions with varying genetic and environmental causes, scientists reported yesterday.

But though the syndrome comes in many flavors, these experts said, the new work also points to an important common feature: The brains and immune systems of affected people do not respond normally to physical and psychological stresses.

The researchers predicted that continued clarification of the precise genes and hormones involved will lead to better diagnostic tests and therapies for the ailment, which may affect close to 1 million Americans.

"This is a very important step forward in the field of chronic fatigue syndrome research," said Julie L. Gerberding, director of the federal Centers for Disease Control and Prevention in Atlanta, which sponsored the project.

The new findings come from the largest clinical trial ever to focus on people with the syndrome, a debilitating condition accompanied by unexplained extreme fatigue, memory and concentration problems, sleep disorders and chronic pain.

Taking a multidisciplinary approach that agency officials said represents the future of public health, the CDC recruited 20 physicians, molecular biologists, epidemiologists, computational biologists -- even physicists and mathematicians -- to collaborate in an effort to tease apart the syndrome.

The results, published in more than a dozen reports and commentaries in the April issue of the journal Pharmacogenomics, released yesterday, suggest that many cases of chronic fatigue have links to a handful of brain- and immune system-related genes that either harbor small mutations or are working abnormally for other reasons.

That finding strengthens the case that some people are born with a predisposition to the condition. But those genetic links remain weak and incomplete, researchers conceded, leaving most of the syndrome's roots hidden in a fog of poorly understood physiological, neurological, psychological and behavioral factors.

"Chronic fatigue syndrome is very heterogeneous. It's not just one thing," said William C. Reeves, who oversaw the project with CDC co-worker Suzanne D. Vernon. It will take time to identify all the biological pathways involved, Reeves said, but the growing evidence of genetic links should put to rest the idea that the syndrome is a made-up diagnosis for "a bunch of hysterical, upper-class white women."

The new study involved 227 residents of Wichita, Kan., who spent two full days in a hospital undergoing a series of blood tests, hormone studies, psychological exams and sleep studies.

About one-quarter of them met the formal definition of chronic fatigue syndrome. A similar number proportion had chronic fatigue but did not rank as having the full-blown syndrome -- in many cases because their fatigue was not severe enough. A third group met all of the requirements of the syndrome but also had melancholic depression, which does not fit the current diagnostic guidelines for chronic fatigue syndrome. And a fourth group, for comparison purposes, was healthy.

The CDC, which invested about $2 million in the testing, then made blood-test results and other data available to researchers, who performed a wide variety of analyses.

In one set of studies, scientists looked at the activity levels of 20,000 genes known to be involved in the body's response to such stresses as infections, injuries or emotional trauma. Several hundred were found to be over- or under-active in various subgroups of fatigued patients.

Most of those correlations were weak -- that is, the gene expression patterns alone could not accurately distinguish those whose symptoms had been diagnosed as the syndrome from those whose symptoms had not. But in one analysis, the activity of just 26 genes did accurately predict which of six categories of chronic fatigue a patient had on the basis of symptoms and other clinical tests. That is a powerful hint that those genes -- many of them involved in immune system regulation, the adrenal gland and the brain's hypothalamus and pituitary gland, which are involved in the body's response to stress -- may hold clues to the disease variants.

In other analyses, involving 50 genes that some people inherit with seemingly minor "misspellings," five of the 500 genetic glitches that were tracked repeatedly correlated with an apparent susceptibility to chronic fatigue. Those five include genes that affect levels of serotonin -- the neurotransmitter whose levels are tweaked by many antidepressant drugs -- and glutamate, a chemical that excites certain brain pathways in response to stress.

The specific implications remain uncertain for now, said Vernon, a CDC molecular biologist. "But everybody's finding the same five genes to be involved, which is pretty cool."

Several other studies on the Wichita samples found abnormal levels of various hormones relating to stress and mood -- additional evidence that chronic fatigue syndrome patients are genetically and neurologically "wired" to respond to stress abnormally.

It is already known, Vernon said, that the brain can literally rewire itself -- breaking old connections between neurons while building new ones -- in response to various physical or emotional events. Chronic fatigue syndrome may be the result of a bad rewiring job, she said, in people genetically predisposed to handle stress poorly.

Friday, May 26, 2006

GP walked out on me - Compassion is the greatest healer?

I wrote the following draft sometime during the first week in April and kept it in my drafts folder. I am copying it here for future reference:

After a slight improvement for the first time in 6.5 years these past 3-6 months, I'm sad to note I'm sliding into relapse after carrying out a household task two weeks ago. My cleaner had emptied the contents of bathroom shelves into bathtub to clear the way. They weren't heavy items - mostly shampoos, toothpaste, soap etc. I thought it easier to re-arrange rather than going through with the cleaner where each item should go.

Once the point of relapse arrives, it's near to impossible to minimise it through complete rest because of having to deal with unexpected things, ie deliveries arriving, front gate left open by postman during a storm making it crash bang, and dozens of other tasks that crop up and can't be postponed until someone visits. When the last straw arrives, symptoms flare rapidly resulting in bad night's sleep, feel rough next morning, unable to prepare food... and so it goes on, having a knock-on effect throughout the coming days, weeks and even months.

The last straw, and what started to tip it into a full blown relapse, arrived yesterday in the shape of a new GP (my regular GP is on extended leave). Here's what I drafted over the following week - I am logging it here for future reference:

The purpose of this statement is for the record and to make a formal complaint in the hope that Dr B might read it. I hope it will give him insight into why I felt he was horrible to me on his visit, during which I believe I was calm, polite, courteous and quietly spoken and am not aware of having done or said anything wrong. I feel he owes me an apology and hope he will agree the practice ought to have a protocol on the treatment of ME/CFS/PVFS patients - particularly in regard to those who are severely affected.

Since March 2003 I have not been much beyond my front gate and most of the time have been too ill for visitors. I manage via phone, computer, mail, home helps, family, friends. In 2003, a specialist GP from the ME Clinic in Wareham, Dr C, visited me at home for a research project she was carrying out on people severely affected by CFS/ME. Dr C assessed my baseline as 15 minutes and advised me to rest for five minutes between every 15-20 minutes of activity.

By August 2005, after streamlining household/food tasks in order to carry out a six week strict rest regime (took me two years to organise) using a timer every 20 minutes throughout, I felt a slight improvement for the first time in six years, enough to be up to home visits from a dentist and doctor.

In November 2005, Dr A started visiting me every four weeks. I asked him if there was anything to help the muscle pain and stress, he said there was nothing - I agreed. He recommended Bach Rescue Remedy which helped a little (if only it could be 200% stronger!) so I paid a herbalist to visit me for a consultation but could not afford to continue after I'd started a trial of Q10 co-enzyme c£40 per pack + fish oil capsules @ £10-£20 + rescue remedy, plus Ketovite and Zincomed multi vitamin liquid.

Trying Q10 came about as a result of a paper I'd read by an ME specialist. Dr A prescribed me Ketovite and Zincomed and took time out to read the paper. Zincomed came about as a result of my asking about Magensium. Dr A felt Zincomed would be better. Among other things, Dr A helped reduce my high cholestoral from 8.1 to 7.1, arranged follow up blood tests and prescribed statens and HRT after a visit from the practice nurse.

After a few months, when I'd managed to stomach the vitamins daily and take them at correct intervals with food, I felt a slight but marked improvement: I was able to sit up and tolerate sun for 5-10 minutes each day and initiated several half-hour visits from aromatherapist X to see if it would help me build up to walks outside. I'd planned to ask Dr A on his next visit if a physiotherapist could visit me or if there was a way to prescribe aromatherapy visits on the NHS.

When Dr A did not visit me for two months, I phoned the practice for a renewal of statens, HRT, Ketovite and Zincomed and was told he was on extended leave, there was no telling when he would return. Since Dr A advised me to keep on with what I was taking, that I'd know if it was working when I managed to do something extra, like a walk outside, there was no need for me to see a GP. But they could find no record of HRT to renew, it had to be prescribed by a doctor in person, and arranged for Dr B to visit me at home the following day.

Upon his arrival at my front door, Dr B handed me two packages containing Ketovite and statens, for which I am grateful. He said he needed to go back to his car and return again so I offered to open the back gate for him (a big deal for me) to save him coming to the front door again. He rushed around so quickly, it took me by surprise and he talked so quickly, it was difficult to everything take in. Unlike Dr D or Dr A, his mind seemed hurried, like he was in a rush talking at me, not to me.

Dr B asked me questions about my being housebound and how I managed. I spent about five minutes answering them and told him my brain had already started to slow, hoping he would talk less quickly. It didn't take long for me to realise he was not really listening. As I don't often see a doctor, it made me feel disappointed.

Dr B then went off on a tangent about Disability Living Allowance, telling me about rumours and changes he'd heard and how he wasn't sure whether they were to do with long term claims or new claimants being stopped. When I told him he was shaking me up, he changed the subject without concern that he'd left me worried my DLA could be stopped at anytime even though I rely on it to pay for my home help.

When Dr B proceeded to write a prescription for the HRT I mentioned needing renewal of the Zincomed. He flicked through some of his papers and said he would not be prescribing me Zincomed. When I asked why, he said Zincomed is damaging but refused to elaborate. I asked him why Dr A would have prescribed it. Dr B became officious, snapping that the other GPs (he reeled off their names) at The Practice would not prescribe Zincomed either, implying Dr A was in the wrong to do so. Dr B's refusal to enlighten me as to what I had been ingesting, undermined and cast a bad light on Dr A which I found upsetting, unfair and disrespectful.

Instead of discussing an alternative to Zincomed or how its omission might impact on the trial, Dr B suggested anti-depressants and graded exercises and said I was not motivated enough to go out or get well. I was taken aback by such talk. I asked him why I struck him as not being motivated, he said he thought I was intelligent but not motivated as I lived alone with nobody to move me along (a family member I'd spoken to later on, said at this point I should have thrown him out). Although I'd not felt depressed and had no problems sleeping, Dr B gave me the impression if I refused to take anti depressants and go out for a five minute walk every day and see people (as if I did not want this for myself!) there could be no doctor-patient relationship between he and I. I felt he was bullying me into taking anti depressants.

Dr B spoke a little about what he knew about ME/CFS, its cause and something about the immune system, saying "chronic fatigue" sufferers who refused anti depressants and graded exercises and talked about symptoms were the 'negative' ones who never got well - even implying I was one of those. Since I'd declined anti-depressants he appeared to be telling me I would never recover. He had judged and tagged me as 'negative and not motivated' and was putting the burden of the illness on me, like it was within my gift to recover if I wished. His lack of understanding of severe ME/CFS made me feel worried about what he would be marking on my file.

It was demoralising for me to hear Dr B unfairly denigrating ME support groups and sufferers turning to alternative (non-NHS) practitioners in desperation of help. As an example, he derided one doctor for subjecting sufferers to injections of 'green stuff' (sorry this is unclear, his derisory tone and callousness took me by surprise). I don't know how I would have managed these past six years without practical help from volunteers, 25% ME Support Group and Dorset ME Support Group and help with the ordeal of obtaining DLA when it was turned down.

Dr B spoke of a young lad with ME/CFS who'd been ill for six years and became bedbound, needing his mother to turn him over. The way he'd described it made it sound like it was an unbelievable story. Also, he said something about the extent of my mobility being comparable to that of an 80 year old woman - like such a thing seemed ridiculous and medically didn't ring true. I could not understand why Dr B was telling me such things and, given my situation, found his lack of empathy disturbing.

Dr B seemed emphatic that if I took anti depressants and graded exercises I would improve. In other words, he was saying there was a treatment/cure that I was refusing and by doing so I was choosing not to recover. He more or less said there could be no doctor-patient relationship between he and I if I refused to take his advice. When I told him he was shaking me up and wished he could hear back what he'd told me and then put himself in my position, his response was to mutter something about being in a rush and not being able to stay long.

In an attempt to address my concerns, while he was here in person, I calmly and quietly told him I felt he'd been horrible to me. His reaction was to grab his jacket and case and storm out of the door in a fit of anger without a goodbye, slamming the back door so hard behind him it banged back open again.

In conclusion, I felt Dr B did not believe much of what I told him and he judged me. It is not for him to judge me or burden me with his ignorance and prejudices, I have a difficult enough life as it is. Clearly, he had no understanding of severe ME/CFS and showed no empathy or compassion. He referred to my condition as chronic fatigue - ME/CFS a neurological condition that should not be confused with chronic fatigue. Dr B got shirty when I declined his recommendation of anti depressants. I'd explained they were forced on me by another GP and did not work, they made symptoms worse - I was diagnosed with ME/PVFS by a consultant psychiatrist who advised the GP I was not depressed and to stop the anti depressants.

Dr B showed no interest in what Dr A had prescribed or the trial we'd been working on. After explaining to Dr B how I manage and keep occupied - knowing also he could see for himself I was not unkempt or living in a neglected household - I felt insulted that he saw fit to denigrate me as a person who was negative and not motivated. Going by his comments on MS he takes ME nowhere near as seriously. Years ago, they used to think MS was a form of hysteria too.

Dr B's visit lasted for about 30 minutes, maybe more or less, it's difficult to guess as it was intense, rushed and went by in a blur. He left me feeling in worse shape than when he arrived and worried about the future - that he'd tagged me as difficult, there was no hope as my bones and muscles would deteriorate to the point where I would never recover and become bedbound like the young lad he'd mentioned, and that anytime I could lose the DLA I depend on to pay my home help.

On hearing my version of Dr B's visit, a member of my family said the only thing that explains his behaviour is he thought I was a malingerer, swinging the lead - I agreed. It takes a lot of grit to manage and learn to deal with long term chronic illness (especially with one that is so contentious and has such a stigma) without becoming demanding and a burden. Aside from his rattling of my cage and making me feel worse than usual, nobody had ever stormed out on me before. Dr B's visit, not to mention the grief of its aftermath (this has taken me a week to put together) has set me back unnecessarily.

Please see attached papers (1) My experience of living with severe ME (2) 25% ME Group's Submission to DWP Draft Document V6 25 April 2005

Monday, May 22, 2006

The puzzle of ME moves a little closer to being solved

A friend has just emailed me a very good report by Barbara Lantin, Telegraph 15 May 2006. Copy in full:

Could a reduction in grey matter be to blame for Chronic Fatigue Syndrome? Barbara Lantin reports

It is a disease with no cure, diagnostic test or clearly identifiable cause and few treatments. People cannot even agree about its name. And yet, there is no doubting the impact of Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome (CFS), or Post-Viral Fatigue Syndrome.

A survey published last week suggests that of the 250,000 sufferers in this country, 77 per cent have lost their jobs because of the illness - at a cost to the economy of £6.4 billion a year. Fifty-five thousand cannot leave their homes; some of them are bed-bound.

For years, ME was dismissed by the medical profession - and almost everyone else - as the figment of fevered imaginations; it was branded as "yuppy flu" and said to strike those with nothing else to worry about. In 2002, that canard was skewered by an announcement from the Chief Medical Officer, Dr Liam Donaldson, that "CFS/ME is a debilitating and distressing condition", a chronic illness, requiring early diagnosis - which, in the absence of a test, is made from symptoms - appropriate care and scientific research.

Since then, there has been good and bad news. The Government ring-fenced £8.5 million to develop new services for people with ME, which included the funding for 47 multi-disciplinary medical teams that have treated around 9,000 people. To date, the Medical Research Council (MRC) has funded two major trials into therapies for the condition and, next April, the National Institute for Health and Clinical Excellence (Nice) will deliver guidelines for assessment and treatment.

Certainly, attitudes have shifted. The new survey, published by the charity Action for ME, shows that patients are almost twice as likely to be diagnosed within six months as they were 10 years ago, and that most are confident their doctors recognise ME as a physical illness.

But the Department of Health's commitment to advancing research into ME has, so far, come to nothing. Researchers are slowly building up a picture of what lies behind the illness - which is commonly triggered by a viral infection - and believe that drug treatments and a diagnostic test are not far away. But not one biomedical study - which relates the application of science to medicine - has received MRC funding.

Dr Jonathan Kerr, whose team at St George's Hospital, University of London - funded by a tiny charity, the CFS Research Foundation - will later this year begin a clinical trial of beta Interferon (an immuno-modulatory drug usually used in multiple sclerosis), says: "It seems extraordinary and very sad that there is no Government support for biomedical studies of ME. We have applied for funding from the MRC and been turned down."

Trish Taylor, chairman of Action for ME, which, in a bid to attract researchers into the field, is organising a joint conference with the MRC later this year, says: "We were all very optimistic when the Chief Medical Officer made his statement, but until there is fully funded research, people are essentially being left to cope on their own.

"This must be the only condition where the more seriously you are affected, the less care you receive, because there are very few domiciliary services or hospital beds available. ME is much more than feeling a 'bit tired': it devastates lives, robs people of their ability to work and destroys relationships."

Two-thirds of respondents to the charity's survey say they experience constant or daily pain and three-quarters had been bed- or house-bound at some time.

"We heard of a teenage boy who went to his bedroom six years ago and hasn't come down since, and a 28-year-old woman who has been paralysed and bed-bound for 14 years. She used to sail and swim and play the piano and hoped to go to music school. Now she is unable to speak, is fed through a tube and was only recently discharged from hospital."

ME is notoriously hard to diagnose. The usually accepted definition is: newly acquired fatigue lasting for more than six months that is not the result of known disease or exertion and is not alleviated by rest. At least four of the following eight symptoms must also be present: impaired memory or concentration, sore throat, tender lymph nodes, muscle pain, joint pain, headaches, unrefreshing sleep, and malaise after exertion.

Although many treatments are touted for ME, scientific evidence for their efficacy is scant. Most children eventually recover, adults rarely do without treatment.

BestTreatments, the British Medical Journal website, lists only Cognitive Behaviour Therapy (CBT) and Graded Exercise Therapy (GET) - a closely monitored aerobic exercise programme - as "treatments that are likely to work" for the condition.

Some dismiss these as coping strategies rather than cures. Others are concerned that their use reinforces the view that ME is "all in the mind". Peter White, professor of psychological medicine at Queen Mary School of Medicine, London, who is running the MRC-funded trial into these therapies -"Pacing, Activity and Cognitive behaviour therapy: a randomised Evaluation" (PACE) - disagrees.

"CBT has been shown in five trials to be an effective treatment for ME and in uncontrolled studies people who are quite severely disabled have made significant improvements on a GET programme that is tailor-made for the individual. I do not believe that ME is a psychological illness. It is one that affects the mind and the body - and which illness does not? We do a disservice to patients if we try to separate the two."

In some studies, CBT has been shown to restore abnormal brain function to normal. Researchers in Holland are investigating whether it can reverse the reduction in the size of grey matter in the brain, which is associated with ME.

"An ME patient of 35 has grey matter the same size as a non-affected person 15 years older," says Jos van der Meer, professor of internal medicine at Radboud University Medical Centre in Nijmegen. "We do not know whether this is a cause or an effect of ME, or whether it is reversible."

Prof van der Meer has also found that patients with ME react more to normal stimuli. "They sense more fatigue and more pain. This is about perception, but it is not psychiatry. It is very real and probably at the level of neurotransmitters giving signals that are too strong - as we can see when we do MRI scans on ME patients performing simple tasks."

Other research has shown excessive levels of cell-damaging free radicals in blood, urine and muscle tissue. And Dr Kerr has identified 100 "faulty" genes. "The gene expression in white blood cells appears to be very different. These are genes involved in the immune response and regulation of cell processes.

"We need to make sure these abnormalities are specific to ME and connect them with particular symptoms. We will use this information to tell us which metabolic pathways are abnormal and then use novel treatments to normalise these pathways. Within five years, I think we will have a diagnostic test for ME and hopefully a treatment that works for a significant percentage."

Many now believe that ME will turn out to be not a single syndrome with a unique "thumbprint" but a ragbag of common symptoms with many causes. "The medium- to long-term aim is to determine a clinical or scientific thumbprint for each of the specific subgroups of ME patients," says Dr Neil Abbott, director of operations for MERGE, a national ME research charity. "For the first time in many years, I feel optimistic about potential biomedical advances."

Action for ME; 0845 123 2380, MERGE;