Wednesday, March 23, 2005

Symptoms of Myalgic Encephalomyelitis and Post Viral Fatigue Syndrome (PVFS)

The following information is taken from the website and March newsletter of Shropshire & Wrekin ME Support Group, England, UK. In my experience, it is one of the best M.E. support groups in the country as they provide up to date information and have good relations with other M.E. support groups and specialists like Dr Betty Dowsett, probably the most experienced and knowledgeable M.E. specialist in the world, and Dr Charles Shepherd, longstanding Medical Adviser for the M.E. Association, an M.E. sufferer whose book "Living with M.E." is the most popular and useful handbooks on M.E. available.

A few years ago, I spoke to Dr Dowsett on the phone several times and was disappointed to find that although she is still as active as possible, and continues to be a great champion for M.E. sufferers, she is getting on in years and finds things particularly hard since the death of her husband and various colleagues who were a great source of inspiration and support. M.E. is a dreadful illness to be working with. Not many doctors really want to know, which is what makes her so special. She deserves a medal and much greater recognition within the medical profession. Dr Dowsett, currently Patron of the S&W Group and 25% M.E. Group, is a terrific person and a mine of information who worked with the late Dr Melvin Ramsay, a British doctor who defined M.E. over 50 years ago. Dr Dowsett inherited thousands of Dr Ramsay's patient files and, to this day, continues to maintain that M.E. is caused by an enterovirus, Coxackie B. Having read a great deal on M.E., over the past four years, I feel sure Dr Dowsett is correct. Recently, she rang S&W Secretary Peter Ruberry (also an M.E. sufferer) to correct two statements made in the group's February newsletter. One of the statements said:

"The most common cause of ME/CFS is thought to be a viral infection related to polio (a whole family of viruses which affect the muscles and brain)."

Dr Dowsett avers that this is the ONLY cause of [correctly defined] M.E.
- - -

For the past two years I have subscribed to the S&W Group and receive its monthly newsletters via land mail. The Group has 150 members but not everything it publishes is useful for severely affected M.E. sufferers.

For those with severe M.E., I highly recommend the 25% M.E. Group, which I joined 3-4 years ago. If it weren't for them, I would think I am the only person in the world suffering as I do. Through the group, I now know there are 800 others in exactly the same situation as myself. Without each other, I think we would all feel like we were going mad. Just knowing there are others out there, experiencing the same things while knowing there is no treatment or cure - and no real good research being done in a big way - helps in a way that is very special. We are all in the same boat, experiencing the same problems, battles, ignorance and lack of understanding or appreciation what it means to be struck down with such a mysterious and complex illness.

My heart goes out to the thousands of fit young soldiers who were struck down and became profoundly disabled by Gulf War Syndrome. They experience the same as us suffering from severe M.E. and also get little understanding or sympathy because nobody can really appreciate the day to day battles of living with such a devastating long term illness. Being disabled is one thing but being disabled and ILL is altogether different. I've said it before: I'd rather have both legs chopped off than this: at least with only two legs missing you can adapt and LIVE, get around on false legs, in a wheelchair or whatever, play sport and get involved in things that are invigorating, life giving and useful to others.

Today, on reading Shropshire & Wrekin's March newsletter, I found the following snippets that should prove useful to newly diagnosed sufferers.

Symptoms of Myalgic Encephalomyelitis

Information courtesy Shropshire & Wrekin M.E. Support Group:

N.B. Not all these symptoms are normally present at one time - symptoms are variable.

A feeling of unnatural fatigue, muscles like lead, unable to lift arms or open a cupboard door at times.

Easily exhausted, inexplicably tired, sometimes first thing in the morning. Also after any exertion, however slight.

Sore throat, loss of voice control, dry sore mouth, ulcers in gums.

Drinking more frequently than usual.

Poor circulation. Cold extremities. or perspiring excessively.

Pins and needles in fingers.

Glandular swellings in any areas. (Above or below the belt).

Legs giving way. Painful joints. Burning muscle pains, maybe patchy.

Unable to move feet properly, dragging one behind the other.

Heart palpitations. Panic attacks.

Backache, top to base of spine. Localised pain, diaphragm, neck and chest.

Urinary infections, (possibly indicative of Candida or Cystitis).

Needing to visit the toilet more than usual.

Stools wrong size and shape, thin, small pieces, diarrhoea or constipation/ often watery discharge from anus.

Swelling of the stomach, bloating flatulence, indigestion.

Pallor of face. Dark circles round the eyes, or underneath.

Disturbed sleep.

Severe hunger, or alternatively/ not wanting to face food.

Forgetfulness, a feeling as though mental faculties are impaired.

Loss of concentration.

Short-tempered, even though usually placid. Too ill to cope, cannot be bothered.

Headaches, inflamed eyes, (itching, red, swollen area around lids) Blurring of vision, dizziness.

Feeling of despair, even to the point of being overcome by suicidal thoughts. (In some cases, doctors have failed to recognise this as a genuine part of the illness, and have told patients to "Pull themselves together-get out more-get a part time job, etc") This is stressful to the patient, and in fact the opposite of what they should do. Rest, rest and more rest is required. In the case of actual suicides, it has often been because patients have not had the correct advice.

Not wanting to meet people, or having the energy to dress and go out.

A feeling as though the patient has a permanent 'flu-like' illness head like cotton-wool.

Hyperacusis, an abnormally acute sense of hearing, can't stand noise.

Tinnitus, ringing in the ears.

Inability to digest certain foods.

Sickness, nausea.

Reactions to chemical sprays, odours, etc.
- - -

Myalgic Encephalomyelitis and Post Viral Fatigue Syndrome (PVFS)

By Peter Ruberry (Group Secretary) Shropshire & Wrekin M.E. Support Group: Guidelines, based on personal and others' experience.


PVFS commonly follows an attack of flu, severe cold or other viral infection. It can last for a few days, weeks or months. Symptoms may include headaches, general muscle pain, feeling faint, lack of concentration etc. It is important to take adequate rest in the early stages as this helps the body to overcome the infection.

If such symptoms last beyond six months it is possible that the condition has developed into ME, or what some doctors now call Chronic Fatigue Syndrome (CFS). It is believed that the viruses, which initiate the problem, persist in the brain cells, and in muscle cells in 70% of cases. There they become modified 'so as not to unduly disturb the body's immune system'. During periods of remission the viruses lie quiet and don't cause symptoms. But stress, trauma, accident, over-exertion, immunisation or another infection can upset this balance and the virus and immune system become re-activated, causing a relapse and return of ME/CFS symptoms.

ME is not an immune deficiency disease like AIDS

The virus concerned does not generally cause tissue damage, so none is detected by normal laboratory tests. This is the cause of the frustrating lack of proof that we are physically ill and why so many doctors have been sceptical about the illness. However special research techniques have shown that viral material is present within tissues and SPECT scans have demonstrated restricted blood flow to the brain and damage lesions in certain vital brain areas. Even if they were generally available these tests could only support a diagnosis based on clinical symptoms and case history; they cannot be used on their own to diagnose the illness.


The best way to cope with ME is to UNDERSTAND what is happening to your body and realise that you are NOT GOING MAD. It is NOT a fatal illness and, given time, you stand a good chance of making a considerable recovery.

Joining your local self-help group and the 'ME Association' or 'Action for ME' will provide you with the latest medical and research findings and news about ME. You will also find that you are not on your own, but can contact directly local sufferers, who have a wealth of experience of coping with the illness. There is also a free Group library service, which comprises books, cuttings, sound- and video-tapes on the subject of ME.


There is no known magic cure for ME, so it may not be helpful to spend a fortune chasing private treatments. However some self-help and changes in lifestyle can relieve symptoms and eventually help the body come to terms with the virus. As with chicken pox, measles etc. the ME/CFS viruses will remain in the body life-long.

REST AND AVOIDANCE OF STRESS is important, especially in the early stages. Tapes or courses on relaxation benefit many sufferers. (Stress can be mental or physical, even including climatic changes). On your better days you may be able to manage more physical and mental activity, BUT ME sufferers are usually operating very close to their energy limit and this must not be exceeded or RELAPSE will occur.

CHANGE of DIET may help. You may find certain foods worsen your symptoms. All stimulants should be avoided including ALCOHOL and CAFFEINE. Drink plenty of fluids, e.g. water, fruit juices, herbal teas, 1'Caro", 11Barleycup". Try to eat fresh foods without artificial additives, colouring and sweeteners.

Animal fats tend to encourage viral growth which destroys Essential Fatty Acids, whereas unsaturated plant and fish oils replace EFAs and help the immune system. [Evening Primrose and cod-liver oils taken together daily help restore the correct balance of EFAs. In one scientifically controlled trial, financed by the 'Efamol' company, they were found to improve symptoms in over 80% of ME sufferers].

Some ME sufferers have considerable '1irritable bowel" symptoms, due to disturbance in the autonomic nervous system. Reducing animal fats and refined sugars and increasing starch and fibre in the diet often helps.

(Brown rice, wholemeal bread*, potatoes and cereals* are good sources)

**Some ME sufferers are unable to take foods containing wheat; in others, dairy products must be avoided. Such sensitivities and/or allergies can only be determined by trial and error. Your GP may be able to help or refer you to a dietitian.

Due to viral damage to the hypothalamus (a vital part of the brain which controls hormone output), production of certain growth hormones are reduced, rendering ME patients resistant to insulin. This can cause sudden drops in blood sugar levels and feeling wobbly and strange if you miss a meal, or following a sudden burst of activity. A sweet snack or drink will quickly restore blood sugar levels, but a slice of toast or digestive biscuit is advisable to stop the sugar level crashing again.

Eating a good diabetic diet, i.e. regular meals containing plenty of starch and slow-release natural sugars, found in fresh fruit and vegetable, will help reduce episodes of low blood sugar. Refined sugars can lead to rapid fluctuations in blood-sugar levels and symptoms of hypoglycaemia. They may also increase susceptibility to Candida (a fungal growth in the gut) which can cause thrush. Unsweetened, LIVE Yoghurt, eaten daily may help restore gut flora, especially after antibiotic treatment.

[+ NB. Some private dietary practitioners can be very expensive. Some also seem to have a tendency to diagnose multiple allergies in most patients and prescribe very restricted diets which can be difficult to cope with and may even be dangerous to ME sufferers.)

You may be very sensitive to strong-smelling chemicals like perfumes, paint, petrol and TOBACCO SMOKE. Pesticides may also cause problems. Your hearing may fluctuate between intolerance of noise and near deafness. Tinnitis is sometimes experienced.

Fluctuating vision problems are common and are probably due to fatigue in the optic muscles. An eye test may be advisable to eliminate other causes of severe problems.


He/she is a vital link in aiding your recovery, and holds the key to Sickness and other Social Security benefits. If you have a sympathetic GP you are fortunate. If s/he does not believe in ME you may need to consider changing doctors.

However, even the most supportive GPs and consultants are frustrated by the nature of our illness.

They have no simple diagnostic tests to confirm ME but can only make a diagnosis based on a full case history and the pattern of symptoms. It will help if you write down ALL your symptoms and keep a diary of how you feel from day to day. It is so easy to forget important facts when you go to the surgery; you may then describe only the one or two problems that are prominent at the time.

Your GP may need to carry out a number of investigations to eliminate the possibility of other illnesses with similar symptoms (which may be treatable and could be life threatening).

Your doctor can help you most by listening and believing you, which will help you psychologically. Physically s/he may be able to prescribe treatments/drugs to alleviate the most troublesome symptoms. E.g. painkillers may help with muscle pains and headaches, and other drugs may assist the circulation and balance problems.


These can be essential to treat true depression, which affects some ME sufferers. But their main benefit is to help you get a good night's sleep. The tricyclic group, such as prothiaden and amitriptyline are often the most beneficial. ME sufferers can usually only take these in low doses (not the levels appropriate for people with depression). It is believed that the benefit of these drugs to ME sufferers is their antihistamine effect. You may find "Piritont' which is sold over the counter for insect bites etc. may be helpful in this respect.


Some ME sufferers find osteopathy, chiropractic, acupuncture, herbal remedies, homoeopathy, etc. to be very helpful. Some GPs offer such remedies themselves or may refer you on the NHS. If you take any such treatments privately or "over the counter" it is vital to inform your GP, since some "natural" products may adversely affect the potency of prescribed medicines. Some "remedies" may even be poisonous, e.g. Germanium, tryptophan, some Chinese herbal remedies.


These are best avoided whenever possible, since people with ME can react badly to their use. Always explain to your anaesthetist that you have ME should a general anaesthetic be required for an operation.

If local anaesthetic is required for dental treatment ask for ADRENALIN-free ~ 'CITANEST' to be used.

BENEFITS AVAILABLE (NB. This is for general guidance only)

If your GP considers you are unfit for work (and you have paid enough NI stamps (in the last year) you may get INCAPACITY BENEFIT at LOW rate for 26 weeks, MIDDLE rate for the next six months and LONG TERM rate from 12 months after you last worked. This lasts as long as your GP issues regular sickness certificates (and you pass periodic DSS medicals).

If you have not paid sufficient NI contributions (e.g. if unemployed or full-time housewife/mother) you may claim Severe Disablement Allowance if you are under 20 when first ill. If you are over 20 years old you must be classified 80% disabled to qualify. Proposed new legislation may stop this benefit for those over 25.

If you cannot qualify for any of the above you may be able to get INCOME SUPPORT, even if you have some earned income in the family. (DLA - see below - does not count as family income in calculating your entitlement). Income Support also entitles you to free milk, school meals, dental and optical treatment and free prescriptions. Help with Council Tax and Rent may also be available.

[Leaflets are obtainable from Social Security and Post Offices.]

DISABILITY LIVING ALLOWANCE - DLA - (UK Tel. 0800 882200 for a claim pack)

If you are under 65, in addition to the above, you may be entitled to one of THREE levels of benefit to help with CARE in the HOME and/or one of TWO levels of HELP WITH MOBILITY. You may qualify for payments (to buy care or transport) even if the care or transport you need is not readily available. This benefit does not require NI contributions.

The highest rate for care in the home may also enable you to receive INVALID CARE ALLOWANCE.

The higher rate of mobility payment also provides free road fund licence and a blue badge* (which allows for "disabled parking" facilities) for any car you travel in. You may be able to get a blue badge if your doctor is willing to endorse your application, even if DLA is refused. *Orange badge before April 2000.

There are various Government schemes to help those on Incapacity Benefit to return to work. It may be possible to get "therapeutic earnings" while receiving IB, if you are only capable of part-time employment. Also a "tax-rebate scheme" has been introduced to help those unable to earn high wages due to infirmity.

Consult your GP about these benefits before you make any decisions about returning to work.


This Act is considered to be one of the most significant developments in legislation for those who care for sick and disabled people. There are two main provisions:

- Carers now have the right to ask for a formal assessment of their ability to care for someone else.
- Local authorities have a duty to take this assessment into account when looking at the kind of support that needs to be provided for either the carer or the person cared for.

This applies whether the carer is caring for other adults or sick/disabled children. The carer does not have to be living with the disabled person, nor need he/she be the sole carer, as long as they provide a regular and substantial degree of care.

Don't wait until you are no longer able to cope. Apply for assessment as soon as the caring starts to take up a significant degree of your time and energy.

Apply to your local social security department who will then make an appointment for an assessor to visit your home. You can get a leaflet, 'How can I get my carers assessment' from Carers' National Association - 0171 490 8898.

Following assessment you should receive a full written report on additional help required, e.g. meals on wheels, domestic help, and day/night-sitting service to provide regular respite breaks.

A recent CNA survey showed that 55% of applicants had their care services increased following assessment, so it is worth applying.
- - -

DISCLAIMER NB. The accuracy and currency of the above information cannot be guaranteed. You will need to check with your GP, the DSS, Citizens' Advice Bureau etc. to check what benefits etc. may apply to you.

I hope you find these GUIDELINES helpful. Please don't hesitate to contact me if you need further help.- Peter Ruberry.

Monday, March 21, 2005

ME/CFS: "Some may be so bad they need a feeding tube because they haven’t got the energy to chew their food"

21 Mar 2005 report from The Scotsman:

When Lynne Mackay hit her teens, tantrums and days lying in bed followed. But this wasn’t down to normal hormones - it was the onset of a debilitating illness

STROPPY, argumentative and disrespectful, teenager Lynne Mackay’s wayward behaviour was on the verge of seeing her suspended from school.

Once a sporty outdoors type often found racing down ski slopes or competing in the swimming pool, suddenly she barely even bothered to take her PE kit to school. Previously a pupil with a perfect 100 per cent attendance record, there were entire weeks when she was hardly behind her desk.

At home, her sudden tantrums, unpleasant outbursts accompanied by long spells languishing in bed, were testing her family’s patience to the absolute limit too.

"She came very close to being suspended from school," admits mum Nicky, 41, with a sigh. "It seemed she had issues with everything, there were quite a few outbursts and a lot of inappropriate behaviour. It was hard at school and very difficult at home too, it was tough for us all."

Yet today, just two years later, Lynne, of Livesey Terrace, Penicuik, is buckling down to sit eight Standard Grade exams in a few weeks’ time. She regularly attends Air Cadet training and there’s at least another year at Beeslack High School in Penicuik, before she eventually heads for university to study engineering.

The change is remarkable, agrees Nicky. She was suffering from a weakening illness that, despite affecting 25,000 children around the UK, is still widely misunderstood. In fact Lynne, then aged 13, was suffering from ME - Myalgic Encephalopathy - the debilitating condition that leaves sufferers fatigued from just the slightest activity, with aching muscles, pounding headaches and often leaves them feeling frustrated, hopeless and depressed.

Medical experts now agree ME is a bona fide biological condition and not a psychological problem - with around 20,000 adults and 600 children in Scotland affected. Funding has just been announced for a new ME outreach worker in the Capital, whose role will be to provide support throughout the area for young people such as Lynne, linking health, education and social services professionals. The post will be based at Edinburgh’s Royal Hospital for Sick Children.

FOR Lynne, however, it was thanks to a series of self-help techniques, that she can now hope to face each day. "It was a huge relief to everyone - Lynne in particular - when the doctors diagnosed ME," continues mum Nicky. "I think she was starting to believe she was going off her head while others might well have thought she was just playing up."

Lynne, now 15, agrees that her eventual diagnosis - which followed months of extensive tests - lifted a weight from her shoulders.

"I was a normal kid," she says. "I was in the swimming race team, I did lots of dancing ... I was really active, usually doing two activities every night. Then I started to feel ill, there were headaches and earaches, I’d get a sore throat or aching muscles and joints - like a flu feeling. I was mostly staying in bed watching DVDs or speaking to my friends on the internet.

"I kept going to the doctor and they kept saying: ‘It’s a viral infection. Don’t worry’. I had been referred to the Sick Kids for a series of tests aimed at eliminating what could be wrong. All came back negative except for one test for glandular fever."

Glandular fever has been widely linked to ME, also known as chronic fatigue syndrome, for the way it leaves sufferers so weak and listless that they can barely get out of bed.

ME’s existence was only confirmed as recently as early 2002, after medical studies finally confirmed that sufferers were not simply "lazy".

Nicky explains: "I became convinced something was wrong when she took part in a ski race at the Lecht, came home and spent two days afterwards in bed. This wasn’t normal behaviour."

The family spent months challenging doctors’ assumptions that Lynne was simply suffering from a series of viral conditions - their efforts finally justified when she was diagnosed with ME while in her second year at high school.

"But Lynne felt a lot of frustration," adds Nicky. "She was so ill, she couldn’t keep up with her brother, Ian, who is now 13, or her own friends. She struggled to deal with it all and got depressed, then angry, frustrated and cross."

Children as young as five have been confirmed to have the condition, which can last from six months to six years - and longer.

"People learn to manage the condition and their lives by balancing out ‘activity’ with rest and relaxation," explains a spokesman for the Association for Young People with ME (AYME).

Mary-Jane Willows, chief executive of AYME, says sufferers’ symptoms often make the condition difficult for teaching staff and medical workers to spot.

"Some may be so bad they need a feeding tube because they haven’t got the energy to chew their food. Others may be able to continue coping with normal daily activity."

Lynne has her own self-help methods. "You have got to pace yourself to be able to cope with what you want to do," she explains.

And Nicky has nothing but praise for the staff at Beeslack High School who have supported Lynne. "They have been fantastic," she says.

And Lynne is once again a model pupil. "I do get really tired and really tearful," she says. "But I’m managing."

- Contact AYME on 08451 23 2389, or at

A biological mystery

EXPERTS believe cases of ME have been around for centuries - Florence Nightingale is thought to have been a sufferer - although the condition was first confirmed in the 1950s.

After years of controversy, during which some questioned whether ME really existed, it is now seen as a bona fide biological condition and not a psychological problem, often referred to as Chronic Fatigue Syndrome (CFS) or Post Viral Fatigue Syndrome (PVFS).

It often follows a viral infection but no-one has yet established how or why some people develop ME and others don’t.

It also affects sufferers in varying ways. Some become so weak they can barely move while others can continue to live normally.

The symptoms include extreme fatigue, which can strike quickly - sufferers often have to sit or lie down quickly, wherever they are - sleep disturbance, muscular pains, balance problems, poor short-term memory, and sensitivity to food, drugs and chemicals.

Mary-Jane Willows, of AYME, adds: "There is no predictable pattern to ME and symptoms can fluctuate greatly over short periods of time. Patients usually fall into categories of ‘mild’, ‘moderate’ or ‘severe’ ME, depending on how badly they are affected by their symptoms."

Friday, March 18, 2005

The Interface of Chronic Lyme Disease, CFS and FM

This post, along with several others following, is taken from the American "Mass. CFIDS/FM Association's Quarterly Publication". Although the items were published in 2002, I am posting them here for future reference, to check progress made on the various treatments and trials since that time. The following item was published under the name of Dr. Sam Donta:

The Interface of Chronic Lyme Disease, CFS and FM by Bonnie Gorman RN
Dr Sam Donta presented a comprehensive, compassionate, cutting-edge lecture to Mass. CFIDS/FM Association members on November 3rd.  His topic was "The Interface of Lyme Disease with CFS and FM: Diagnostic and Treatment Issues."  Dr. Donta is a nationally recognized expert on Lyme disease.  He is the Director of the Lyme Disease Unit at Boston Medical Center and a Professor of Medicine at BU Medical School.  He is a bacteriologist and an infectious disease specialist, who views CFS and FM from that vantage point.  He is also a consultant to the National Institutes of Health (NIH), and presented at NIH's scientific meetings on CFS research. 

What does Lyme disease have to do with CFS and FM you might be asking?  Some people believe that Lyme disease may be one of the causative factors in both CFS and FM.  Others believe that some CFS and FM patients are really misdiagnosed chronic Lyme disease patients and vice versa.  Some believe that there is no such thing as chronic Lyme disease, instead these patients actually have CFS or FM.  We asked Dr. Donta to help sort all this out.

Parallel Symptom Patterns

Dr. Donta presented the symptom lists for chronic Lyme disease, chronic fatigue syndrome (CFS), fibromyalgia (FM), and Gulf War Illness (GWI).  He pointed out the similarities between them, and found there were few differences.  He has treated hundreds of patients with these illnesses.  He found that CFS and GWI have identical symptoms, and FM is only distinguished by a positive tender point exam, that is often positive in CFS and GWI as well.  Clinically it is almost impossible to distinguish or differentiate these illnesses. 

He has concluded that chronic Lyme disease is remarkably similar to CFS, FM, and GWI.  These multi-symptom disorders have similar symptom patterns consisting of fatigue and neurocognitive dysfunction, along with numerous other symptoms that probably relate to altered neurological function.  Musculoskeletal symptoms may be more frequent in FM and in some patients with chronic Lyme than in CFS, but the definition of CFS and GWI also includes muscle aches (myalgias) and joint aches (arthralgias).

Lyme Disease Symptoms

Flu-like illness, fever, malaise, fatigue, headache, muscle aches (myalgia), and joint aches (arthralgia), intermittent swelling and pain of one or a few joints, "bull's-eye" rash, early neurologic manifestations include cognitive disorders, sleep disturbance, pain, paresthesias (including numbness, tingling, crawling and itching sensations), as well as cognitive difficulties and mood changes.  

The only symptom difference in Lyme disease is the expanding circular rash with a clearing area and center resembling a "bull's eye."  He pointed out that Lyme has multiple types of rashes and half of the rashes are not typical, they may not even include the "bull's eye" rash.  They can appear from two day after the bite, then go on for a week or so.  Patients who are infected may not develop or see the rash, and may not develop any future symptoms.  In studies, only one third of the patients were actually aware of their tick bites. 

30-50% of acute Lyme disease patients went on to develop chronic Lyme disease.  Additionally, some previously asymptomatic patients may reactivate their infection following various stressors such as trauma, surgery, pregnancy, coexisting illness, antibiotics treatment, or severe psychological stress.  The Lyme vaccine can also reactivate their infection.  Similar triggers such as trauma, surgery etc. are known to precipitate CFS, FM and GWI as well.  This is not a new phenomenon with infectious diseases.  We know infectious diseases (i.e. TB) will reactivate after illnesses or surgery-- any stressor.

Dr. Donta reported on the effects of gender on host susceptibility in Lyme disease, CFS, FM and other multi-symptom diseases.  In all these disorders, women appear to be more affected than men, usually at about 2:1 ratios.  He noted that neural cells contain estrogen and progesterone receptors, and that herpes viruses can utilize estrogen receptors to gain access to the reservoir in the cell nucleus.  Treatment of chronic Lyme disease also seems to be gender-dependent to some degree, with men generally having more speedy and complete recoveries compared to women.  He concluded that gender relationships are known for a number of infectious diseases, so it would not be surprising that such a relationship exists for chronic Lyme disease, CFS, FM and other multi-symptom disorders.


Lyme Disease: A distinct difference between Lyme disease, CFS and FM is that the origin of Lyme is clear.  Lyme disease is caused by spirochetal bacteria transmitted by the bite of an infected deer tick.  This bacteria is the Borrelia burgdorferi bacteria.  It was identified in the late 1900s in Europe.  The US was late to recognize what Europe had described.  Lyme disease was not formally identified by the CDC until 1977 when arthritis was observed in a cluster of children in and around Lyme, CT.  Since that time Lyme disease has been identified in many states.  The CDC reports that it causes more than 16,000 infections per year in the US.  Some researchers feel that the prevalence is higher than that. 

CFS and FM: Dr. Donta feels that Lyme disease is an important cause of CFS and FM.  In addition to Lyme, there are a number of other possible causes.  The evidence is still circumstantial though.  Epstein-Barr virus (EBV), the major cause of infectious mononucleosis, continues to be debated as a cause of CFS.  It is uncertain whether EBV can cause symptoms other than fatigue, such as myalgias and arthralgias that are not seen during acute or reactivated EBV infection in patients who are being immunosuppressed, but it remains possible that EBV could cause one type of chronic fatigue disorder.  There are also other herpes viruses i.e. HHV6 that are being evaluated as potential culprits.

Dr. Donta reported that recently recognized species of Mycoplasma (Mycoplasma fermentans, Mycoplasma genitalium) have been implicated in CFS, FM and GWI.  These same bacteria have also been implicated as causative agents of rheumatoid arthritis, based on PCR-DNA evidence in patients with these disorders in which 50 percent are found to have the DNA of the Mycoplasma in circulating white blood cells, compared to 5-10 percent of a normal population.  Whether the presence of this DNA represents past exposure or ongoing infection remains to be resolved.  No long-term studies have yet been performed in patients with CFS and FM to determine whether the finding of Mycoplasma DNA persists over months or years or whether such patients have any evidence of other infection such as Lyme disease or infection with Chlamydia species.

Central Nervous System Involvement

Dr. Donta reported that in Lyme disease, the nervous system seems to be the primary target for the bacteria causing the disease.  Patients with Lyme disease express many neurologic symptoms such as pain, paresthesias including numbness, tingling, crawling and itching sensations, as well as cognitive difficulties and mood changes.  Even the joint pains and occasional arthritis appear to be neuropathic in origin, as anti-inflammatory agents such as ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAID) have little if any effect on the pain.  Experimental evidence from animal models also affirm the localization of B. burgdorferi DNA to the nervous system.  Dr. Donta postulates that the disease mechanisms could involve inflammatory responses, autoimmune responses or toxin-associated disruption of neural function.  Any inflammatory responses appear to be weak, and there is no compelling evidence that Lyme disease is a result of immunopathologic mechanisms.

Commenting on his research, Dr. Donta speculated that if they are correct, and lyme bacteria is a nerve toxin that interferes with the transmission of the nerve impulse, then that is all you need to impede the normal flow of information.  There is a lot of cross-talk in the nervous system.  This toxin will decrease that cross-talk causing delayed responses resulting in cognitive problems-- the brain fog so commonly described in all these multi-symptom disorders. 

Although the disease pathways for other possible causes of CFS and FM have not been defined, Dr. Donta postulates that the central nervous system would appear to be a logical target for other pathogens or other disease processes.  These illnesses clearly affect the brain and are bound to cause many neurological manifestations.  Any changes in immunologic function would not appear to be sufficient to explain the various symptoms, and are likely to be secondary to other disease processes.

He feels we have been thinking too simplistically about finding whole organisms replicating in chronic diseases.  It is highly likely that there is no single cause for these illnesses.  It's more likely that there are multiple causes-- different organisms causing the same final set of symptoms.  Researchers need a better algorithm to study these fatiguing illnesses.  We need to be more inclusive, rather than trying to separate the illnesses.  Sometimes in medicine, if an illness is too complex to study, research interest dwindles.  We have the technology to do the research, but there hasn't been the will and the momentum to get it done.

Clinical Diagnosis

Dr. Donta reiterated that the diagnosis of Lyme disease is primarily based on clinical grounds, just as with CFS and FM.  Once other disorders are ruled out, the combination of symptoms over months is sufficient to make a presumptive clinical diagnosis.  The diagnosis of Lyme is made easier if a typical rash is present during the early phase of infection.  After that, it is difficult to distinguish the flu-like illness that can occur a few weeks later, or can recur over a number of months. 

Dr. Donta reported that some patients develop severe headaches and an aseptic (infection free) meningitis, which frequently is diagnosed instead as viral meningitis.  If a Bell's palsy occurs (drooping of one side of the face), the possibility of Lyme disease is likely.  If an unprovoked arthritis occurs, causing swelling of a single joint, especially the knee, but sometimes more than one joint, then the possibility of Lyme disease should also be given high consideration. 

He emphasized that it is the chronic phase of the disease that causes most problems for physicians and patients, because of the lack of objective signs and the presence of so many symptoms that it causes some doctors to attribute psychological reasons for the patients' symptoms.  Many patients then receive a diagnosis of CFS or FM, when they may have underlying chronic Lyme disease as the cause of their symptoms.

Diagnostic Tests

Tests for Lyme disease, like tests for other infectious diseases, are often confusing and circumstantial, and their analysis and interpretation has often been flawed.  In infectious diseases you do a Western blot test to see if you have a specific reaction.  Western blot separates out proteins antigens of an organism you are looking for.  It tells you if a person has been exposed.  It is not a direct measurement of the organism.  It is a measurement of whether the person has antibodies to it.  Antibody tests are useful in the early stages of illness as with other acute infectious illnesses.  Once the illness is in a chronic phase, antibody tests are not useful.

Just as viruses change from year to year, we know the Lyme bacteria mutates.  There are a number of organisms that can shift their surface protein in a matter of hours and that is how they evade detection and patients test negative.  These organisms attach themselves to proteins and conceal themselves-- creating a cloaking mechanism that defies detection.  This allows them to get where they want to go-- the nervous system.  Once they are inside a cell, the immune system can't see them. 

That said, Dr. Donta explained that lab tests have been helpful is some patients with Lyme disease, especially those with arthritis, in whom there are stronger antibody responses than in those with the chronic, multi-symptom form of Lyme.  The criteria for the laboratory diagnosis has been patterned after the arthritic form of the disease, and not the chronic form; as a result, there are many physicians who are misinformed about the test's lack of value in chronic Lyme disease.  The Lyme Western Blot is helpful when it shows reactions against specific proteins of B. burgdorferi, but can be negative in 25-30 percent of patients who otherwise have chronic Lyme disease. 

PCR-DNA tests for Lyme in blood, urine and spinal fluid are rarely positive, most likely because the bacteria and their DNA are not present in those body fluids, but inside nerve cells.  Additionally, PCR-DNA studies are very easy to contaminate.

In chronic Lyme disease, the MRI exam of the brain is positive in about 10-20 % of patients.  It can show some white spots (unidentified bright objects- UBO) in various areas, similar to those seen in multiple sclerosis (MS), a neurologic disease of unknown cause that has some overlapping symptoms with Lyme disease, CFS and FM, such as the numbness and tingling or paresthesias.  (There are also positive MRI findings in CFS and FM patients as well.)

Dr. Donta reported that the brain SPECT scan shows some changes in blood flow to various parts of the brain, primarily the temporal (cognitive processing) and frontal (mood) lobes in about 75 percent of patients with chronic Lyme disease.  Patients with CFS have also been reported to have some brain SPECT scan changes, frequently involving the occipital lobe.  No comparative studies have been made among patients with chronic Lyme disease, CFS and FM.  The mechanisms underlying these changes remain to be defined, but may be due to a mild vasculitis (inflammation of blood vessels) or to a signaling problem within the nerve network of the brain in those specific areas.  It is promising that these changes are reversible in most patients treated with antibiotics that appear to be effective in treating the chronic Lyme disease.  These MRI changes are often slow and may take a year to reverse themselves.

These are covert organisms we are dealing with.  We need more direct detection methods for blood, spinal fluid and other body fluids.  How do you detect organisms in spinal nerve roots or brain?  Right now we can't.  Nobody is going to biopsy patients.  We need an illness registry so we can do direct detection studies, particularly of the brain, after death.   

Treatment: Persistence Pays Off

Dr. Donta reported that there are lots of drugs that are active against the Lyme bacteria in the test tube, but the big question is whether the drug can get to the bacteria?  Lyme bacteria lives in the cells of the nervous system, perhaps other cells.  Dr. Donta has experimented with various intracellular-type antibiotics.  He reviewed his journey through various antibiotics.  After listening to his patients he decided that some antibiotics were better than others.  He then looked at clarithromycin (Biaxin) and azithromycin (Zithromax) which he found had powerful activity against Lyme bacteria in a test tube. 

But the antibiotics, by themselves, did not seem to do any good.  He found that you need to change the cellular pH (the degree of acidity or alkalinity), making it more or less acidic, to maximize the effectiveness of the antibiotic.  This allows the antibiotic to work better i.e. doxycycline seemed to work better when the pH was higher.  Dr. Donta has experimented with various agents to adjust pH i.e. amantadine (used to treat flu) and plaquenil (used to treat malaria).  He just submitted proposals to NIH to study various agents to determine which is most effective. 

Dr. Donta emphasized that the most important aspect of treatment is that it must be long-term-- 12-18 months, sometimes 24-36 months.  This length is not unusual in the treatment of infectious diseases i.e. TB.  In the first few months of treatment patients can expect an adverse reaction, symptoms will increase and you'll feel worse.  You need to be able to hang in through this period, and allow 3-6 months of a treatment trial to determine if it is working.  The earlier in the disease process that you start on treatment, the more successful it is.  The more chronic the condition the less successful it is, and you'll need to treat over a longer period of time.  This treatment resulted in substantial improvement and cures in 80-90% of patients with chronic Lyme disease.  There are 10-20% who do not respond-- generally those with a strongly positive Lyme test. 

Dr. Donta reported that similar results have been found in some patients with CFS and FM of unknown cause, supporting the hypothesis that some patients with CFS and FM have an underlying infection responsive to those antibiotics.  Antibiotic trials in CFS and FM have been limited to one month, a duration that is inadequate to properly evaluate the potential of certain antibiotics to have a positive effect on the disease.  Additional studies, examining both potential etiologic agents of CFS and FM as well as treatment trials should lead to a better understanding of both the cause and treatment of patients with CFS and FM.


Q:  If the Lyme lab tests are inadequate and the symptoms are the same as CFS and FM, why not just treat all CFS and FM patients with the Lyme protocol? 

A:  You want to be conservative with your medicines.  I think we have enough info now to tell CFS and FM patients to consider going on a 3-6 month trial of antibiotics and see if you're better.  Consider all the other meds you are already taking that just treat symptoms and not the cause of your illness.  They all have side-effects that can be hazardous.  Is it worth it to you to consider a primary treatment aimed at a cause?  There will be resistance from some MDs.  They need to be educated.  Your primary MD will need to consult an LD specialist re the treatment protocol.

Q:  Do patients with Lyme disease also have bowel and bladder problems like interstitial cystitis (IS) and irritable bowel syndrome (IBS)?  How are they affected by treatment?

A: Yes, many patients with Lyme have IS and IBS.  He was surprised how much the bowel disorders affected treatment.  Tetracycline generally helps the IBS.  Plaquenil can sometimes irritate the bowel. 

Q:  I have received different results for the western blot Lyme test.  Why?

A:  Lyme test results are not reproducible from one lab to the next.  You will get different findings from different labs.  The western blot is not a great test for Lyme since the responses to Lyme bacteria are already very small responses.

Q:  I've been sick for 15 years with CFS and my Lyme test was negative.  Is there any value in treating now?

A:  If the test was negative but you have the complex of symptoms and there is no other obvious answer, why not give antibiotics a try.

Q:  I had the Lyme vaccine then got Lyme symptoms.  Why?

A:  Lyme vaccine was pulled from the market because it was causing reactions and reactivating a slow onset of Lyme disease. 

Q:  What are the ocular problems in Lyme?

A:  He sees optic neuritis, similar to that seen in atypical MS patients.

Q:  Is there any Lyme connection to cutaneous lymphoma?

A:  He has looked closely for any cancer/ Lyme associations, but has not seen many.

Q:  Is there a connection with thyroid problems?

A:  Thyroid problems are a very common co-existing condition with Lyme, as they are with CFS.

Q:  How do I differentiate itching from allergic reactions? 

A: The same sensory nerve fiber pathways that carry pain carry itching, numbness, tingling etc.  Rash is common symptom.  Rashes could be caused by medications, especially if they are body-wide.  Is it an allergic reaction or hypersensitivity reaction?  Get a complete blood count (CBC) with differential.  Eosinophils will be elevated if allergic reaction.  If not, then it's a hypersensitivity reaction.  Treatments are similar. 

Q:  How do we get funding for research to advance these illnesses?

A:  He stressed how important it is to combine advocacy and research efforts.  Ultimately it will be a political solution.  Get active legislatively in DC.  The CFS Coordinating Committee is a very good forum.  Lyme does not have anything like that.  Groups need to work together, not fight with each other.  There should be a coalition of all these groups.  We also need to show insurance companies the benefits of primary treatment to patients, as well as to insurer's bottom line.

Comprehensive Treatment of Fibromyalgia

by Robert Bennett M.D., FRCP

Advice from an FM Expert

Editor's Note: We suggest you pass this article on to your treating physicians.  Much of Dr. Bennett's treatment protocol also applies to individuals with CFIDS, as the two conditions closely parallel each other.

If you are reading this you probably have a common syndrome of chronic musculoskeletal pain called fibromyalgia (FM).  This chronic pain state is caused by abnormalities of sensory processing within the spinal cord and brain.  As such you will usually experience a bewildering array of bodily and psychological problems that can seldom be “cured”.  However, armed with both patience and knowledge, many FM patients can be helped to live with less pain and be more productive.  In my own evolving experience of dealing with this problem, I can identify seven aspects of management that are of importance for your doctor to successful manage your FM.

My Advice to Doctors who care for FM Patients

1. Realize that FM patients are going to be a chronic challenge.

2. Be non-judgmental and prepared to be an advocate.

3. Understand the pathophysiological basis for symptoms.

4. Analyze and treat pain complaints in a systemic approach.

5. Recognize and treat psychological problems at an early stage.

6. Recognize associated syndromes of disordered sensory processing.

7. Involve all FM patients in a program of stretching and gentle aerobic exercise.

Treatment of Pain

Pain is the primary over-riding problem for most of you.  Many of the problems you experience are largely a secondary consequence of having chronic pain.  When pain is even partly relieved, FM patients experience a significant improvement in psychological distress, cognitive abilities, sleep and functional capacity.  A total elimination of pain is currently not possible in the majority of FM patients.  However, worthwhile improvements can nearly always be achieved by a careful systematic analysis of the pain complaints.

As a generalization, FM-related pain can be divided into general pain (i.e., the chronic background pain experience) and focal pain (i.e., the intensification of pain in a specific region – usually aggravated by movement).  The latter is probably a potent driving force in the generation of central sensitization.  Attempts to break the pain cycle, to enable patients to be more functional are especially important.

In general, most FM patients do not derive a great deal of benefit from non-steroidal anti-inflammatory drugs (NSAID) preparations or acetaminophen, although NSAIDs are very useful in the treatment of associated joint pain problems such as osteoarthritis.  Prednisone and other steroids have been shown to be ineffective in the long-term treatment of FM.

General Pain

The use of NSAIDs (e.g., ibuprofen, aspirin, etc.) is usually disappointing.  It is unusual for FM patients to experience more than a 20% relief of their pain, but many consider this to be worthwhile.  Narcotics (propoxyphene, codeine, and oxycodone) often provide a worthwhile relief of pain.  In most patients, concerns about addiction, dependency and tolerance are ill-founded.  Ultram (Tramadol) and Ultracet (Tramadol + Tylenol), are the most useful pain medications in many patients.  They both have the advantages of having a low abuse potential and are not a prostaglandin inhibitor.  Tramadol reduces the epileptogenic threshold and it should not be used in patients with seizure disorders.

Currently, opiates are the most effective medications for managing most chronic pain states (Friedman OP 1990, Portenoy 1996).  Their use is often condemned out of ignorance regarding their propensity to cause addiction, physical dependence and tolerance (Melzack 1990, Portenoy et al 1997, Wall 1997).

While physical dependence (defined as a withdrawal syndrome on abrupt discontinuation) is inevitable, this should not be equated with addiction (Portenoy 1996).  Addiction is a dysfunctional state occurring as a result of the unrestrained use of a drug for its mind-altering properties.  Manipulation of the medical system and the acquisition of narcotics from non-medical sources are common accompaniments.  Addiction should not be confused with "pseudo-addiction".  This is a drug-seeking behavior generated by attempts to obtain appropriate pain relief in the face of under-treatment of pain.

Opiates should never be the first choice for pain relief in FM, but they should not be withheld if less powerful analgesics have failed.  In my experience many FM patients want to try opioid medications, but then give up on them due to unacceptable side effects, such as mental fog, increased tiredness, dizziness, constipation and itching.

Local Pain

Although you are experiencing widespread body pain -- a manifestation of central sensitization -- you will also have multiple areas of tenderness in muscles - so called "myofascial trigger points."  The severity of pain and the location of these "hot spots" typically varies from month to month, and the judicious use of myofascial trigger point injections and spray and stretch (see section on focal pain) is worthwhile in selected patients.  It is often worthwhile for your physician to identify the most symptomatic points for myofascial therapy.  The steps involved in the injection of trigger points are:

1. Accurate identification of the trigger point.

2. Identification and elimination of aggravating factors.

3. The precise injection of the myofascial trigger points with 1% procaine (a local anesthetic).

4. Passive stretching of the involved muscle after the local anesthetic has taken effect; this is often aided by spraying the overlying skin with an ethyl chloride spray.  In most FM patients, this myofascial therapy needs to be repeated over a period of several weeks and occasionally over several months.

Unresponsiveness is usually due to failure to eliminate an aggravating factor, imprecise injection of the trigger point, or failure to inject satellite trigger points.  Trigger points are usually injected with 3 to 5 ml of 1-% procaine.  Please note that these are not “steroid shots.”

Performing “myofascial spray and stretch” often enhances the efficacy of trigger point injections immediately after the injections.  Spray and stretch consists of an application of a vapocoolant spray, such as ethyl chloride over the muscle with simultaneous passive stretching.  A fine stream of the spray is aimed toward the skin directly overlying the muscle with the active trigger point.  A few sweeps of the spray are passed over the trigger point and the zone of reference.  This is followed by a progressively increasing passive stretch of the muscle.

Evaluation by an occupational and physical therapist often provides worthwhile advice on improved ergonomics, biomechanical imbalance and the formulation of a regular stretching program.  Hands-on physical therapy treatment with heat modalities is reserved for major flares of pain, as there is no evidence that long-term therapy alters the course of the disorder.  The same comments can be made for acupuncture, TENS units and various massage techniques.

Treatment of Sleep Disorders

Non-restorative sleep is a problem for most of you and contributes to your feelings of fatigue and seems to intensify their experience of pain.  Effective management involves (1) ensuring an adherence to the basic rules of sleep hygiene, (2) regular low grade exercise, (3) adequate treatment of associated psychological problems (depression, anxiety etc.) and (4) the prescription of low dose tricyclic antidepressants or TCAs (amitryptiline, trazadone, doxepin, imipramine etc.).

Some FM patients cannot tolerate TCAs due to unacceptable levels of daytime drowsiness or weight gain.  In these patients, benzodiazepine-like medications such as Ambien (zolpidem) are usually very useful.  Some FM patients suffer from a primary sleep disorder, which requires specialized management.  About 25% of male and 15% of female FM patients have sleep apnea.  Unless specific questions about this possibility are asked, sleep apnea will often be missed.  Patients with sleep apnea usually require treatment with positive airway pressure (CPAP) or surgery.  By far the most common sleep disorder in FM patients is restless leg syndrome.  This can be effectively treated with L-Dopa/ carbidopa (Sinemet 10/100 mg at suppertime) or clonazepam (Klonopin 0.5 or 1.0 mg at bedtime).

Exercise for FM

FM patients cannot afford not to exercise as de-conditioned muscles are more prone to microtrauma and inactivity begets dysfunctional behavioral problems.  However, musculoskeletal pain and severe fatigue are powerful conditioners for inactivity.  All FM patients need to have a home program with muscle stretching and gentle strengthening, and aerobic conditioning.

There are several points that need to be stressed about exercise in FM patients: (1) Exercise is health training, not sport’s training; (2) Exercise should be non-impact loading; (3) Aerobic exercise should be done for 30 minutes each day.  This may be broken down into three 10-minute periods or other combinations, such as two 15 minute periods, to give a cumulative total of 30 minutes.  This should be the aim -- it may take 6-12 months to achieve this level.  (4) Strength training should emphasize on concentric work and avoid eccentric muscle contractions.  (5) Regular exercise needs to become part of the usual lifestyle; it is not merely a 3-6 month program to restore you to health.  Suitable aerobic exercise includes: regular walking, the use of a stationery exercycle or Nordic track (initially not using the arm component).  Patients who are very de-conditioned or incapacitated should be started with water therapy using a buoyancy belt (Aqua-jogger).  [We highly recommend ongoing pool exercise programs for both FM and CFIDS patients to reduce pain and to safely increase conditioning.--Ed]

Recognition of Secondary Distress

As you suffer from chronic pain there is a distinct possibility that you may develop secondary psychological disturbances, such as depression, anger, fear, withdrawal and anxiety.  Sometimes these secondary reactions become the "major problem" for some patients.  The prompt diagnosis and treatment of these secondary features is essential to effective overall management of FM patients.  Some FM patients develop a reduced functional ability and have difficulty being competitively employed.  In such cases your doctor will hopefully act as an advocate in sanctioning a reduced or modified load at work and at home.

Unless you have a severe psychiatric illness (e.g., major depressive illness or a psychosis), referral to psychiatrists is usually non-productive.  Psychological counseling, particularly the use of techniques such as cognitive restructuring and biofeedback, may benefit some patients who are having difficulties coping with the realities of living with their pain and associated problems.

Fibromyalgia Associated Syndromes

It is not unusual for FM patients to have an array of bodily complaints other than musculoskeletal pain.  It is now thought that these symptoms are a result of the abnormal sensory processing as described in the previous section.  Recognition and treatment of these associated problems are important in the overall management of your FM.

-Chronic fatigue

-Restless Leg Syndrome

-Irritable Bowel Syndrome

-Irritable bladder syndrome

-Cognitive dysfunction

-Cold intolerance

-Multiple Sensitivities


-Neurally Mediated Hypotension

-Non-restorative sleep (above)

1. Chronic fatigue: The common treatable causes of chronic fatigue in FM patients are: (1) inappropriate dosing of medications (TCAs, drugs with antihistamine actions, benzodiazepines etc.); (2) depression; (3) aerobic deconditioning; (4) a primary sleep disorder (e.g. sleep apnea); (5) non-restorative sleep (see above); and (6) neurally mediated hypotension.  A new drug called Provigil is of some help when used intermittently for management of fatigue.

2. Restless leg syndrome: This strictly refers to daytime (usually maximal in the evening) symptoms of (1) unusual sensations in the lower limbs (but can occur in arms or even scalp) that are often described as paresthesia (numbness, tingling, itching, muscle crawling); and (2) a restlessness, in that stretching or walking eases the sensory symptoms.  This daytime symptomatology is nearly always accompanied by a sleep disorder -- now referred to as periodic limb movement disorder (formerly nocturnal myoclonus).  Treatment is simple and very effective – DOPA / Levodopa (Sinemet) in an early evening dose of 10/100 (a minority require a higher dose or use of the long acting preparations).

3. Irritable bowel syndrome: This common syndrome of GI distress that occurs in about 20% of the general population is found in about 60% of FM patients.  The symptoms are those of abdominal pain, distension with an altered bowel habit (constipation, diarrhea or an alternating disturbance).  Typically the abdominal discomfort is improved by bowel evacuation.  Due to abnormal sensory processing these symptoms may be quite distressing to FM patients.  Treatment involves (1) elimination of foods that aggravate symptoms; (2) minimizing psychological distress; (3) adhering to basic rules for maintaining a regular bowel habit; (4) prescribing medications for specific symptoms; constipation (stool softener, fiber supplementation and gentle laxatives such as bisacodyl), diarrhea (loperamide or diphenoxylate) and antispasmodics (dicyclomine or anticholinergic / sedative preparations such as Donnatal).

4. Irritable bladder syndrome: This is found in 40-60% of FM patients.  The initial incorrect diagnoses are usually recurrent urinary tract infections, interstitial cystitis or a gynecological condition.  Once these possibilities have been ruled out a diagnosis of irritable bladder syndrome (also called female urethal syndrome) should be considered.  The typical symptoms are those of suprapubic discomfort with an urgency to void, often accompanied by frequency and dysuria.  In a sub-population of FM patients this is related to a myofascial trigger point in the pubic insertion of the rectus abdominus muscles and may be helped by a procaine myofascial trigger point injection.  Treatment: involves (1) increasing intake of water; (2) avoiding bladder irritants such as fruit juices (especially cranberry); (3) pelvic floor exercises (e.g. Kagel exercises); and (4) the prescription of antispasmodic medications (e.g. oxybutinin, flavoxate, hyoscamine).

5. Cognitive dysfunction: This is a common problem for many FM patients.  It adversely affects the ability to be competitively employed and may cause concern as to an early dementing type of neurodegenerative disease.  In practice the latter concern has never been a problem and patients can be reassured.  The cause of poor memory and problems with concentration is, in most patients, related to the distracting effects of chronic pain and mental fatigue.  Thus the effective treatment of cognitive dysfunction in FM is dependent on the successful management of the other symptoms.

6. Cold intolerance: About 30% of FM patients complain of cold intolerance.  In most cases this amounts to needing warmer clothing or turning up the heat in their homes.  Some patients develop a true primary Raynaud’s phenomenon (which may mislead an unknowing physician to consider diagnoses such as Lupus (SLE) or scleroderma).  Many FM patients have cold hands and feet, and some have cutis marmorata (a lace like pattern of purple discoloration of their extremities on cold exposure).  Treatment involves: (1) keeping warm; (2) low-grade aerobic exercise (which improves peripheral circulation); (3) treatment of neurally-mediated hypotension; and (4) the prescription of vasodilators such as the calcium channel blockers (but these may aggravate the problem in-patients with hypotension).

7. Multiple sensitivities: One result of disordered sensory processing is that many sensations are amplified in FM patients.  In general FM patients are less tolerant of adverse weather, loud noises, bright lights and other sensory overloads.  Treatment involves being aware that this is an FM-related problem and employing avoidance tactics.

8. Dizziness: This is a common complaint of FM patients.  Before this symptom is attributable to FM a thorough evaluation for other neurological causes should be pursued (e.g. postural vertigo, vestibular disorders, 8th nerve tumors, demyelinating disorders, brain stem ischemia and cervical myelopathy).  In many cases no obvious cause is found, despite sophisticated testing.  Treatable causes related to FM include: (1) proprioceptive (awareness of posture, movement, changes in equilibrium) dysfunction secondary to muscle deconditioning; (2) proprioceptive dysfunction secondary to myofascial trigger points in the sterno-cleido-mastoids and other neck muscles; (3) neurally mediated hypotension (see below); and (4) medication side effects.  Treatment is dependent on making an accurate diagnosis.  In patients in whom no obvious cause is found a trial of physical therapy, concentrating on proprioceptive awareness may prove worthwhile relief.

9. Neurally mediated hypotension: Patients with this problem usually have a low blood pressure that does not go up normally on standing or on exercise.  Although such patients often have a low ambient BP with postural changes, these findings are not a prerequisite for diagnosis.  A tilt table test (sometimes with the infusion of isproterenol) is the most reliable way to confirm this diagnosis.  Treatment involves: (1) education as to the triggering factors and their avoidance; (2) increasing plasma volume (increased salt intake, prescription of florinef); (3) avoidance of drugs that aggravate hypotension (e.g. TCA’s, anti-hypertensives); (4) prevent the involuntary response (prescribe beta-adrenergic antagonists e.g. propranolol (inderal) or metoprolol (lopressor) or disopyramide (norpace), but these agents are only used as a last resort because they reduce exercise tolerance); and (5) minimize the efferent limb of the involuntary response (prescribe alpha-adrenergic agonists e.g. midodrine (proamatine) or anti-cholinergic agents.

See the companion article by Dr. Bennett on his Report on the 10th World Pain Conference in this issue.  Dr. Bennett is an internationally known FM specialist, Professor of Medicine at Oregon Health Sciences University (OHSU), and Chairman of Arthritis and Rheumatic Diseases Division.  Permission was granted to publish this article from the Oregon Fibromyalgia Foundation's website: © 2002 Robert Bennett M.D., FRCP. 

FM Highlights from 10th World Congress on Pain

CONFERENCE SUMMARY by Dr. Robert Bennett

The 10th World Congress on Pain was held in San Diego CA August 17 to 22, 2002.  This is a triennial meeting organized by the International Association for the Study of Pain (IASP), the leading world body for pain researchers and clinicians.  It was a truly massive and overwhelming meeting with 1788 presentations of one type or another.  I do not have a precise number for the attendees, but my estimate is about 3500. 

The first day was devoted to refresher courses.  I took part in one of these courses devoted to rheumatic pain disorders, giving a one-hour talk on fibromyalgia.  The other two speakers were from the UK; Professor Michael Doherty spoke on osteoarthritis and Professor Bruce Kidd spoke on rheumatoid arthritis.  I was gratified to learn that at least some UK rheumatologists are focusing their attention on pain mechanisms -- but as in many countries this continues to be an uphill battle.  There were many sessions devoted to the basic mechanisms underlying chronic pain states such as FM.  Indeed, FM was frequently referred to in many of these presentations as being the classical example of a “central pain state”.  By this is meant that peripheral tissue causes of pain cannot be readily identified in most FM patients and that most of the action is at the level of the spinal cord and above.  The neurophysiological and biochemical basis of central sensitization is now being unraveled in minute detail.  Much of this work relates to neurochemicals and their interaction with specific receptors.  This is the basis of the transmission of sensory impulses from one nerve cell to another.  In order to make advances in this field one must devote a large chunk of a research career to just one very specialized topic.  Needless to say, the arcane nature of this work makes it very difficult to understand unless one is an "insider".  However, understanding the detailed mechanisms of neurochemical receptor interactions will be pivotal in the creation of designer drugs for treating chronic pain, while minimizing the unwanted side effects that plague many of the currently available medications.

Glial Cells Lecture
A state-of-the-art lecture, by Professor Linda Watkins from the University of Colorado in Boulder was particularly noteworthy.  For the past 10 years or so, she has studied glial cells.  Until fairly recently glial cells were considered boring, as their only known role was to provide a skeletal type support for nerve cells of the brain and spinal cord.  Prof. Watkins discovered that glial cells can be activated by infections and other stresses, and they then interact with nerve cells to produce chronic pain states via the secretion of small proinflammatory molecules called cytokines.  For instance, 90 percent of patients with HIV infection have chronic pain.  Prof. Watkins has shown that one component of the HIV virus (gp 120) interacts with glial cells to induce a chronic pain syndrome.  This of course may be of relevant to FM patients who trace the onset of their problem to an antecedent flu like illness.  Furthermore she has recently shown to that the introduction of a cytokine called interleukin 10 into the nervous system of mice with an experimentally induced chronic pain syndrome, attenuates their pain.  Interestingly, interleukin 10 inhibits the actions of the pro-inflammatory cytokines.  This is obviously exciting and important work which may eventually have a relevance to FM patients -- stay tuned.

Fibromyalgia and CFS
There was an interesting symposium entitled "The Biopsychosocial Approach to Fibromyalgia and Chronic Fatigue Syndrome".  It featured researchers with differing views as to the nature of FM and CFS.  Dr. Milton Cohen, from Australia, asserted that two fundamental errors have been perpetuated in contemporary research on the clinical phenomenon of widespread pain and fatigue.  The first is the failure to distinguish a clinical feature from a disease process, without a unifying concept.  The second major error is the failure to focus on the neurobiology of the defining clinical finding -- i.e. increased pain sensitivity. 

Dr. Lawrence Bradley from Birmingham AL contested Dr. Cohen’s statement regarding the lack of research on the neurobiology of FM and presented impressive evidence for abnormal pain processing and dysregulation of neuroendocrine function in FM.  He noted that disorders such as FM, CFS and irritable bowel syndrome (IBS) had a large degree of overlap.  But he also noted that not all persons with CFS showed the abnormal pain sensitivity of typical FM patients.  Dr. Bradley concluded that a better understanding of the natural history of these overlap syndromes, looking at genetic contributions, developmental stressors and triggering events, will be essential in unraveling the relationships of these common disorders. 

Fibromyalgia Posters
There were 27 individual poster presentations devoted to the topic of FM.  Here I review the 9 that I consider to be most relevant and understandable for patients.

1- A study from France explored the efficacy of subcutaneous ketamine on improving pain in FM patients.  Ketamine is a class of drugs known as NMDA receptor antagonists.  In high doses it is used as an anesthetic.  Activation of the NMDA receptor is a critical event in the biochemistry of chronic pain states.  Fifty patients received subcutaneous ketamine (up to 50 mg daily) for ten days via an infusion pump similar to that used by diabetic patients.  There was a significant improvement in pain scores in 78 percent of the subjects.  At six months after discontinuation of the ketamine 45 percent of the patients still showed improvement.  This is an intriguing study but suffered from lack of a control group using a placebo.

2- There was a fascinating study from a New York group exploring the effects of the September 11th World Trade Center disaster on symptoms of FM.  In a study prior to September 11th, this group had screened a population of 9000 women in metropolitan New York and New Jersey for FM symptomatology and psychiatric symptoms.  In February and March of 2002 they re-contacted 1000 of the same women to determine whether existing symptoms had changed.  Interestingly they did not find any major changes in FM like symptomatology, although there was a minor increased in anxiety related symptomatology.  Interestingly, there was a significant reduction in the number of doctor visits.  I asked the author of this study for her interpretation of the reduced doctor’s visits.  She conjectured it was due to a changed perspective of their problems in the light of the devastation wreaked upon so many others.

3- There is an ongoing question as to whether FM may be set off by whiplash injuries resulting from motor vehicle accidents.  A study from Switzerland applied an objective measure of increased central nervous system sensitization (the nociceptive withdrawal reflex) to 3 groups of subjects; one group with whiplash, another group with FM and a group of healthy controls.  The FM and whiplash patients, but not the healthy controls, showed unequivocal evidence of increased central nervous system sensitization.  This is an important study that brings some objectivity to this issue.

4- On the same subject, a group from Seattle looked at the onset of FM following whiplash injury.  This is an ongoing NIH funded study which aims to eventually enter 400 whiplash subjects.  To date 25 subjects have been studied and 20 percent have developed widespread pain, and 80 percent met the tender point criteria for a diagnosis of FM.  The authors concluded that some of the findings of FM are common in women 2 to 3 months following whiplash injury.  They suggest that part of this increased prevalence may be due to a clustering of tender points in the neck region – as expected in the soft tissue trauma following hyperextension/flexion injuries to the neck.  But they also noted that the high prevalence of FM symptomatology is probably not entirely artifactual, as 68 percent of the whiplash subjects also demonstrated tender points in other parts of the body.

5- A psychophysical research study from Gainesville Florida studied FM patients and healthy controls with an objective measure of central sensitization called “temporal summation.”  They asked the question as to whether central sensitization could be modified by the placebo response, fentanyl (a long acting opioid drug) or naloxone (a drug that antagonizes the analgesic actions of opioids and the placebo response).  They found that FM patients had increased levels of central sensitization compared to healthy controls.  Temporal summation was attenuated by both placebo and fentanyl to a similar degree and was not influenced by naloxone.  It was concluded that central sensitization, which is thought to be a critical component of increased pain sensitivity in FM, can be centrally modulated by both endogenous (i.e. placebo) and exogenous (i.e. fentanyl) manipulations.  There is increasing evidence that one's own endogenous pain modulating apparatus, modulated by endorphins, involves the same neural pathways as opioid analgesics.  Thus strategies aimed at activating a patient's own endorphin system, such as exercise, adopting positive coping strategies and having an optimistic outlook, are important tools in the effective management of FM.

6- Most physicians who specialize in managing FM patients believe that a multidisciplinary approach to treatment is an essential prerequisite for success.  A Canadian group developed a ten-week program for FM patients which included education, group support, coping skills training, physical exercise in a pool, goal setting and daily activity diaries.  Patients were seen in groups of 10 to 15.  Overall 395 patients had been analyzed at the time this study was reported.  Highly significant improvements were seen in the Fibromyalgia Impact Questionnaire (FIQ), a widely used outcome measure in FM studies.  Women showed greater improvements than men, and women under 40 showed the most improvement.

7- A study from Brazil reported on the effects of acupuncture on pain and quality of life in patients with FM.  Forty-eight women with FM were randomly allocated into 2 treatment groups.  Group 1 received amitriptyline plus twice-weekly acupuncture sessions for 3 months.  Group 2 received amitriptyline plus stretching and relaxation exercises twice a week.  There was a significant reduction of pain intensity and improved function in both groups, but the acupuncture group had significantly better response than the other group.  The authors concluded that acupuncture is an effective tool for treatment of FM patients.

8- A study from Salt Lake City attempted to evaluate whether FM patients would be more susceptible to pain experience during mammography and Pap smears.  A questionnaire was sent out to 100 women who were randomly selected from a database of FM patients.  Fifty nine patients agreed to take part in the survey.  They rated pain and anxiety during their last mammography and Pap smear on a scale of 0 to 10.  The mean pain score was 4.32 for mammography and 2.45 for Pap smears.  Mean anxiety scores were 2.33 during mammography and 2.2 to during Pap smears.  It was concluded that women with FM experience a moderate amount of pain during mammography, and rate mammography as significantly more painful than Pap smears.  Anxiety levels were comparable between the two procedures.  As pain is a deterrent to women for undergoing mammography, the authors suggested that more effective pain management during this procedure should be considered for those women susceptible to discomfort during mammography, such as FM patients.

9- A study from the UK evaluated the use of a new antidepressant drug called Reboxitine in a study of patients with FM and neuropathic pain.  Reboxitine is a class of drugs that selectively inhibits the reuptake of noradrenaline.  Thus its mode of action is somewhat similar to fluoxetine (Prozac) but it inhibits noradrenaline reuptake rather than serotonin reuptake.  One of the mechanisms whereby the brain can control the relay of pain impulses upwards from the spinal cord is via a descending pathway from the midbrain which uses noradrenaline as a neurotransmitter.  Thus it was conjectured that Reboxitine would modulate pain via this descending noradrenaline system.  Twenty-five women with FM and 14 with neuropathic pain (nerve pain arising from conditions such as diabetes or shingles) were included in the study.  Eight (32%) of the FM patients had a very significant reduction in pain intensity and 6 elected to continue with Reboxitine after the trial ended.  Six (43%) patients in the neuropathic pain group reported significant pain reduction but only one wished to continue using Reboxitine after the study ended.  The reason for not continuing with the medication after the end of the study was the side effects of insomnia and agitation.  However, in some patients the sense of agitation was interpreted as a feeling of increased energy, which was particularly welcome in some FM patients.  This study did not contain a placebo control group and thus the specificity of the Reboxitine effect cannot be assessed.

Overall the 10th World and Congress on Pain was a stimulating and somewhat exhausting experience.  As is often the case with large international conferences one was subjected to intense information overload.  However, I came away with a sense of awe at the magnitude and quality of the research which is being done worldwide to reduce the burden of chronic pain.  As an FM researcher, I was gratified to see that the diagnostic term "fibromyalgia" is being used increasingly by pain researchers who often refer to it as a "classical example of central sensitization."  As a rheumatologist, I am increasingly impressed that FM is primarily a neurological disorder which presents as a musculoskeletal pain syndrome.  Having said that, I believe that rheumatologists will continue to be the major specialty who treat FM, as the correct diagnosis of musculoskeletal pain is complex, and furthermore there is often an overlap of FM with chronic rheumatic problems such as osteoarthritis, lupus, and rheumatoid arthritis.  Interestingly, neurologists seem to be one of the last standouts in accepting the FM concept.  Hopefully that will change over the next few years before the next World Congress on Pain which will be held in Sydney Australia in August of 2005.

See the companion article by Dr. Bennett on the Comprehensive Treatment of FM in this issue.  Dr. Bennett is an internationally known FM specialist, Professor of Medicine at Oregon Health Sciences University (OHSU), and Chairman of Arthritis and Rheumatic Diseases Division.  Permission was granted to publish this article from the Oregon Fibromyalgia Foundation's website: © 2002 Robert Bennett M.D., FRCP. 

ME/CFS/CFIDS New Clinical Trial of Procrit

by Lucy Dechene Ph.D

New Clinical Trial of Procrit

The CFS Research Center at the University of Miami is conducting a study funded by the National Heart, Lung, and Blood Institute of the NIH.  Barry Hurwitz Ph.D. and Nancy Klimas M.D. are the principal investigators of this study.  The study is investigating a very promising potential treatment for CFIDS.  The study is a placebo-controlled clinical trial in which Procrit is prescribed to the participants for 13 weeks.  Procrit is a drug that has been used for over a decade to treat anemia which is low red blood cell volume.  The drug increases the production of red blood cells, which they have discovered is low in many CFIDS patients.  Because the red blood cell delivers oxygen to the body, it is projected that this treatment may reduce the debilitating fatigue experienced by individuals with CFIDS.  Their web page describes the study and also has links to download the brochure, as well as the electronic forms that they use to determine eligibility (they are looking for South Florida residents).  The web page is:  For more information contact Alex at
(Source: U Miami, CFS Research Center)

Will Nutrients Help Memory Problems?

Bruce Ames, a well-known biochemist who invented the “Ames test” for carcinogens, has been conducting experiments in rats (and now has started human trials) to improve memory in aging beings. He had excellent results in improving memory in rats and has started trials in humans. He is using 200 mg of alpha-lipoic acid and 500 mg acetyl-L-carnitine twice a day. In rats he was able to show that rat-comparable doses lessened oxidant damage to rat brains and improved mitochondrial functioning. Several types of memory improved significantly for the rats. Early results of his human trials seem promising.

(“Free Radical,” Wright. (Discover Oct: 63-67, 2002).)

Fish Oil May Help CFIDS

Recent research conducted by doctors from Imperial College Medical School in London, compared eight patients with CFIDS and eight healthy individuals. It was found that levels of the chemical choline were higher at the back of the brain in healthy individuals than they were at the front. In patients with CFIDS, the choline levels were the same at the back and at the front of the brain. They also found that the ratios of choline and another chemical, creatine, were higher in the back of the brain in CFIDS patients than in controls. Taking fish oil supplements, which are rich in the fatty acid EPA (eicosapentaenoic acid) ought to correct the chemical imbalance.

(Source: British Medical Journal Sept. 2002)

New Drug for Female IBS

The FDA recently approved the first drug ever for constipation-predominant IBS. Tegaserod is maleate (Zelnorm) approved for treatment of women only. Makers of the drug compared the effects of tegaserod and placebo in three trials involving 2470 women with IBS. About 14% more tegaserod users than placebo users reported complete or considerable relief for at least two of the first four weeks of use, or reported some relief for all four weeks. Tegaserod is unusual because it is the only drug which reduces bloating, as well improving constipation and pain.

(“FDA OKs Two Drugs for Irritable Bowel Syndrome,” Horwitz. (Health News Oct: 1-2, 2002) and “First Drug for Women with Constipation-Predominant IBS,” Crawford. (JAMA 288 (10): 1225, 2002))

Supplements May Combat Muscle Loss

An amino acid and carbohydrate supplement is being studied to determine its value as a nutritional countermeasure to muscle loss. To study space travel's effect on muscles, Dr. Robert Wolfe of the University of Texas Medical Branch at Galveston enlisted healthy subjects to stay in bed 28 days during a National Space Biomedical Research Institute study.

"One cause of muscle atrophy in space is lack of muscular activity. That's why bed rest is a good model because it minimizes activity, and like astronauts, you lose muscle mass primarily in the legs," said co-investigator Dr. Arny Ferrando, a professor of surgery at UTMB and Shriners Hospital for Children in Galveston. "When muscles are inactive, as they are in space, they don't make new proteins. If muscle breakdown rates are the same, that means you lose muscle."

Researchers are attempting to increase protein synthesis rates with supplements of amino acids. Participants received the supplements three times a day, and researchers compared the protein synthesis/breakdown rates and muscle mass before and after the bed-rest study. This data was compared to results from a control group that received a placebo drink instead of the supplements. "Early results suggest that the amino acid supplement is able to maintain synthesis rates and body mass," Ferrando said.


Spinal Fluid Chemicals Predict FM

Researchers from San Antonio, Texas, found that the neurochemicals from the cerebrospinal fluid (CSF) which could best discriminate FM patients from healthy normal controls were:  Substance P (SP), nerve growth factor (NGF), and 5-hydroxyindole acetic acid (5HIAA). The researchers determined that the best discriminant formula for these three neurochemicals was: Log [y/1-y] = -7.156 + 0.359 (SP) + 0.051 [NGF] -0.067 [HIAA].

This formula distinguished FM patients from healthy controls with 90.6% accuracy, an accuracy comparable to that of the ACR's 1990 criteria. The Texas research group noted that the new formula not only provided a new study tool for fibromyalgia research but also served as additional evidence of FM as a clinical disorder with objective neurochemical abnormalities.

(Source: Fibromyalgia Frontiers, Vol. 9, # 4, 2002)

Delayed-type Hypersensitivity in CFIDS

French researchers found delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with CFIDS. Delayed-type responses are T-cell mediated and not Ig-E mediated as in typical allergy and occur 12-48 hours after exposure to the antigen.

(Source: Allerg Immunol (Paris) 34(2): 38-44, 2002)

Hearing Loss Linked to Vicodin

High doses of Vicodin and other painkillers that combine the codeine-like drug hydrocodone with acetaminophen can cause intense tinnitus and hearing loss. Doctors at the House Ear Institute first noticed the link in 1993. They encountered a group of cases with the same constellation of symptoms: ringing in the ears followed by fluctuating hearing loss in alternating ears, and then total hearing loss in both ears. The pills damage the delicate hair cells inside the ear that detect sound vibrations. When the cells are destroyed, the ability to sense sound is lost. Most people who have lost their hearing were taking 20 or more pills a day, but at least one woman was just taking a normal dose. See your doctor immediately if you are taking this type of medication and experiencing hearing problems.

(Source: “A Painkiller’s Quiet Problem,” Marsa. (Health June, 2002: 58-62))


Medical Journal Summaries by Lucy Dechene, Ph.D.


“Influence of Melatonin on Quality of Life in Patients with Chronic Fatigue and Late Melatonin Onset,” Smits et al. (J CFS 10 (3/4): 25-36, 2002). 

38 CFIDS patients with delayed Dim Light Melatonin Onset (DLMO) were given the Medical Outcome Study Short Form questionnaire before and after treatment with 5 mg melatonin given 5 hours before DLMO daily for 13 weeks. Results of the questionnaires were compared to those of 43 patients with Delayed Sleep Phase Syndrome and 1063 healthy controls. Before treatment, CFIDS patients were similar to the Delayed Sleep Phase patients, except for worse physical functioning, lower energy/vitality and general health perception. After treatment, the CFIDS patients had significant improvement on “physical functioning,” “energy/vitality,” “bodily pain,” and “general health perception.”


“Levels of Nitric Oxide Synthase Product Citrulline Are Elevated in Sera of Chronic Fatigue Syndrome Patients,” Pall. (J CFS 10 (3/4): 37-41, 2002).

Serum levels of citrulline, a product of nitric oxide synthase activity, were measured in 36 CFIDS patients and 16 controls. Serum citrulline levels were significantly elevated in CFIDS patients and there was a trend towards higher levels in CFIDS patients with stronger symptoms. Dr. Pall concludes, “These results provide support for the inference that overall nitric oxide synthesis is elevated in CFS as compared to controls. They confirm an important prediction of the elevated nitric oxide/peroxynitrite theory of CFS. They also suggest that similar serum studies should not only be repeated in CFS, but also performed in multiple chemical sensitivity, fibromyalgia and post traumatic stress disorder, other conditions also proposed to be caused by elevated levels of nitric oxide and its oxidant product, peroxynitrite.”


“Toxins and Immunity in Chronic Fatigue Syndrome,” Richardson. (J CFS 10 (3/4): 43-50, 2002).

This was, unfortunately, probably Dr. Richardson’s last paper on CFIDS, since he died in July.  Dr. Richardson illustrates links between exposure, absorption and effects of viruses, bacteria, and inorganic toxins and their toll on the immune and endocrine systems as potential causes of chronic symptomatology as seen in CFS. One of the oddest cases was that of a young female who had what at first appeared to be epilepsy, but instead was found to have times of severe low blood sugar brought upon by excessive use of products with the sweetener aspartame. Most of the paper relates cases of pesticide poisoning which at first appeared to be CFIDS. He points out that while these cases have many similar symptoms to CFIDS, there are many common symptoms missing that occur in CFIDS caused by reactions to pathogens.

“NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as mechanism of chemical sensitivity in multiple chemical sensitivity,” Pall. (FASEB J 16: 1407-1417, 2002). This is a highly technical paper which explains Dr. Pall’s peroxynitrite hypothesis applied to MCS. A few of his arguments are: 1. Several organic solvents known to induce MCS all induce increases in nitric oxide levels, 2. Neopterin, a marker of the induction of the iNOS, is elevated in MCS, 3. Increased oxidative stress exists in MCS and antioxidant therapy may lead to improvement in MCS, 4. Intramuscular injections of B-12 sometimes improve symptoms and B-12 is a potent scavenger of nitric oxide.


 “Ribonuclease L Proteolysis in Peripheral Blood Mononuclear Cells of Chronic Fatigue Syndrome Patients,” Demettre et al. (J Biological Chem 277 (38): 35746-35751, 2002).

This highly technical paper from Dr. De Meirleir’s lab reports on attempts to find out the relationship of the 37-kDa and 30-kDa fragments found in CFIDS peripheral blood mononuclear cells to RNase-L. The researchers found that both fragments did come from RNase-L. The 37-kDa fragment includes the 2-5A binding site and the N terminal end of native RNase-L and the 30-kDa fragment includes the catalytic site in the C-terminal part of RNase-L. Interestingly enough, the fragments remain active. The researchers conclude, “RNase-L proteolysis removes the Cys-rich region (in the protein kinase homology domain) of RNase-L, which is believed to be involved in protein-protein interactions. It is, therefore, conceivable that the proteolysis of RNase-L might alter its interaction with regulatory proteins or its compartmentalization. Such dysregulation could in turn lead to the degradation of cellular mRNA species, which are not normal targets of native RNase-L.” [Commentary: This would suggest that it is possible that the active fragments of RNase-L found in some CFIDS patients are actively degrading messenger RNA in cells. This would greatly interfere in the manufacture of important cellular proteins, mitochondrial function and general cellular functioning. This would certainly explain the strange symptoms CFIDS patients have, as well as the difficulty in detecting the reasons for them, since the cause is intracellular disruption.—L.D.]

“Markers of Viral Infection in Monozygotic Twins Discordant for Chronic Fatigue Syndrome,” Koelle, et al. (Clin Infect Dis 35: 518-25, 2002).

22 pairs of monozygotic twins discordant for CFS were studied for evidence of infections with a long list of viruses including EBV, CMV, HHV-6, HHV-7, and HHV-8. While some twins were infected with the various viruses (most commonly CMV and herpes-1), the researchers found no differences between the CFS twins and healthy twins. The researchers conclude, “This co-twin control study of 22 monozygotic twin pairs discordant for CFS did not demonstrate a major contribution for viral infection in perpetuating CFS. This study does not exclude the possibility that infectious agents trigger the illness.”

“Evidence for the Presence of Immune Dysfunction in Chronic Fatigue Syndrome,” Natelson et al. (Clin Diagnostic Laboratory Immun 9 (4): 747-752, 2002).

Dr. Natelson’s group did a careful and thoughtful review of the medical literature on immune dysfunction in CFS. There was one oddity in their approach—if a group published more than one paper, they only “counted” the one done with the largest group of patients. This may have skewed the results. Most useful is the group’s conclusion: “ In summary, any further studies seeking to identify immunological abnormalities in CFS patients require careful attention to methodological issues. First, efforts should be made to reduce the heterogeneity of the patient sample; alternatively, large sample sizes are required in order to evaluate the importance of subgroups within the overall CFS population. Similarly, efforts must be made to reduce any potential major differences between patients and controls in areas such as the level of fitness and the presence of psychiatric disorders. Next, samples should be coded [for blind analysis] and, perhaps, provided as split samples to evaluate within-assay variability in a laboratory. Finally, appropriate statistical methods are required if differences between patients and controls are done on more than one immunological parameter. Our conclusion is that the available evidence does not support chronic fatigue syndrome as being due to any consistent immunological dysfunction. Until that evidence is better documented, we believe that the term ‘chronic fatigue syndrome’ is preferable to the older ‘chronic fatigue and immune dysfunction syndrome.’”

Lyme Disease

“A 58-Year-Old Man with a Diagnosis of Chronic Lyme Disease, Steere. (JAMA 288 (8): 1002-1010). 

This is a report of a Grand Rounds that occurred at Beth Israel Deaconess Medical Center in Boston.  It gives a good overview of chronic Lyme disease.


“Using an interleukin-6 challenge to evaluate neuropsychological performance in chronic fatigue syndrome,” Arnold et al. (Psychological Med 32: 1075-1089, 2002).

This is a strange study done at NIH with Dr. Straus as a co-author.  19 CFIDS patients (1994 definition) and 10 controls were given neuropsych tests before, during and 24 hours after being given Interleukin-6 to induce flu-like symptoms. The researchers conclude that IL-6 exacerbated the patients’ self-reported symptoms, but did not reveal notable cognitive impairments or differences between patients and controls during cytokine-induced acute influenza-like symptoms. [Commentary: This was a strange study because 5 of the 19 patients had histories of chemical dependence (throwing their CFIDS diagnosis in doubt), the one type of test most likely to show neurocognitive problems in CFIDS patients—the Task Switching Test—was thrown out because some patients messed it up, and there is no evidence that IL-6 is one of the cytokines that influences alertness and cognitive functioning. In addition, in spite of the claim the “follow-up” tests were done 24 hours later, it was admitted in the paper that many of the participants actually didn’t complete those tests until 2 or more days later. So I am less than impressed with the results.—L.D.]


“Cluster Analysis to Define Typology of CFS,” Jason et al. (Psychology Health 17 (3): 323-337, 2002).

165 subjects with chronic fatigue medically evaluated as part of Dr. Jason’s large Chicago study participated in this analysis. 31 participants had been diagnosed with CFIDS, 45 had idiopathic chronic fatigue, 33 had chronic fatigue explained by a medical condition, and 56 had chronic fatigue explained by a psychiatric condition. Factor analysis done earlier separated this group of 166 from the other fatigue groups on the basis of three of four factors—Lack of Energy, Physical Exertion symptoms, and Cognitive Problems. For this analysis, each subject had a factor scale score for the three factors and also one for Fatigue and Rest. The statistical technique of cluster analysis was done to group subjects with similar factor scores. Three clusters were found: 35 people in Cluster 1, 45 in Cluster 2, and 85 in Cluster 3.  1 CFIDS patient was in Cluster 1, 8 were in Cluster 2, and 22 were in Cluster 3. Cluster 3 subjects had high post-exertional fatigue that was not alleviated by rest, severe lack of energy and severe cognitive problems. The researchers concluded that “Findings for comparable levels of post-exertional fatigue severity among CFS and medically-explained chronic fatigue groups suggest that post-exertional fatigue represents a key symptom that differentiates individuals with CFS and other medical explanations for chronic fatigue from those with idiopathic and psychiatrically-explained types of chronic fatigue…One key characteristic that distinguished Clusters 2 and 3 (containing all but 1 CFIDS subject) from Cluster 1 was markedly high severity of post-exertional fatigue. This symptom has been designated as a major criterion for the London definition of myalgic encephalomyelitis (CFS), but as one of the minor criteria for the US definition of CFS. Results from the present investigation highlight the relative importance of this symptom as a diagnostic marker for CFS and point to the potential utility in designating post-exertional fatigue as a major criteria for CFS in future attempts to define this syndrome.”


“Joint hypermobility is more common in children with chronic fatigue syndrome than in healthy controls,” Barron et al. (J Pediatr 141: 421-5, 2002).

This was a matched case-control study comparing the Beighton joint hypermobility scores in 58 consecutive new cases of children with CFIDS, 58 otherwise healthy controls referred to a dermatology clinic, and 58 previously diagnosed CFIDS cases. The Beighton scores were significantly higher for both CFIDS patient groups compared to the healthy controls. The odds ratio for hypermobility in all CFS patients versus healthy controls was 3.5. The researchers explain the possible significance of this. “ Joint hypermobility may be the most visible reflection of a generalized connective tissue hyperextensibility, and an etiologic association with CFS symptoms may rely on circulatory or neural reflexive changes that accompany such connective tissue abnormalities.” So this could cause neurally mediated hypotension and related symptoms.

Gulf War Syndrome

“Antinuclear autoantibodies (ANA) in Gulf War-related illness and chronic fatigue syndrome (CFS) patients,” Skowera et al. (Clin Exp Immunol 129:354-358, 2002).

This British study examined 130 symptomatic GW vets, 90 well GW vets, 128 symptomatic Bosnia vets, 100 CFS patients and 111 healthy controls matched for age and sex for antinuclear antibodies, in particular the novel ones against the nuclear envelope found in one study of CFIDS patients. While some of the vets had ANA antibodies, no participant in the study had ANAs to the nuclear envelope.



“Effects of Strength Training on Muscle Strength, Cross-Sectional Area, Maximal Electromyographic Activity, and Serum Hormones in Premenopausal Women with Fibromyalgia,” Hakkinen et al. (J Rheumatol 29: 1287-95, 2002.). 

This Finnish study randomized 11 female FM patients into a 21-week strength-training program and 10 female FM patients into a control group, and used 12 premenopausal sedentary women as controls in the strength-training program. The researchers found that the magnitude and time course adaptations of the neuromuscular system to resistance training in women with FM were completely comparable to those taking place in healthy women. They concluded, “Observations recorded during the acute loading conditions might be considered an indication of the training induced adaptation of the endocrine system, showing that the acute growth hormone response may become systematic after strength training in both women with FM and controls.”


 “Impaired growth hormone secretion in fibromyalgia patients: Evidence for augmented hypothalamic somatostatin tone,” Paiva et al. (Arthritis Rheum 46(5): 1344-50, 2002). 

Twenty female FM patients were compared with 10 healthy female controls. All subjects exercised to volitional exhaustion on a treadmill. A standard metabolic cart was used to monitor pulse, blood pressure, electrocardiography, oxygen uptake, carbon dioxide output, anaerobic threshold, and maximal workload. Blood was drawn for growth hormone (GH) and cortisol measurements 1 hour before exercise, immediately before exercise, immediately after exercise, and 1 hour after exercise. One month later, testing that was exactly similar was performed, except all subjects were given pyridostigmine bromide (Mestinon; 30 mg orally) 1 hour before exercise. Compared with controls, FM patients failed to exhibit a GH or cortisol response to acute exercise (P = 0.003). After administration of pyridostigmine, 1 hour before exercise, the GH levels of FM patients increased 8-fold (P = 0.001), to a value comparable with that of controls. Pyridostigmine did not increase the cortisol response to exercise in FM patients. Pyridostigmine alone did not stimulate GH secretion in FM patients, nor did it improve exercise-induced GH secretion in controls. FM patients with normal insulin-like growth factor 1 (IGF-1) levels had an impaired GH response to exercise. The researchers concluded, “1) FM patients have a reduced GH response to exercise, 2) pyridostigmine reverses this impaired response, and 3) defective GH secretion in FM can occur in patients with normal IGF-1 levels. Because pyridostigmine is known to reduce somatostatin tone, it is surmised that the defective GH response to exercise in FM patients probably results from increased levels of somatostatin, a hypothalamic hormone that inhibits GH secretion.”


 “Latent class analysis of symptoms associated with chronic fatigue syndrome and fibromyalgia,” Sullivan et al. (Psycholog Med 32: 881-888, 2002). 

Latent class analysis (a statistical technique) was applied to data from 646 patients who had CFIDS, FM or both. The major defining symptoms of CFIDS (fatigue) and FM (widespread pain) were not considered in the analysis. Of the large amount of symptoms in the database, the researchers chose 32 which were common to one or both syndromes. The latent class analysis showed that there was little difference in CFIDS and FM when these symptoms were considered. The researchers found a four-class solution. The classes seemed to differ in a gradual fashion (rather than qualitatively) for symptom endorsements, pre-morbid characteristics, and co-morbidity with panic disorder and major depression. The researchers conclude, “These results were unexpected given the usual assumption of the distinctiveness of chronic fatigue syndrome and fibromyalgia. These results support a conceptualization of chronic fatigue syndrome and fibromyalgia as being characterized by greater similarities than differences.”