Notes on Dr. David Bell's talk on 25 August 1998, given at the invitation of AYME (Association for Youth with ME)

Dr. Bell has been interested in ME in children since 1985 since an outbreak in his practice in Lyndonville, New York.

He feels the name is controversial. The term CFS is inadequate. CFS has a similar definition to ME - in that it requires substantial neurological deficits, not just fatigue.

The illness occurs as both epidemics and sporadic cases. There has been speculation from the clusters of cases in epidemics that the illness might be contagious. He feels that this might only be the case at the
beginning of the illness, but not after two to three months.

The only thing required for a diagnosis is a physical examination. It should not be a diagnosis made by exclusion, as there is no other illness which is similar. Those doctors who are not familiar with the
illness do tend to exclude everything else. However it is important to run certain tests like thyroid tests. The diagnosis should be made quite quickly as the illness is so unique. ME has a prolonged chronic
course, with the symptoms the same month after month, year after year even after normal test results have been obtained.

3/4 of sufferers have an acute onset and 1/4 a gradual onset. 60% of sufferers are female and 40% male. 30 outbreaks have been recorded and in all of them 70% of sufferers were adults and 30% were children. Not all the outbreaks were assumed to be the same thing, but the same figures kept coming up in each community.

There are immunological abnormalities in the illness, but it's not possible to make a diagnosis by them. The 1994 CDC criteria is used for diagnosis in USA. This has allowed a body of research to take place.

In a list of symptoms of sufferers, fatigue is mentioned 100% of the time, but when asked what the worst symptom is, 49% stated fatigue, with the rest mentioning headaches, cognitive dysfunction etc. The underlying fatigue and the pattern of symptoms taking place, are the most important thing. The symptoms are virtually identical in children and adults. However, below the age of 10 there is a different symptom
pattern, and the child can't verbalize their symptoms such as cognitive dysfunction and fatigue. They have always felt like that and it is not unusual to them.

Fatigue
-------

A poor word to describe the feeling. Fatigue doesn't really occur in ME. It is a symptom which implies recovery. After resting from exertion, you feel recovered. This doesn't happen in ME. The fatigue is tiredness which also isn't a good word. The closest word to describe it is asthenia.

The fatigue is:
+ new onset,
+ relapse after exertion,
+ limits activity,
+ fluctuations in intensity during the day.

There is often an activity window, a time during the day when the patient feels more able to do things. Sufferers usually incorporate this into their day. However activity levels tend to be more constant when studied day to day.


Neurological Symptoms
---------------------

He is reluctant to make a diagnosis of ME without these symptoms.
Cognitive dysfunction means:

+ brain fog and mental exhaustion,
+ poor short-term memory and concentration,
+ poor balance, dizziness, pins and needles.

Almost all patients have it. Many are afraid of these symptoms because they are likened to degenerative diseases like Alzheimer's. However, the symptoms are a function of the fatigue and not due to organic damage to memory.

In healthy people, tasks are done unconsciously - they don't need to think about it. When you are tired, you can't recall them. The same happens when you keep a healthy person up all night, but they recover. However, when you get better, your memory also gets better. When the memory starts getting better, you are on the right path and are going to improve.

Pain (virtually everywhere)
---------------------------

+ Variable intensity,
+ Severity parallels fatigue,
+ relapsing/remitting,
+ headache, joint and muscles, sore throat, lymph nodes, abdominal
+ laterality - worse on the left than right, or vice versa.

Pain is from the CNS, from the thalamus - the pain recognizing centre, and not from the particular organ which hurts.


Sensitivity (relatively minor)
------------------------------

+ Light, noise, odour sensitivity,
+ alcohol intolerance,
+ MCS,
+ drug sensitivity,
+ temperature sensitivity,
+ food sensitivity.

Drug sensitivities follow a discrete pattern. Could make a diagnosis from spending 6 hours in a mall - with all the light, noise, echoes and confusion. After 10 minutes a sufferer would be ready to explode. Call it the Mall Test!

Pattern of Symptoms

Disagree with diagnosis by exclusion. Plot the symptoms on a radial graph (as in his book). Give the patient a questionnaire and ask them to rate symptoms from zero (mild) to ten (severe). Plot the points on a graph and then calculate the area. Both depression and school phobia cover very small areas. Mild ME covers a larger area and severe ME covers a very large area. This is VERY different from depression. No
other illness show this type of pattern.

"All these atypical something's make a typical something." – The Awakenings.

It is easy to diagnose as it is a unique illness. This is shown by the ability of support groups to recognize the illness very quickly when talking to another sufferer.

The medical profession have not accepted it as a unique clinical illness.


Theories
--------

There are probably 50 good theories on the cause of ME, each of which is very interesting. And there are also lots of bad ones.

Different theories: Persistent infection leading to immunological abnormalities (induced by infectious agent), neurocirculatory (which doesn't imply a cause, merely a mechanism causing symptoms to persist although the cause disappears), asthenia, abnormal adrenal function, psychiatric (but NOT depression).

Psychiatrists don't know what to do with sufferers. It's a difficult illness for them to treat. No-one has yet recovered through the use of psychotropic drugs and counseling.

Need to take despair seriously - to help learn coping mechanisms, which in itself can be life saving.

Post-polio syndrome is indistinguishable from ME/CFS. The pattern of symptoms of the two illnesses are quite similar. 91% of polio survivors have:

+ moderate to severe fatigue (primary cause of disability);
+ significant cognitive dysfunction;
+ poor concentration and memory etc.
+ Polio virus lesions have been found at autopsy.

NMH - Peter Rowe. Children with CFS took the tilt table test and there were a large number of abnormal tests where the children passed out. There is an abnormality in the ability of the body to compensate in a change of position. The brain blood flow decreases. After taking Florinef many felt better, but it has not turned out as well as hoped. 1/3 done well. The young do better than the old and the sickest don't respond. It expands the circulating blood volume - and maintains the flow to the brain. He linked ME and NMH.

Dr. David Streeton. Didn't realize he was working on ME/CFS patients - they didn't have fatigue. He joined up with Dr. Bell and decided their patients had the same illness. They had 19 sufferers who met the criteria and measured their blood volume. This was done by drawing 10cc of blood and labeling the red blood cells with chromium 51. The blood was then injected back into the body, where it distributed equally round the body. Another 10cc of blood was drawn and the chromium 51 level was measured. From this it's possible to work out the amount of blood in the body. This is a very reliable test.

Blood pressure is normal. Peripheral hematocrits are normal. Proportion of red blood cells to plasma. Even if blood volume is low, hematocrits are normal. In one person, they had half the normal red blood cell volume.

Plasma volume - one had a very high level, but it is really changeable, and they had drunk a lot before the test. When the test was repeated, the level was low. Not an accurate marker.

If you combine the two (red blood cell volume and plasma volume), you get the total circulating blood volume. Virtually everyone tested was below normal range. Some were dramatically abnormal, even half the normal level.

If a healthy person had an accident and lost 25% of their blood – would cause shock. It's not possible to survive with 40% below normal blood volume (in healthy people). This is a reliable tests - it's been done
for years.

Showed a SPECT scan of a 14 year old girl who'd had ME for 5 years. The scan shows the distribution of blood flow in the brain. It's possible to compare the blood flow on one side of the brain to the other. There was a decreased flow in one area, which was strikingly abnormal compared to the other side. This is typical in ME.

There HAS to be a fairly dramatic abnormality behind this illness. If an athlete becomes housebound - a subtle change can't cause this. But we can't find what is it - which is a problem. In 1985 scientists said that EBV being the cause of ME was absurd. They didn't believe that it could cause this degree of

disability. Coxsackie and enteroviruses aren't dramatic results from biopsies so are unlikely candidates.

Symptoms are volume dependent.

Trigger factor
|
Damage to Autonomic Nervous System
|
Low RBC mass
|
Symptoms

This pattern was what was thought to be the process, but isn't correct.

Trigger factor
|---------------------|----------------------|


Low RBC mass ANS damage Abnormal Immunology
|

Symptoms

Orthostatic Hypotension - blood pools in the legs, a lower blood flow in the brain. Feel faint but recover. Hypovolemic - decreased blood volume but the same distribution round the body (feel faint). Nurse noticed this - wouldn't draw blood because patient felt faint/fainted when blood was drawn - made them lie down.

ME, however, has low blood volume and blood trapping in legs.

They're working on a test. Patient lies down and take BP and pulse for 10 minutes. Patient then stands quietly next to a wall. Take the pulse every few minutes for 30 minutes plus, and watch the BP. Patients have normal resting BP and pulse pressure. As soon as they stand up, within one minute, pulse pressure narrows significantly as time goes by.

Circulating blood is dependent on pulse pressure. It's the circulating force getting the blood through the body. Essentially the blood flow stops (when it drops). Patient has to stand still in test, and not fidget, which most sufferers do automatically, which pumps the blood through the muscles. Most patients felt nauseous, pale, headache, crying when the test was stopped. Usually ask the patient to say when
they can't do it anymore.

Pulse pressure = 8ml of mercury. Almost no blood to brain. Most sufferers continue to stand even though they are in severe distress. They think they are not doing anything so why do they feel so bad?

A rise in pulse - compensatory mechanism - not all sufferers have it . Have POTS (postural orthostatic syndrome. Narrowing pulse pressure and BP so low (50% normal blood volume) - no wonder she can't function standing up. An orthostatic illness.

We put out adrenaline to help circulate the blood - but this doesn't work when we stand up.

One patient had hypertension, had a high BP response to low blood volume. Gave a diuretic to get rid of some fluid. Gave him 2 units of saline - acts as a volume expander - BP fell. Felt good for next 24-48 hours.

If there's a decreased blood volume, BP changes - put out adrenaline - blood flow decreased to brain. Decrease circulating blood volume - traps it in legs.

Principles of Treatment
-----------------------

Need to have an ongoing diagnosis to be sure that you're not missing something, as sufferers do get other illnesses whilst they have ME, e.g. low thyroid might come on - symptoms are very similar.

The role of the physician in any illness.
+ symptom reduction
+ educational support
+ treat activity limitation

Physical Support
----------------

+ Encourage common sense in using vitamins etc.
+ understand exercise values vs. drawbacks
+ encourage autonomy - important for young people. Develop autonomy to think/act for themselves and become who they want to be
+ encourage discrimination - what they won't/don't want to do. Get involved in their own treatment
+ understand reasons to treat - practical issues, look for worst and most disabling symptoms to treat, e.g. headaches and depression
+ symptom vs. activity limitation

Emotional Support
-----------------

+ clarify diagnostic issues
+ identify coping method - experiment with different coping methods to find the best
+ identify emotional needs
+ provide ongoing support
+ provide medication to treat emotional difficulties (rare)

Educational Support
-------------------

+ assess activity potential
+ assess cognitive difficulties
+ determine "activity window"
+ tailor needs to services available
+ aggressively pursue services needed

He encourages his patients to take risks. Sufferers maybe worried that they will get worse. But you should push yourself as much as feel you need to. There are times when it may be worth getting sick - e.g. going to a wedding - have to learn to discriminate. Learn what is worth the risk. You won't become worse if you push yourself within limits. Use common sense.

Exercise - a wonderful treatment if you can do it. When you are getting better, that's when you can exercise. You should exercise when you're getting better. But it's important to remember that when you're very sick you can't get through it by exercising. He has never seen someone who got themselves better because of exercise.

Questions & Answers
-------------------

Q. Could this test be used as a diagnostic tool?
A. He hopes it will be. Although it will take quite a long time before it's determined. If a patient gives a list of complaints, a doctor should be able to make a diagnosis on standard tests. The decrease in pressures in the test is unique. When a healthy person loses blood in a car accident, they have the same decrease in pressure as seen here. Blood volume is not by itself an absolute diagnosis, but is useful. Now wants to evaluate the responses of under 18's and compare them with normal teenagers.

Q. Are recurring mouth ulcers and inflammation of the oesophagus symptoms of ME?
A. Mouth ulcers are very common in ME. 40% of the initial group studied had them, but never really cultured much from them. Immunological abnormality - decreased function of natural killer cells. These would normally suppress the herpes group virus, which maybe why ME sufferers have more mouth ulcers. In American studies of EBV, there was an increase in replication of EBV in ME sufferers. Cytomegalovirus and chickenpox too. Cher - had chickenpox five times - only possible in ME, because NK cells are down.

Q. My daughter has lowish BP lying down which drops when she stands up. The doctor says this is because she's not exercising.
A. Doctors explain it away through inactivity, which will cause physiological changes and decreases in circulating blood volume by 10%. However, there are larger values than this in ME. Orthostatic
inactivity - can't walk, but up and about the house all day resting on and off. Total inactivity causes BP to drop but not by the same amount.

Q. My daughter is in hospital with severe ME. They sit her up in bed for 10 minutes and she has fits and dystonic movements of her muscles. Should they continue with the sitting up/activity?
A. No, in his opinion don't continue it. You want to increase activity as much as possible, but if sitting up and no blood going to brain and is causing dystonia - not good. First you need to increase the circulating blood volume to normal, then decrease peripheral resistance, and increase circulation to the brain. Had good results from saline infusion - which could be a good diagnostic test. Give one or two units of normal saline by vein - expands circulating blood volume by one or two litres. Patient feels temporarily very well. The sicker you are, the shorter the time it has an effect. There is very little risk from normal saline infusions.

Q. There is a similarity in the symptoms of GWS and ME. Could there be a common denominator?
A. He hasn't seen any GWS patients and has no personal experience. The two illnesses do seem very similar and the pattern of symptoms seem similar too. CFS maybe due to injury to the brain and ANS dysfunction. There are many ways GWS can take place - became dehydrated, carrying heavy packs, not getting enough fluid. Quite likely they're related. Interesting minor symptom of CFS - those who have a very clear memory of getting sick say they urinated a lot in the first few days of being ill. Anti-diuretic hormone being turned off. Shows in ME; don't know if it shows in GWS.

Q. Are there any steps an individual can take to increase their own blood volume without medical intervention?
A. The Hopkins group has been vocal on this, and had some criticisms. They say you should eat salt to hold on to more water. If you have low blood volume and your BP is on the low side, they you should be safe to eat lots of salt. Some patients crave salt. Also try to drink lots of fluid. Some patients feel better from this, but usually only noticed in mild stages. Increase the plasma volume particularly. Astronauts have to helped out of the capsule - get orthostatic symptoms.

Q. Alcohol can act as a diuretic - could this affect blood volume?
A. Alcohol is very rarely enjoyed by ME sufferers. If you can drink - only mild ME. Alcohol dilutes the blood vessels and decreases the blood flow to the brain. It turns off adrenal hormone more than before. Next day - brain is shrunk and have lost circulating blood volume. To avoid a hangover drink three or four glasses of water before bed. Exacerbates ME.

Q. Can drugs be used to increase low blood volume?
A. Yes and no. Don't know any real answers. Using a number of different agencies - still preliminary. Theoretically. Alcohol and drug sensitivity - the drugs which make you feel ill are almost always vasodilators - widens blood vessels.

Q. Could starving the body of oxygen provide more red blood cells and therefore more energy?
A. High altitude sickness is similar to ME. Don't know. There are ways of doing it with medicines - safer.

Q. Have problems drawing blood.
A. Everyone has problems. Really hard to start IV with ME sufferers. The body is using the blood in central organs, and peripheral organs are poorly perfused. Difficult to get good veins.

Q. Daughter diagnosed with renal failure. Given cortisol. Side effects. Have you found this?
A. Half his patients have defect in adrenals. Adrenal failure causes fatigue. Addison's disease might be confused with ME. Cortisol and algesterone (adrenal hormone) (Florinef) - need to replace both.

Deficiencies cause severe fatigue.

Q. Daughter has developed hyperthyroidism. Will it regulate itself?
A. Don't know. Wouldn't use such a patient in research protocols. Have two similar patients - don't know if they have ME as well. If thyroid is regulated perfectly, after that symptoms could mean ME.