York Conference June 2004 - Dr Andy Wright

If I'd known what I'd known a year ago - I should have just walked out the door! It's certainly been an exciting year – and it's all Marie's fault! (Marie Kroun).

Bill's (Bill Harvey) been staying with me all week. My presentation of symptoms wasn't quite as traumatic as his. I was in the bath. I'd had 6 pints of Tetley's. I was a medical student staying in a really grotty flat. I got parathesiae in my feet and muscle twitches.

But that's not why I got into CFS. I got into that because patients of mine went to see psychiatrists and were told they were hyperventilating – despite the fact that their lives were totally wrecked. I thought there must be a bit more to this illness than hyperventilation.

Eventually, I turned up here last year because I'd already started to think about whether ME and other disorders were bacterial. I talked to a few people about this and started to do some work with Milton Wainwright and got there eventually.

My experience is exclusively in ME. I still am, though I don't do very much for them now because I have such a different view of the illness now that they think I'm even madder than they thought I was. Because when you have to write articles and answer doctor's questions and not mention the word borreliosis, it's really difficult! So I've got to tell black lies all the time. For example, when they say, "Why do you get this in ME?" I can't say, "It's obvious. It's cause you've got vasculitis." But I'm still one of their medical advisers.

We did a literary search which was quite a useful exercise for me, basically showing research into CFS and ME is not very good and never has been mainly because of funding, and because if you didn't have the words Member of the Royal College of Psychiatry after your name, you didn't get published anyway. That's still the problem.

Because no-one knows what causes ME and people just look around for epiphenomena – things that seem to be going wrong in the body – hoping that they stumble across a cause.

And these are some of the things that have been published that I've noticed.

Circadian rhythms – one of the first things I got into. It seemed obvious that people's ability to control their internal environment was disturbed. They didn't sleep very well, they were tired, they couldn't adapt to change be it temperature or exercise or whatever. I looked at melatonin – the hormone which helps put you to sleep. I found that 75% of my ME patients no longer made melatonin at all. It had gone, which is a major, major thing. Because you can put somebody underground in a cave for 4-5 months and it might move their melatonin curve a bit, but they don't stop making it. So something profound was happening in the brain. Some people were making it in the middle of the afternoon, but 5 times too much and they felt very jet-lagged.

There were lots of studies looking at cortisol, stress-hormone levels, and DHEA levels. Things within the normal range, but they didn't change over time as you'd expect them to.

There was quite a nice little PhD thesis that came out on adrenal glands by ? Scott. A lot of ME patients have adrenals that are 50% shrunk in size. It's an observation really.

Then there was a whole lot of stuff from Marti Pall, a biochemist from Washington. He found that oxidative stress and free radicals were high. It's like when you leave iron outside and it gets wet and rusts – free radicals rust us from the inside. The reason we take vitamins is to stop that really. People with CFS have high levels of peroxinitrite particularly. This nasty little thing stops us making ATP, it stops us making energy because it uncouples ATP in the mitochondria, so you just can’t make the energy you need anymore. It turns out it's high levels of nitric oxide synthase which relates to a chronic bacterial infection. Marti didn't know why they had high levels, but interestingly, he said the only thing which will stop it is high dose vitamin B12, which is one of the fashionable treatments in ME.

David Berg produced some work that showed that 85% of ME patients have sticky blood in standard laboratory tests. He felt it was a mild form of disseminated intravascular coagulation. He postulated that it was of infectious origin, but he didn't know which one it was. He said he has data to say that 50% of these are infected because of genetic predisposition. i.e. whatever is making you sick is making you sick because you are genetically predisposed to sticky blood. So somebody else might get it, but if their blood doesn't thicken up, they don't get sick. And that might be true to some degree.

So heparin is a treatment, warfarin is a treatment, and I've been using that occasionally - not as much as I used to – and it does work very well in some people. You only use it in very small doses. You don't make their blood thin, you just make it normal.

There is an upset to the sympathetic nervous system with CFS/ME. There are two balancing systems. The parasympathetic nervous system is when you've had a couple of pints and you're lying in front of the telly and you've had a meal and you nod off. The sympathetic nervous system is the Fight or Flight response. People with CFS/ME disorders always tend to have overactive sympathetic nervous systems, so something is stressing the body. Some psychiatrists say it's your inability to cope – you poor, poor person! The stress response in the body comes from any stress – dietary, environmental, toxic, bacterial - it doesn't have to be psychological. Your adrenal glands do not know – they're not intelligent. They can't say, "Oh, we can ignore that one, it's only the wife!" But the sympathetic nervous system has profound effects on the immune system. It opens up membranes, particularly the blood-brain barrier. It actually makes lymph flow the wrong way because sympathetic nerves plug into the lymph vessels. So if you've got overactive sympathetic activity, your major lymph vessels which drain the toxins will go into spasm (this work was done by Manchester University and Ray Perrin). This is one of the reasons why you don't get well because you're not actually physically shifting these inflammatory cytokines or possible bacterial lipoproteins from your body because your lymph is all clogged up. One of the things which help is correction of mechanical lymph drainage by lymph massage.

And there's a whole host of immune dysfunctions which have been found, but I'm not going to go into that – because I don't understand them! There's a couple in there which don't seem to tie in with Borreliosis. But I don't know if that's because of how the studies were done. I don't know the patients, the methods, the assays; so I can’t comment.

One of the things I'm currently interested in is that people with fatigue disorders have a lot of abnormal tryptophan metabolites. Trytophan is an amino acids derived from proteins in your diet. It normally makes serotonin and melatonin in your brain, but instead it makes this toxic trans-Indolyl-Acryloyl Glycine which damages membranes. This is work which is still ongoing with Roz Anderson.

Basically we've seen that all these patients have disorders with homeostasis, homeodynamics, they can't co-ordinate control. It’s all to do with the problems with the interaction which is seamless between the nervous and endocrine systems and loss of rhythmical activity. But still no cause.

Now there was something which gave us a clue as to what might be going on like Teitelbaum's study, which is a double-blind, placebo-controlled trial, where he took 2 groups. He gave half the placebo, half active therapy, and he treated all the hormone deficiencies like sleep disorders, possible hypotension, any bacterial infections he could find in the gut, and any borderline nutritional deficiencies. Although, on their own, none of these were major, he said, "Let's treat every single deficiency or abnormality we can find, and we'll see what happens." Of those in the active therapy group, many many more got better – much better – than those in the placebo group. So just by treating the symptoms, he was getting people well. At the end of the day, a third did very well, a third did moderately well, and a third stayed the same. Very rarely did anyone get worse. I did this for a long, long time, but still, nobody got really really better. But obviously, by correcting some of the homeostasis and homeodynamics and getting the system working better, people were getting better.

Now, when I was looking at the urine tests from Sunderland, we sent everybody a questionnaire. These people had been diagnosed with various illnesses. There was CFS, ME, fibromyalgia. We were looking at the symptoms these people had and basically they all had the fatigue and the cognitive problems, but there were some symptoms which weren't in the definition of these illnesses which kept cropping up and cropping up: tinnitus; painful reaction to sound; disliking of lights and sounds; sinusitis; irritable bowel.

And it seemed from this little study that maybe these disorders were variations on the same thing, but people just manifested them in different ways.

Obviously I now know that clearly these are all symptoms of Borreliosis as well. And when I go to talk to ME groups I often say, "Right, put your hands up if you've got any of these symptoms, or if you've got 5, 6 of them, etc., and they've all got their hands up by the end. And of course these are all symptoms of chronic Borreliosis as in the recent archived general infectious disease supplement on chronic Borreliosis. So the symptoms are exactly the again. So another clue...

But a lot of these symptoms aren't in the definitions of ME and CFS, and these are the definitions that are around, and more money has been spent on actually defining them than trying to find out what's wrong with people. The Canadian consensus criteria which has just come out is probably the best. But none of them will actually say what's wrong with you – they just tell you what symptoms you've got. But the original Ramsey definition in ’56 was an infectious disease when you read it – it was acute onset: gastroenteritis, upper respiratory dizziness, and tinnitus. People were suffering something really really infectious – it just screamed at you. 90% got better, 10% remained chronically unwell.

The major setback was in the early 1990s when a group of psychiatrists got hold of this and decided to look at CFS and ME. They changed the definition to the Oxford criteria, and most of the published work in the UK is using this criteria. And the only thing you have to have according to this criteria is fatigue. The definition says you may have myalgia, you may have sleep disturbance, etc., but you don't have to. You just have to be fatigued. It's an incredibly broad definition. The political and social implications that a simple change of definition has had are huge. Such so, we now have the chronic fatigue clinics set up – there are 12 clinics now - and some people in Action for ME got a lot of money and set up fantastic clinics and all the ME patients get 'treated.' There is £8.3 million over 3 years for all the ME patients – so what you going to do with it? Well, the psychiatrists are running their CBT/graded activity studies again – they got £12 million for that in the clinics.

Anyway, in ME – no consistent infection has ever been found, but patients kept reporting infections like Staph, Chlamydia, Mycoplasma. I did a little study of endotoxins and about half of ME patients had higher levels than normal. But none of these were persistent and none were consistent, and there's no serial measurement which is always nice to have. The first one we got into was a Staph – with Milt (Milton Wainwright) in Sheffield - as an opportunist infection. We've grown it from about 20% of patients' blood. Lots of studies were done, for example by Prof Roberts who said that if you treat the Staph, the pain goes. And Walter Torello cultured his own blood and treated it with Fowler's solution, and he got better, but I think he killed the Borrelia with his arsenic!

But anyway, I got Walter (Torello) to look at 78 peripheral blood stains of my CDC defined CFS and ME patients. He came back and said 52 have got micrococci (either alone or as a co-infection), 33 have got Babesia-like bodies, 10 have Ehrlichia, 1 Bartonella and 9 were negative. So it sounds like a zoonotic infection really. The only thing is that Babesia is puzzling. I only see 10% co-infected with Babesia in the UK (by Bowen testing). And Borrelia looks like Babesia on a stained film, so it's difficult to say which one it is.

[Shows a slide] This was a slide that changed everything when Marie (Kroun) flashed it up last year (at the conference). Because I've got one of these microscopes that magnifies about 10x more than normal and dark field. She said this is how spirochaetes go through life cycles and these here and there – that's what I see all the time in my patients within the first hour of taking a drop of blood. And I didn't know what they were... and then this slide.

So what happened next was a decision to leave the blood overnight and see what happened, and when that happened, you got everything – you got the growth into spirochaetes, but it's not spiral, and this is very important to get across. It's more like a sidewinder snake. The corkscrew is culture Borrelia, not in vivo Borrelia. Just a bit again about pleomorphism – there are 3 forms of Borrelia: normal (seen in serum), the spirochetes (spheroblasts) and the cyst form. And I call another form 'transitional' as it is changing from one form to another –because I've seen it and I have to call it something. Now how do I know it's Borrelia? Well, it's exactly the same as I've seen in sero-positive Lyme patients with fluorescent antibody detection.

[Shows a slide] This is from a drop of blood left overnight and these have emerged out of the blood cells. And I've got a video showing them emerge, which is really mind-blowing stuff. [Shows another slide] This is spirochetes entwined with blebs – sidewinder spirochetes. I have watched these for hours and hours and hours. I've seen them grow from a peanut to a dumbbell to a 20-30 microns to 400 microns – these are extreme pleomorphic forms. Artifacts don't do that – they don't grow, they don't change shape, they don't develop internal structures, that are reproducible. But this doesn't happen in the body, because this is extreme pleomorphism because the blood is under a slide and there is low oxygen.

One of the big questions is 'Is intra erythrocytic Borrelia a problem?' Or is it only when Borrelia is in white cells that it's a problem? I get a feeling from looking at hundreds of these slides that when you see Borrelia coming out of a white cell, that's the sickest people. You can get asymptomatic carriers where you only see it coming out of a red cell. Bill's (Harvey) thought a lot about this and it maybe that Borrelia enters in the red cell in the bone marrow and it comes along and because our red cells only die every 120 days, they just drip feed Borrelia. I think maybe 5% of red cells are infected so there's a constant drip feed into the system, then they become tissue invaders, and it just keeps going and going and going.

We have a research group. It's going to be expanded. Milt (Milton Wainwright) is going to do all the culture and electronmicroscopy and fluorescent microscopy. Joanne Mitchell - a good microbiologist – is going to help us with western blots. We're going to try and get Nick Harris to help us with the set up of this. Roz Anderson is going to do urine examinations for chemicals. There may be a biochemical Borrelia marker in the urine, a consistent marker. We also want to look at all the different fatigue syndromes. For example, is Gulf War Syndrome the same? And do multi-sensory studies.

In the end it's a treatable illness and that's what it's all about. Shall I read a letter I had recently? This was a lady who was very sick. I saw Borrelia-like spirochaetes in her blood. She did the Bowen test and was positive. David's (David Owen) looked after her ever since. She wrote to me this week. She says, "I just thought I'd let you know how I'm progressing with my treatment. Seeing Dr. Owen in 2003 has benefited me immensely. I've been taking Doxycycline for 6 months, plus Samento and supplements, and made a remarkable recovery." This lady was bed bound, fed by her family, and completely wrecked by this illness. The first 3 months she regressed to being spoon-fed by her family and it took her 5 months to get past being bed-ridden. Now she's fully mobile. This lady had been told she had ME –tough. She had bizarre neurological symptoms for 2 years. She's not right yet, but she's a long way to getting right.

That's what it's all about. And I feel it will get there eventually. The big problem is how? And the big problem is Political.