A Cure For Chronic Fatigue?

Stimulated by kind words about this blog by someone on Scotgoespop here after a long lapse is a new post. Blogging on published research:

An article and editorial in New Scientist alerted me to the following research paper (free to view).


From the labs of Øystein Fluge and Olave Mella in Bergen, Norway. It’s a good example of serendipity in research. They were treating a patient who had lymphoma and happened to also have Chronic Fatigue Syndrome (CFS) with a drug that lowers the numbers of a type of white blood cell that produces antibodies. This patient’s CFS improved markedly as a result. Intrigued they did a study in a small group of other CFS patients (without lymphoma). This paper describes the result of a phase II clinical trial. Phase I trials in humans test for toxicity and define the effective dose. Phase II test initial effectiveness.

CFS, also known as Myalgic Encephalomyolitis (ME) or more pejoratively as ‘yuppie flu’ is characterised by extreme loss of energy, vague flu like symptoms, muscle pains and a general malaise. Sufferers were often referred to psychiatrists with fitful results or derided as malingerers. My first encounter was because the woman now my wife had it in Halls at university. A neighbour of mine said she would appreciate some visits and company so I began to stop by and we became more and more friendly and 29 years later here we are. Seeing her collapse in the dinner queue and elsewhere convinced me it was more than a mirage. She had been a keen sportswoman, playing hockey and cricket. She got better, it seems pregnancy is an excellent gradual fitness program.

But back to the research. The hypothesis is that CFS/ME is as was suggested back in the ’80s a post viral syndrome, but not one caused by the virus hanging around but by rogue antibody producing cells attacking the body: an auto-immune syndrome. The treatment is with rituximab which is an antibody which removes CD20 antibody producing cells. The advantage of an antibody treatment is that it allows you to remove specific subsets of white blood cells. Removing all of them would open patients to opportunistic infections.

So, 29 patients were treated with infusions of the antibody two weeks apart then maintenance doses over 3, 6, 10 and 15 months. Patients were followed up over 36 months (3 years), no short term study this. They compared them to a saline infused control group from the phase I trial.

What did they find? 18/29 treated patients had both self reported decreases in fatigue score and showed clinically significant improvements. After the full 3 years 11 of the 18 were still in full remission. There were minor side effects but no toxicity of the treatment.

So it seems partially effective. It remains to be seen if the 7/18 who showed improvement but did not maintain it just need longer treatments or a repeat treatment cycle. Similarly with the 11/29 who showed no improvement. Or maybe their CD20 cells have a slight variant of the target protein and the antibody is thus less effective.

This is not a magic bullet, the quickest responders to treatment took 23 weeks to detect and improvement. Most took 32 weeks. This is also not a final word, more of a better proof of efficacy from their Phase I trial and working out doses. They seem to have done the best scientific job they could have within the constraints they have. And finally, it doesn’t work for everyone.

But the headline result is it a strong indication that CFS/ME is a real condition and that it is an auto-immune post viral syndrome. With any luck they will get funding for a larger Phase III trial and it will be approved for general release. People with CFS/ME are generally economically inactive and this costs society a lot, they also impact on the health service. So any treatment that gets them active again is likely to be cost effective. Especially as CFS/ME generally hits young adults. The good news is that since rituximab is already licensed for lymphoma rather than being a new compound rolling this out into clinics will be relatively quick.

As for my wife, the developing embryo and foetus, acting a bit like a parasite, dials down aspects of the mother’s immune system to avoid rejection. Important as the embryo/foetus is only half related to the mother. It thus seems likely that as well as the gradual fitness program that is pregnancy that this dialing down of the immune system cured her ME, as we knew it then.

Light at the end of the tunnel, one cheer for serendipity, one for the researchers and one for the patient guinea pigs.


Judging Risk, And Benefit

The Royal College of Obstetricians and Gynaecologists this last week released a report offering advice to pregnant women which advised mothers to be to avoid things like tinned food or food in plastic packaging because of unquantified and unidentified fears. This has got me thinking, not for the first time, about risk and how our society is ridiculously risk averse and has forgotten that we should assess risks in a risk-benefit analysis, something we are equipped to do naturally. Every time you approach a corner in the road in your car you are doing this in assessing how fast you should take it. Back in New Zealand corners on open roads in the countryside have speed advisory boards on them giving a suggested safe speed to help. It means when you see 20 (km/hr) you know the corner is a hairpin, and there are some.

What the RCOG report writers have forgotten is to factor in the benefits of food packaging and what life was like before we started to use it, especially for pregnant women. One risk in particular is Listeria which can cause miscarriages. Campylobacter and a new one E. coli 0157 which are both nasty. All of these, and more, can be caught from food. Packaging has not removed these risks entirely, which is why you should wash store bought salad leaves, but they have lowered them enormously. To the benefit of many, but especially the very young, the old, pregnant women and the immune compromised.

To ignore the benefits of the packaging, less handling from humans some of whom will carry viruses and bacteria. Remember the norovirus that causes winter vomiting needs just 9 virus particles to start an infection.

So if anything pregnant women are better off buying fresh veg, fruit and meat in plastic packaging than loose material that could have been handled by anyone.

We tend to live in a world where no risk can be accommodated just like nothing bad can happen without someone being held responsible.

And that is before we get to popular media reports of statistical scientific risks. They shout X doubles the risk of Y but often fail to point out that your risk of Y is a fraction of a percent.

Life is never risk free, you might choke on a pretzel, or just about anything but you have to eat. Too much water can kill as happens to some back markers in warm weather marathons who overestimate how much they are sweating and drink too much, yet we have to drink to stay alive. We must breathe but the air is full of microparticles and they don’t have to be viruses. Polluted air such as in London gives me asthma, yet when we lived there I had to breathe it. There were benefits from living where we lived, the jobs my wife and I did and the schools the kids went to. Having said that we were also happy to leave.

So next time some report, even from a Royal College tells you about a risk, think about benefits too, and ask what the absolute risk is and if it is some fraction per 1,000 people or whatever. Go about your life worry free.

My Tentacled Avatar

Dumbo Squid80X80

I’ve been asked about the origin of my tentacled orange avatar. So a quick explanation. It’s a screen grabbed and cropped still from The Deep episode of the BBC’s excellent Blue Planet series. I was given the DVD set for my birthday once. I have long had a fascination with cephalopods (octopus, squid and nautilus) ever since as a kid in Dunedin I saw a common octopus up close in the university’s Marin Aquarium. I found young ones in the local rock pools and in summer large dead ones washed up on the shores of Anderson’s Bay Inlet and stank in the sun. I now know they are probably females who have expired after protecting their eggs until they hatched. The females don’t eat and die of starvation.

In The Deep episode we meet Grimpoteuthis the Dumbo octopus. So named because it appears to have ears like Dumbo, Disney’s elephant which it uses to ‘fly’ through the water. What fascinated me was how it moved, like a fish’s fin or a bird’s wing: flat on the downstroke and rotated edge on on the upstroke. It will have evolved from the long fin which fringes the mantle of squid. Ripples in it help cuttlefish and the like to manoeuvre slowly and carefully. Grimpoteuthis has taken this basic design, reduced it and obviously added greater muscular and nervous control. It’s roughly equivalent to the evolution of fish fins from those of sharks and rays. A shark cannot swim with it’s pectoral fins (the ones at the front that stick out the side like stubby wings), it can only incline them like wing flaps on a plane. Rays can undulate their long fringing fins like a cuttlefish. Bony fish (teleosts) have pectoral fins that can be rotated and moved and used for propulsion. Some fish can swim backwards using them, useful for backing out of crevices that might contain food. Those fish fins became our legs and hands.

Dumbo octopus have made a similar evolutionary change. Taking a simple structure and elaborating it for further function.

But a picture is worth a thousand words so here are some videos of Grimpoteuthis in action.

You won’t find Grimpoteuthis in a rock pool though, they are creatures of the very deep, the deepest Octopus known, some living as far down as 7,000metres. About as far down as Everest is high. They hover over the seabed or in the water column eating polychaete worms and small arthropods.

Can B Vitamins Help in Alzheimer’s?

Recent media reports on new research suggest taking B Vitamins (B6, B12, Folic Acid) can prevent the mental decline in Alzheimer’s. This piqued my interest so I decided to find out more. The original research is here (full text behind paywall). Reports in the popular media are here and here. But they are, unsurprisingly, a bit too upbeat and as we shall see the study does not look at the impact on Alzheimer’s. The excellent NHS Choices site has a much better report here and I would urge anyone wondering about a popular media health report to check NHS Choices. There are a couple of problems with that though.

So, what’s the story? 270 men and women over 70 with mild cognitive impairment were randomly split into two groups. One group got high dose B Vitamins (B6, B12, Folic Acid) while the other got a placebo. As NHS Choices says this is the best experimental design for this study. They took those B Vitamins or the placebo for 2 years and their brains were scanned at the start and end of the study. This is a secondary study, the first looked at whole brain shrinkage while this one used the same data to look at which brain regions were most affected. Brain shrinkage is associated with the mental decline seen in dementias and Alzheimer’s in particular. This study looked particularly at grey matter, cells rather than axon tracts (in electronic terms transistors not the wires that connect them). They found that the B Vitamin treated group had smaller shrinkages in brain regions associated with Alzheimer’s symptoms than the placebo group. It’s important to note that the vitamins did not stop the shrinkage, they just slowed it. They further found that patients with high homocysteine levels had the biggest effects in terms of shrinkage reduction. The brain regions the shrinkage was found in are those that shrink and are affected most in Alzheimer’s.  Continue reading

The Vicissitudes of Gout

Last year the penny dropped that my sore toe wasn’t a niggling running injury when the toe on the other foot began to hurt too. The GP confirmed my hunch and so to get rid of it and hopefully avoid a kidney stone I reformed my diet, again (I’m gluten and lactose intolerant, sadly). Things have been going well, the other toe is now pain free and the original one very much better.

I’ve recently had a bout of flu and was feverish for three days which made me dehydrated and that made my right kidney hurt and a new penny dropped. I couldn’t avoid a kidney stone because I already had one at diagnosis. In the latter stages of a long run I had felt my right lower back and thought it a muscle strain.

Diagnosis is like that, the most likely scenario is the one we naturally look to and there are good reasons for that too. As I’ve aged I’ve pulled more muscles and tendons in the last ten years than the previous 25.

In keeping with the realities of life as a middle aged runner I instituted some back strengthening exercises, largely latter planks. Which have done me no harm and probably something I should have been doing anyway. I’ve added it to the list of exercises I do to stave off pain and strengthen those muscles I used to be able to take for granted. All this knowledge of muscle anatomy has it’s uses.

So, I now must face the fact I have a kidney stone, it’s rumbling away right now so I shall have to drink something. I’m always drinking something. At least the GP took me seriously and I have been blood and urine sampled and had my kidneys and bladder x-rayed. The NHS here in Scotland can be efficient.

I know I’ve got off lightly and there are other horrors I could be enduring. But that doesn’t lessen my chagrin that the thing I had tried so hard to avoid had already snared me. I had better be on my best dietary behaviour then. It’s a good thing my wife likes chicken.