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JUGULAR VENOUS NARROWING AND MS

 

A radiologist in Italy has claimed that as a consequence of venous narrowing there is a build-up of pressure within the brain and this leads to deposits of iron and the development of multiple sclerosis lesions.

It is further proposed that by doing an invasive treatment known as balloon angioplasty this would reverse those changes.


SCIENTIFIC BACKGROUND

The original study in Italy looked at one hundred consecutive patients with MS. Every single one of them was said to have this particular abnormality. There has now been a further study in the United States looking at five hundred patients where it is said that 56% of patients, that is approximately half, have this particular disturbance which also means that approximately half the patients do not have it.


CURRENT THINKING ON MS

The cause of MS is not known. We do know a lot however about the way the disease is generated and the associated immunological responses. For instance, the abnormalities on the spinal fluid testing confirm that there is an immune process involving the central nervous system. We do not know however if that immune response is primary, that is associated with cause of the condition, or secondary, that is a reaction to whatever process is taking place. We also know that there is an inflammatory process involving the myelin sheath of the central nervous system neurones. This inflammatory response is later replaced by a degenerative process. The MS Society website carries a lot of helpful scientific information as do a number of other websites in relation to the pathogenesis, that is the cause of multiple sclerosis.


TREATMENTS

We know that acute relapses of multiple sclerosis, particularly in the early phase of the disease, respond to high dose steroids. These are not a cure but there is no doubt that an improvement follows their use.

At the moment there are four drugs licensed for use in the treatment of MS in the UK and these work on the immune system. There are a number of other drugs currently in development and the next year will almost certainly see two orally active drugs fingolimod and cytarabine get their license for treatment again focusing on the immune process.


PROBLEMS WITH THE VENOUS NARROWING HYPOTHESIS

I do not want anyone to perceive that just because I am a neurologist I am hesitant about the current observations.

Over the years, and I have been interested in multiple sclerosis for more than three decades, we have repeatedly heard about a new wonder treatment or cure that has in effect just fallen by the wayside with appropriate scientific research.

We have learnt through bitter experience and also good scientific practice that any treatment needs to have a full scientific process adopted in order to know whether it works or not.

This isn’t just important from a safety perspective, there are also very significant costs involved in the assessment and treatment of a condition particularly if the treatment is
invasive, potentially dangerous and following expensive imaging, all of which would apply with regard to the current proposed treatments.

Having said that, if of course this treatment proved itself to be effective then almost no cost would be too much in my mind to deny the treatment to anyone with MS who so needed.

The scientific process involves setting up what is known as a double blind trial which means that those who receive the treatment don’t actually know what they are actually receiving and the people assessing those patients don’t know which treatment they have had.

This may seem unduly complex but in medicine we know that there is a remarkable phenomenon called the placebo effect which can apply both to a patient with any treatment and the assessing doctor who is the treating clinician who can falsely consider that hope that a treatment is the same as actual benefit. MS itself is particularly difficult to assess because the disease can go through remarkable periods of relative remission even at a time during the disease when it isn’t expected. For instance, invasive procedures do cause intrinsic steroid production within the body and that in itself may lead to benefit without there necessarily being an actual specific treatment response.

If the venous obstruction hypothesis is right then it will be necessary to try and explain why there are immune responses in the body that would not be caused by venous blockage. Why is there improvement with immune treatments? Perhaps more important why is it we don’t see MS like diseases in people who have problems with their venous return from the brain or spinal cord for other reasons?

Remember also that multiple sclerosis affects the spinal cord particularly in the cervical that is the neck region and a jugular venous narrowing hypothesis would need also to consider that there were various spinal venous blockages as well on both sides. Likewise, the question would need to be asked why would there be a narrowing on one side causing a problem on both sides of the brain.


WHAT TO DO NEXT?

If after reading about the procedures and what is being suggested you still feel encouraged to seek further guidance and/or investigation, then you will need further imaging.

As yet I do not know if such imaging will be available on the NHS and likewise there has been no indication from private insurers whether they will allow such testing to be carried out. You would require a further type of MR scanning. This is a non-invasive pain-free test as you know though you will almost certainly need to have an injection during the procedure. If an abnormality was found it would then be necessary to find a neuro-radiologist who could do so-called interventional neuro-radiology in doing a balloon angioplasty, that is widening a narrow vein and this would be on an experimental basis. At the moment I haven’t heard of any neuro-radiologist in the UK offering this treatment but perhaps this would be for future discussion.

My only experience in this situation is a recent young man who was well-versed in the scientific literature. We did do the necessary MR venogram on him looking at the veins both inside his head and in the neck. The study was entirely normal with no evidence of narrowing. Unfortunately, he had a particularly severe form of MS and so if the hypothesis was going to hold water then one would have expected that he would have had an abnormality.

I think my final comment on this matter is that we do need to watch this space so to speak and keep an eye on the further trials that are bound to take place and see what emerges.

The BBC had a news article on the 11th February 2004 indicating that someone they had interviewed was going to Poland to get the procedure carried out for a cost of £7000 (presumably plus all the air fares and hotel costs) so this is not an insignificant sum of money and hence there does have to be a degree of caution with regard to recommending first the investigation and then the possible invasive treatment without knowing for certain that it is going to be beneficial.

Obviously you can come and see me in order to discuss this in more detail if you wish.


MICHAEL GROSS, MA MD FRCP
CONSULTANT NEUROLOGIST