MigraineNews.co.uk

Introducing Tezampanel

Tezampanel is another new drug in development to treat migraine. At present it is administered by injection (like Imigran injections - also called Sumatriptan). It appears to work on the glutamate system, which is a new mode of action for a pain relieving migraine drug.

Phase IIb trial results being announced this week (June 26th-29th 2008)
The latest trial of tezampanel, as a migraine treatment, is to be announced at the American Headache Society Meeting in Boston later this week. According to its developers TorreyPines Pharmaceuticals subcutaneous injections of Tezampanel will show efficacy as an acute, pain-relieving drug for migraine. Previous work using an intravenous compund was well tolerated.

What position will this drug occupy?

With effective oral competitors (Aspirin, metoclopramide, buccal prochlorperazine, other oral triptans) this drug will probably compete with subcutaneous sumatriptan as a migraine treatment. If available to me today, I would try it in people reporting disabling attacks, in whom oral medicines have not worked. The side-effect profile could be crucial - triptans can make people feel unwell - chest or neck tightness for example. I’d be interested to hear of any significant side-effects or contra-indications for example. However, there is no shortage of people with migraines that are resistant to the currently available oral medications. Migraine affects 6% of men and 16% of women.

I will post more on this and other promising treatments from the American Headache Society Meeting.

In the second in this series I will explain how drinking a reasonable amount of water each day can help prevent migraine headache.

What is hydration?
The word hydration means to keep topped up with water. If you go dry that is called dehydration. Hydration is not a new, expensive therapy for migraine, it simply means that you should aim to drink plenty clean water each day to avoid dehydration.

How strong is the link betwen dehydration and migraine
Suprisingly, there are very few formal studies of how often migraine can be associated with dehydration. One remarkable effort on how water may prevent migraine headache was reported last year by Drs Martins and Gouveia from Lisbon, Portugal.

• An engineer with migraine that did not seem to go away with standard medicines set an alarm to go off every 15 minutes. This acted as a prompt to drink some extra water. This water was in addition to any fluid he would drink from juice, milk tea, or coffee. As a scientifically trained engineer, he kept precise records of the numbers of migraine headaches he experienced. The effect was dramatic - a 50% reduction in migraine episodes when his water intake increased from about 50ml per day to about 1500ml (3 pints).

I always mention hydration to my own patients - many do drink extra water, as they have worked it out for themselves - go dry = get sore.

Is there any danger in drinking too much water to prevent migraine?
If you have other medical conditions such as kidney disease or pituitary disease you may need medical advice before increasing your water intake. Also, your own climate is important - in hot climates, you may need to drink more water to prevent dehydration.

Is it really that simple?
Water is essential for all life forms we know. Your brain is no exception! So it is perhaps commonsense that your brain will not function properly if you are dehydrated. However, in migraine the difference between pain and no pain can be very slight. All it may take to provoke a headache is a slight reduction in the water content of your body to allow a migraine episode to break through. It is in some ways astonishing that there is not a lot more scientific study of how water influences the migraine process.

In brief how do I drink water to prevent migraine headache?
Small amounts regularly! Avoid the sensation of thirst. If you think you have a medical condition that affects your body’s water control (kidney disease, heart disease, pituitary disease, liver disease) you should discuss this with your doctor. As ever this information is not medical advice for you - it is an observation, relayed to you as news, to allow you to be better informaed on how to prevent migraine headaches.

Where can I read more about migraine headache treatment and prevention?
This is part 2 in a series called 7-steps-to-treat-migraine. The 7 steps are:

1. Sleep
2. Hydration
3. Exercise >/li>
4. Diet/Weight management
5. Stress avoidance
6. An acute treatment that works
7. A preventative treatment that works

Does migraine affect your child’s social development?
Parents of children with migraine are all too aware of lost days at school and lack of participation in sports/activities due to migraine episodes. But is there a more disturbing effect on long term social development?

New research into childhood social development and migraine
Dr Kathryn Vannatta from Columbus, Ohio, has published her research into friendships and social interaction in children with migraine, in the leading medical journal Cephalalgia. She studied about 70 children with migraine and asked over 1300 classmates and nearly 70 teachers about friendships - an impressive undertaking. They made come interesting observations which should reassure any parents of children with migraine.

Children with migraine may have fewer friends, but show no sign of social isolation
Younger children with migraine did have, on average, fewer friends. However, there was no difference in the number of friends among older children. More importantly, the older children actually had a greater tendency to be seen as leaders or popular - there was no evidence that children with migraine were “loners” or socially isolated from others.

Boys with migraine less aggressive?
I think an interesting observation is that boys with migraine were less likely to be perceived as aggressive or troublesome. Could this reflect the brain’s sensory sensitivity in migraine - the last thing you want to do if you have migraine is get hot and bothered or confront someone - you want to be left in peace!
Is this all just stating the obvious?
Any social science research runs the risk of this accusation. However, this has been a rigorous study of a large number of children. The conclusions are therefore robust and worth repeating. Children with migraine may, in their younger years, have fewer friends, but as they mature they are not going to end up isolated or excluded becasue of migraine - if anything they may be seen as leaders and more popular.

A full version of the article will require a subscription to Cephalalgia, which you are only likely to find in a university hospital library.

What is MK0974?
It is a new migraine treatment.
How does MK0974 work?
It works by preventing the release of the pain-inducing chemical CRGP. At the beginning of a migraine attack, CRGP is released into the lining of the brain (the meninges). CRGP starts a series of unfortunate events, called neurogenic inflammation, within the meninges. It is this neurogenic inflammation of the lining of the brain that leads to the intense pain of migraine. The theory is that if you can stop CRGP from getting out, you may block the development of neurogenic inflammation, and stop the migraine pain in its tracks.
How do we know that MK0974 really does work?
To develop the drug its license holders - Merck - have conducted several large studies. A similar compound called BIBN 4096 BS has previously been researched as a migraine treatment, published in the New England Journal of Medicine.
The final results of the most recent migraine treatment research on MK0974 are due next week at the American Headache Society Meeting in Boston, and the rumble in the jungle is that it might prove to have a powerful effect in treating migraine headache - I will bring you one of the earliest updates from the Meeting.
How is MK0974 taken?
In the research studies, Merck used a 150mg and 300mg gel-filled capsule. So it would be a capsule that is swallowed.
I have migraine, when will I be able to get hold of MK0974?
To be able to get hold of MK0974 as a regular prescription from your doctor or neurologist, MK0974 will have to be approved by the FDA as a migraine treatment. Once approved, you could obtain it from your doctor in the usual way. Sometimes a compassionate use scheme is set up by the manufacturer. Ina compassionate use scheme, a drug with proven efficacy, but which is still going through FDA approval, can be made available on a “named-patient basis” to people who have no other option. It can take a year or even more, to get FDA approval. I do not know if Merck are planning a compassionate use scheme.
I have migraine, will MK0974 be suitable for me?
You need to remember that there are already a lot of proven treatments for migraine attacks out there: Aspirin, metoclopramide, prochlorperazine, Migraleve, Anadin, Tolfenamic Acid, Sumatriptan, Zomig etc etc etc. To begin with I would anticipate reserving MK0974 for people with migraine who have had no benefit from the alternatives or in whom the alternatives are contr-indicated.
Will MK0974 prevent migraine?
As far as I can tell, this drug will not prevent migraine, but is designed to stop a migraine from building into a full-blown attack.
Please remember that if you are having a lot of migraine attacks to take steps to ensure that you are looking after yourself properly - don’t make migraine a drug-fest - look after yourself better. Remember migraine-7-steps?

Latest news on MK0974 will be automatically linked in here - so if you subscribe to this post with RSS you will be kept up to date automatically:

What’s the fuss about tonabersat?
Tonabersat is in the news. Last week, its developers, Westminster Pharmaceuticals, announced that it had managed to reach a crucial stage in the testing of the drug. They needed 500 people to take part in their research study, and that goal has now been achieved.
Why does this matter?
It matters because unless you can a large number of human volunteres, you will never be able to prove a drug works. Westminster are now able to test the drug properly. They intend to be able to report the full findings mid-2009. It also matters to their investors who will be anxious about whether this compund will ever see the light of day as a viable migraine treatment.
How does Tonabersat work?
Tonabersat started out in the late 1990s as an experimental treatment for epilepsy. However, research showed that it did not have good potential to treat epilepsy. Migraine and epilepsy are both conditions of hyperactivity or hypersensitivity of the surface of the brain (the cerebral cortex). So the developers (I’m pretty sure it was Glaxo-Smith-Klein) then thought it might be a useful migraine prevention drug. The traditional types of migraine prevention drug are beta-blockers, anti-convulsants and anti-depressants. Tonabersat is a new type of migraine prevention drug. It works by stopping chemical interaction between cells - by blocking a zone between brain cells called the gap junction.
Should I try and get Tonabersat to treat my migraine headache?
At the moment no - it is not available outside the trial being run (called the Tempus IIb study). Remember that treating migraine headache is not just about drugs - a lot of it is about looking after yourself : a good sleep pattern, keeping hydrated, regular gentle exercise, weight management/diet and stress avoidance. Medicines are only part, albeit an important one, of the picture. Remember Migraine-7-steps!

Oxygen consumption and migraine with aura
For over 50 years a reduction in oxygen consumption to the occipital cortex (the back of the brain where we perceive vision) has been proposed as a key problem in the development of Migraine with aura. The underlying mechanisms for this are being slowly unravelled.

Oxygen consumption and migraine without aura
However, the debate continues about the vast majority of migraine sufferers who do not experience aura - do they also have changes in oxygen supply i.e. blood flow within the occipital cortex?
PET scanning can measure oxygen consumption in areas of the brain. The latest study by Denuelle and colleagues from Toulouse examined the oxygen consumption in 6 people with spontaneous migraine attacks. These patients did not have aura (visual) symptoms at all. They were scanned using a PET scanner to see if they could identify reduced oxygen consumption as a factor or cause of migraine headache .  The results are very interesting. Even without visual aura symptoms Dennuelle and colleagues demonstrated reduced oxygen consumption in the occipital cortex.

What does this mean?
Like all good research it asks more questions. However, there is ongoing debate about the whether the original problem in migraine is in the cortex (surface of the brain) or in the pain generating structures in the brainstem (base of the brain). There is evidence for both.  This study from Toulouse suggests can be used to argue for a primary role of reduced oxygen consumption in the development of migraine, although the authors tend to dismiss this and favour a role for the brainstem. They argue that the evidence points towards a change within the brainstem switching off control of oxygen supply to the occipital cortex. In patients without aura they say the the reduced blood supply is just not severe enough to produce symptoms. Their argument implies that people who get aura are just having a more pronounced reduction in oxygen consumption - one that is bad enough to give symptoms.
Future work
Expect many more studies like this on the cause of migraine headache. The debate on whether brainstem or cortex is the primary problem in migraine will continue to run.

Here’s some scenes from the acclaimed flickr.com collection of Edward Dullard:

I will be attending the 50th Anniversary Meeting of the American Headache Society. The next MigraineNews.co.uk newsletter will contains highlights from the conference, and if I have time to post from Boston I’ll do so if there is anything noteworthy.

My eye has been drawn by a recent article on cardiac cephalalgia about to appear in Cephalalgia. Cardiac Cephalalgia - literally headache caused by your heart - is an uncommon non-migrainous headache disorder.

Exertional headache can be a symptom of heart disease. I have discussed this type of case with cardiologists, and there is some scepticism (why don’t people with heart attacks ever report headache is the first response?)

The first cases of headache related to heart disease appeared in the late 1970’s and early 1980’s. To my mind the most convincing case was a person who experienced cardiac cephalalgia at the precise point at which his coronary artery was occluded during an angioplasty procedure (Bowen 1993). Once the narrowed coronary artery was treated the headache stopped, so Bowen’s paper demonstrated in a live subject a direct link between reduced oxygen supply to heart muscle and the appearance of headache.

It should be said that the type of heart disease associated with headache is coronary artery disease, and that the headache is usually brought on by exertion. To prove that the headache is heart related, it should resolve when any underlying problem in the coronary artery is relieved. These are the criteria used by the International Headache Society for cardiac cephalalgia.
The 2 cases just reported from Korea in Cephalalgia are reasonably convincing, but it is difficult to understand how such a common condition (ischaemic heart disease) should only have 32 cases in the English medical literature from 1978. If my own practice is representative, I could vouch for one probable case in 4 years, and I know of one other attending a cardiologist. That is approximately 2 cases per 250,000 people over 4 years, or 2 per milion per annum.
While there is agreement that anatomical connections exist between the autonomic nerves from the heart and the sensory system for the head (the trigeminal system). If that is true, why so few headaches?
I suspect that the real reason is that no one has actually asked a representative sample of people the precise question - “do you experience headaches during angina attack or heart attack?” The only way to answer this conundrum is to survey a high risk population - such as everyone admitted to hospital with a heart attack or everyone attending for a coronary angiogram and find out if their angina or heart attack pain ever spreads into the face, eye, head or back of neck. This may be an important study to perform as 4/32 cases reported by Dr Wang in the forthcoming edition of Cephalagia had adverse outcomes from the headache- related heart disease.
It is important for neurologists assessing patients with exertional headache to be aware of the rare, but treatable condition of cardiac cephalalgia - sometimes the heart does indeed rule the head.

Here’s the contents of this June 2008 news:

1. Welcome
2. What is migraine?
3. 7 steps to treat migraine #1: Sleep
4. Latest Scientific development #1: Migraine brains are different
5. Latest Treatment News #1: Anti-convulsants can help control migraine
6. International Migraine #1: Indian Headache Clinic Mumbai
7. June 2008: Migraine Video of the Month
8. The MigraineNews.co.uk Migraine Directory: Listings for Migraine alternative treatments
9. 50th Anniversary Meeting of The American Headache Society, Boston June 26th-29th