News from the AAN meeting:

For a large number of migraine sufferers (myself included) and neurologists (again, myself included) the development of the triptans for acute migraine was something of a miracle. But there are some migraines (and some migraineurs) that are not helped by these wonder drugs. That's why it is so encouraging that there are some fundamentally different medications coming down the pipeline.

Just to review, the triptans work by stimulating the 5-HT 1B/1D receptors. Sumatriptan (imitrex) was the first one developed. I use rizatriptan (Maxalt) for my own migraines. Others include zolmitriptan (Zomig) (I prescribe this a lot at my VA hospital because it is the only triptan pill on the formulary), frovatriptan (Frova), naratriptan (Amerge), almotriptan (Axert), and eletriptan (Relpax).

Here are some new treatment mechanisms that are getting close to the stage at which actual drugs may soon be approved (say in a year or two):

CGRP (calcitonin gene-related peptide) Antagonists. One of these, telcagepant, is actually in phase III trials right now. That means it is very close to the end of the testing process (again, a year or two).

Vanilloid receptor antagonists. Some of the vanilloid receptors are located on the same neurons as are the CGRP receptors. The vanilloid receptor antagonists seem to be less well studied and thus further from clinical readiness.

I do not have an in depth understanding of the mechanisms of either the CGRP or the Vanilloid receptors, but, apparently, blocking either the CGRP or the vanilloid receptors antagonizes the dilation of blood vessels located on the dura (a membrane surrounding the brain) by interfering with the action of capsacin (which is independently known to be a pain inducing substance). So this seems to make sense. The extra good part of both the CGRP and the Vanilloid story is that neither of these appear to induce vasoconstriction, which is sometimes a problem with the triptans (but it seems to me that blocking dilation of the dural blood vessels is somewhat akin to vasoconstriction, but I guess it is not direct vasoconstriction).

There is also a new type of serotonin agonist being studied. The new type activates the 1F receptors rather than the 1B and/or 1D receptors. The first prototype studied had too many side effects and was abandoned. But other such compounds are being developed.

Finally, some scientists are working on drugs that block nitric oxide synthase. But work on these is not as far along as work on the others. Frankly, I would think this could be dangerous because nitric oxide synthase is very beneficial. It is one of the good guys in helping to relieve cardiovascular and cerebrovascular constriction. I would be scared to block my nitric oxide synthase. But perhaps some smart person will find a safe way of doing it.

News from the AAN meeting: Headaches in Veterans returning from Iraq and Afghanistan

I treat a lot of Veterans at the VA, and I have been struck by the remarkable number of them who are returning from Iraq and Afghanistan with headaches. In most cases these are headaches that they never had before deployment. In the patients I commonly see, the cause seems to be exposure to a blast. The blast rarely involves being hit in the head with an object and it is unusual for the patient to have lost consciousness. Usually the source of the blast is an IED, an improvised explosive device, though it can be a bomb shot from a military weapon or some other type of explosion. I even thought of writing up some of the individual cases because some of them have very classic migraines that one rarely sees begin later in life. For example, I commonly see 50 year old patients who never had a problem with headaches. Then they were merely exposed to blast at quite a distance (sometimes more than the length of a football field), shaken a bit, but not knocked unconcious or otherwise visibly affected by the explosion. And then they they started having headaches which are often very similar to those of established migraineurs who have had migraines starting in childhood and extending throughout their whole adult lives. This impression of mine has now been strongly supported by a presention at the AAN. Brett J Theeler, M.D., of the Madigan Army Medical Center and his co-workers studied the case histories of 1000 returning soldiers. They found that 98% of soldiers who had suffered any type of blast injury, including the mild ones that I mentioned above. developed some type of headache problem. Many were migraines. Others seemed more like chronic tension headaches. There is a lot more to be learned about the problems associated with traumatic brain injury, even the type that initially appears to be extremely mild. From my perspective, however, there is a bit of good news. I have found that most of these headaches are quite treatable. I have gotten good results with standard headache medications in most of the patients. In some cases the underlying headache problem appears to be getting milder over time allowing me to taper down the levels of medication.

Just a quick post, almost a Tweet (but I'm not into "Twittering" at the moment) to mention that I am off to the American Academy of Neurology Meetings. They are in Seattle this year. Though I have been doing some research on Post Traumatic Stress Disorder (PTSD) and Traumatic Brain Injury (TBI) I did not write up an abstract this year. There is a good chance that I will have something instead for the Neuroscience meeting which is usually in November. If nothing else, I should come back with many things to add to "Updates in Neurology."

I am reactivating this blog to coincide with the rejuvenation of my "flagship" webpage, http://www.neurospotlight.com/. Though initially I had hoped to produce a constant flow of in depth analysis of neuroscience research, I did not have the time to make frequent detailed posts. In reactivating this blog, I am going to emphasize medical and scientific information gathering as well as whatever new and interesting things pique my interest in science, medicine, or even subjects further afield. Every now and then I will try to produce an in depth summary of current research as I did in my initial post in 2003. I think that was a pretty good post back then, though it is now quite out of date. I also will be adding some more links to other blogs. I just added four of them. They are the blogs of Joseph Kim MD MPH. They are

http://www.ultramobilehealth.com/
http://www.medicineandtechnology.com/
http://www.nonclinicaljobs.com/
http://www.medicalsmartphones.com/

The names are self explanatory, except perhaps for the third one, which is about non clinical jobs for physicians. The average person might say "How many physicians are interested in a job outside of clinical medicine?" The answer, apparently, is loads of them. Of course it depends on exactly what one considers nonclinical. Is teaching at a medical school nonclinical? Is public health nonclinical? Many doctors in those jobs would say "definitely not." But probably pure research, writing and journalism (even on medical related subjects), or development of software (even medical software) would be considered nonclinical. And, believe me, there are a lot of doctors going into those areas and many more considering it. In a future posting I may write a bit about what, I think, are the reasons.