Hypothalamic Deformity

Excerpts from Radio National's the health report

interview with Natasha Mitchell, 08/09/1999,

Hypothalamic Deformity

Peter Goadsby: We don't know what causes them in the sense of what the initial problem is. But our understanding of where the problem is has really taken off in the last 12 months, and particularly in the last couple of months. We have found that the area where the abnormality is in the brain, an area called the hypothalamus, which is in the deep part of the brain, it's the same area that's involved in what's called circadian rhythm, in the day/night rhythm. There's an area of the brain called the suprachiasmatic nucleus, a group of cells that is the master pacemaker if you like, it's the thing that apart from the fact that we get paid to get up in the morning, it's the thing which wakes you up and the thing which puts you to sleep. It's the thing which causes our body clock, that cycles over the slightly more than 24 hour period. Now the abnormalities we found in cluster headache are in the same part of the brain, and we think that in understanding this group of cells within the brain, we'll start to understand some very important principles about the way the body cycles; not only cycles from the day/night sense, but cycles in bigger cycles that go over months and years.

The two pieces of dogma that there've been about cluster headache are 1) that the brain was normal, what's called structurally normal, and this is true of primary headaches. It's dogma, a tension-type headache or migraine or cluster headache, that the brain itself is normal and that there's a functional, biochemical change that occurs when the attack gets turned on. The other piece of dogma about cluster headache, and this also applies to migraine, is that they were forms of vascular headache. That is to say that blood vessels in the head were in some way generating the attack. Now what we've found in recent times with the work we've been doing, is that both of those things are almost certainly completely incorrect.

The study that's just come out in Nature Medicine involves looking at the structure of the brains of patients with cluster headache and comparing them to a group of controls. What we were interested in doing is asking the fundamental question, Is the brain of the cluster headache patient normal in a structural sense, in an appealing sense, to a control, to a person in the street? And what we found was very subtle changes in this area of the brain called the hypothalamus.

The observations that we made were made using a newly-developed technique called Voxal based morthometry. Now what that does is it breaks down the brain of the control group and the patient group into voxals, volume areas that are about 1x1x1 millimetres. That volume is compared between the control group and the patient group, to see if there are any areas within the brain that are different between the two.

Yes, we used MRI, Magnetic Resonance Imaging scans which are standard brain scans, and then applied a very special analytic technique to compare the brains. When we compared the patients in the study with cluster headache to controls, what we saw was a subtle enlargement, an increase in the size of the posterior, the back part, of the hypothalamus. So a subtle increase in size in that group of neurones, nerve cells.

The first thing that the finding says to us is X marks the spot, if you want. It says to me that here is the place that I need to understand if I want to understand how cluster headache works. Conversely it means that here is the place that I need to understand if I want to treat patients better. The main implication for future treatment is knowing which group of nerve cells to study.
The simple answer to that is that it's not clear. We know that there's more grey matter, more neuronal density there, but we don't know whether the neurones are normal, whether there's more normal neuron, or the neurones are abnormal, because the technique doesn't allow that sort of resolution. What we need is pathologies, microscope pathology now. One of the nice things about the finding is that it tells us instead of looking around the brain for a needle in a haystack, it tells you which area of the brain that you need to be applying microscope technique to, to take the next step, which is to understand what this structural change means.

We think that the results have two generic implications. The first one is clearly cluster headache is the problem of brain function, not of blood vessels. That is probably true of migraine as well, and it's important that when we're thinking about migraine and studying migraine, that we think very hard about what's going on in the brain. I think simply thinking that migraine is a blood vessel disorder is almost certainly completely incorrect.

The second general, and really quite radical thing to think, if it's true that cluster headache, which has been one of the typical primary headaches where the brain should be normal, if it's true that the brain is subtly abnormal, then you really have to stand back and ask yourself the question, 'Is our most cherished belief about migraine or our most cherished belief about tension-type headache, that the brain is normal, is that correct? When you have a result like this that comes unexpectedly, you have to ask questions about the whole range of views that you hold.

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