The gene mutation which causes at least some cases of hemiplegic migraine alters a calcium channel protein which is in the cell membranes of nerve cells.  This allows calcium ions to enter the nerve cells in greater numbers than occurs normally in response to a nerve impulse.  Research in mice which have been given this gene mutation shows that they are more likely to develop spreading depression in their cerebral cortex in response to a variety of stimuli than normal animals are.

It is likely, then, that people with migraine with aura have a slight biochemical change in the nerve cells of their cerebral cortex which makes them more likely to develop spreading depression. This spreading depression can perhaps be triggered by a variety of factors, depending on the individual, including some of the known migraine triggers. The spreading depression causes the aura, and then is followed by the painful phase of the migraine attack.

This  story is fascinating, although complicated. It illustrates how careful research is slowly unraveling the mysteries of migraine. The more fully we understand migraine, the more likely it will be that we can develop more and more effective treatments.

This consists of a slow moving wave of nerve cell activation which spreads across the cerebral cortex, and which usually starts in the visual areas of the brain (the occipital lobe).  This is followed by a longer lasting depression of nerve cell activity which follows the wave of activation. Together these can account, for example, for the bright visual lines which some migraine sufferers experience during their aura, and for the temporary partial loss of vision which then often follows. Spreading depression by its nature spreads rather slowly across the cerebral cortex, and this explains why the migraine aura symptoms also often spread slowly over minutes, either across the field of vision on one side, or in the form of numbness and tingling which spreads slowly across the hand and to the face.

In most people who experience migraine auras, the aura is usually followed by the headache attack.  Recent research has suggested that, at least in animals, enough irritating molecules of various types can be released as spreading depression sweeps across the surface of the cerebral cortex so that nerve fibers are stimulated in the nearby blood vessels on the surface of the brain.  This stimulation of nerve fiber endings on the blood vessels can start the painful, long lasting, cascade of nerve cell activity that produces the pain experienced during a migraine headache.

So, in conclusion, for people who have migraine auras, the aura itself seems capable of starting off the pain which make up the headache. It is unclear how headaches are triggered in migraine patients who do not have auras.  Something similar to spreading depression may happen on the surface of the brain, but in the case of migraine without aura, it may be somewhat different and not able to cause aura symptoms.

This has been suggested by studies on identical twins which have exactly the same genetic makeup. If one twin has migraine, the other usually does as well, but not always. It is unclear what differences in the environmental exposures or things that these twins have experienced determine why one develops migraine and the other does not. If this can be determined, it could help us both in the treatment and perhaps even in the prevention of migraine.

So, to summarize, migraine is caused by genetic factors. You don’t have migraine unless you have the migraine genes.  However, many other factors will determine how frequently individuals will experience migraine headache, or in fact if they will have them at all. Much remains to be learned about migraine, but already today much can be done to make the individual with migraine less headache prone, and to make the headaches that occur less severe and less troublesome.

They can bring on migraine attacks only in people who are predisposed to have them because they have migraine. The migraine disorder is caused by changes in a person’s biochemistry, which in turn are largely due to genetic factors.

The migraine tendency is therefore at least to some degree inherited, although the details of this have not been worked out for the common types of migraine. For one of the rare migraine types, however, which is called hemiplegic migraine, it has been proven that many although not all cases are due to mutations in two specific genes. These patients have migraine attacks similar to those of most migraine patients, except that they often have a prolonged aura phase which includes weakness on one half of the body as part of the attack.  One of the gene mutations which causes hemiplegic migraine is known to produce changes in an ion channel protein. These proteins determine the electrical properties of nerve cells. It is believed that small changes in the way the nerve cells of the brain react to each other can trigger recurrent aura symptoms and headache.

The research on hemiplegic migraine therefore tells us several things.