HeadWise HeadWise: Volume 4, Issue 4 - Page 19

M igraine and epilepsy are often mentioned together, in both research and patient care. Why? First, both migraine and epilepsy are paroxysmal disorders of the nervous system; they consist of recurrent attacks with return to baseline function between attacks. Second, attacks of migraine and epileptic seizures may have similar symptoms, such as changes in vision or tingling. Sometimes, it may even be difficult to distinguish certain types of seizures from certain types of migraine, especially those which cause confusion or loss of consciousness. Third, migraine and epilepsy are comorbid conditions—in other words, they occur together within individuals more than would be expected by chance alone. Individuals with migraine are more likely to have epilepsy, and people with epilepsy are more likely to have migraine. Finally, there are overlaps in the treatment of migraine and epilepsy. Research studies have identified genetic causes of some rare types of migraine, and separate genetic causes of some rare types of epilepsy. However, it was not known whether genetics might play a role in the co-occurrence of migraine and epilepsy, particularly common types of migraine and epilepsy. In our study, we attempted to determine whether the comorbidity of migraine and epilepsy might be caused by shared genetic causes between the two disorders – i.e. whether there could be genes that cause both migraine and epilepsy. In order to answer this question, we studied participants from a very large study of epilepsy, the Epilepsy Phenome/ Genome Project (EPGP). EPGP is a consortium of 27 medical centers in the U.S. and internationally, made up of several hundred physicians and staff who have worked together to enroll over 4,000 individuals with epilepsy and their family members. One part of the study enrolled families in which more than one person had epilepsy of unknown cause. Most of these families included two siblings who both had epilepsy or at least one child with epilepsy who had one parent with epilepsy. Our research was based on the concept that if two disorders share a common genetic cause, then if one of the disorders occurs in a family, particularly in many individuals in that family, then the other disorder is more likely to occur in that family. Using this principle, we predicted that more individuals with seizures within the family, made migraines more likely to occur in the enrolled EPGP participants. If in families with more individuals with seizure disorders, migraine was also more common, then that would provide evidence for a shared genetic contribution to migraine and epilepsy. We used this cohort of families in which two or more individuals had epilepsy. Detailed information was collected from interviews about participants’ epilepsy and headaches. In our interviews, we also asked a question about whether there were additional people in the family who had seizures, beyond the two people who had already been enrolled. “Was there anyone else in the family who has seizures? Who are they and what is their relationship to you?” We were able to use the information about these additional individuals with epilepsy to understand more about the genetics of migraine and epilepsy. We studied 730 participants, age 12 or older, in families with two or more individuals with seizures. Individuals were included who had either generalized epilepsy, in which seizures begin on both sides of the brain at once, or focal epilepsy, in which seizures begin in one part of the brain and may spread. Those with a known cause of their epilepsy, such as stroke or head trauma, were not included in the study. In families with four or more individuals with seizure disorders, (ie two or more additional affected individuals beyond the enrolled pair), migraines were three times more likely to occur, compared to families with only two affected individuals with seizures. This indicates that the stronger the genetic effect on epilepsy in the family, the higher the rates of migraine in the participants. This relationship between seizure disorders and migraine was only demonstrated when we examined the closest, ie first-degree relatives (parents, children, and siblings) with seizure disorders. When we included more distant relatives, the effect did not persist. This provided additional evidence that the strength of the genetic effect on epilepsy predicts the occurrence of migraine in these families. We then wanted to determine whether evidence for www.headaches.org | National Headache Foundation 19