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
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