To anyone but a neurologist, Patrick Rennich's migraines would
seem a curse. With perverse regularity, they strike after he plays
sports like soccer or basketball.
Not long before he's hit with nauseating pain on one side of his
head, Rennich experiences something called a visual aura - a
neurological disturbance that starts with a slowly expanding blind
spot near the center of his left visual field. Soon after, Rennich
sees static, like on a television screen.
The pattern is so predictable that Rennich, a 28-year-old
electrical engineer from Acton, Mass., can say, ``If you want me to
get a migraine with aura at two in the afternoon, I can.''
That's exactly what neurologist Michael Cutrer wanted. Based at
both Boston's Massachusetts General Hospital and Brigham and
Women's Hospital, Cutrer had been looking for someone like Rennich
for years. The neurologist hoped that a magnetic resonance imaging
(MRI) scan of such a patient's brain during the aura would provide
clues to what happens inside his skull.
Cutrer asked Rennich and his wife, Jean, to come to the YMCA
next door to his research lab. The couple played games of free
throws, running sprints back and forth across the basketball court.
After an hour, Rennich began to notice distortions in his vision
and hustled next door to the lab, where he lay prone inside the MRI
machine.
The MRI monitored the activity in Rennich's cerebral cortex,
specifically the sections that control vision. Later, the results
would be processed and color coded - red indicating areas of high
neural activity; orange and yellow showing lower levels; and white
showing the smallest amount.
According to the MRI results, an area of darkness appeared on
the image of his brain, indicating that the neurons in a small
region of the cerebral cortex were no longer transmitting visual
information. The region grew slowly, ``like ripples from a pebble
tossed into a pond,'' Cutrer says. Rennich's aura had begun.
Observing the brain's electrochemical activity during a migraine
aura is just one of the new routes to understanding the mysteries
of headaches.
Neurologists have long understood the physical evidence. Blood
vessels in the outer covering of the brain, the meninges, become
overdilated and hypersensitive to the blood coursing through them.
But finding the actual reason for headache pain has frustrated
neurologists for years.
With developments like Cutrer's MRI the mystery becomes more
vexing. The path to the pain is clearly marked, but why that path
exists at all remains unknown.
The activity of neurons, though complex, is usually predictable.
When the neuron is stimulated, sodium ions rush into the cell and
potassium ions rush out, leaving the neuron with a positive
electrochemical charge. This forces the cell to fire and thus
transmit information to other neurons.
In a migraine sufferer, however, neurons cease to behave
rationally. Cutrer believes that during Rennich's aura, his visual
neurons began firing slightly out of sync with one another and not
in response to a visual stimulus. On the MRI this firing pattern
resembled a wave rolling toward a shoreline.
The phenomenon, observed before only in animal experiments, is
called cortical spreading depression. The dark area on Rennich's
MRI, Cutrer believes, is a photographic record of this process and
reveals the progression of Rennich's expanding blind spot. The
scintillations of light that Rennich also saw in his aura, Cutrer
says, were most likely a result of sodium ions flooding and
overexciting the visual neurons.
After about 30 minutes, Rennich's aura subsided, and he felt
relatively normal for nearly an hour. Then his migraine began. The
visual neurons, which had fired abnormally during the cortical
spreading depression, had released large amounts of potassium ions.
Over time, the potassium spread from the visual cortex to the
pain-controlling neurons in the meninges.
These neurons, located in the walls of the meningeal blood
vessels, began to fire and released neuropeptides, telling the
brain to register pain and the blood vessels to dilate. The dilated
vessels then prompted the pain neurons to fire again. Essentially,
a pain-causing feedback loop was set in motion, creating the agony
of a migraine.
In people with chronic headaches, the brain appears to be
sensitive to light and stress, hormones or quirky things such as
eating a raw onion or playing basketball.
Chronic tension-type headaches are similar to the ones everyone
has at least occasionally - except that for these people they
strike almost daily.
Migraines tend to affect one side of the head.
Cluster headaches are an excruciating phenomenon that hits
mostly men. According to the first recorded description of such a
headache, dating from the 1700s, the sufferer felt ``as if his eye
was slowly being forced out of its orbit with so much pain that he
nearly went mad.''
Perhaps the first clue that the brain itself might be
responsible for headaches was discovered in the 1940s. Researchers
in Italy found evidence that the urine of those who had just
experienced a migraine contained breakdown products of the
neurotransmitter serotonin.
The finding hinted that serotonin played an important role in
migraine headaches, but the process remained a mystery.
The idea gained momentum when researchers found that injecting
anyone with a serotonin-depleting chemical caused a migraine, even
if the person had never suffered one before.
``The quest became to develop drugs that would mimic the effects
of serotonin,'' says neurologist David Dodick of the Mayo Clinic in
Scottsdale, Ariz. This approach paid off spectacularly, beginning
in the early 1990s with the release of a class of designer drugs
called triptans, sold under such brand names as Imitrex and Zomig.
For many sufferers, they can stop a migraine in mid-process.
With new research, more possibilities for tailoring effective
drugs have emerged. The most promising research focuses on
understanding the role of another compound - nitric oxide.
Neurologists studying headaches have long known an unusual fact:
When a heart patient places a small pill of nitroglycerin under his
tongue to ward off angina attacks, the nitroglycerin changes to
nitric oxide in the body and immediately dilates blood vessels in
the heart. Yet in some of these patients, it also triggers a
migraine attack within six hours.
Jes Olesen, chairman of the neurology department at the
University of Copenhagen, says that by unlocking the precise action
of nitric oxide, researchers may be able to develop even more
potent antiheadache medications than the triptans.
And increasingly, neurologists suspect that genetic
abnormalities may be at the root of some headaches. In the 1990s,
researchers traced the cause of a particularly rare type of
headache called familial hemiplegic migraine - which is passed in
families as a dominant trait - to a single gene on chromosome I9.
This chromosome codes for a component of a calcium channel in
neural membranes. By modulating the intake of ions into the neuron
cell, the channel controls when the neuron will fire. The mutation
leaves the nerves in the arteries around the brain in a constant
state of hyperactivity, causing them to register pain.
Meanwhile, practitioners and patients search for more immediate
remedies. The triptans are far from sure-fixes.
Some patients explore alternatives, trying everything from
acupuncture to the bacterial concoction known as botulinum toxin
type A, or Botox.
``This is the same stuff that people have injected into their
foreheads to temporarily paralyze muscles and reduce wrinkles,''
says Alex Mauskop of the New York Headache Center in Manhattan.
Plastic surgeons noticed that Botox injections had a surprising
side effect: They seemed to keep migraines at bay.
In the case of cluster headaches, causes and remedies are even
more obscure. Cluster headaches tend to come in cycles, hitting the
sufferer once or twice a day. They are more likely to strike
smokers, can be triggered by alcohol and can often be soothed by
breathing pure oxygen.
For now, patients are left to sort out their own treatments and
wait for the next phase of research for better drugs.
``I'll probably cool it on the basketball,'' Patrick Rennich
says. ``But I know now that the problem's not with me - it's just
with my brain.''
