Migraines and brain damage study

May 1, 2007

I don't have a link to this long article, but feel it's worthwhile for

us to know about.

Frances Gander

Athens, Ohio

University of Rochester Medical Center April 30, 2007

Migraines may be doing more than causing people skull-splitting pain.

Scientists have found evidence that the headaches may also be acting

like tiny transient strokes, leaving parts of the brain starved for

oxygen and altering the brain in significant ways.

The scientists say the work makes it crucial for migraine sufferers

to do everything they can to prevent their headaches. While avoiding

severe pain has long been a motivating factor, the scientists say the

risk of brain damage makes it imperative to prevent the headaches, by

avoiding a person's triggers for the headaches and by using

medications prescribed by doctors to prevent them.

" Normally, the focus of migraine treatment is to reduce the pain.

We're saying that migraines may be causing brain damage, and that the

focus should be on prevention, which will stop not only the pain but

also minimize potential damage, " said Maiken Nedergaard, M.D., Ph.D.,

the neuroscientist who led the research team. She is a professor in

the Department of Neurosurgery and a member of the Center for Aging

and Developmental Biology and worked closely with Takahiro Takano,

Ph.D., research assistant professor, who is first author of the paper.

By combining two recently developed imaging technologies,

Nedergaard's team was able to get an unprecedented look at the events

that happen in the brain of a mouse as a migraine unfolds. The team

uncovered a complex, unexpected tale of supply and demand regarding

blood flow and oxygen.

In short, the team found that the brain develops a voracious demand

for energy as the organ attempts to restore the delicate chemical

balance that is lost in the initial throes of a phenomenon known as

cortical spreading depression, which is thought to underlie many

migraines.

Even though the brain's arteries expand dramatically and make a great

deal more oxygen-rich blood available to meet the demand for energy,

some parts of the brain still wind up experiencing severe oxygen

shortage, or hypoxia. This causes parts of brain cells' sophisticated

signaling structures to disintegrate, similar to what occurs when a

person has a mini-stroke, or after a severe injury, or when blood

flow to the brain is completely stopped, such as during a heart

attack.

" In mice, the damage from these episodes looks exactly like the

damage that occurs to the brain from repeated TIAs, or transient

ischemic attacks, " said Takano. " It's long been known that patients

having a migraine attack are functionally impaired from the pain.

It's also been shown recently that with repeated migraines, a

person's cognitive abilities decrease. But actually doing damage to

the brain -- that is a surprise. "

Deborah Friedman, M.D., a neurologist who was not involved in the

study, says that a few studies have found that people who get auras

with their migraines are at increased risk for vascular problems like

heart attack and stroke. The Women's Health Initiative, for instance,

found that such women had a 50 to 70 percent higher risk of stroke

compared to other women. And a study led by Michel Ferrari of Leiden

University in the Netherlands showed that in women under the age of

45, those who suffered from migraines were much more likely to have

the type of brain damage done by a stroke, even though they had never

reported symptoms of stroke.

Friedman, a member of the board of directors of the American Headache

Society who has treated thousands of headache sufferers, echoes

Nedergaard's call for a greater emphasis on prevention.

" It's astounding just how many migraine sufferers do not see a doctor

and are not on a medication to prevent a recurrence, " said Friedman,

professor of Ophthalmology and Neurology. " It's estimated that less

than 20 percent of people who should be on preventive treatment

receive such treatment. Doctors and patients need to be diligent and

rigorous about using preventive medications for migraine. "

The work puts the visual disturbances known as auras that many

migraine sufferers report in a different light. The aura that

precedes the headaches for at least one out of four migraine

sufferers might involve floating black spots, flashing light, or some

other visual changes. Nedergaard says those disturbances might

actually be a visual sign that parts of the brain are short of oxygen.

In the work described in Nature Neuroscience, Nedergaard studied a

phenomenon known as cortical spreading depression, or CSD. The

process is now considered by many scientists as the basis for some

migraines, particularly those involving an aura. CSD is an electrical

event that initially involves a burst of intense activity among the

neurons on the surface of the brain, followed by a gradually

spreading wave of suppressed brain cell activity.

Many scientists believe that the phenomenon contributes to injury

from stroke and from traumatic brain injury as well as migraine.

While it's been widely recognized that CSD underlies some migraines,

Nedergaard's team linked the phenomenon for the first time to both

severe hypoxia and to damage to brain cells. As a result of CSD, the

team found changes to the synapses, the connections between brain

cells known as neurons. The team observed that nerve cells swell and

begin to disintegrate, with neurons shedding important connections

known as dendritic spines -- the tiny extensions of an individual

neuron's body that usually number in the thousands within a synapse.

Mice in the grasp of a migraine lost up to three-quarters of these

important cellular components.

Ironically, the team found that during CSD, even though blood flow in

the brain overall increases dramatically, some parts of the brain

still suffer from a lack of oxygen.

The problem begins as the brain tries to recover from CSD, which

throws the proportion of crucial ions like potassium and sodium out

of balance, taking away the brain's ability to function efficiently.

This change in the proportion of chemicals gradually sweeps across

the brain like a slowly spreading wave.

The brain, in turn, is under tremendous stress, developing a

voracious appetite for oxygen as it works frantically to restore the

proper chemical balance. Oxygen-rich blood pours into the area to

allow brain tissue to work overtime; the team found that the brain's

arteries expand by more than 50 percent to keep up with the demand.

It's at this stage that Nedergaard observed the unexpected: While

blood flow increased, bringing more oxygen overall to the brain,

there were still pockets of severe hypoxia. The brain was working so

hard to restore the chemical balance and to resume normal cellular

function, using so much oxygen, that the brain simply couldn't keep

up with the demand.

" Basically, even though the body has really stepped up the

availability of oxygen, the brain's demands for oxygen are suddenly

so great that the blood vessels in the brain can't keep up, " said

Nedergaard. " It's a mismatch between supply and demand. "

Brain tissue closest to the oxygen-rich blood vessels soaks up the

oxygen as fast as they can, leaving tissues further away with a

diminished supply. It's like a pride of lion cubs fighting for their

mother's milk -- a few may get nudged away, go without, and will

eventually die. In a brain in the midst of cortical spreading

depression, brain cells closest to oxygen-rich blood vessels survive,

while cells further away don't get access to the oxygen and are in

jeopardy.

" People have always thought that in order to treat a migraine, you

treat the pain. We're going beyond that. Migraines could be

dangerous. The focus should be on prevention, " said Nedergaard, who

notes that by the time a person feels pain or notices a visual

disturbance, the changes to the brain are already well underway.To

make the finding, the team used a sophisticated laser system known as

two-photon imaging to look at the activity of live cells in the

intact brain of a mouse. They combined that with a new technique to

precisely measure how brain cells allocate and use energy.

May 1, 2007

Dear Frances,

An important article. It is anecdotally significant, that my wife suffered

splitting migraines all throughout the 70s and 80s before she had her first

seizure in 1990. No foci were ever found, but I am convinced, that from a

western perspective, that her seizures are a functional rather than a structural

disorder, and involve oxygen deprivation from self-induced stress.

Yehuda

" Frances L. Gander " <threetreasures wrote: