Why do humans have so many headaches? Stasha Gominak, M.D. East Texas Medical Center Neurologic...

Why do humans Why do humans have so many have so many headaches? headaches?

Stasha Gominak, M.D.Stasha Gominak, M.D.

East Texas Medical Center Neurologic InstituteEast Texas Medical Center Neurologic Institute

700 Olympic Plaza, Suite 912 Tyler, Texas 75701700 Olympic Plaza, Suite 912 Tyler, Texas 75701

April 25 , 2014April 25 , 2014

Headache is Headache is described in every described in every

human society human society throughout written throughout written

historyhistoryWhy would it be so common?Why would it be so common?

Headache is a genetic Headache is a genetic disorderdisorder

Why would we want to pass Why would we want to pass on these horrible headaches on these horrible headaches

to our kids?to our kids?

We think that genes We think that genes providing a survival providing a survival

advantage get spread advantage get spread throughout the throughout the

populationpopulation

What would be the survival What would be the survival advantage of having a headache?advantage of having a headache?

Could the genes for Could the genes for headache convey some headache convey some other thing that might other thing that might

improve survival?improve survival?

Why have we taught Why have we taught each other that each other that

“normal headache” “normal headache” and migraine are two and migraine are two

different things?different things?

What if headache and What if headache and migraine are the same?migraine are the same?

What if “migraine” and What if “migraine” and “normal headache” occur by “normal headache” occur by

the same mechanism? the same mechanism?

Why do my patients use the Why do my patients use the phrase phrase

“normal headaches”?“normal headaches”? Why do we think it Why do we think it

is “normal” for the is “normal” for the head to hurt without head to hurt without injury?injury?

Why haven’t we Why haven’t we fixed our most fixed our most common neurologic common neurologic problem?problem?

Are we thinking Are we thinking about it the wrong about it the wrong way?way?

What is the evidence that What is the evidence that migraine and headache are on migraine and headache are on

a continuum?a continuum? All migraine sufferers also have “normal headaches”.All migraine sufferers also have “normal headaches”. When the triptans became available (triptans are When the triptans became available (triptans are

migraine medications; sumatriptan, rizatriptan, migraine medications; sumatriptan, rizatriptan, naratriptan…etc.) we told our patients ”save these naratriptan…etc.) we told our patients ”save these for your migraines” for your migraines”

Their response: “if I take the medicine soon enough Their response: “if I take the medicine soon enough it works.” it works.”

The patients found that triptans worked for their The patients found that triptans worked for their milder, “normal headaches” before they grew into a milder, “normal headaches” before they grew into a “migraine”.“migraine”.

The triptans work for “normal The triptans work for “normal headaches” tooheadaches” too

We may not prescribe triptans for normal We may not prescribe triptans for normal headaches because they’re very expensive, but headaches because they’re very expensive, but they they dodo work well. work well.

That probably means serotonin plays a role in That probably means serotonin plays a role in “normal headache” as well as migraine “normal headache” as well as migraine

Baby migraine, which is “just a headache”, Baby migraine, which is “just a headache”, may grow into a bigger headache that acquires may grow into a bigger headache that acquires other features which make it recognizably other features which make it recognizably “migraine”. “migraine”.

What do we know about the What do we know about the mechanism of the triptans?mechanism of the triptans?

Triptans work on 1B and 1D serotonin receptorsTriptans work on 1B and 1D serotonin receptors 1B and 1D receptors are feedback inhibitors; 1B and 1D receptors are feedback inhibitors;

they decrease serotonin release.they decrease serotonin release. Does that mean that the mechanism of action Does that mean that the mechanism of action

has to do with the blood vessels? (Which is what has to do with the blood vessels? (Which is what we’ve been taught.)…… Not necessarily. we’ve been taught.)…… Not necessarily.

Serotonin appears in many areas of the brain. Serotonin appears in many areas of the brain.

Serotonin ReleaseSerotonin Release Most of the serotonin Most of the serotonin

measured in the brain measured in the brain originates from the originates from the raphe nuclei in the raphe nuclei in the posterior brainstem.posterior brainstem.

Serotonin acts like a Serotonin acts like a neuro-transmitter as neuro-transmitter as well as a hormone. It is well as a hormone. It is released along the axon released along the axon as well as at the nerve as well as at the nerve terminals bathing the terminals bathing the entire brain in “happy entire brain in “happy juice” every few secondsjuice” every few seconds

Sleep and SerotoninSleep and Serotonin

REM sleep and triptans have something in REM sleep and triptans have something in common: They both drop serotonin levels. In order common: They both drop serotonin levels. In order to enter REM sleep we must have low serotonin. to enter REM sleep we must have low serotonin.

Serotonin is high when we are awake but low Serotonin is high when we are awake but low when we enter deep sleep.when we enter deep sleep.

Your brain wants to be very, very sure that you are Your brain wants to be very, very sure that you are indeed sleeping before you start to dream. indeed sleeping before you start to dream. Because REM and awake are similar states the Because REM and awake are similar states the serotonin level helps the brain know which state serotonin level helps the brain know which state you’re in .you’re in .

Refs: 1. 2

Migraine and SleepMigraine and Sleep If our patients have told us for the If our patients have told us for the

last 100 years that getting into deep last 100 years that getting into deep sleep is how they “break” the sleep is how they “break” the headache, why are there so few headache, why are there so few articles showing us what the sleep articles showing us what the sleep looks like in migraine sufferers?looks like in migraine sufferers?

Why have we been told that sleep Why have we been told that sleep disorders only happen in fat, old disorders only happen in fat, old men?men?

Migraine and SleepMigraine and Sleep I became interested in sleep 10 years ago when one I became interested in sleep 10 years ago when one

of my young, normal weight patients insisted that I of my young, normal weight patients insisted that I send her for a sleep study. Her husband said she send her for a sleep study. Her husband said she “snored like a train”.“snored like a train”.

She had been on four preventative medicines over a She had been on four preventative medicines over a period of two years and still had daily headache. period of two years and still had daily headache.

She had severe sleep apnea and 6 weeks of sleeping She had severe sleep apnea and 6 weeks of sleeping with CPAP mask completely cleared her headaches. with CPAP mask completely cleared her headaches.

For the following 5 years I ordered sleep studies on For the following 5 years I ordered sleep studies on all of my daily headache patients. They were all all of my daily headache patients. They were all abnormal.abnormal.

Migraine and SleepMigraine and Sleep Ten years later there are still few studies looking at the Ten years later there are still few studies looking at the

results of sleep studies in migraine sufferers. Why? results of sleep studies in migraine sufferers. Why? Academic neurologists who are sleep specialists do not Academic neurologists who are sleep specialists do not

usually study migraine?usually study migraine? Those who are migraine specialists do not study sleep?Those who are migraine specialists do not study sleep? Those who study astrocyte anatomy do not see Those who study astrocyte anatomy do not see

patients? patients? Most physicians feel more comfortable going along with Most physicians feel more comfortable going along with

the currently accepted medical theories.the currently accepted medical theories. But what if the theories don’t explain what the patient But what if the theories don’t explain what the patient

feels?feels?

““Explanations” of headache Explanations” of headache are theoriesare theories

What the patient experiences is the only “truth”. What the patient experiences is the only “truth”. Headache patients are, by definition “normal” ; Headache patients are, by definition “normal” ;

normal scan, normal neuroanatomy. They don’t die normal scan, normal neuroanatomy. They don’t die from headache so there are no autopsy studies.from headache so there are no autopsy studies.

Every one of our explanations is made up; it’s a Every one of our explanations is made up; it’s a theory. theory.

There is no user’s manual that confirms which is There is no user’s manual that confirms which is the real “truth”.the real “truth”.

But my explanation of cause But my explanation of cause willwill direct my search direct my search for how to fix it.for how to fix it.

Sleep study results in Sleep study results in migraineursmigraineurs

Many of my migraine patients don’t sleep normally. They have Many of my migraine patients don’t sleep normally. They have various forms of insomnia, “light sleeper”, “not a morning various forms of insomnia, “light sleeper”, “not a morning person”.person”.

All of them had abnormal sleep studies, just not necessarily All of them had abnormal sleep studies, just not necessarily apnea. apnea.

The most common sleep study results in my young, healthy The most common sleep study results in my young, healthy migraine patients were delayed onset of REM, decreased REM migraine patients were delayed onset of REM, decreased REM and REM related apnea. Some slept for 10 hours and had no and REM related apnea. Some slept for 10 hours and had no REM.REM.

We have not been treating migraine by treating sleep because We have not been treating migraine by treating sleep because we haven’t known how. we haven’t known how.

The sleep medications we have do not produce normal sleep.The sleep medications we have do not produce normal sleep. But if you know how to fix the sleep, fixing the sleep does But if you know how to fix the sleep, fixing the sleep does

indeed fix the headaches.indeed fix the headaches.

Are we the only ones?Are we the only ones?

I hope to convince you of the I hope to convince you of the following:following:

Migraine does not occur in the cerebral blood Migraine does not occur in the cerebral blood vessels.vessels.

Sleep and migraine are intertwined.Sleep and migraine are intertwined. Migraine is a genetic disorder that leads to hyper- Migraine is a genetic disorder that leads to hyper-

excitability of the posterior brainstem and occipital excitability of the posterior brainstem and occipital lobe.lobe.

The posterior brainstem sleep nuclei are designed to The posterior brainstem sleep nuclei are designed to turn on and off spontaneouslyturn on and off spontaneously..

That spontaneous “on” signal can accidently “leak” That spontaneous “on” signal can accidently “leak” into the surrounding nuclei causing them to into the surrounding nuclei causing them to accidently turn on also, even though they’re not accidently turn on also, even though they’re not “supposed to”.“supposed to”.

The trigemino-vascular The trigemino-vascular theory of migraine is the theory of migraine is the

oldold theory theory This theory, which has been the most popular This theory, which has been the most popular

explanation for migraine, grew out of the fact that explanation for migraine, grew out of the fact that there are there are no pain fibers in the brain itself.no pain fibers in the brain itself.

The pain fibers are only on the meninges, (the linings The pain fibers are only on the meninges, (the linings that cover the brain), and on the cerebral blood vessels.that cover the brain), and on the cerebral blood vessels.

As they are the only pain receptors in the brain the As they are the only pain receptors in the brain the trigemino-vascular theory suggests that the pain is trigemino-vascular theory suggests that the pain is experienced experienced in these receptors. in these receptors.

It proposes that “inflammatory” signals generated in It proposes that “inflammatory” signals generated in the trigeminal fibers at the meninges and the blood the trigeminal fibers at the meninges and the blood vessels cause the head pain. vessels cause the head pain.

Is there a minority Is there a minority opinion?opinion?

Dr. Michael Welch and Dr. Peter Goadsby Dr. Michael Welch and Dr. Peter Goadsby have been the major proponents of an have been the major proponents of an alternative view which suggests that the alternative view which suggests that the trigeminal caudal nucleus and the trigeminal caudal nucleus and the occipital lobe are hyper-excitable in occipital lobe are hyper-excitable in migraine patients. migraine patients.

The pain is The pain is experienced in the brain experienced in the brain stem stem not in the blood vessels.not in the blood vessels.

Some of Dr. Welch’s articles Some of Dr. Welch’s articles establishing hyper-excitability of the establishing hyper-excitability of the

brainstem in migraine patientsbrainstem in migraine patients Brain hyperexcitability: the basis for antiepileptic drugs in migraine prevention.Welch KM. Brain hyperexcitability: the basis for antiepileptic drugs in migraine prevention.Welch KM.

Headache. 2005 Apr;45 Suppl 1:S25-32. Review.Headache. 2005 Apr;45 Suppl 1:S25-32. Review. Contemporary concepts of migraine pathogenesis.Welch KM. Neurology. 2003 Oct 28;61(8 Contemporary concepts of migraine pathogenesis.Welch KM. Neurology. 2003 Oct 28;61(8

Suppl 4):S2-8. Review.Suppl 4):S2-8. Review. Functional MRI-BOLD of brainstem structures during visually triggered migraine. Cao Y, Functional MRI-BOLD of brainstem structures during visually triggered migraine. Cao Y,

Aurora SK, Nagesh V, Patel SC, Welch KM.Neurology. 2002 Jul 9;59(1):72-8.Aurora SK, Nagesh V, Patel SC, Welch KM.Neurology. 2002 Jul 9;59(1):72-8. Cortical spreading depression and gene regulation: relevance to migraine. Choudhuri R, Cui L, Cortical spreading depression and gene regulation: relevance to migraine. Choudhuri R, Cui L,

Yong C, Bowyer S, Klein RM, Welch KM, Berman NE. Ann Neurol. 2002 Apr;51(4):499-506.Yong C, Bowyer S, Klein RM, Welch KM, Berman NE. Ann Neurol. 2002 Apr;51(4):499-506. Magnetoencephalographic fields from patients with spontaneous and induced migraine aura. Magnetoencephalographic fields from patients with spontaneous and induced migraine aura.

Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch KM. Ann Neurol. 2001 Nov;50(5):582-7.Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch KM. Ann Neurol. 2001 Nov;50(5):582-7. Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Welch Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Welch

KM, Nagesh V, Aurora SK, Gelman N. Headache. 2001 Jul-Aug;41(7):629-37.KM, Nagesh V, Aurora SK, Gelman N. Headache. 2001 Jul-Aug;41(7):629-37. The occipital cortex is hyperexcitable in migraine: experimental evidence. Aurora SK, Cao Y, The occipital cortex is hyperexcitable in migraine: experimental evidence. Aurora SK, Cao Y,

Bowyer SM, Welch KM. Headache. 1999 Jul-Aug;39(7):469-76.Bowyer SM, Welch KM. Headache. 1999 Jul-Aug;39(7):469-76. MRI of the occipital cortex, red nucleus, and substantia nigra during visual aura of MRI of the occipital cortex, red nucleus, and substantia nigra during visual aura of

migraine.Welch KM, Cao Y, Aurora S, Wiggins G, Vikingstad EM. Neurology. 1998 migraine.Welch KM, Cao Y, Aurora S, Wiggins G, Vikingstad EM. Neurology. 1998 Nov;51(5):1465-9.Nov;51(5):1465-9.

Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine. Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine. Aurora SK, Ahmad BK, Welch KM, Bhardhwaj P, Ramadan NM.Neurology. 1998 Aurora SK, Ahmad BK, Welch KM, Bhardhwaj P, Ramadan NM.Neurology. 1998 Apr;50(4):1111-4.Apr;50(4):1111-4.

Brain excitability in migraine: evidence from transcranial magnetic stimulation studies.Aurora Brain excitability in migraine: evidence from transcranial magnetic stimulation studies.Aurora SK, Welch KM.Curr Opin Neurol. 1998 Jun;11(3):205-9. Review.SK, Welch KM.Curr Opin Neurol. 1998 Jun;11(3):205-9. Review.

Dr. Goadsby’s articles regarding hyper-Dr. Goadsby’s articles regarding hyper-excitability of the brainstem in excitability of the brainstem in

migraineursmigraineurs Brain activations in the premonitory phase of nitroglycerin-triggered migraine

attacks. Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ. Brain. 2014 Jan;137(Pt 1):232-41.

Diencephalic and brainstem mechanisms in migraine. Akerman S, Holland PR, Goadsby PJ. Nat Rev Neurosci. 2011 Sep 20;12(10):570-84.

Pathophysiology of migraine. Goadsby PJ. Neurol Clin. 2009 May;27(2):335-60. Trigeminocervical complex responses after lesioning dopaminergic A11 nucleus

are modified by dopamine and serotonin mechanisms. Charbit AR, Akerman S, Goadsby PJ . Pain 2011 Oct;152 (10):2365-76.

The vascular theory of migraine--a great story wrecked by the facts. Goadsby PJ . Brain 2009 Jan;132(Pt 1):6-7.

Functional neuroimaging of primary headache disorders. Cohen AS, Goadsby PJ. Curr Pain Headache Rep. 2005 Apr;9(2):141-6.

A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RS, Goadsby PJ. Brain 2005 Apr;128(Pt 4):932-9.

Activation of 5-HT(1B/1D) receptor in the periaqueductal gray inhibits nociception. Bartsch T, Knight YE, Goadsby PJ . Ann Neurol. 2004 Sep;56(3):371-81

The Minority Opinion:The Minority Opinion:

Is that migraine is not Is that migraine is not experienced at the endings of experienced at the endings of the nerves but is instead the nerves but is instead experienced experienced in the nucleus in the nucleus where the wires send their where the wires send their messagesmessages ; the ; the Trigeminal Trigeminal Nucleus CaudalisNucleus Caudalis..

Unfortunately Dr. Welch, who Unfortunately Dr. Welch, who originated this viewpoint, has originated this viewpoint, has been effectively drummed out been effectively drummed out of the headache meetings of the headache meetings because his ideas are different.because his ideas are different.

If the blood vessels are the If the blood vessels are the only part of the brain with only part of the brain with

pain fibers it seems perfectly pain fibers it seems perfectly logical to blame them for the logical to blame them for the

headache headache

And, by the way, why And, by the way, why doesn’tdoesn’t the the brain have pain fibers? brain have pain fibers?

The brain and the spinal The brain and the spinal cord don’t have pain fibers in cord don’t have pain fibers in the pinkish- grey gooey stuff the pinkish- grey gooey stuff

because they don’t need because they don’t need themthem

The brain and the spinal cord are the The brain and the spinal cord are the only parts with the skeleton on the only parts with the skeleton on the

outsideoutside

The skull protects the brain The skull protects the brain from penetrating objectsfrom penetrating objects

But the skull does But the skull does not keep the soft, not keep the soft, fragile brain from fragile brain from banging against banging against the inside of the the inside of the skull when shakenskull when shaken

The pain fibers are The pain fibers are on the vessels and on the vessels and the meninges the meninges to to tell us not to bang tell us not to bang our headsour heads..

This still doesn’t tell me This still doesn’t tell me why it’s “normal” to have why it’s “normal” to have

a headachea headache

(when it’s not normal for any other (when it’s not normal for any other part of our body to start hurting for part of our body to start hurting for

no reason.)no reason.)

Is there something Is there something different about the pain different about the pain system of the brain that system of the brain that

would make it more likely would make it more likely to turn on spontaneously?to turn on spontaneously?

The head pain systemThe head pain system is in is in two partstwo parts

The The Trigeminal Trigeminal Nucleus CaudalisNucleus Caudalis : : in in blueblue perceives perceives pain for the face pain for the face and the front of the and the front of the scalp shown in scalp shown in pinkpink and and lavenderlavender

The dorsal horn of The dorsal horn of C 1-C4 shown in C 1-C4 shown in greengreen perceives perceives pain for the back of pain for the back of the head and upper the head and upper neck.neck.

Dorsal horn C1-C4

Headaches happen in head Headaches happen in head and in the neckand in the neck

Headaches start Headaches start just as commonly in just as commonly in the neck as in the the neck as in the head, even though head, even though the neck is not really the neck is not really “in” the head.“in” the head.Why do they both Why do they both turn on turn on spontaneously? spontaneously? Why those two and Why those two and not other nuclei?not other nuclei?

Dorsal horn C1-C4

Pain system extends down Pain system extends down the spinal cord but does not the spinal cord but does not

just “turn on”just “turn on”

There are analogous cells There are analogous cells all the way down the all the way down the spinal cord perceiving spinal cord perceiving pain from the rest of the pain from the rest of the body called the body called the dorsal dorsal horn of C4-C8, the dorsal horn of C4-C8, the dorsal horn of T1-T12horn of T1-T12……

Why don’t they turn on Why don’t they turn on spontaneously too? spontaneously too?

What’s the difference What’s the difference between dorsal horn C1-between dorsal horn C1-C4 and those below?C4 and those below?

Dorsal horn C1-C4

Why just the trigeminal Why just the trigeminal nucleus and upper cervical nucleus and upper cervical

roots and not the rest?roots and not the rest? Could the top two; the trigeminal Could the top two; the trigeminal

nucleus and the top part of the nucleus and the top part of the dorsal horn dorsal horn have something have something nearby that affects only themnearby that affects only them, , that doesn’t extend down into the that doesn’t extend down into the spinal cord?spinal cord?

What about the periaquiductal grey What about the periaquiductal grey nuclei that govern sleep, including nuclei that govern sleep, including the raphe serotonergic nuclei?the raphe serotonergic nuclei?

Sleep happens here too. Could it Sleep happens here too. Could it affect the nearby trigeminal and affect the nearby trigeminal and

dorsal column nuclei?dorsal column nuclei?

Nucleus reticularis pontis oralis

The Periaquiductal Gray runs the The Periaquiductal Gray runs the timing and paralysis of sleeptiming and paralysis of sleep

The The pacemaker cells pacemaker cells in in the periaquiductal grey the periaquiductal grey pictured in red, pictured in red, beat all beat all day all night.day all night.

They are theThey are the brain clock brain clock that determines when that determines when we sleepwe sleep

The paralysis switch is The paralysis switch is here also, Nucleus here also, Nucleus Reticularis Pontis Oralis.Reticularis Pontis Oralis.

The two are heavily The two are heavily intertwined to be sure intertwined to be sure that we only get that we only get paralyzed while we are paralyzed while we are deeply asleep.deeply asleep.

Nucleus Reticularis Pontis Oralis

Why would areas of the Why would areas of the brainstem that are next brainstem that are next

to each other affect to each other affect each other?each other?

(That seems rather sloppy)(That seems rather sloppy)

Genetic Genetic mutations that mutations that cause migrainecause migraine

(Or, how your hyperactive (Or, how your hyperactive neighbor in the brainstem neighbor in the brainstem

might just make you cranky might just make you cranky too.)too.)

Genes that cause migraine Genes that cause migraine affect the electrical affect the electrical

excitability of brain cellsexcitability of brain cells

There are now about 40 genes that There are now about 40 genes that are linked to migraineare linked to migraine

All of these genes are mutations in All of these genes are mutations in the cellular apparatus that allows us the cellular apparatus that allows us to turn our cells on and off: to turn our cells on and off:

Ion Channel Mutations.Ion Channel Mutations.

Ca++ channel in a membraneCa++ channel in a membrane

Our cellular electricity is like a car battery; we use Our cellular electricity is like a car battery; we use ions floating in water. ions floating in water.

Our brain uses Ca++, K+, Cl-, Na+.Our brain uses Ca++, K+, Cl-, Na+. The channels move these ions in and out of our The channels move these ions in and out of our

cells to turn them “on” or “off”. cells to turn them “on” or “off”. We have multiple Ca++ channels, K+ channels, We have multiple Ca++ channels, K+ channels,

etc., each has a specific role, or several specific etc., each has a specific role, or several specific roles, in our body.roles, in our body.

Ca ++ channels turn cells“on” Ca ++ channels turn cells“on” Ca++ pumps turn them “off”Ca++ pumps turn them “off”

To turn the cell “on” Ca+To turn the cell “on” Ca++ channels open.+ channels open.

The cell is now very The cell is now very positive inside; it is “on”.positive inside; it is “on”.

To turn “off” it pumps out To turn “off” it pumps out the positive charges.the positive charges.

The mutation leads to a The mutation leads to a malfunctioning channel; malfunctioning channel; the cell goes “on” but the cell goes “on” but can’t turn “off “ again. can’t turn “off “ again.

Voltage gated Ca++ channel

Lots of +’s cell Lots of +’s cell is ONis ON++++

++++

++++

++++++

++++

++++

++++

Migraine is a Channel Migraine is a Channel DisorderDisorder

There are now multiple Ca++ and There are now multiple Ca++ and Na+ channel mutations linked to Na+ channel mutations linked to migraine. migraine.

Also mutations of Ca++ pumps and Also mutations of Ca++ pumps and most recently Na-K ATPase.most recently Na-K ATPase.

But which cell type has these But which cell type has these mutated channels and how does a mutated channels and how does a malfunctioning channel produce malfunctioning channel produce headache?headache?

Is their proof that the Is their proof that the posterior brainstem posterior brainstem

is too “on” in is too “on” in migraine?migraine?

PET Scans in Migraine PET Scans in Migraine PatientsPatients

show that the posterior brain stem is too “on”show that the posterior brain stem is too “on”Weiller C, May A, Limmroth V, et al. Nature Med 1995;1:658-660Weiller C, May A, Limmroth V, et al. Nature Med 1995;1:658-660

Refs: 5,7,10,21

How do the channel How do the channel mutations result in mutations result in

brainstem and occipital brainstem and occipital lobe hyper-excitability?lobe hyper-excitability?

Which brain cell has the Which brain cell has the mutant channels? Is it the mutant channels? Is it the

neurons or some other cell in neurons or some other cell in the brain?the brain?

Are there other imaging Are there other imaging procedures that show what procedures that show what happens in the brain during happens in the brain during

a migraine?a migraine?

1960’s Experiments: 1960’s Experiments: “Spreading Depression”“Spreading Depression”

Enrolled migraine patients who had Enrolled migraine patients who had a warning, a visual aura, telling a warning, a visual aura, telling them the headache was about to them the headache was about to happenhappen

They rushed them into a magnetic They rushed them into a magnetic field as they were experiencing the field as they were experiencing the visual symptoms to measure the visual symptoms to measure the electrical events during and after electrical events during and after the visual aura.the visual aura.

Magnetic Field StudiesMagnetic Field StudiesStarting with the visual aura they observedStarting with the visual aura they observed electrical electrical suppression, starting in the back during visual aura, suppression, starting in the back during visual aura, moving slowly forward taking 15 minutes to go from moving slowly forward taking 15 minutes to go from

back to frontback to front

Magnetic Field StudiesMagnetic Field Studieselectrical suppression, starting in the back during electrical suppression, starting in the back during

visual aura, moving slowly forward, 15 minutes to go visual aura, moving slowly forward, 15 minutes to go from back to frontfrom back to front

But what did it mean?But what did it mean?

Why was it moving so slowly, about Why was it moving so slowly, about 3mm/min?3mm/min?

Why was it moving in a wave spreading Why was it moving in a wave spreading outward like a ripple in water instead of outward like a ripple in water instead of jumping from one place to another like jumping from one place to another like neurons transmit messages?neurons transmit messages?

What did it have to do with the headache?What did it have to do with the headache? What cell in the brain produced this wave?What cell in the brain produced this wave?

Spreading Depression of Spreading Depression of Dr. LeaoDr. Leao

observed in rabbit brain slicesobserved in rabbit brain slices

Stimulating the brain electrically caused a slowly spreading Stimulating the brain electrically caused a slowly spreading electrical wave.electrical wave.

Traveling 3mm/min, contiguously, taking about 15 minutes to Traveling 3mm/min, contiguously, taking about 15 minutes to cross the braincross the brain

Why is it so slow? What moves at this rate in the brain? It’s ? What moves at this rate in the brain? It’s too slow for neurons. too slow for neurons.

Is it related to migraine in humans?Is it related to migraine in humans?

Spread of the visual aura was at the same speed as the

Spreading wave in the brain

Bella can’t tell us if she has a Bella can’t tell us if she has a headache and sometimes she looks a headache and sometimes she looks a

little depressed about itlittle depressed about it

I always get a headache when I

have to ride in the car.

Astrocytes to the Astrocytes to the Rescue!Rescue!

Astrocytes may explain Astrocytes may explain “spreading depression”“spreading depression”

Confocal microscopes Confocal microscopes show us brain cells in show us brain cells in 3 dimensions.3 dimensions.

We thought these We thought these little “star-like” cells little “star-like” cells were the skeletal were the skeletal system of the brain system of the brain as they had many as they had many processes spreading processes spreading out like a star.out like a star.

Neuron

Astrocyte

Astrocytes are more Astrocytes are more influential than previously influential than previously

imaginedimagined Astrocytes are Astrocytes are

electrically active cells electrically active cells that can talk to one that can talk to one another and other brain another and other brain cells. cells.

Their dendrites wrap Their dendrites wrap around 20-30 neurons around 20-30 neurons with multiple endings on with multiple endings on the surface of the the surface of the neurons giving excitatory neurons giving excitatory or inhibitory input to the or inhibitory input to the neurons.neurons.

Each astrocyte is Each astrocyte is assigned several neurons assigned several neurons and a blood vessel. and a blood vessel.

Spreading Depression of Spreading Depression of Leao is an inter cellular Leao is an inter cellular

calcium wavecalcium wave Astrocytes have gap Astrocytes have gap

junctions that open between junctions that open between adjoining cells allowing them adjoining cells allowing them to directly share their ionic to directly share their ionic environments.environments.

Spreading depression may Spreading depression may be a spreading inter-be a spreading inter-cellular calcium wave cellular calcium wave traveling through the traveling through the astrocyte population.astrocyte population.

The wave travels slowly, The wave travels slowly, 3mm/min, and contiguously, 3mm/min, and contiguously, because it is because it is transmitted transmitted by the astrocytes, not the by the astrocytes, not the neuronsneurons

The Astrocyte The Astrocyte Neurovascular UnitNeurovascular Unit

A single astrocyte and it’s A single astrocyte and it’s neurons are called neurons are called ““astrocyte astrocyte neurovascular unitneurovascular unit””

A chemical blood signal A chemical blood signal can be received by the can be received by the astrocyte, then sent to astrocyte, then sent to the neurons amplifying the neurons amplifying the messagethe message

Thus, spreading Thus, spreading depression has a similar depression has a similar arterial vasoconstrictive arterial vasoconstrictive wave that accompanies it.wave that accompanies it.

The change in mental The change in mental status and paralysis is the status and paralysis is the neuronal effect not the neuronal effect not the vascular effectvascular effect..

What have we suggested What have we suggested so far?so far?

Headaches happen equally in the neck and Headaches happen equally in the neck and headhead

Small headaches may grow into big migraineSmall headaches may grow into big migraine Brain stem hyper-excitabilty has been Brain stem hyper-excitabilty has been

observed in various types of studies.observed in various types of studies. Astrocyte physiology seems to explain Astrocyte physiology seems to explain

spreading depression spreading depression The astrocytes probably carry the channel The astrocytes probably carry the channel

mutations and are the “hyperexcitable “ mutations and are the “hyperexcitable “ cellscells

Are there other migraine Are there other migraine symptoms that must be explained symptoms that must be explained

by our theory?by our theory?

DizzinessDizziness Hypersensitivity to light sound and smellHypersensitivity to light sound and smell Ringing or buzzing in the earsRinging or buzzing in the ears Visual auraVisual aura NauseaNausea Nasal congestionNasal congestion SleepinessSleepiness Stroke like episodes; weakness, aphasiaStroke like episodes; weakness, aphasia

What about the other migraine What about the other migraine symptoms? They’re not in the symptoms? They’re not in the

trigeminal caudal nucleus but they’re trigeminal caudal nucleus but they’re right nearby right nearby

Nausea from the Nausea from the Chemotrigger Zone Chemotrigger Zone

Facial congestion Facial congestion from the from the Salivatory Salivatory Nucleus Nucleus which which innervates the innervates the mucosa of the sinus mucosa of the sinus cavitiescavities . .

Several, nearby Several, nearby brainstem nuclei brainstem nuclei are being excited are being excited together.together.

Chemotrigger zone

Can this theory explain the Can this theory explain the accompanying symptoms of accompanying symptoms of

migraine?migraine?

Dizziness - brain stem cerebellar nucleiDizziness - brain stem cerebellar nuclei Hypersensitivity to light sound and smell-lat and Hypersensitivity to light sound and smell-lat and

med. geniculate med. geniculate Tinnitus - VIIIth nerve nucleusTinnitus - VIIIth nerve nucleus Visual aura - occipital lobeVisual aura - occipital lobe Nausea - chemotrigger zoneNausea - chemotrigger zone Nasal congestion - salivatory nucleusNasal congestion - salivatory nucleus Sleepiness - raphe nucleiSleepiness - raphe nuclei Stroke like episodes; weakness, aphasia- brain Stroke like episodes; weakness, aphasia- brain

stem or cortexstem or cortex

Astrocyte anatomy is regionalAstrocyte anatomy is regional

Astrocytes do not Astrocytes do not follow neuronal follow neuronal anatomy, they anatomy, they overlap adjoining overlap adjoining nuclei supplying nuclei supplying regionsregions of the of the brain. brain.

There may be There may be regional differences regional differences in astrocyte in astrocyte physiology. physiology.

What about the visual What about the visual “aura” of migraine“aura” of migraine

The visual warning of The visual warning of migraine is thought to be migraine is thought to be a spontaneous electrical a spontaneous electrical discharge of the occipital discharge of the occipital lobe as seen in the lobe as seen in the spreading depression spreading depression experiments.experiments.

We know that some We know that some migraines start there and migraines start there and not in the brainstem, not in the brainstem, what what would link the would link the brainstem to the brainstem to the occipital lobe making occipital lobe making both hyper-excitable?both hyper-excitable?

PGO wavesPGO waves Pons Geniculate Occipital Pons Geniculate Occipital

Lobe PGO WavesLobe PGO Waves Waves that go back and forth Waves that go back and forth

between the brainstem and between the brainstem and the occipital lobe at the rate of the occipital lobe at the rate of REM eye movements. ( Even REM eye movements. ( Even while we’re awake.)while we’re awake.)

These waves may suggest a These waves may suggest a special population of special population of astrocytes linking the astrocytes linking the posterior brainstem to the posterior brainstem to the occipital lobe ( and probably occipital lobe ( and probably hypothalamus geniculate hypothalamus geniculate ganglia and thalamus). ganglia and thalamus).

Ref: 33, 34Ref: 33, 34


Lobe PGO WavesLobe PGO Waves Waves that go back and Waves that go back and

forth between the brainstem forth between the brainstem and the occipital lobe at the and the occipital lobe at the rate of REM eye movements. rate of REM eye movements. ( Even while we’re awake.)( Even while we’re awake.)

These waves may suggest a These waves may suggest a special population of special population of astrocytes linking the astrocytes linking the posterior brainstem to the posterior brainstem to the occipital lobe ( and probably occipital lobe ( and probably hypothalamus geniculate hypothalamus geniculate ganglia and thalamus). ganglia and thalamus).


Lobe PGO WavesLobe PGO Waves Waves that go back and Waves that go back and

forth between the brainstem forth between the brainstem and the occipital lobe at the and the occipital lobe at the rate of REM eye movements. rate of REM eye movements. ( Even while we’re awake.)( Even while we’re awake.)

These waves may suggest a These waves may suggest a special population of special population of astrocytes linking the astrocytes linking the posterior brainstem to posterior brainstem to the occipital lobethe occipital lobe ( and ( and probably hypothalamus probably hypothalamus geniculate ganglia and geniculate ganglia and thalamus). thalamus).

Why are all these Why are all these waves and waves and excitable excitable astrocytes astrocytes important?important?

The channel mutations The channel mutations probably didn’t arise to probably didn’t arise to

cause headachescause headaches The same astrocyte population which The same astrocyte population which

affects the “excitability” of the sleep affects the “excitability” of the sleep switches also affects the whole posterior switches also affects the whole posterior brainstem.brainstem.

Since sleep is the most important thing Since sleep is the most important thing we do every day, mutations that we do every day, mutations that improve sleep ( make it “switch on” improve sleep ( make it “switch on” easily) might convey a survival easily) might convey a survival advantage and become common in advantage and become common in humans.humans.

Key Points of Brainstem Hyper Key Points of Brainstem Hyper excitabilityexcitability

•Activation observed in the posterior brain stem Activation observed in the posterior brain stem on PET scans in migraine patients.on PET scans in migraine patients.

•Activation of the posterior brain stem can result Activation of the posterior brain stem can result in pain anywhere along the trigeminal-cervical in pain anywhere along the trigeminal-cervical network; including the head, the neck, and the network; including the head, the neck, and the face.face.

•Activation of the Salivatory Nucleus can lead to Activation of the Salivatory Nucleus can lead to sinus congestion, nausea from the chemotrigger sinus congestion, nausea from the chemotrigger zone, hypersensitivity to light sound and smell zone, hypersensitivity to light sound and smell from connections to the geniculate ganglia.from connections to the geniculate ganglia.

•Dizziness, tinnitus, double vision, all brain stem Dizziness, tinnitus, double vision, all brain stem nucleinuclei

How do we fix the How do we fix the headaches?headaches?

If I’ve had this “mutation” If I’ve had this “mutation” since I was born why is it since I was born why is it

only showing up now?only showing up now?

Fix the sleep fix the Fix the sleep fix the headachesheadaches

We have to fix the hyper excitability of the We have to fix the hyper excitability of the brain stem nuclei, make them go back to brain stem nuclei, make them go back to “off” .“off” .

The pills we’ve used for prevention of The pills we’ve used for prevention of migraine (even before the mutations were migraine (even before the mutations were described) are described) are calcium channel blockers calcium channel blockers like verapamil, and like verapamil, and sodium channel sodium channel stabilizers stabilizers like topiramate. like topiramate.

They work by stabilizing cranky, easily They work by stabilizing cranky, easily excitable cells that are turning “on “ too excitable cells that are turning “on “ too easily. easily.

Most people only Most people only get an occasional get an occasional mild headache mild headache They have the mechanism to They have the mechanism to

make a headache but it make a headache but it doesn’t act up all the time doesn’t act up all the time

and make their life miserable.and make their life miserable.

How do I get How do I get back to being back to being one of those one of those

people?people?

What I learned from sleep What I learned from sleep apnea masks apnea masks

Why did the CPAP mask make my patient’s Why did the CPAP mask make my patient’s headaches better?headaches better?

The masks are not about getting oxygen to the The masks are not about getting oxygen to the brain, that’s what the blood does. brain, that’s what the blood does.

We all get We all get paralyzedparalyzed in deep sleep and we in deep sleep and we have to be paralyzed to repairhave to be paralyzed to repair

Apnea occurs when the paralysis system gets Apnea occurs when the paralysis system gets goofed up and we get too paralyzed in deep goofed up and we get too paralyzed in deep sleep sleep

The mask blows air in to allow the brain to stay The mask blows air in to allow the brain to stay in deep sleep long enough to get work done.in deep sleep long enough to get work done.

The Periaquiductal Gray runs the The Periaquiductal Gray runs the timing and paralysis of sleeptiming and paralysis of sleep

The The pacemaker cells pacemaker cells in in the periaquiductal grey the periaquiductal grey pictured in red, pictured in red, beat all beat all day all night.day all night.

They are theThey are the brain clock brain clock that determines when that determines when we sleepwe sleep

The paralysis switch is The paralysis switch is here also, Nucleus here also, Nucleus Reticularis Pontis Oralis.Reticularis Pontis Oralis.

The two are heavily The two are heavily intertwined to be sure intertwined to be sure that we only get that we only get paralyzed while we are paralyzed while we are deeply asleep.deeply asleep.

Nucleus Reticularis Pontis Oralis

What I learned from What I learned from CPAP masksCPAP masks

My patients returned and said not only were My patients returned and said not only were their headaches gone but they were on fewer their headaches gone but they were on fewer blood pressure meds and they were off their blood pressure meds and they were off their diabetes pills.diabetes pills.

Their knee pain was gone they could think Their knee pain was gone they could think more clearly and they didn’t feel depressed any more clearly and they didn’t feel depressed any more,more,

And oh, yeah, I think my memory is better too.And oh, yeah, I think my memory is better too. Does that mean we repair everything in sleep , Does that mean we repair everything in sleep ,

do we make insulin in sleep, do we make our do we make insulin in sleep, do we make our serotonin in sleep?serotonin in sleep?

Sleep is not just being Sleep is not just being unconsciousunconscious

We all know what it feels like to wake tiredWe all know what it feels like to wake tired Sleep is not a passive processSleep is not a passive process There are specific stages of sleep in which we There are specific stages of sleep in which we

get paralyzed and get the “work” of sleep doneget paralyzed and get the “work” of sleep done I believe that we all make enough chemicals in I believe that we all make enough chemicals in

sleep to last about 16 hours, then we run out sleep to last about 16 hours, then we run out and we have to go back to sleep to make more.and we have to go back to sleep to make more.

I believe all repair of all systems only happens I believe all repair of all systems only happens while we’re sleepingwhile we’re sleeping

Apnea is not the only sleep Apnea is not the only sleep disorderdisorder

My 18 year old patient with daily headache slept My 18 year old patient with daily headache slept for 10 hours during her sleep study but had no for 10 hours during her sleep study but had no deep sleep at all, no apnea, but also no deep deep sleep at all, no apnea, but also no deep sleep.sleep.

Most of my headache patients have reduced or no Most of my headache patients have reduced or no REM sleep.REM sleep.

They all say the same thing: “I have a headache They all say the same thing: “I have a headache every day, I can’t remember anything and I’m in a every day, I can’t remember anything and I’m in a bad mood.”bad mood.”

The chemicals that prevent headache are made in The chemicals that prevent headache are made in deep sleep, memories are made in deep sleep deep sleep, memories are made in deep sleep serotonin to make us happy is made in deep sleep.serotonin to make us happy is made in deep sleep.

How do we get the REM How do we get the REM back?back?

Why is there no REM ?Why is there no REM ? Apnea is the end stage terrible disease before Apnea is the end stage terrible disease before

we die, none of us want to get even close to we die, none of us want to get even close to that.that.

Why does everyone who comes to see me, Why does everyone who comes to see me, regardless of the problem; headache, vertigo, regardless of the problem; headache, vertigo, tremor, burning in the feet, balance difficulty, tremor, burning in the feet, balance difficulty, parkinson’s, seizure, tics, stroke, all have an parkinson’s, seizure, tics, stroke, all have an abnormal sleep study? Even little 8 year olds?abnormal sleep study? Even little 8 year olds?

This is an epidemic that began in the early This is an epidemic that began in the early 1980’s as did fibromyalgia and chronic fatigue1980’s as did fibromyalgia and chronic fatigue

Why do I want my REM Why do I want my REM sleep back?sleep back?

While we’re sleeping we make millions of While we’re sleeping we make millions of chemicals that allow our bodies to run normally. chemicals that allow our bodies to run normally.

If you’ve always had the migraine gene mutation If you’ve always had the migraine gene mutation but didn’t always have a headache then you made but didn’t always have a headache then you made modifications in other chemicals that allowed your modifications in other chemicals that allowed your cells to run normally, to stay “off” …… until.cells to run normally, to stay “off” …… until.

You stopped sleeping in deep sleep long enough You stopped sleeping in deep sleep long enough every night to make those chemicals that “shored every night to make those chemicals that “shored up” your weakness.up” your weakness.

Each of us have genetic weaknesses we’re born Each of us have genetic weaknesses we’re born with.with.

Give me back my REM Give me back my REM sleepsleep

Could it be that each drug that helps migraine is Could it be that each drug that helps migraine is really just duplicating a chemical the brain ran out really just duplicating a chemical the brain ran out of?of?

And my brain knows how to make my And my brain knows how to make my chemical ,which exactly fits the gene mutation I chemical ,which exactly fits the gene mutation I have, but I only make that chemical in REM sleep.have, but I only make that chemical in REM sleep.

40 different channel mutations may explain why I 40 different channel mutations may explain why I have only partial success with the medicines I use, have only partial success with the medicines I use, and they “wear off”, the headaches get better, then and they “wear off”, the headaches get better, then they’re back again.they’re back again.

Your brain knows exactly which chemical to make Your brain knows exactly which chemical to make for you, it’s been doing it since you were born.for you, it’s been doing it since you were born.

Sleep DisordersSleep Disorders There are many types of abnormal sleep, one There are many types of abnormal sleep, one

is “I sleep all night but wake with a is “I sleep all night but wake with a headache”.headache”.

If you wake up every morning with mild neck If you wake up every morning with mild neck pain or facial pain your sleep is not “normal”pain or facial pain your sleep is not “normal”

If you sleep all night, wake feeling “fantastic” If you sleep all night, wake feeling “fantastic” and have no pain and no medical problems, and have no pain and no medical problems, then your sleep is normal.then your sleep is normal.

That is common now in my practice but not That is common now in my practice but not common in the developed world today. common in the developed world today.

Vitamins are DangerousVitamins are Dangerous Fixing the sleep is not just a matter of taking Fixing the sleep is not just a matter of taking

vitamins, they are chemicals that have to stay in a vitamins, they are chemicals that have to stay in a specific range for sleep to occur normally, use specific range for sleep to occur normally, use them carefully.them carefully.

But humans and all other animals lived here on But humans and all other animals lived here on this planet for millions of years before doctors this planet for millions of years before doctors arrived.arrived.

They missed those “well rounded diet” lectures, They missed those “well rounded diet” lectures, most of the squirrels still don’t get those lectures.most of the squirrels still don’t get those lectures.

That means the things our bodies can’t make That means the things our bodies can’t make were actually partly from the intestinal bacteria were actually partly from the intestinal bacteria and partly from the food.and partly from the food.

Humans lived before Humans lived before doctorsdoctors

Most died of infectious diseases that we Most died of infectious diseases that we have eliminated to large extenthave eliminated to large extent

What remains is slow death by organ What remains is slow death by organ failure; diabetes, heart attack, stroke, failure; diabetes, heart attack, stroke, parkinsons, alzheimers, cancer.parkinsons, alzheimers, cancer.

All of these diseases result from incomplete All of these diseases result from incomplete healing during sleep and can be partially or healing during sleep and can be partially or fully reversed by sleeping normally.fully reversed by sleeping normally.

Headache can be cured by sleeping Headache can be cured by sleeping normally normally

D and B vitaminsD and B vitamins The epidemic of low vitamin D in the developed world The epidemic of low vitamin D in the developed world

started with computer, television and air started with computer, television and air conditioning in the late 70s early 80’s when we all conditioning in the late 70s early 80’s when we all went indoors.went indoors.

Since there are no drugs to bring back REM what Since there are no drugs to bring back REM what we’re left with is trying new things.we’re left with is trying new things.

Go to the vitamin D lecture to see the connection in Go to the vitamin D lecture to see the connection in detail but vitamin D deficiency is the cause.detail but vitamin D deficiency is the cause.

Get the D to 60-80 ng/ml and fix the secondary Get the D to 60-80 ng/ml and fix the secondary effects of low D (intestinal bacterial change) so the effects of low D (intestinal bacterial change) so the B’s get made daily in the right amountsB’s get made daily in the right amounts

And the REM comes back and the headaches go awayAnd the REM comes back and the headaches go away

Why sleeping pills are Why sleeping pills are valuablevaluable

16 year olds with their first bout of daily headache 16 year olds with their first bout of daily headache are easy to fix with vitamins are easy to fix with vitamins

52 year olds with daily headache for the last 30 52 year olds with daily headache for the last 30 years are not easy to fix with just vitaminsyears are not easy to fix with just vitamins

Every night the brain tries to fix the sleep Every night the brain tries to fix the sleep switches but doesn’t have the time in deep sleep switches but doesn’t have the time in deep sleep to succeed.to succeed.

Daily headache for 30 years means that patient Daily headache for 30 years means that patient has old, rusty, poorly functioning sleep switches has old, rusty, poorly functioning sleep switches and even when those cells get the raw materials and even when those cells get the raw materials they’ve needed, (the vitamins) they don’t just snap they’ve needed, (the vitamins) they don’t just snap to it and work perfectly. to it and work perfectly.

Long standing sleep Long standing sleep disorders usually require disorders usually require

sleeping pillssleeping pills If you give a sleeping pill but don’t fix what’s If you give a sleeping pill but don’t fix what’s

wrong in the background they may work for a wrong in the background they may work for a little while but then they “wear off” and they little while but then they “wear off” and they need more and they “get addicted” need more and they “get addicted”

They can’t sleep without the medication, but They can’t sleep without the medication, but they couldn’t sleep in the first place.they couldn’t sleep in the first place.

The medications aren’t bad they just aren’t the The medications aren’t bad they just aren’t the whole answer. whole answer.

Fix what’s wrong in the background and use Fix what’s wrong in the background and use the sleep meds as a bandaid to help while the the sleep meds as a bandaid to help while the brain is repairingbrain is repairing

It is sleep, not vitamins that It is sleep, not vitamins that cures the headaches cures the headaches

Sleep is the cure for headache, if the sleep Sleep is the cure for headache, if the sleep is not normal the headaches won’t resolve.is not normal the headaches won’t resolve.

Be patient. If the sleep has been abnormal Be patient. If the sleep has been abnormal for 30 years it doesn’t get fixed over night.for 30 years it doesn’t get fixed over night.

Find the sleeping pill that is right for you.Find the sleeping pill that is right for you. Fall asleep stay asleep and wake feeling Fall asleep stay asleep and wake feeling

great means that medication is what the great means that medication is what the brain has been needing to get into the right brain has been needing to get into the right phasesphases

They won’t work alone but they are helpfulThey won’t work alone but they are helpful

CPAP is still helpfulCPAP is still helpful

Anyone with apnea will still get better faster Anyone with apnea will still get better faster with the mask on. with the mask on.

Many people who have apnea will not get fixed Many people who have apnea will not get fixed unless they are able to wear the mask and unless they are able to wear the mask and sleepsleep

Listen to your body, if you sleep better in the Listen to your body, if you sleep better in the recliner stay in the recliner.recliner stay in the recliner.

People end up sleeping on the couch because People end up sleeping on the couch because they sleep better there than in the bed. The they sleep better there than in the bed. The couch keeps them in a position where their couch keeps them in a position where their apnea is lessapnea is less..

Listen to your bodyListen to your body

As you get better, the drugs I have used to As you get better, the drugs I have used to help you will start to have different effectshelp you will start to have different effects

The sleep medicine that used to help you now The sleep medicine that used to help you now makes you dopey in the morningmakes you dopey in the morning

Just like taking away the blood pressure meds Just like taking away the blood pressure meds when the blood pressure normalizes you need when the blood pressure normalizes you need to take away sleep meds as the sleep gets to take away sleep meds as the sleep gets betterbetter

Always wait until your body tells you it doesn’t Always wait until your body tells you it doesn’t want them, they make you feel funny now want them, they make you feel funny now instead of betterinstead of better

Listen to your bodyListen to your body Once the sleep gets better and the headaches go Once the sleep gets better and the headaches go

away you have to learn what to watch for so they away you have to learn what to watch for so they don’t come backdon’t come back

The vitamin D is hard to keep in range. Every The vitamin D is hard to keep in range. Every person needs a different dose depending on their person needs a different dose depending on their skin color, where they live, how much they’re in the skin color, where they live, how much they’re in the sun in the summer and how long they were sicksun in the summer and how long they were sick

This means the D dose usually goes down over the This means the D dose usually goes down over the first 2-3 years as we get better, we have to have a first 2-3 years as we get better, we have to have a way to tell when to get the level checked and catch way to tell when to get the level checked and catch it before our sleep falls apart again and the it before our sleep falls apart again and the headaches come back. headaches come back.

Little headaches are Little headaches are importantimportant

If you learn that those little “normal If you learn that those little “normal headaches” are warning you that your head headaches” are warning you that your head pain switch is getting cranky again and you pain switch is getting cranky again and you do something about it right away, like check do something about it right away, like check the D level, you’ll fix your sleep before the D level, you’ll fix your sleep before you’ve spent another six months not sleeping you’ve spent another six months not sleeping and the headaches are out of control again.and the headaches are out of control again.

Each time your sleep gets goofed up for Each time your sleep gets goofed up for more than a brief period the headaches will more than a brief period the headaches will return until you’ve had months on end of return until you’ve had months on end of normal sleep.normal sleep.

Headache meds are still Headache meds are still importantimportant

The preventatives such as verapamil and topiramate are The preventatives such as verapamil and topiramate are still necessary for many patients. There’s nothing wrong still necessary for many patients. There’s nothing wrong with using them but the improvement won’t last if the with using them but the improvement won’t last if the sleep remains abnormal.sleep remains abnormal.

The triptans are very important.The triptans are very important. The warnings per the FDA are not correct. The receptors The warnings per the FDA are not correct. The receptors

that they work on do not increase serotonin, they decrease that they work on do not increase serotonin, they decrease serotonin, and they do indeed cause chest and joint aching serotonin, and they do indeed cause chest and joint aching but they are generally very safe.but they are generally very safe.

They do not work in the daily headache sufferers because They do not work in the daily headache sufferers because they work best when the headache is in the earliest stages.they work best when the headache is in the earliest stages.

Even if they failed when the headaches were daily, they Even if they failed when the headaches were daily, they will usually work later when the headaches are once a will usually work later when the headaches are once a week.week.

Always have a CT scanAlways have a CT scan

Any patient with headaches bad Any patient with headaches bad enough to talk to their doctor or watch enough to talk to their doctor or watch this lecture needs a CT of the head at this lecture needs a CT of the head at least once.least once.

There is no difference between the There is no difference between the headache of a brain tumor and “normal headache of a brain tumor and “normal headache” at the beginning. Always headache” at the beginning. Always confirm that the anatomy is normal confirm that the anatomy is normal before assuming that it’s migraine.before assuming that it’s migraine.

ReferencesReferences1. Why does serotonergic activity drastically decrease during REM sleep? Sato K . Med Hypotheses. 2013 Oct;81(4):734-7.2. Serotonin control of sleep-wake behavior. Monti JM Sleep Med Rev. 2011 Aug;15(4):269-81

3. Brain hyperexcitability: the basis for antiepileptic drugs in migraine 3. Brain hyperexcitability: the basis for antiepileptic drugs in migraine prevention. Welch KM. Headache. 2005 Apr;45 Suppl 1:S25-32. Review.prevention. Welch KM. Headache. 2005 Apr;45 Suppl 1:S25-32. Review.

4. Contemporary concepts of migraine pathogenesis.Welch KM. Neurology. 4. Contemporary concepts of migraine pathogenesis.Welch KM. Neurology. 2003 Oct 28;61(8 Suppl 4):S2-8. Review.2003 Oct 28;61(8 Suppl 4):S2-8. Review.

5. Functional MRI-BOLD of brainstem structures during visually triggered 5. Functional MRI-BOLD of brainstem structures during visually triggered migraine. Cao Y, Aurora SK, Nagesh V, Patel SC, Welch KM. Neurology. migraine. Cao Y, Aurora SK, Nagesh V, Patel SC, Welch KM. Neurology. 2002 Jul 9;59(1):72-8.2002 Jul 9;59(1):72-8.

6. Cortical spreading depression and gene regulation: relevance to 6. Cortical spreading depression and gene regulation: relevance to migraine. Choudhuri R, Cui L, Yong C, Bowyer S, Klein RM, Welch KM, migraine. Choudhuri R, Cui L, Yong C, Bowyer S, Klein RM, Welch KM, Berman NE. Ann Neurol. 2002 Apr;51(4):499-506.Berman NE. Ann Neurol. 2002 Apr;51(4):499-506.

7. Magnetoencephalographic fields from patients with spontaneous and 7. Magnetoencephalographic fields from patients with spontaneous and induced migraine aura. Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch induced migraine aura. Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch KM. Ann Neurol. 2001 Nov;50(5):582-7.KM. Ann Neurol. 2001 Nov;50(5):582-7.

ReferencesReferences8. Periaqueductal gray matter dysfunction in migraine: cause or 8. Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Welch KM, Nagesh V, Aurora SK, Gelman N. the burden of illness? Welch KM, Nagesh V, Aurora SK, Gelman N. Headache. 2001 Jul-Aug;41(7):629-37.Headache. 2001 Jul-Aug;41(7):629-37.

9. The occipital cortex is hyperexcitable in migraine: experimental 9. The occipital cortex is hyperexcitable in migraine: experimental evidence. Aurora SK, Cao Y, Bowyer SM, Welch KM. Headache. evidence. Aurora SK, Cao Y, Bowyer SM, Welch KM. Headache. 1999 Jul-Aug;39(7):469-76.1999 Jul-Aug;39(7):469-76.

10. MRI of the occipital cortex, red nucleus, and substantia nigra 10. MRI of the occipital cortex, red nucleus, and substantia nigra during visual aura of migraine. Welch KM, Cao Y, Aurora S, during visual aura of migraine. Welch KM, Cao Y, Aurora S, Wiggins G, Vikingstad EM. Neurology. 1998 Nov;51(5):1465-9.Wiggins G, Vikingstad EM. Neurology. 1998 Nov;51(5):1465-9.

11. Transcranial magnetic stimulation confirms hyperexcitability of 11. Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine. Aurora SK, Ahmad BK, Welch KM, occipital cortex in migraine. Aurora SK, Ahmad BK, Welch KM, Bhardhwaj P, Ramadan NM. Neurology. 1998 Apr;50(4):1111-4.Bhardhwaj P, Ramadan NM. Neurology. 1998 Apr;50(4):1111-4.

12. Brain excitability in migraine: evidence from transcranial 12. Brain excitability in migraine: evidence from transcranial magnetic stimulation studies. Aurora SK, Welch KM. Curr Opin magnetic stimulation studies. Aurora SK, Welch KM. Curr Opin Neurol. 1998 Jun;11(3):205-9. Neurol. 1998 Jun;11(3):205-9.

ReferencesReferences13. Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ. Brain. 2014 Jan;137(Pt 1):232-41. 14. Diencephalic and brainstem mechanisms in migraine. Akerman S, Holland PR, Goadsby PJ. Nat Rev Neurosci. 2011 Sep 20;12(10):570-84.15. Pathophysiology of migraine. Goadsby PJ. Neurol Clin. 2009 May;27(2):335-60. 16. Trigeminocervical complex responses after lesioning dopaminergic A11 nucleus are modified by dopamine and serotonin mechanisms. Charbit AR, Akerman S, Goadsby PJ . Pain 2011 Oct;152 (10):2365-76.17. The vascular theory of migraine--a great story wrecked by the facts. Goadsby PJ . Brain 2009 Jan;132(Pt 1):6-7. 18. Functional neuroimaging of primary headache disorders. Cohen AS, Goadsby PJ. Curr Pain Headache Rep. 2005 Apr;9(2):141-6.

ReferencesReferences19. A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RS, Goadsby PJ. Brain 2005 Apr;128(Pt 4):932-9. 20. Activation of 5-HT(1B/1D) receptor in the periaqueductal gray inhibits nociception. Bartsch T, Knight YE, Goadsby PJ . Ann Neurol. 2004 Sep;56(3):371-8121. Brain stem activation in spontaneous human migraine attacks. Weiller Brain stem activation in spontaneous human migraine attacks. Weiller C, May A, Limmroth V, et al. Nat Med. 1995 Jul;1(7):658-60.C, May A, Limmroth V, et al. Nat Med. 1995 Jul;1(7):658-60.22. Joutel A, Bousser MG, Biousse V, et Joutel A, Bousser MG, Biousse V, et aal. l. A gene for fA gene for faamilimiliaal hemiplegic l hemiplegic migrmigraaine maps to chromosome 19. Nat Genet 1993;5:40-45.[ine maps to chromosome 19. Nat Genet 1993;5:40-45.[23. Joutel A, Ducros A, V23. Joutel A, Ducros A, Vaahedi K, et hedi K, et aal. Genetic heterogeneity of fl. Genetic heterogeneity of faamilimiliaal l hemiplegic migrhemiplegic migraaine. Am J Hum Genet 1994;55:1166-1172. ine. Am J Hum Genet 1994;55:1166-1172. 24. Ophoff RA, Terwindt GM, Vergouwe MN, et 24. Ophoff RA, Terwindt GM, Vergouwe MN, et aal. Fl. Faamilimiliaal hemiplegic l hemiplegic migrmigraaine ine aand episodic nd episodic aattaaxixiaa type-2 type-2 aare cre caaused by mutused by mutaations in the Ctions in the Caa2+ 2+ chchaannel gene Cnnel gene CAACNL1CNL1AA4. Cell 1996;87:543-552. 4. Cell 1996;87:543-552. 25. Terwindt GM, Ophoff R25. Terwindt GM, Ophoff RAA, H, Haaaan J, et n J, et aal. Vl. Vaaririaable clinicble clinicaal expression of l expression of mutmutaations in the P/Q-type ctions in the P/Q-type caalcium chlcium chaannel gene in fnnel gene in faamilimiliaal hemiplegic l hemiplegic migrmigraaine. Neurology 1998;50:1105-1110.ine. Neurology 1998;50:1105-1110.

ReferencesReferences26. 26. Ophoff ROphoff RAA, v, vaan Eijk R, Sn Eijk R, Saandkuijl Lndkuijl LAA, et , et aal. l. Genetic heterogeneity of Genetic heterogeneity of ffaamilimiliaal hemiplegic migrl hemiplegic migraaine. Genomics 1994;22:21-26.ine. Genomics 1994;22:21-26.27. Ducros 27. Ducros AA, Joutel , Joutel AA, V, Vaahedi K, et hedi K, et aal. Ml. Maapping of pping of aa second locus for f second locus for faamilimiliaal l hemiplegic migrhemiplegic migraaine to 1q21-q23 ine to 1q21-q23 aand evidence of further heterogeneity. nd evidence of further heterogeneity. AAnn nn Neurol 1997;42:885-890.Neurol 1997;42:885-890.28. H28. Haans M, Luvisetto S, Willins M, Luvisetto S, Williaams ME, et ms ME, et aal. Functionl. Functionaal consequences of l consequences of mutmutaations in the humtions in the humaan n aalphlphaa11AA c caalcium chlcium chaannel subunit linked to fnnel subunit linked to faamilimiliaal l hemiplegic migrhemiplegic migraaine. J Neurosci 1999;19:1610-1619 ine. J Neurosci 1999;19:1610-1619 29. Jurkat-Rott, K., Freilinger, T., Dreier, J. P., Herzog, J., Gobel, H., Petzold, 29. Jurkat-Rott, K., Freilinger, T., Dreier, J. P., Herzog, J., Gobel, H., Petzold, G. C., Montagna, P., Gasser, T., Lehmann-Horn, F., Dichgans, M. (2004). G. C., Montagna, P., Gasser, T., Lehmann-Horn, F., Dichgans, M. (2004). Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase variants. variants. NeurologyNeurology 62: 1857-1861 62: 1857-1861 30. Elliott MA, Peroutka SJ, Welch S, May EF. Familial hemiplegic migr30. Elliott MA, Peroutka SJ, Welch S, May EF. Familial hemiplegic migraaine, ine, nystagmus, and cerebellar atrophy. Ann Neurol 1996;39:100-106.nystagmus, and cerebellar atrophy. Ann Neurol 1996;39:100-106.31. van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, 31. van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T, van de Ven RC, Tottene A, van der Kaa J, Plomp JJ, Frants RR, Cesetti T, van de Ven RC, Tottene A, van der Kaa J, Plomp JJ, Frants RR, Ferrari MDFerrari MD. . A Cacna1a knockin migraine mouse model with increased A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 2004 Mar susceptibility to cortical spreading depression. Neuron. 2004 Mar 4;41(5):701-10. 4;41(5):701-10. 32. Knight YE, Bartsch T, Kaube H, Goadsby PJ. P/Q Type Calcium-channel 32. Knight YE, Bartsch T, Kaube H, Goadsby PJ. P/Q Type Calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: A blockade in the periaqueductal gray facilitates trigeminal nociception: A functional genetic link for migraine? Jour Neurosci 2002 ;22: RC213 1-6.functional genetic link for migraine? Jour Neurosci 2002 ;22: RC213 1-6.

ReferencesReferences33. Pontogeniculooccipital waves: spontaneous visual system activity 33. Pontogeniculooccipital waves: spontaneous visual system activity during rapid eye movement sleep. Callaway CW1, Lydic R, during rapid eye movement sleep. Callaway CW1, Lydic R, Baghdoyan HA, Hobson JA .Cell Mol Neurobiol. 1987 Jun;7(2):105-Baghdoyan HA, Hobson JA .Cell Mol Neurobiol. 1987 Jun;7(2):105-49.49.

34. Waking and dreaming consciousness: neurobiological and 34. Waking and dreaming consciousness: neurobiological and functional considerations. functional considerations. Hobson JA1, Friston KJ. Prog Neurobiol. Hobson JA1, Friston KJ. Prog Neurobiol. 2012 Jul;98(1):82-98. 2012 Jul;98(1):82-98.

Why do humans have so many headaches? Stasha Gominak, M.D. East Texas Medical Center Neurologic...

Documents

Transcript of Why do humans have so many headaches? Stasha Gominak, M.D. East Texas Medical Center Neurologic...