Why do humans have headaches?

Why do humans have headaches? (see Lecture section also)

The trigemi­no­vas­cu­lar theory:

Most of what is writ­ten about why we have headaches is based on a the­ory of head pain that was gen­er­ated in the 1960’s called the “trigemi­no­vas­cu­lar the­ory”. This the­ory, of how and why headache or migraine occurs, is based on where the pain nerves are located in the head. That’s not such a bad place to start but it turns out it doesn’t have any­thing to do with spon­ta­neous head pain, bet­ter known as “headache”.

Sur­pris­ingly the pink­ish grey “stuff” of the brain does not “feel” pain when touched. The only parts of the brain that feel pain when touched are the blood ves­sels and the lin­ings that cover the brain, called “meninges”. Because the patient only feels pain when those parts are touched the doc­tors try­ing to under­stand headache incor­rectly con­cluded that spon­ta­neous head pain was also “gen­er­ated” there.
It is impor­tant to real­ize that the pain sys­tem in our body exists to tell us about the mechan­i­cal lim­i­ta­tions of our body. The brain is vul­ner­a­bly soft, and although the skull is well designed to pro­tect from pen­e­trat­ing injury, the hard skull is quite unfor­giv­ing when the brain smashes against it. Both the brain and the spinal cord rely on the boney skull and spinal col­umn to pre­vent injury, but as the brain is float­ing in fluid it can still be injured by bang­ing against the inside of the skull. Thus, we need the head pain sys­tem to tell us not to bang our heads.

Ouch!

The pain end­ings on the sur­face of the brain and on the blood ves­sels, that are teth­ered into the neck,  send pain mes­sages when the brain is shaken or smacked against the skull. The mus­cles and skin of our body do not have a pro­tec­tive layer like the skull so they need pain fibers inside them to tell us not to hurt them. That explains why there are no pain fibers in the brain itself but it does not explain why we have headaches.
The trigemi­no­vas­cu­lar the­ory is named for the trigem­i­nal nerve, which is one of the nerves that trans­mits head pain. It is respon­si­ble for the front 2/3^rd’s of the head and the face, trans­mit­ting a pain mes­sage to the brain stem trigem­i­nal nucleus caudalis.

The trigem­i­nal nerve sup­plies the face and front of scalp
When we get hit on the head we do actu­ally per­ceive the pain through the trigem­i­nal nerves and upper  cer­vi­cal roots. They trans­mit a mes­sage to the brain where we think “ouch”. But nor­mal peo­ple, who have not been hit on the head, do not have headaches gen­er­ated in this way.

Where is spon­ta­neous head pain generated?

If the trigemi­no­vas­cu­lar the­ory isn’t the answer how do headaches occur?Over the last 15 years there have been amaz­ing advances in the genet­ics of migraine as well as some very novel ideas about a brain­stem “migraine gen­er­a­tor” that pro­vide a very sen­si­ble expla­na­tion of migraine and headache in gen­eral. This new view is quite dif­fer­ent than the “trigemi­no­vas­cu­lar” the­ory, and has not yet been widely embraced by the headache estab­lish­ment who write the books on migraine.
To under­stand the newer genetic lit­er­a­ture and our own expe­ri­ences with our headaches we must direct our atten­tion to this brain­stem “headache gen­er­a­tor”, a con­cept pro­posed by Dr. KMA Welch and Dr. Peter Goadsby (1,2) based on PET scan lit­er­a­ture show­ing that headache suf­fer­ers have a stripe of abnor­mally increased sig­nal in the pos­te­rior brain stem, sug­gest­ing that this seg­ment of the brain­stem is “hyper meta­bolic”, or too “turned on”. (3, 4)

The pos­te­rior brain stem “lights up”on PET scans of migraine patients

The anatomy of the head pain system:

The head pain sys­tem is in two parts. The front two thirds of the head and the face send pain sig­nals to the brain through the trigem­i­nal nerves to the trigem­i­nal cau­dal nucleus, a long, thin stripe of cells in the pos­te­rior brain stem. The back one third of the head and the neck send pain sig­nals through cer­vi­cal roots 1–4 into a sim­i­lar nucleus in the pos­te­rior cer­vi­cal cord. These two nuclei are sup­posed to sit qui­etly until a pain mes­sage is received, then trans­mit that mes­sage to the brain areas where the pain is per­ceived. Unfor­tu­nately the headache suf­ferer inher­its a gene that makes these brain stem nuclei “hyper excitable”, i.e. they turn on with­out a blow to the head.

Genetic chan­nel muta­tions caus­ing migraine:

The most impor­tant advance in the under­stand­ing of migraine has come with the genetic muta­tions that cause migraine. The first reported gene muta­tion linked to migraine was in a pro­tein called a Cal­cium Channel.(5) Over the last 15 years there have been sev­eral other cal­cium chan­nel gene muta­tions and sodium chan­nel gene muta­tions linked to migraine.(5,6,7) The dif­fi­culty with link­ing these genetic dis­cov­er­ies to the tra­di­tional expla­na­tion of migraine has been that most of the migraine lit­er­a­ture is still look­ing at the nerve end­ings on the blood ves­sels and it’s hard to put together the chan­nel muta­tions with the older the­o­ries on migraine phys­i­ol­ogy. How­ever, if one is look­ing at migraine as an inher­ited dis­or­der of brain­stem “hyper excitabil­ity” the chan­nel muta­tions make sense.

                 Cal­cium Channel
What are Chan­nels and why are they important?
All of the cells in our body turn on and off using “elec­tric­ity”. The elec­tric­ity that we use is not like the wires in the walls, but more like a car bat­tery. The car bat­tery is a box con­tain­ing liq­uid that has pos­i­tive and neg­a­tive charges float­ing on either side of a par­ti­tion. The charges want to be together so wires con­nect­ing one side to the other let the neg­a­tive charges flow over to join the pos­i­tive. We use pos­i­tive and neg­a­tive charges in our body too. The pos­i­tive and neg­a­tive charges that we use, float­ing in the liq­uid that makes up our body, are cal­cium; Ca++, sodium Na+, potas­sium; K+, chlo­ride Cl-. Each of our cells is “off” when it has many neg­a­tive charges inside, and “on” when it has many pos­i­tive charges inside. The trick is, how to get the “+”s and “-“s to go where we want, when we want. The way we con­trol the charges enter­ing is by using “chan­nels”. Chan­nels are pro­teins that are tubu­lar, shaped like a hot­dog bun. The chan­nels are incor­po­rated into the mem­brane of the cell. When they open they cre­ate a hole in the mem­brane. If it’s a cal­cium chan­nel it only lets cal­cium in, a potas­sium chan­nel only lets potas­sium in.

How do chan­nels help turn our cells on and off?

A cell receives a neu­ro­trans­mit­ter mes­sage to turn on, that recep­tor is linked to a cal­cium chan­nel. The chan­nel opens, cal­cium enters the cell. As more pos­i­tive charges enter the cell the cell is “on”, it sends its mes­sage and then it must turn “off” again. It turns off by pump­ing the cal­cium out with spe­cial­ized cal­cium pumps. The first muta­tion linked to migraine cre­ated a cal­cium chan­nel that gets stuck in the “open” posi­tion. Thus, as the cell is pump­ing out the cal­cium, try­ing to turn “off”, the cal­cium is leak­ing back in through the chan­nel that is stuck open and the cell is unable to turn com­pletely “off”. (8) The migraine suf­ferer inher­its a gene that makes the brain­stem cells stay a lit­tle more “on” all of the time.

Why do doc­tors use epilepsy and “blood pres­sure” med­ica­tions to pre­vent headaches?

With the chan­nel muta­tion dis­cov­er­ies we have finally been pro­vided an expla­na­tion for the suc­cess of both the seizure med­ica­tions and the “blood pres­sure” med­ica­tions in pre­vent­ing migraine. The cal­cium chan­nel block­ers such as ver­a­pamil, the “beta block­ers” such as pro­pra­nolol and atenolol (which are also cal­cium chan­nel active), and the seizure med­ica­tions, such as val­proic acid and topiramate,(sodium chan­nel sta­bi­liz­ers) are all med­i­cines that act on channels.

Are headaches and “migraine” different?

The next impor­tant con­cept in under­stand­ing headache is that almost all the headaches that we expe­ri­ence are “migraine” in mech­a­nism. We’ve learned this from our patients as they have used the trip­tan med­ica­tions (suma­trip­tan. nara­trip­tan, eletrip­tan, zol­ma­trip­tan, etc.) for their migraines. The trip­tans act on sero­tonin 1B and 1D recep­tors, which are feed­back inhibitors of the release of sero­tonin. The trip­tans are spe­cific for the chem­istry of migraine, they are not gen­eral pain reliev­ers. We orig­i­nally told our patients “save this med­i­cine for your migraine headaches” but our patients were smarter than we were and found that they were more suc­cess­ful when they took the med­ica­tions ear­lier. When they used the trip­tans suc­cess­fully for their milder headaches we learned that their milder headaches (that we had told them were “stress” or “mus­cle con­trac­tion” or “sinus” headaches) were also “migraine” in mechanism.
The major­ity of patients with “migraine” have milder headaches as well as what they call “migraines”. It is my belief that most of the headaches we all have are “migraine” in mech­a­nism, and that there is a con­tin­uum of headache from milder headaches to very severe headaches. Patients with the migraine gene not only turn on their headache cen­ter with­out a blow to the head but they are also unable to turn off the headache cen­ter and are more likely to get a headache that won’t go away after minor head injury.

Why do migraine suf­fers go to bed when they get a headache?

Any of you who have had a migraine know it is not just head pain. There is an accom­pa­ny­ing feel­ing of “my brain is not right” that makes it dif­fi­cult or impos­si­ble to func­tion, so the migraine suf­ferer goes to bed. Most peo­ple with milder migraine can “break” the headache if they can get to sleep and sleep long enough. The migraine gen­er­a­tor that I explained above does not do “think­ing” it just does pain, so how does this global mal­func­tion of the brain occur?
The first obser­va­tions on the elec­tri­cal events of “migraine” were per­formed, in the late 1960’s, by putting patients in a mag­netic field and observ­ing the elec­tri­cal changes in the whole brain dur­ing a migraine.
In order to know when the headache would start, and then record what hap­pened in the brain, they had to use patients who expe­ri­enced a visual “aura” or warn­ing, pre­ced­ing the headache. This allowed them to put the patient into the machine as the headache was start­ing. What they observed was a wave of elec­tri­cal activ­ity that started at the back of the brain (the visual cor­tex), dur­ing the visual aura, and spread slowly for­ward, from back to front, tak­ing about 15 min­utes to cross the brain.

Spread­ing Depression

At the same time Dr. Leao, in exper­i­ments on rab­bit brain slices, showed that elec­tri­cal stim­u­la­tion of the brain pro­duced a spread­ing wave of elec­tri­cal depres­sion, mov­ing across the brain in three dimen­sions at about the same rate, 3mm/minute. This phe­nom­e­non was then called: spread­ing depres­sion of Leao. The next sec­tion explains this spread­ing wave of activity.

Why the astro­cyte is impor­tant in under­stand­ing migraine:

The next big break­through in under­stand­ing migraine came with a bet­ter under­stand­ing of the brain cell that makes up the back­ground, pinkish-grey sub­stance of the brain, called the astro­cyte. Astro­cytes are called that because they look like a star, they have many lit­tle “finger-like” processes called den­drites, spread­ing out in all directions

Astro­cytes and Neurons
Because of these spread­ing fin­gers we thought that the astro­cytes were a sort of “skele­tal” sys­tem of the brain. Recently, with micro­scopes that can see the brain cells in three dimen­sions, we can see that the den­drites are not a sup­port­ing net­work, they are much more impor­tant than that. Each den­drite ends on the sur­face of neu­rons. Each small astro­cyte is assigned 20–40 neu­rons and their finger-like processes end on the sur­face of those neu­rons to talk to them.

The Astro­cyte Neu­rovas­cu­lar Unit
The astro­cyte also has a process that wraps around the sur­face of a nearby blood ves­sel. This col­lec­tion of 20–40 neu­rons, their astro­cyte, and its blood ves­sel con­nec­tion has been called an “astro­cyte neuro-vascular unit”. (10) The astro­cyte talks to its neu­rons, and can have “inhibitory” or “exci­ta­tory” input on the neu­rons it con­tacts, i.e. it can make the neu­ron more “on” or more “off”. The astro­cyte also has a very spe­cial adap­ta­tion that other brain cells do not have, namely the abil­ity to open pores between adjoin­ing astro­cytes, called “gap junc­tions”. When a gap junc­tion opens between two brother or sis­ter astro­cytes, the ionic envi­ron­ment of the two astro­cytes is directly shared.
With these dis­cov­er­ies con­cern­ing the anatomy and func­tion of the astro­cyte, it was time to repeat the orig­i­nal Dr. Leao exper­i­ments, and it was shown that the wave mea­sured mov­ing slowly through the brain, is actu­ally a cal­cium wave spread­ing through the astro­cyte pop­u­la­tion. (11)

Spread­ing depres­sion is a cal­cium wave spread­ing through the astro­cytes of the brain
The mis­be­hav­ing cal­cium chan­nels that cause migraine are prob­a­bly in the cell mem­brane of the astro­cyte, not the neu­ron. Thus the migraine usu­ally starts in the brain­stem but can quickly spread through the astro­cyte pop­u­la­tion into the whole brain caus­ing our inabil­ity to think, and our need to go to bed. The astro­cytes are inhibit­ing or turn­ing “off” the func­tion of large areas of neu­rons in our brain. All of our neu­rons are think­ing “I just don’t feel right”.
The astro­cyte neuro-vascular unit also explains another obser­va­tion made dur­ing exper­i­ments car­ried out in the late 1960’s. Exper­i­ments per­formed to show changes in blood flow of the brain dur­ing a migraine showed a spread­ing wave of decreased blood flow that was seen to par­al­lel the change in neu­ronal excitabil­ity. The mis­be­hav­ing astro­cytes are affect­ing the diam­e­ter of the blood ves­sel that they enve­lope. But, when our migraine suf­fer­ers tell us that they “can’t think right” dur­ing their migraine it is not the change in blood flow, but a change in the neu­rons’ func­tion­ing that is affect­ing their think­ing. Their neu­rons are being inhib­ited, turned down or “off” by the astrocytes.

If I’ve had this migraine gene all my life why are my headaches so bad now? And why do I have a headache every day?

The level of excitabil­ity of the brain stem “migraine gen­er­a­tor” (as well as the rest of the brain), is affected by many other chem­i­cals that affect the brain. The major fac­tors that worsen migraine, in my view, are sleep dis­or­ders, gonadotropin releas­ing hor­mone (GnRH), and monosodium glutamate.

Why do we humans have so many genes that cause headaches?

It’s inter­est­ing to note that the trigem­i­nal cau­dal nucleus and its anal­o­gous nucleus of the upper cer­vi­cal roots that trans­mit pain sig­nals con­tinue down the entire spinal cord per­form­ing the same func­tion for the body below the neck, yet it’s not com­mon for that por­tion of the spinal cord to turn on spon­ta­neously. If the genes that cause this hyper excitabil­ity were man­i­fested in the pain stripe itself the entire stripe should turn on spon­ta­neously. For instance why don’t I have the other half of my Neu­rol­ogy prac­tice filled with patients in whom pain occurs spon­ta­neously in the body below the neck just like headache? There cer­tainly are peo­ple who have pain below the neck but humans do not think it’s “nor­mal” for that lower 2/3 of their body to just start hurt­ing the way they do the head. My expla­na­tion is that the trigem­i­nal cau­dal nucleus and the cer­vi­cal pain nucleus that turn on spon­ta­neously do so because they’re next to another set of nuclei, that do not con­tinue into the spinal cord, called the peri­aquiduc­tal grey, where the tim­ing mech­a­nism for sleep resides. It is my belief that the entire pos­te­rior brain­stem and upper spinal cord becomes hyper excitable in migraine suf­fer­ers because the genes that cause migraine are actu­ally intended to make the sleep mech­a­nism work properly.

There are sev­eral other nuclei in the brain­stem that turn on spon­ta­neously in migraine but have noth­ing to do with head pain. The chemotrig­ger zone, that is just behind the trigem­i­nal cau­dal nucleus, is really there in order to pro­tect us from eat­ing dan­ger­ous chem­i­cals, it causes nau­sea and vom­it­ing when we eat some­thing dan­ger­ous. There’s a nucleus just ante­rior to the trigem­i­nal cau­dal nucleus, the supe­rior sal­va­tory nucleus, that causes nasal con­ges­tion. It also tends to turn on spon­ta­neously, thus the migraine suf­ferer who thinks they have “sinus headache” really does have a stuffy nose but it’s really a part of this spon­ta­neous “turn­ing on” of sev­eral parts of the pos­te­rior brain stem.

Migraine and sleep are intertwined:

It is my belief that the mul­ti­ple genes for migraine that have been car­ried on for gen­er­a­tions in humans are not there to cause headache. They’re prob­a­bly con­served within the pop­u­la­tion because they improve sleep. Sleep is always designed to turn on and off spon­ta­neously. That is absolutely by design, and it trumps all other func­tions of human life. There­fore any gene that makes sleep hap­pen more per­fectly, but “oops” causes an occa­sional headache in the process will prob­a­bly be passed on because sleep­ing well is one of the things that improves sur­vival and suc­cess­ful repro­duc­tion. It is actu­ally the most impor­tant thing we do every day. Unfor­tu­nately, you and I are liv­ing in a time when much or most of the pop­u­la­tion of the devel­oped world does not sleep well, this means that the genes that were meant to improve things leave us with pain syn­dromes that are more notice­able, fre­quent and severe than they were really “intended” to be.
Sleep and migraine have always been inter­twined. Most of the teenagers I see with daily headache have trou­ble falling asleep. Most of the women in menopause who now have daily headache can’t stay asleep. Most migraine suf­fer­ers have already real­ized that if they have one or two nights of bad sleep they’re more likely to get a headache the fol­low­ing day. It turns out that the women who wake with a headache in the mid­dle of the night usu­ally do so at a time when they stop breath­ing in REM sleep, and sleep dis­or­ders turn out to be the major cause of daily headache in my prac­tice. (Please see the sec­tion on Sleep).

Gonadotropin releas­ing hor­mone and migraine:

My expla­na­tion for the men­strual fluc­tu­a­tion of migraine relates not to estro­gen and prog­es­terone, but to the boss hor­mone that comes from the brain to tell the ovary when to make estro­gen. This hor­mone is called Gonadotropin Releas­ing Hor­mone (GnRH). We know that migraines usu­ally begin at puberty. They are worse in the females in the fam­ily. They get worse dur­ing menopause and usu­ally go away after menopause. We know from our expe­ri­ence with replace­ment hor­mones that estro­gen and prog­es­terone don’t take the headaches away. But Lupron, which acts as a GnRH blocker, is very effec­tive for severe, men­strual related migraine. (13)
GnRH is released from the brain dur­ing puberty in both boys and girls. In boys, through leu­tiniz­ing hor­mone (LH) it causes testos­terone to be formed by the testes. Then testos­terone feeds back to the brain to inhibit GnRH. In girls, also through LH, GNRH causes the ovaries to make estro­gen, which also feeds back to the brain to inhibit GnRH. The boys, at about 18, begin to make the same amount of testos­terone every day, so their GnRH does not fluc­tu­ate like the girls’, which spikes twice a month; at ovu­la­tion and men­stru­a­tion. Around menopause, when the ovaries run low on eggs, the estro­gen lev­els fall and GnRH goes up to try to tell the ovaries to make more estro­gen. GnRH is a hor­mone, mean­ing it is made in one part of the body to tell another part what to do, but it is also a “neu­ro­trans­mit­ter” which means it has recep­tors in the brain­stem, per­haps adding to the brain­stem hyper excitabil­ity, lead­ing to increase in migraine, and inter­rupted sleep.

What should I do about my headaches?

If the over the counter pain reliev­ers don’t com­pletely take the headache away and your headaches are once a week or less, your doc­tor will usu­ally start with one of the “trip­tans”. The trip­tans work on sero­tonin recep­tors in the brain­stem. When you get the right dose early enough, they turn all the recep­tors to “off” and the head pain, nau­sea, light and sound sen­si­tiv­ity, and the “I can’t think right” feel­ing all go com­pletely away together. All of the med­ica­tions in this cat­e­gory: suma­trip­tan, nara­trip­tan, eletrip­tan etc, have scary side effects of chest pres­sure, body stiff­ness, and a feel­ing of throat clo­sure that will freak you out if you aren’t warned about them. You are not hav­ing a heart attack or an aller­gic reac­tion, but if you feel bad you’re not likely to want to take that med­ica­tion as early as you need to. Most peo­ple can find one of the trip­tans that takes the headache com­pletely away with­out sig­nif­i­cant side effects. It’s well worth find­ing that med­ica­tion and using it as early as pos­si­ble. In my view there is no one trip­tan that is “the best”. Find one that has no side effects and use it early. Use what­ever dose is suc­cess­ful at the begin­ning. Once the headache is severe and has lasted more than one day, the med­ica­tions, even strong nar­cotic med­ica­tions, are not usu­ally very suc­cess­ful, and the only thing that really “breaks” the headache is sleep.
If the trip­tans fail it’s often because you’re not tak­ing them at the begin­ning. Usu­ally because you have fre­quent or daily headaches that the doc­tors have told you are some other type of headache. You wait to take the trip­tan until “it’s a migraine” and by then it’s too late. In my view all the headaches we all have are migraine in mech­a­nism, some are baby migraine, some are big migraine but they all hap­pen in the same way. Many of the daily headache suf­fer­ers find that the trip­tans don’t work for them. Once your sleep has improved or you find the right daily headache pre­ven­ta­tive the trip­tans will work for you again, so once the headaches are once a week or less try them again.

When should I take a daily, pre­ven­ta­tive medication?

Migraine suf­fer­ers with daily, or almost daily, milder headache, (or daily neck pain) usu­ally will see a Neu­rol­o­gist and be started on a “pre­ven­ta­tive med­i­cine”. This is a med­ica­tion that changes the excitabil­ity of the brain stem and will hope­fully pre­vent the headaches; ver­a­pamil (180-240mg), pro­pra­nolol (120-180mg), or atenolol (50-100mg). Top­i­ra­mate (50−100 mg hs, higher doses in some patients cause the headaches to return), zon­isimide (200-500mg start <100mg), val­proic acid (250-1000mg). Suc­cess is one mild headache a week that goes away imme­di­ately with a trip­tan med­ica­tion. If the first med­i­cine fails, your doc­tor will usu­ally stop it and try another. If the med­ica­tion ‘wears off” after it worked it usu­ally means you have a sleep dis­or­der, you’re sleep­ing but not get­ting into the deeper “work” phases of sleep.

Rebound headaches:

I dis­agree with the authors who think that most daily headache suf­fer­ers have caused their own headaches by tak­ing med­ica­tions daily. I see no rea­son to blame the patient for their own dis­ease. Most of my patients stop their daily med­i­cine and still have a headache daily or almost daily. I believe it’s the doctor’s job to treat the headaches by find­ing a med­ica­tion that pre­vents the headache.

What about MSG?

Watch for monosodium glu­ta­mate (MSG). Glu­t­a­mine is the main exci­ta­tory neu­ro­trans­mit­ter in the brain. It is used to excite the taste buds but in the patient with migraine it also turns on their hyper excitable brain­stem. Any­thing fla­vored with “smoky” “hick­ory” “Cajun” etc, is likely to have added MSG. Most canned soups and bouil­lon cubes have MSG, as do many diet foods.

How does sleep affect my headaches?

Sleep dis­or­ders are much more com­mon than we real­ized. Many of my young, female patients with severe daily headache have turned out to have abnor­mal sleep on a sleep study. Usu­ally it is the main rea­son for their lack of suc­cess with the pre­ven­ta­tive med­i­cines. Sleep apnea is not a dis­or­der of obese, older men. It is a dis­or­der that can come at any age, and it is only one of the sleep dis­or­ders that are seen in daily headache suf­fer­ers. (See sleep dis­or­ders sec­tion for more detailed dis­cus­sion of sleep disorders.)
Vit­a­min D defi­ciency, with or with­out accom­pa­ny­ing B12 defi­ciency appears to be the most com­mon cause of these sleep dis­or­ders in my patients. It may be the most com­mon cause of sleep apnea and non rest­ful sleep in the US and the world. (Please see Sleep sec­tion and Vit­a­min D for a more in depth dis­cus­sion of these topics.)

Chan­nel dis­or­ders and ver­tigo and epilepsy.

There are sev­eral other dis­or­ders of brain cell hyper excitabil­ity that are also chan­nel dis­or­ders. Famil­ial Episodic Ataxia (FEA) is an inher­ited dis­or­der that causes abrupt onset of severe ver­tigo and stag­ger­ing. It is a muta­tion of the same cal­cium chan­nel that can cause migraine, but the muta­tion affects another part of the pro­tein (5) FEA and migraine have sev­eral sim­i­lar­i­ties. Both occur spon­ta­neously, in nor­mal peo­ple, with­out any clear trig­ger­ing event. The patient’s brain mal­func­tions for hours to days, then is able to cor­rect the mal­func­tion and return to nor­mal. The MRI of the brain is nor­mal, i.e., there is no per­ma­nent injury. The anatomy is nor­mal, but the phys­i­ol­ogy is not. Some fam­i­lies have muta­tions that can man­i­fest some­times as ver­tigo, some­times as migraine. The most com­mon pre­sen­ta­tion is migraine before menopause, ver­tigo after menopause. Most fam­ily mem­bers have been told they have “benign posi­tional ver­tigo” which is prob­a­bly a dis­or­der of the gyro­scope appa­ra­tus in the exter­nal ear and is a dif­fer­ent prob­lem. Most patients with this benign posi­tional ver­tigo will have one or two attacks and they will resolve and not recur. Patients with repeated attacks should be treated like migraine: after the nor­mal MRI of the head, fix the sleep dis­or­der (check the vit­a­min D and B12 lev­els) or use a cal­cium or sodium chan­nel blocker.
Sim­i­lar cal­cium chan­nel muta­tions occur spon­ta­neously in mice. (9) The mice could never tell the inves­ti­ga­tors whether they had a headache, but they did have stag­ger­ing episodes and seizures. Not sur­pris­ingly most of the inher­ited epilepsy dis­or­ders in humans have also been found to be chan­nel dis­or­ders, usu­ally chlo­ride or sodium chan­nel muta­tions, more rarely cal­cium chan­nel muta­tions. Obvi­ously epilepsy is also a dis­or­der of hyper excitable brain cells, which is treated with seizure med­ica­tions that are gen­er­ally sodium or cal­cium chan­nel sta­bi­liz­ers. In my expe­ri­ence seizure dis­or­ders can also get worse when the sleep is worse. ( See sleep sec­tion and vit­a­min D section.)
Ref­er­ences:
1) Imag­ing the brain of m igraine suf­fer­ers. Flip­pen C, Welch KMA. Cur­rent Opin Neu­rol 1997;10:226–230.
2) The peri­aque­duc­tal grey mat­ter mod­u­lates trigemi­no­vas­cu­lar input: A role in migraine? Knight YE, Goadsby PJ. Neu­ro­science 2001;106(4):793–800.
3) Brain stem acti­va­tion in spon­ta­neous human migraine attacks. Weiller C, May A Limm­roth V, et al. Nature Med 1995 Jul;1(7):658–660.
4) A positron emis­sion tomo­graphic study in spon­ta­neous migraine. Afridi SK, Gif­fin NJ, Kaube H, Fis­ton KJ, Ward NS, Frack­owiak RS, Goadsby PJ. Arch Neu­rol 2005; 62(8): 1270–5.
5) Famil­ial hemi­plegic migraine and episodic ataxia type-2 are caused by muta­tions in the Ca++ chan­nel gene CACNL1A4. Cell 1996;87:543–552.
6) Muta­tions in the neu­ronal voltage-gated sodium chan­nel SCN1A in famil­ial hemi­plegic migraine type 3. van den Maag­den­berg A, Van­molkot KRJ, Welch KMA, et al. Cepha­lal­gia 2005;25:1189–1205.
7) Famil­ial basi­lar migraine asso­ci­ated with a new muta­tion in the ATP1A2 gene. Ambrosini A, D’Onofrio M, Grieco GS, et al. Neu­rol­ogy 2005;65:1826–1828
8) Three new famil­ial hemi­plegic migraine mutants affect P/Q type Ca++ chan­nel kinet­ics. Kraus RL, Sin­neg­ger MJ, Koschak A, et al. Jour Biol Chem 2000;275:9239–9243.
9) Migraine, ataxia and epilepsy: a chal­leng­ing spec­trum of genet­i­cally deter­mined cal­cium chan­nelopathies. Ter­windt GM, Ophoff RA, Joost Haan, Sand­kuijl LA, Frants RR, Fer­rari MD. Eur Jour Hum Gen 1998; 6(4): 297–307
10) Glial cells under phys­i­o­logic and patho­logic con­di­tions. Kurosin­ski P, Gotz J. Arch Neu­rol 2002;59:1524–1528.
11) Meningeal cells can com­mu­ni­cate with astro­cytes by cal­cium sig­nal­ing. Graf­stein B, Liu S, Cot­rina ML, Gold­man SA, Ned­er­gaard M. Ann Neu­rol 2000;47:18–25.
12) Mag­ne­toen­cephalo­graphic fields from patients with spon­ta­neous and induced migraine aura. Bowyer SM, Aurora SK, Moran JE, Tep­ley N, Welch KMA. Ann Neu­rol 2001;50:582–587.
13) Effec­tive treat­ment of severe men­strual migraine headaches with gonadotropin-releasing hor­mone ago­nist and “add-back” ther­apy. Murry SA, Muse KN. Fer­til­ity and Steril­ity 1997;67(2)390–393.
14) Trip­tans in migraine: the risks of stroke, car­dio­vas­cu­lar dis­ease, and death in prac­tice. Hall GC, Brown MM, Mo J, MacRae KD. Neu­rol­ogy 2004;62(4):563–8.
Other good reviews:
Recent advances in the diag­no­sis and man­age­ment of migraine. Goadsby PJ. BMJ 2006;332:25–28.
Peri­aque­duc­tal gray mat­ter dys­func­tion in migraine: cause or the bur­den of ill­ness? Welch KMA, Nagesh V, Aurora SK, Gel­man N. Headache 2001;41:629–637.