Headache, neck pain, and chondroitin sulfate

Many patients with chronic headache develop associated neck pain. In most cases, neck pain can be considered as “kindled” by chronic headache.

For example, when you accidentally touch a hot stove, your hand withdraws immediately, an action that is mediated by spinal reflexes without requiring the extra time involved in sending the message to the brain. Repeated experiences of pain will lead to a chronic withdrawal of neck muscles.

An interesting way to think about this phenomena is in terms of Pavlovian classical conditioning; with repeated experiences, the neck “learns” to stay tight in anticipation of an attack of head pain, and conversely neck pain may begin to trigger headaches. This “forward feedback loop” is an important mechanism for progression of intermittent migraine to chronic migraine.

We distinguish two types of reactivity of neck muscles in headache, the type above being a learned or conditioned response. In some patients, however, there is “good cause” for continued guarding, which most commonly are from arthritic changes of the cervical spine (arthritis of the neck).

Arthritic changes of the neck may cause pain from the joints of the neck, as well as nerve or spinal cord impingement from narrowing of the spinal canal or of the exiting canals for nerves.

Nonsteroidal medications (aspirin, ibuprofen, etc.) are often used to reduce arthritis of the cervical spine, but their effectiveness is limited over time, and the risks of serious complications (including heart attack and gastroinestinal hemorrhage) rises over time.

The article linked here http://www.medscape.com/viewarticle/749328 suggests that chondroitin sulfate, a component of cartilage and essentially a food, can be effective for arthritis (at least of the hands) when taken over several months. The compound is used commonly in Europe for generalized arthritis. It may be advisable to start chondroitin sulfate when cervical pain occurs, or when headache is associated with arthritic conditions of the neck, along with an NSAID, and discontinue the NSAID after a few months, when chondroitin becomes effective.

Sleep Retraining with Chronic Headache

Sleep Retraining

Many patients with chronic headache of all types, but especially those with migraine, commonly experience insomnia. Research on brain changes in migraine headaches indicates that insomnia is part of the condition of migraine; that is, if you have headaches long enough, you will have trouble sleeping.

Poor sleep is much more than an inconvenience. Deep sleep is necessary for interrupting pain cycles.

All too often, patients with headache and insomnia will begin to take sleep medications which lose effectiveness over time. When this occurs, we often recommend sleep retraining.

Sleep retraining is a technique you manage yourself. It does not require pills, office visits, or special equipment. And, it is the most effective way to develop natural sleep patterns for almost all patients with headache and insomnia.

How do I do it?

The easy way that works-

1) Stay up all night.

2) Stay in bed one hour the next night.

3) Stay in bed two hours the next night.

4) Stay in bed three hours the next night.

5) Stay in bed four hours the next night.

6) Keep increasing sleep each night.

Frequently asked questions:

1) How do I choose my time to awake?

-Any time you like. Many people choose 7AM. Set your alarm clock.

2) Can I nap during the day?

-No.

3) Can I sleep late on weekends?

-No.

4) What should I do if I get off schedule?

-Restart the sleep restriction program.

5) How do I stop the sleep medications?

- Medications intended only for sleep (Ambien, zolpidem, Lunesta) can be stopped when you stay up the first night. Some medications may help with sleep and are actually used to prevent headaches, such as certain anticonvulsant medications and antidepressants, and these should be continued (such as Limbitrol, Elavil, amitriptyline, Lyrica, gabapentin).

6) I was in the bed for one hour the second night and did not sleep at all. Is this OK?

-Yes. The important part is that you gave yourself the opportunity to sleep for one hour. Eventually your body will start to naturally use the time you allow yourself in bed to achieve sleep.

7) What if I’m too sleepy to stay awake until the next night?

-The important part is that you set your alarm clock for the same time each morning; increase the time you allow yourself in bed progressively over time; and do not nap during the day. The exact schedule isn't important, and you can write yourself an easier one.

8) What if my headaches get worse?

-Withdrawal of sleep medicine may be associated with some symptoms similar to withdrawal of alcohol or other addictive substances. If the headaches are unusual in any way or persist longer than three days after withdrawal make an appointment to be re-evaluated.

9) I just can’t tolerate the schedule, it’s too strict.

-It’s fine to stretch out the schedule, just start by restricting your sleep, and progressively lengthen the time in bed.

10) I did the sleep restriction program and slept well for two weeks, then I had trouble sleeping again. What should I do?

-Some people will need to stay up once a week, once a month, once each season, or from time to time, to “re-set their brain clock”. You may only need to stay up for ½ night or a few hours.

11) Anything else I can do to help sleep?

-No lights or TV at night, stop caffeine, and keep the room cool at night. Staying active during the day. A progressive exercise program keeps you awake during the day and prepares your body to sleep that night.

Psychiatric Co-Morbidity and Botox for Chronic Migraine

Dear Psychiatrist,

Botox (onabotulinumtoxinA) was approved by the FDA in Septermber of 2010 for the treatment of chronic migraine.

The IHS definition of chronic migraine requires migraine symptoms with total headache days greater than 14 days each month for the previous three months. Most patients with chronic migraine have very close to continuous, if low grade, daily headache. The benefit of Botox in controlled trials was evident even in the absence of other treatments for migraine (such as treatment of medication overuse and caffeine related headache) or a general treatment program through a headache clinic.

At the North Carolina Comprehensive Headache Clinic, we have administered approximately 800 doses of Botox for migraine since 1993 with no serious complications.

Treating chronic migraine with Botox has been well tolerated, and when combined with general measures to treat chronic migraine, we have found it to be clinically useful. The selection criteria here is strict: other headache syndromes must be excluded (hemicrania continua, primary thunderclap headache, new persistent daily headache, cluster headache, hypnic headache, disorders of cerebrospinal fluid pressure, and headache secondary to other causes), medication and caffeine overuse withdrawn under supervision, and lack of efficacy of preventive medications documented before Botox is recommended.

The patient with chronic migraine and significant psychiatric co-morbidities presents complex diagnostic challenges and management difficulties. In patients with ongoing psychiatric care, adding psychotropic medications to treat chronic migraine as a separate condition may increase management complexity and patient risk. Concerns for the risk of serotonin syndrome, hyperthermia, suicide, inadvertent over-dosage, automobile accidents, and increase in metabolic complications (weight gain, hypertension, cardiac arrythmias, glucose intolerance) have previously significantly limited options for psychiatric patients.

Of all the groups of headache patients we see, we believe that the FDA approval of Botox will most benefit the care and management of the patient with chronic migraine and psychiatric co-morbidities.

For long-term management, Botox is administered only once every three months, which significantly reduces the need for Headache Clinic visits. Psychotropic medication may then be selected by the psychiatrist for optimal management of psychiatric conditions.

It is important to note that Botox has not been shown to benefit patients whose headache occurs less than 15 days/month.

We find that many patients with chronic headache “under count” their headache days, often because they do not wish to be seen as complaining of “normal” daily headache. We are also concerned that patients with true episodic migraine occurring less that 15 days/month will “over count” in hopes of obtaining Botox coverage. However, we feel it is well established that Botox will not benefit patients with intermittent migraine. Possibly, this is because Botox suppresses classical conditioning and kindling that may be involved in migraine transformation over time, thus allowing chronic migraine to be converted back to a more manageable intermittent migraine.

It is also important to note that Botox carries a black box warning and that patients should be selected appropriately.

Neurologists in our area that administer Botox can be found at the Allergan web site, or through the American Council on Headache Education. Patients may also be referred directly to NCCHC for neurological evaluation.

Sincerely,

Charles Matthews M.D

North Carolina Comprehensive Headache Clinic

Raleigh, N.C.

About Headaches: Botox Approved by FDA for treatment of Chronic Migraine

About Headaches: Botox Approved by FDA for treatment of Chronic Migraine

Botox Approved by FDA for treatment of Chronic Migraine

Dr. Charles Matthews is a board certified neurologist and Director of the North Carolina Comprehensive Headache Clinic. Here is an interview by Health and Healing with Dr. Matthews about the recent FDA approval of Botox for chronic migraine follows.

Q- Dr. Matthews, can you tell us about Botox, and why it’s being used for the treatment of migraine headaches?

Dr. Matthews: Sure. But first, my usual caution: Botox was FDA approved for chronic migraine. if you have frequent headaches, they are likely to be migraine, but they may not bemigraine. I apologize if I can get tiresome on this point!

There are many causes of chronic headache. Other types of chronic headache include chronic or paroxysmal hemicrania, hypnic headache, cluster headache, primary thunderclap headache, spontaneous intracranial hypotension, benign intracranial hypertension, trigeminal neuralgia, and others.

Infections and inflammatory disorders like temporal arteritis can also cause chronic headache. Botox doesn’t help any of these conditions. Typically in these conditions a standard MRI will be negative, so you really should have a neurologist go over these possibilities with you. The Triangle area has many outstanding neurologists who are knowledgeable about headache.

Q- Maybe not migraine, got it. So, tell us about Botox for migraine!

Dr. Matthews: Botox is a trademark of Allergan, the pharmaceutical company that makes onabotulinumtoxinA for medical use. Botox received FDA approval for the treatment of chronic migraines in October of 2010. So, when I say “Botox”, I’m referring to that particular type of botulinum toxin.

Botulinum toxin is made by a bacterium, Clostridium botulinum, that causes botulism. Botulism is one of the great old medical diseases, not common now, but very dramatic and it played an important historical role in understanding neurophysiology. The word “botulism” derives from German for sausage, as I understand it; it was described in Germany when people became ill from bad sausages.

Clostridium is a family of bacteria that grow best in low oxygen environments. You may have heard of “C. difficile”, an infection that occurs in the bowel when someone has wiped out the normal bacteria there with antibiotics. That’s another closely related “anaerobic” bacterium. C. botulinum, the organism that makes Botox, grows in canned foods that weren’t adequately sterilized, like sausages and green beans.

Q- Why do bacteria make toxins?

Hey, that’s a great question! Bacteria as a group can reproduce very rapidly. Let’s say that a bacterium divides once every twelve hours...in a month, if you don’t have something constraining the growth, that means you will have 2 to the sixtieth bacteria. That’s a lot of bacteria! In very short order, the surface of the earth would be covered unless something happens. The reason this doesn’t happen is, partly, they run out of food, but mostly, bacteria make poisons to kill off their competitors. Sometimes the poisons cause problems for people.

Q- You’re kind of a geek, aren’t you? (laughing).

Dr. Matthews: You were the one who asked the question! (laughing).

Botulinim toxin is really a muscle relaxant. It has some other effects, but the one best understood is how it works to relax muscles. Nerve endings very close to the muscle surface secrete a chemical that tell the muscle to contract. The chemical is called acetylcholine, and it is squirted out of the nerve and sticks to the muscle at sites that are called acetylcholine receptors, and that tells the muscle contract.

Botox works at least partly as an injectible muscle relatant. When Botox is injected into the muscle, it binds to a receptor on the muscle surface, and stays there. It blocks the signal from the brain to make the muscle contract. The binding is like hair dye; it’s permanent, but after awhile the roots start showing! It’s the same with Botox; after awhile new receptors are made, so the Botox falls out with the receptor. There are no known permanent side effects of Botox.

The word “toxin” can be misleading. When properly injected in low doses, it doesn’t make you toxic all over; it’s just toxic to the acetylcholine receptor at the injection site, and then you grow new ones.

Q: How long does Botox last?

Dr. Matthews: New receptors are made after about three months, about the same length of time as it takes to make new red blood cells.

Q- How do you use Botox to treat migraine?

Dr. Matthews: It’s important to realize that Botox has only been shown to work for chronic migraine. “Chronic” means you have migraine headaches more than half the time (more than 14 days a month).

Q- What if the person has migraine headaches only 13 days/month?

Dr. Matthews: Good question! I think you’re turning into a geek yourself!

It’s a complicated question, and it’s under discussion among headache specialsts. But basically, “chronic migraine” is in important ways different from episodic migraine. I don’t believe there is any benefit at all from using Botox for headaches that occur on fewer than 15 days a month. So, if you’re thinking you could add just a few headache days to your count and get the magic Botox paid for, you’re wrong, I think. Don’t do it!

It isn’t that Botox will one day be seen to benefit episodic migraine, or that people with episodic migraine are getting shortchanged since Botox is not covered for them. It’s that it just doesn’t work with episodic migraine.

Q- What’s special about chronic migraine?

Dr. Matthews: Nothing definite, but this is what I think is happening. For many people, they start out having episodic migraine, maybe a few times a month, then a few times a week. What causes this transformation from episodic to chronic migraine? I personally think that classical conditioning, like Pavlov described, plays an important role in transformation to chronic migraine, and suppressing that conditioning with Botox can convert chronic migraine back to episodic migraine, hopefully the frequency you had migraines when you started. So, Botox may cause aremission of chronic migraine by keeping headaches suppressed for long periods of time.

I’ll caution here that long term remission of chronic migraine has not been adequately studies experimentally. But I’ve administered Botox about 800 times for migraine since 1993, and in my experience there has not been a single case of continued need for Botox beyond about three years. The most common is three applications, once every three months, and then we wait and see if they are still needed.

Q- What’s classical conditioning again?

Dr. Matthews: I knew it, you really are a geek!

Ivan Pavlov was a Russian psysiologist. You can read about him athttp://en.wikipedia.org/wiki/Ivan_Pavlov .He was the one who rang the bell when the dog was fed, and after awhile you didn’t need food, the dog salivated anyway when the bell rang.

In migraine, every time you have a headache attack, and something else happens at the same time, your brain learns to link these up. I think this is one reason (there are others) that people with migraine attacks eventually get neck pain- the neck “learns” that a migraine is coming, and starts to guard just like the dog learns to salivate when the bell rings. After awhile, the neck stays tight, and the brain learns this as a trigger for migraine. This mutual “conditioning” eventually leads to progression, with the neck pain triggering migraine, and the migraine triggering neck pain.

In general, people who have migraine usually have triggers- odors, weather, food, fatigue, menses. Sometimes they will run their lives trying to avoid all their triggers. They come to the headache clinic hoping I will help them identify all their triggers. Unfortunately, when the migraine is chronic, avoiding triggers is like arranging deck chairs on the Titanic. If you avoid one trigger, your brain will learn a new one.

So, in my view, Botox may work by suppressing chronic migraine for a sufficiently long period of time for your body to unlearn those classical conditioned responses.

Q- How well does Botox work to suppress chronic migraine?

Dr. Matthews: The available studies show only a modest effect, that continues to increase for about six months though the second administration. Longer outcomes haven’t been studied adequately.

The studies were done in specialty headache clinics. My colleague headache specialists that did this work, and the subsequent FDA recommendations, I think everyone did a terrific job here. The approved dose, and administration schedule, shows great thought. OK, I said it: I’m proud of the FDA on this one!

They did not look at how well this modest effect would hold up when used outside of headache centers, and I think it won’t work quite as well in the followup studies. So, I have some sympathy with the hesitancy of some insurers. On the other hand, combining Botox with other treatments, I expect, will work out much better than previous studies, since in my view the whole point is to suppress chronic migraine completely for months in an attempt to get a remission to episodic migraine. So, Botox for chronic migraine may work best in an overall headache program.

Combining properly chosen preventive medicines, treatment for factors that make migraines worse such as sleep disturbance and pain medication overuse, and nerve blocks when indicated, when combined have a high rate of success in inducing chronic migraine remission.

At the Headache Clinic, when treating chronic migraine we look down the road five years, sometimes twenty years. We want the patient to be way better for the long term than they would have been if they had not seen us.

I think treating chronic migraine with the goal of remission does people a lot of good. In the long term, less OTC painkillers that cause so many problems, fewer migraines, no lost days at work or with your family, hopefully few or no doctor visits for headache, better health overall.

And that’s what medicine is all about.

------------------------------------------------------------------------

Dr. Charles Matthews was the 1978 Jefferson Fellow in Medicine at the University of Virginia.

You can make an appointment at the North Carolina Comprehensive Headache by calling 919 781 7423.

Botox, Chronic Migraine, and Psychiatric Co-Morbidities

As you may know by now, Botox (onabotulinum toxin A) was approved by the FDA in October of 2010 for the treatment of chronic migraine. The IHS definition of chronic migraine requires the existence of migraine symptoms, with total headache days greater than 14 days each month for the previous three months. Most patients with chronic migraine have very close to continuous, if low grade, daily headache. The benefit in controlled trials was evident even in the absence of other treatments for migraine (such as treatment of medication overuse and caffeine related headache) or a general treatment program through a headache clinic.

At the North Carolina Comprehensive Headache Clinic, we have administered approximately 800 doses of Botox for migraine since 1993 with no serious complications. The treatment has been well tolerated, and when combined with general measures to treat chronic migraine, we have found it to be clinically useful. The selection criteria here is strict. Other headache syndromes must be excluded (hemicrania continua, primary thunderclap headache, new persistent daily headache, cluster headache, hypnic headache, intracranial hypotension and intracranial hypertension, and secondary headaches). Before recommending Botox, in the past we have treated medication overuse and prescribe preventive medications tailored to the patient’s symptoms, along with a wellness program, before recommending Botox.

The patient with chronic migraine and significant psychiatric co-morbidities has long presented special diagnostic challenges, followed by management difficulties. In patients whose psychiatric condition is sufficiently serious to require ongoing psychiatric care, the use of additional psychotropic medications to treat chronic migraine as a separate condition often provides few options at considerably increased risk of complications, and clear increase in management complexity. Serotonin syndrome, assessment of suicide risk, inadvertent overdosage, automobile accidents, and increase in metabolic complications (particularly weight gain) have previously significantly limited safe options for these patients.

Of all the groups of headache patients we see, we believe that the FDA approval of Botox will most benefit the care and management of the patient with chronic migraine and psychiatric co-morbidities.

For long-term management, Botox is administered only once every three months, which significantly reduces the total burden of Headache Clinic visits for the patient, and allows psychotropic medication to be selected on the basis of optimal management of the psychiatric condition alone.

. Much that we do could be confined to self-directed instructions or our Web-based information on self-care. Recommendations for adding pharmaceutical treatment can be suggested to the treating psychiatrist to use or not, as they find appropriate to the overall psychiatric program of care.

It is important to note that Botox has not been shown to benefit patients whose headache occurs less than 15 days/month.

While we find that many patients with chronic headache “under count” their headche days, often because they do not wish to be seen as complaining of “normal” daily headache. On the other hand, we are concerned that patients with true episodic migraine occurring less that 15 days/month will over count in hopes of obtaining Botox coverage. However, we feel it is well established that patients with intermittent migraine will not benefit from Botox. Possibly, this is because Botox suppresses the processes that produce migraine transformation over time, such as classical conditioning and kindling, thus allowing chronic migraine to be converted back to a more manageable intermittent migraine. It is also important to note that Botox carries a black box warning and that patients should be selected appropriately.

There are other neurologists in the area who are experienced in the use of Botox and in headache diagnosis and treatment who can be accessed through the Allergan web site or through the American Council on Headache Education. Appointments for evaluation can be made though the link to the office.



Sincerely,


Charles Matthews M.D.

Director, the North Carolina Comprehensive Headache Clinic
Raleigh

Botox Approved by FDA for treatment of Chronic Migraine

The following article is reprinted from WebMD and reviews the FDA approval of Botox for the treatment of chronic migraine.
The article is accurate but I will add some further observations and cautions.

1) We have administered 800 applications of Botox at the Headache Clinic since 1993. The total number of applications is large,but the frequency is low: this represents less than one application a week over a very long period of time. We have not had a single significant complication during that time.

2) Although I have been a critic of the FDA in many cases, I believe that the particular protocol approved by the FDA represents a significant advancement in the treatment of chronic migraine and was reviewed very thoughtfully. The FDA, in short, did a terrific job here. The specific protocol of injection sites, standard administration, and adequate total dose (200 units) is a meaningful improvement over previous protocols for Botox administration, and represents hard work by many of our colleagues in migraine research to optimize this treatment.

3) For many patients with medical problems other than migraine, we have in the past attempted to optimize the treatment of the other problems hoping to improve the chronic migraine. A common example is the patient who has significant depression as well as chronic migraine, where the use of antidepressants may benefit both depression and migraine. When depression is severe, however, it is often best to allow the treatment of depression to be optimized for that problem, rather than trying to find an antidepressant medication that would benefit both. For patients most severely affected by multiple medical problems, the FDA approval of Botox may present a significant new therapy- simpler to use, and without medication interactions, psychotropic side effects, or weight gain concerns.

4) Botox has not been shown to benefit patients with less than 15 headache days/month. This lack of benefit for episodic migraine- as opposed to chronic migraine- probably reflects the fact that patients with chronic migraine have a different disease than episodic migraine in some important ways. For the patient considering Botox, don’t overstate the number of headache days each month you are experiencing! Keep in mind that overstating the humber of headache days/month may lead to treatment with Botox that will not benefit you.

4) There is no experimental evidence that Botox cures migraine- nor is there experimental evidence there it does not. In my experience with 20 years of Botox use for migraine headache, most patients are able to stop Botox after three doses (9 months), a few stayed with treatment every three months for up to three years, but none required treatment beyond three years. Possibly the use of Botox was limited over time by cost, but my guess (and it is a guess) is that any treatment that induces a remission of chronic migraine for a sufficiently long period of time can convert a chronic migraine into a much more easily controlled episodic migraine. My experience is that the migraine characteristics return to those similar to when the headaches started man years ago; that is, from perhaps 20 days/month to three days/month, and from being refractory to all rescue medications to return of effectiveness of standard migraine medications that can be taken at the time of the headache, such as Imitrex.

5) My hypothesis of migraine progression over time involves classical conditioning. Repeated attacks of migraine “link up” with other body functions, in a manner similar to a training effect (as Pavlov described). So, over time, patients with migraine develop more and more migraine “triggers”, neck pain associated with migraine, hypervigilence and insomnia, body pain, and digestive motility disorders (“irritable bowel syndrome”). These “linked”, or classically conditioned, reflexes may be abolished, and these other health problems resolved, with suppression of migraine for a period of time. Three doses of Botox (nine months) often is sufficient.

6) A single treatment of Botox administered for chronic migraine alone is only modestly effective in reducing migraine frequency, and should be administered as part of a headache management plan that includes exercise, general health improvement, sleep regularization, restriction of environmental contributors to migraine, and possibly continued but minimized migraine preventative medication. Botox can be a significant benefit in inducing chronic migraine remission when administered by a headache specialist planning for long term improvement.




FDA Approves Botox to Treat Chronic Migraines
Injections of Botox Can Relieve Migraine Headache Symptoms for up to 3 Months
By Bill Hendrick
WebMD Health News Reviewed by Laura J. Martin, MD

Oct. 18, 2010 -- Botox -- famous for smoothing out wrinkles on the face -- has been approved by the FDA to treat chronic migraine headaches in adults.

The FDA says Botox injections have been shown to be effective in the prevention of migraines, which are debilitating headaches that cause intense pulsing or throbbing pain and affect about 12% of Americans.

“Chronic migraine is one of the most disabling forms of headache,” Russell Katz, MD, of the FDA, says in a news release. “Patients with chronic migraine experience a headache more than 14 days of the month. This condition can greatly affect family, work, and social life, so it is important to have a variety of effective treatment options available.”

Migraine headaches are sometimes called “sick headaches” because they often are accompanied by nausea and sensitivity to light and sound.


How Botox Is Used to Treat Migraines


Botox to treat chronic migraines is given at intervals of about 12 weeks as multiple injections around the head and neck to try to dull future headache symptoms, the FDA says in a statement.

The FDA says it’s important that patients who suffer chronic migraines discuss with their doctors whether Botox is appropriate for them.

Allergan Inc., the maker of Botox, says in a statement that the FDA’s approval applies to people with chronic migraine, which it defines as a “distinct and severe neurological disorder characterized by patients who have a history of migraine and suffer from headaches on 15 or more days per month with headaches lasting four hours a day or longer.”

The company says that when treating chronic migraine, qualified medical specialists administer 31 Botox injections into seven specific head and neck sites.

It says that Botox, when injected at labeled doses in recommended areas, is expected to produce results lasting up to three months depending on the individual patient.

Botox Studies

“Chronic migraine is a debilitating but under-recognized neurological condition,” Scott Whitcup, MD, Allergan’s chief scientific officer, says in the company’s announcement. “Oftentimes, chronic migraine patients mistakenly self-diagnose their symptoms as headaches or infrequent migraine and treat them with drugs that provide rapid, but temporary, relief rather than seeking an evaluation, diagnosis and treatment from a qualified headache specialist.”

He says with the FDA’s approval of Botox to prevent migraines, there is now a new option “to reduce the days and hours spent in pain as a result of this condition.”

It says the FDA’s approval for use of Botox to fight migraines was based on the results of two studies involving 1,384 adults in North America and Europe.

The studies, published in the March 2010 issue of Cephalalgia, report that patients treated with Botox experienced a major decrease in the frequency of headache days, according to the Allergan statement.


The most common adverse reactions reported by patients being treated for chronic migraine have been neck pain and headache, the FDA says.

The FDA also has placed a “boxed warning” on the anti-migraine drug, onabotulinumtoxinA, marketed as Botox and Botox Cosmetic. The warning says the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism.

These symptoms can include swallowing and breathing problems. The FDA says it knows of no confirmed cases of the spread of the toxin effect when Botox has been used at the recommended dose to treat chronic migraines, severe underarm sweating, or conditions such as blepharospasm, an involuntary muscle spasm in the muscles surrounding the eyes.

The drug also can cause muscle weakness, double vision, blurred vision, drooping eyelids, loss of bladder control, and hoarseness, Allergan’s statement says.

The same formulation of Botox was approved by the FDA in 2002 for the treatment of facial frown lines.

The FDA says Botox does not appear to be useful in treating or preventing less frequent migraines that occur 14 days or less per month or other forms of headache

Rescue Medication for Chronic Migraine Pain

Migraine and other types of headache may be so persistent and severe that the use of many medications for pain may actually cause headaches to worsen over time. This is classified as “medication overuse headache” (MOH) in the migraine medical literature.

Patients with over fifteen migraine headache days each month are classified as “chronic migraine”. The management of chronic migraine is significantly different from episodic migraine (less than fifteen days of migraine headache each month). One of the most important ways the management differs is in the need for migraine headache pain medication that will not worsen the headache severity and frequency over time.


For chronic migraine headache pain, medication that does not contribute to Medication Overuse Headache is recommended The reader should be reminded that all drugs when overused can be harmful and potentially fatal, but some are more troubling than others, and at least in moderate overuse patterns some are not likely to prompt the development of Medication Overuse Headache.

Preferred medications include:

Hydroxyzine (oral or parenteral)
Baclofen
Tizanidine
NSAIDs (p.o., IM, p.r.), especially naproxen and indomethacin.
Aspirin specifically, such as Trilisate
Neuroleptics (oral, p.r., parenteral)
Benzodiazepines (oral or parenteral)
Various muscle relaxants, including metaxalone and methocarbamol (which have a central effect).

(This list is adapted from the web site of the Michigan Head Pain and Neurological Institute, an excellent inpatient headache clinic whose link is posted above).

It can be difficult for the patient with chronic migraine to accept that some pain may be necessary to reduce migraine headache frequency. Pain receptors that are adapted to chronic pain medication can increase the sensitivity to pain over time; the experience of pain in medication withdrawal may be necessary for correction of this problem. Although pain medications may need to be limited or stopped completely, other treatments such as those above, and medications that induce relaxation or sleep, are often helpful during the period of pain medication withdrawal.

Novel Treatment for Low Pressure Headache

There are a number of headache syndromes that mimic chronic migraine but require different management. One group of headaches may be characterized by low cerebrospinal pressure. The defining clinical symptom of intracranial hypotension headaches is improvement when lying flat; the flat posture reduces cerebrospinal fluid outflow, possibly increases CSF production, and relieves gravitational traction on the meninges. Causes of intracranial hypotension include headache following lumbar puncture (post-LP headache), spontaneous intracranial hypotension, spinal fluid leaks, and likely a number of other mechanisms that are currently poorly understood. Diagnosis is by history of postural sensitivity, and diagnostic lumbar puncture. Careful measurement of CSF pressure is mandatory, as straining or breath holding may spuriously raise cerebrospinal fluid pressure. An MRI obtained with gadolinium enhancement can show typical meningeal enhancement but this must be looked for specifically, and will likely be missed on a non-contrasted MRI.

There are emerging surgical procedures to intervene in these types of headaches. However, there are some simple measures that may help, both in diagnosis and, in some cases, may be sufficiently effective treatment. These include caffeine administration in high doses, and the administration of ACTH or similar analogues; both of these agents increase CSF production.

Two interesting articles from the literature follow. They refer to post-LP headache, but the mechanism of treatment may be applicable to all headache caused by intracranial hypotension. Both caffeine administration and the use of ACTH are simple to administer and carry little risk.


Reg Anesth. 1997 Sep-Oct;22(5):432-4.
Adrenocorticotropic hormone infusion as a novel treatment for postdural puncture headache.
Kshatri AM, Foster PA.

Department of Anesthesia, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, USA.
Abstract
BACKGROUND AND OBJECTIVES: In two patients, one scheduled for epidural anesthesia and the other for placement of a spinal catheter for operative procedures, severe postdural puncture headache developed and was refractory to conservative therapy.

METHODS: The first patient had several unintentional dural punctures, and the second underwent a planned dural puncture with an 18-gauge needle for insertion of a 20-gauge catheter. When neither patient responded to conservative therapy following development of postdural puncture headache, an infusion of adrenocorticotropic hormone (ACTH) was given prior to consideration of epidural blood patching.

RESULTS: Both patients obtained complete and permanent relief from their headaches.

CONCLUSION: A single treatment with ACTH may offer an alternative therapy in the treatment of postdural puncture headache.

PMID: 9338904 [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances
LinkOut - more resources


Use of Intravenous Tetracosactin in the Treatment of Postdural Puncture Headache: Our Experience in Forty Cases
Luz Cánovas, MD PhD, Carmen Barros, Ana Gómez, Marcos Castro and Andrés Castro

Department of Anesthesiology, Complejo Hospitalario Orense, Spain
To the Editor:

Adrenocorticotropic hormone (ACTH) for treatment of Postdural Puncture Headache (PDPH) has been briefly mentioned in literature (1–4). We present the use of tetracosactin in 40 patients suffering PDPH.

All patients presented with severe headache in the occipital region that worsened in the upright position, associated in most cases with nausea and vomiting (5). Tetracosactin, which contains the first 24 amino acids of the natural ACTH sequence and has the same physiological properties, was administered. Saline solution 1.5 U/kg in 250 mL was administered over 30 min (2,3). Pain intensity was evaluated after 6, 24, and 72 h post-therapy. After 6 h, 38 patients of the study presented complete pain relief, which remained in further controls.

The ACTH-induced production of aldosterone causes an increase in the intravascular volume and may determine the closure of the orifice by others means: dural edema or by physical opposition of the dural orifice margins (6).

It has been speculated with the possibility of ACTH increasing CSF production, through a sodium active transport mechanism, and a possible increase in the production of β endorphins in the central nervous system with a subsequent increase in pain threshold (1,4).

We believe that IV ACTH is an effective alternative to conservative therapy in PDPH.

References

↵ Collier B. Treatment for PDPH. Br J Anaesth 1994; 72: 366–7. FREE Full Text
↵ Foster P. ACTH treatment for post lumbar puncture headache. Br J Anaesth 1994; 72: 429.
↵ Kshatri A, Foster P. Adrenocorticotropic hormone infusion as a novel treatment for postdural puncture headache. Reg Anesth 1997; 22: 432–4. Medline
↵ Carter B, Pasupuleti R. Use of intravenous cosyntropin in the treatment of postdural puncture headache. Anesthesiology 2000; 92: 272–4. Medline
↵ Liu S. Why are postdural puncture headaches still a problem? Reg Anesth Pain Med 2000; 25: 393–402. CrossRefMedline
↵ Baysinger C, Menk E, Horte E, Middaugh R. The successful treatment of dural puncture headache after failed epidural blood patch. Anesth Analg 1986; 65: 1242–4. FREE Full Text

Migraine, Stress, and Inflammation

Dr. Charles Matthews is a neurologist, and the Director of the North Carolina Comprehensive Headache Clinic. An interview with him about migraine, stress, and inflammation follows. We hope you find it of interest for your general health as well as for those who need medical attention for headache and migraine.

Q- Dr. Matthews, is there a connection between stress, inflammation, and migraine?

A- There are some very interesting connections. But before I try to answer your question, I’ll offer my usual warning: there are are many types of headache, but only migraine has been demonstrated to be clearly associated with inflammation. Headache classification and diagnosis have been helpfully formalized by the International Headache Society. If you are curious about what different types of headaches there are, you can access the medical classification of headaches directly through the IHS website, or though our website at ncheadaches.com.

But basically, if you have a problem with headaches whose diagnosis is not yet clear, this discussion may not be relevant to you. An accurate diagnosis is necessary before you begin to even think about the cause. Our discussion today is about a particular type of headache called migraine, which is known to be at least mediated by inflammation.

Q- Dr. Matthews, what is the connection between migraine and inflammation?

A- I though you’d never ask! OK, let’s go back a little bit and talk about Hans Selye. Selye was a brilliant physiologist who laid the experimental foundation for thinking about stress and inflammation. Selye described a generalized stress response that occurs whenever anything changes in your body. The series of changes include hormone secretion such as cortisol, adrenalin, and others. Selye realized that “stress is stress”. The body doesn’t care whether your husband is yelling at you or if you have a stomach virus. According to Selye stress is all the same in how it affects your body.

Stress hormones are secreted under the control of the brain, which senses these changes and tells the glands to get going. So, under the influence of stress hormones, the blood pressure and heart rate go up, your blood glucose goes up just as if you were a little bit diabetic, your hands become cold as the arteries clamp down in case there is blood loss.

Selye’s sequence of physiological events have been called “fight or flight”. If you are interested in stress, get a copy of one of Selye’s many works, they are well worth reading in the original.

Q- If you excrete steroids like cortisol, isn’t this bad for you?

Dr. Matthews: That depends on your situation. Cortisol, like any steroid, is secreted by the body to suppress excess inflammation. With inflammation, we have a Goldilocks situation: it’s best to have not too much, and not too little.

For example, if you have poison ivy, your doctor may give you a prednisone dosepack to reduce the inflammation. And your body will do the same thing under stress naturally, so you can make your own prednisone dosepack. A small amount of steroids under stress will be produced naturally by your body, and that can be a good thing.

If the stress goes on for a longer time, you begin to run out of cortisol. Your adrenal glands can only do so much and they get tired like the rest of you does. When you run out of cortisol you excrete adrenalin, which is very short term. Adrenalin raises your blood pressure, your heart rate, your blood glucose, and generally makes you act like you are running a race for your life and you need all the fuel you can get, right now.

Steroids in general, like prednisone as well as those you naturally excrete yourself, cause suppression of the immune system,. Steroids also cause tissue catabolism, which means that you start using your body for fuel for this stress response. So in one sense your body carries a store of protein and sugar that can be called on by the stress response.

A little stress can be a good thing. If you have poison ivy, or say a sinus infection, the inflammatory response produces dilation of blood vessels in the area of the iirritation. When the vessels dilate they leak white cells into the affected tissue, and the white cells fight the toxin or the infection.

The classic description of localized inflammation, like poison ivy or sinusitis, was “calor, dolor, rubor, and tumor”- Latin for heat, pain, redness, and swelling.

What about when there is a lot of stress? Prolonged stress causes multiple medical problems that appear remarkably identical to those seen with aging. Chronic steroid excretion under stress can cause the same problems as long-term use of prednisone: muscle atrophy, skin atrophy and wrinkles, bone loss (osteoporosis), elevation of blood sugar and changes consistent with diabetes, and exhaustion. Some researchers think that aging is actually a form of stress.

Q- So, what does this have to do with migraine?

Dr. Matthews: There is an interesting animal model of migraine which involves stressing the trigeminal nerve, one of the nerves that supply the head. The researchers place an electrode on the trigeminal nerve and stimulate it continuously, stressing it beyond usual physiological use. The trigeminal nerve supplies the face in areas frequently associated wiith migraine, and also regulates the blood vessels that supply the coverings on the brain.

What happens next is very interesting. The stimulation of the trigeminal nerve causes blood vessels in the coverings of the brain to dilate, and this allows white blood cells to leak into the surrounding space. If you obtain some spinal fluid and look at it under the microscope, you may see white blood cells, which means that you are seeing a little pus in the spinal fluid, just as if you had an infected wound. So, migraine produces inflammation in the coverings of the brain, just like poison ivy produces a rash on the skin or a sinus infection produces inflammatory changes in the nose. This event is called “sterile inflammation”; the sterile part refers to the fact that the meninges are inflamed simply from the continued stimulation of the nerve in migraine, and not because of any infection like we see when someone has Rocky Mountain Spotted Fever or say a virus affecting the coverings of the brain.

One would think that actions which reduce stress-avoiding smoking and caffeine, diet, some exercise- would also reduce the inflammatory response and reduce headaches as well. We have certainly seen this in the Headache Clinic.

Once we obtain a remission of frequent headaches, we say that if you can follow antiinflammatory behavioral changes, your chance of no longer needing medication is about 70% in our experience. If you don’t improve your general health, especially exercise, the chance of being free of headaches without medication drops to about 30%. So, your habits and the environment play a very large rolein stress and migraine.

Q- Do you treat migraine with prednisone?

Dr. Matthews: That’s a really perceptive question! Sometimes we have to use steroids for a very brief period of time to induce a remission. It’s very common in medicine to prescribe a steroid dosepack for migraine that persists for many days, and it can be very effective.

At the Headache Clinic, we prefer to administer an antiinflammatory dose at the exit of nerves along the base of the skull. The procedure is called an occipital nerve block, and it’s effective about 70% of the time in inducing a a remission of headache. A very small amount of steroid can be administered precisely where it can do some good, with very little total body exposure to steroid. It’s a very minor procedure that provides a great benefit for many people.

Dr. Charles Matthews was the 1978 Jefferson Fellow in Medicine at the University of Virginia Medical School. A board certified neurologist, he has been the Director of the North Caroline Comprehensive Headache Clinic since 1993.