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Migraine

Three times as many women are afflicted by migraines as men, according to many large studies. However, 6% of men do suffer from migraines and that means 9 million American men. However, in our clinic, instead of 75%, over 90% of patients are women. Men are often dragged into the office by their wife, girlfriend, or mother.

A new study presented at the recent meeting of the American Headache Society confirms this observation. Dr. Anne Scher and her colleagues established that men are less likely to see a doctor and when they do see one, they are less likely than women to be given the diagnosis of migraine. Only 59% of men with migraines were given the correct diagnosis, while this number was 77% for women. This is probably due to the perception of migraine as a disease of women. The reasons for misdiagnosis in both sexes include the notion that every migraine sufferer has to have a visual aura (it is present only in about 20%), or that the headache has to be one-sided, or the person has to have nausea. In fact, all of the typical migraine features do not have to be present. It is sufficient to have nausea and throbbing pain or light sensitivity and inability to function normally, or light and noise sensitivity and one-sided throbbing pain, etc.

Migraines are often misdiagnosed as sinus headaches because in some people migraine is accompanied by a clear nasal discharge or because the pain is localized in the area of sinuses. True sinus headaches are usually accompanied by yellow or green nasal discharge.

Migraines can be also mistaken for tension-type headaches, but tension-type headaches are milder and never severe, not accompanied by nausea and other symptoms, and typically respond to over-the-counter medications.

One type of headaches that is significantly more common in men, is cluster headache. Cluster headaches are also often misdiagnosed as migraine or sinus headache. The name comes from the fact that these headaches occur in clusters – every day for a month or two and then they go away for a year or longer. The pain is extremely intense, always one-sided and localized around the eye, usually accompanied by tearing and runny nose on the side of the headache. These headaches tend to wake the person from sleep, but can occur during the day and last anywhere from half an hour to a few hours. Some of the treatments for cluster headaches are different from those for migraines, so a correct diagnosis is crucial. There are many posts on this blog and an article on our site devoted to cluster headaches, so please do a search if you are interested in learning more.

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Intravenous magnesium relieves acute migraine attacks in patients with magnesium deficiency, which is present in half of migraine sufferers, according to the study we published in 1995 in the journal Clinical Science. Infusions not only treat an acute attack, but also prevent migraines. Oral magnesium supplementation is not as effective and helps less than 50% of patients because some patients do not absorb magnesium. Most people get enough magnesium from food, but some migraine sufferers have a genetic defect which prevents them from absorbing magnesium or a genetic defect that leads to an excessive loss of magnesium through kidneys.

Our experience with thousands of patients suggests that the majority of migraine sufferers who are magnesium deficient do improve with oral supplementation, but about 10% do not. These patients need regular infusions of magnesium and these infusions are often life-changing. Magnesium not only treats and prevents migraines, but also relieves muscle cramps, PMS, palpitations, “brain fog”, and other symptoms.

There are many mentions of magnesium on my blog and on the nyheadache.com website, so what prompted another post on this topic is a couple of patients with an unusal experience. I would occasionally see such patients but in the past few weeks, I saw several. These patients tell me that when we give them an infusion of magnesium by “slow push” over 5 minutes they get excellent relief, but when they end up in an emergency room or another doctor’s office where they receive the same amount of magnesium through an intravenous drip over a half an hour or longer, there is no relief.

A likely explanation is that a push results in a high blood level, which overcomes the blood-brain barrier and delivers magnesium into the brain, while during a drip, magnesium level does not increase to a high enough level to reach the brain. Studies have shown that migraineurs not only have a systemic magnesium deficiency, but specifically in their brains. A similar phenomenon has been described with sumatriptan (Imitrex). Researchers discovered that migraine sufferers who did not respond to sumatriptan had a much slower increase in the drug level compared to responders, even though the total amount of the drug absorbed into the blood was the same.

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Recently, a patient of mine reported that cramp bark has significantly improved her menstrual migraines. Cramp bark is a common shrub with red berries. Its bark has been used for over 100 years for muscle cramps, menstrual cramps, fluid retention, and other symptoms. Fortunately, it appears to be very safe and even though no scientific studies have been performed on it, it may be worth trying. I will start recommending it to women with menstrual migraines, menstrual cramping and patients with muscle spasms in their neck and upper back.

The two top herbs I recommend to my migraine patients are feverfew and boswellia. Feverfew has been subjected to scientific studies and seems to help some patients while causing almost no side effects. Boswellia has been reported to help even patients with cluster headaches, but no rigorous studies have been done. However, it is safe and because of its anti-inflammatory properties it can also help joint and muscle aches (see my blog post on Boswellia).

Butterbur, on the other hand is not always safe, so I haven’t been recommending it. Here is one of my blog posts on it.

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Vagus nerve stimulation (VNS) with an electrode implanted in the neck is an FDA-approved treatment for depression and epilepsy, when these conditions do not respond to medications. Since antidepressant and anti-epilepsy medications help migraines, I had six patients (four with migraines and two with cluster headaches) treated with VNS. Two of the four chronic migraine patients and both cluster patients had good relief – results that were published in the journal Cephalagia in 2005. This publication led to the development of gammaCore, a device to stimulate the vagus nerve through the skin, without the need for surgical implantation of an electrode. The New York Headache Center participated in one of the earliest studies of this device and the results were encouraging.

An article published in the current issue of Neurology presents the results of another study of gammaCore. In this first double-blind study 59 adults with chronic migraines (15 or more headache days each month) were given either real VNS or sham treatment for two months. After two months they were all given the real treatment for 6 months. The main goal of the study was to examine the safety and tolerability of this treatment, but the researchers also looked at the efficacy by measuring the change in the number of headache days per 28 days and acute medication use.

Both sham and real treatment were well tolerated with most adverse events being mild or moderate and transient. The number of headache days were reduced by 1.4 days in the real and 0.2 days in the sham group. Twenty-seven participants completed the open-label 6-month phase, which suggests that this treatment might work for half of the patients. However, larger sham-controlled studies are needed to prove that this treatment really works. GammaCore is also being tested for the treatment of cluster headaches. Although it has not been definitively proven to be effective, it is already being sold in some European countries.
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Menopause often brings relief to female migraine sufferers. However, many women have worsening of their migraines during the transition. This is thought to be due to the fluctuating levels of estrogen, which is also responsible for menstrual migraines. Steady levels of estrogen during pregnancy and in menopause lead to a dramatic relief of migraines in two out of three women.

A study published in a recent issue of the journal Headache examined the relationship of headache frequency to the stages of menopause. The study looked at 3446 women with migraines with a mean age of 46. Among women who were premenopausal, 8% had high frequency of headaches (10 or more headache days each month), while during perimenopause as well as menopause, 12% of women had high frequency of migraines. This does not contradict the fact that many women stop having migraines in menopause, but it suggests that among those women who continue having migraines, there are more with high frequency of attacks.

By publishing these findings, the authors wanted to draw attention to the fact that many women may need a more aggressive approach to treatment. In women with high frequency of attacks preventive therapies tend to be more effective than abortive ones. These may include magnesium, CoQ10, Boswellia, and other supplements, as well as preventive medications and Botox injections. At the same time, most women may also need to take abortive therapies, such as triptans.

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Tremor of the hands is usually a benign condition. It is even called, benign essential tremor or, if it runs in the family, benign familial tremor. Patients with tremor are twice as likely to have migraines, so this is why I am writing about it. Tremor is also a symptom of Parkinson’s disease, but these two types of tremor can be easily differentiated. Parkinsonian tremor is a resting tremor, which means that hands shake at rest, while essential tremor occurs in action, like when trying to drink from a cup.

Even though it is benign, essential tremor can be incapacitating and socially embarrassing. Fortunately, in most people it responds to treatment. We usually start with propranolol (Inderal), a drug that belongs to the beta-blocker family, which is used for the treatment of high blood pressure and migraines. If propranolol or another beta-blocker is ineffective or causes side effects (due to low blood pressure or slow pulse), tremor can be treated with epilepsy drugs such as primidone (Mysoline), gabapentin (Neurontin), zonisamide (Zonegran), or an alpha-2 agonist such as clonidine (Catapres), which is a different type of blood pressure medicine.

In rare cases, tremor affects not hands but the voice. I recently treated such a patient. He tried some medications, but when they did not help, he was given Botox injections into the vocal cords. This reduced the tremulousness of his voice, but only partially. Botox can also help with hand tremor, but because there are so many small muscles involved, the results are not very good. Taking careful history revealed that this patient tried only 10 mg of propranolol and when it did not help, he stopped it. I decided to give it another try and built up the dose to 30 mg, which provided complete relief without any side effects. For migraines, we usually go up to 60 to 120 mg of propranolol, but some patients need and tolerate even higher doses.

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A new report presented at the last annual scientific meeting of the American Headache Society in San Diego showed that post-concussion symptoms can be helped by an intravenous infusion of magnesium.

Doctors at the department of neurology at UCLA described six patients with a post-concussion syndrome, who were given an infusion of 2 grams of magnesium sulfate. Three out of six had a significant improvement of their headaches and all had improvement in at least one of the following symptoms: concentration, mood, insomnia, memory, and dizziness.

This was a small study, but it is consistent with other studies that show a drop in the magnesium level following a concussion and also studies in animals that show beneficial effects of magnesium following a head trauma.

Our studies have shown that intravenous magnesium can relieve migraine and cluster headaches in a significant proportion of patients.

Considering how safe intravenous magnesium is and how devastating the effect of a concussion can be, it makes sense to give all patients with a post-concussion syndrome if not an intravenous infusion, at least an oral supplement. I usually recommend 400 mg of magnesium glycinate, which should be taken with food. For faster and more reliable effect, we routinely give patients with migraines, cluster, and post-concussion headaches an infusion of magnesium. Patients who do not absorb or do not tolerate (it can cause diarrhea) oral magnesium, come in to for monthly infusions.

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Medication overuse headache (MOH), which is sometimes called rebound headache, is included in the International Classification of Headache Disorders. However, this is one of several headache types whose existence is still debated. After years of indocrination, most neurologists and headache specialists strongly believe that every drug taken for acute treatment of headaches can cause MOH. However, we have good evidence only for caffeine and for opioid (narcotic) pain medications. It is far from proven in case of triptans (sumatriptan or Imitrex, and other) or NSAIDs (ibuprofen or Advil, naproxen or Aleve, and other).

Last week, I attended the annual scientific meeting of the American Headache Society (AHS) and was happy to see that despite an almost universal acceptance of the diagnosis of MOH, the organizers set up a debate on the existence of MOH. The debaters included two top experts in the field, Drs. Richard Lipton of Montefiore Headache Clinic in the Bronx and Ann Scher of the Uniformed Services University in Bethesda. Dr. Lipton and Scher have collaborated on many research projects and have published many important articles on headaches together, so the debate was friendly and based on facts.

Dr. Scher quoted the American Council on Headache Education, an affiliate of the AHS:

“It is important to know that intake of medications for acute treatment should be limited to less than twice a week. Some methods which can prevent the onset of medication overuse headache include following instructions on how to take medications, avoid use of opioid medications and butalbital combination medications and limit use of simple analgesics to less than 15 days a month and triptans less than 10 days a month”.

And then she posed a question: How many are being harmed vs helped by this advice?

While Dr. Lipton quoted scientific articles supporting the existence of MOH, Dr. Scher’s conclusions reflected my clinical experience that MOH is not a proven entity as it relates to triptans and NSAIDs. I see it only in those who overuse caffeine or caffeine-containing drugs (Excedrin, Fioricet, etc) or narcotic pain killers (Percocet or oxycodone, Vicodin or hydrocodone, and other).

Dr. Scher concluded that, “Since the existence of MOH has not been proven (and may be non-provable for practical purposes), one is obligated to remain agnostic about this entity. And the corollary is that there is no evidence that undertreating will prevent headache frequency progression and may harm more people than help”.

In fact, the same headache experts who limit abortive therapies to twice a week, recommend aggressive abortive therapy for migraines because undertreatment of episodic migraine can lead to its transformation into chronic migraine.

She also indicated that “Quality of evidence for medication withdrawal alone as treatment for MOH is poor” and “Medication withdrawal alone is not clearly better than doing nothing and may be worse”. Meaning that in addition to withdrawal of the acute medication, patients should be given prophylactic treatment.

Studies indicate that after one year, 60% and after two years, 70% of those with chronic migraines (15 or more headache days in a month) revert to episodic ones (less than 15 headache days a month) regardless of treatment. In 15% headaches decrease to less than one a week. This is because fortunately, migraines often improve with time on their own.

We have evidence that Botox injections and some preventive medications can make discontinuation of acute medications easier. We always try to stop Fioricet (butalbital, acetaminophen, and caffeine), Fiorinal (butalbital, aspirin, and caffeine), Excedrin (caffeine, acetaminophen, aspirin) with the help of regular aerobic exercise, biofeedback or meditation, magnesium and other supplements, Botox injections, and sometimes preventive medications.

However, we do have several dozen patients whose headaches are controlled by the daily intake of triptans. These patients have tried given prophylactic medications, Botox injections and other treatments, but find that only triptans provide good relief and eliminate migraine-related disability. The most commented on post on this blog (with 175 comments to date) is one on the daily use of triptans.

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Hemiplegic and basilar migraine are rare types of migraine. Hemiplegic migraine is accompanied by a paralysis of one side of the body. Basilar migraine derives its name from the basilar artery, which supplies blood to the brainstem. Symptoms of brainstem dysfunction (double vision, unsteady gait, vertigo, difficulty speaking) made doctors think that ischemia or lack of blood flow in that artery caused these symptoms. We now know that this is not the case and basilar migraine may be just another form of migraine with aura.

The FDA ruled that sumatriptan (Imitrex), other triptans, and ergotamines (DHE-45, Cafergot) are contraindicated in patients with basilar and hemiplegic migraine because of the unsubstantiated fear that these drugs may cause constriction of blood vessels that might be already constricted resulting in a stroke. There is little evidence that symptoms of hemiplegic and basilar migraine are caused by the constriction of blood vessels. It is most likely due to the dysfunction of the brain cells. In addition, constriction of blood vessels by the triptans is very mild.

A study just published in the journal Headache examined 67 patients with basilar and 13 with hemiplegic migraines who were treated with triptans and dihydroergotamine (DHE-45). None of these patients suffered a stroke or a heart attack.

This is not the first report of the safe use of triptans in the treatment of basilar and hemiplegic migraines. Although the total number of patients reported is small, it appears that triptans and ergots are probably safe in these types of migraines. Some doctors are afraid to prescribe triptans to such patients out of fear of litigation. There is a good chance that the next edition of the classification of headache disorders will no longer include basilar migraine because it is recognized as being just a form of migraine with aura. Ergots and triptans are not contraindicated in migraine with aura.

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Intravenous magnesium infusions may not be as safe in pregnant women as it has been always thought. The FDA recently moved intravenous magnesium from category A into category D (see category definitions below). This came about after the FDA reviewed 18 cases of babies who were born with serious problems after their mothers received intravenous infusions of large amounts of magnesium for 5 to 7 days in order to stop premature labor. The FDA strongly discourages this practice and states that “Administration of magnesium sulfate injection to pregnant women longer than 5-7 days may lead to low calcium levels and bone problems in the developing baby or fetus, including thin bones, called osteopenia, and bone breaks, called fractures.”

However, treatment of choice for eclampsia remains intravenous magnesium. Eclampsia, one of the most serious complications of pregnancy can be treated only with high doses of intravenous magnesium. Without intravenous magnesium eclampsia can lead to epileptic seizures, very high blood pressure, kidney failure and death.

The FDA also recommends that “Magnesium sulfate injection should only be used during pregnancy if clearly needed. If the drug is used during pregnancy, the health care professional should inform the patient of potential harm to the fetus.”

We do treat many patients, including pregnant women, with intravenous infusions of magnesium if they are deficient in magnesium and if their migraines respond to such infusions. Typically, these infusions are given monthly and the amount is only 1 gram, while for preterm labor the dose is 4-6 grams to start and then 2-4 grams an hour as needed. This monthly dose of 1 gram is extremely unlikely to cause any adverse effects. We find that migraines triggered by magnesium deficiency do not respond well to any other treatments and considering the risk of drugs, it is much safer to administer 1 gram of magnesium. This amount of magnesium just corrects the deficiency and does not cause very high magnesium levels, which can be detrimental.

Several other drugs routinely used in pregnancy may also not be as safe as we thought. Acetaminophen (Tylenol) has been considered one of the safest choices. However, recent evidence suggests possible link to attention deficit disorder with hyperactivity (ADHD).

Butalbital, which is an ingredient in the popular headache drugs such as Esgic, Fioricet and Fiorinal is associated with an increased risk of congenital heart defects. Fioricet also contains caffeine, which has negative effects on the fetus and which can cause rebound (medication overuse) headaches.

FDA drug categories in pregnancy

Category A
Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Example drugs or substances: levothyroxine, folic acid, liothyronine

Category B
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Example drugs: metformin, hydrochlorothiazide, cyclobenzaprine, amoxicillin, pantoprazole

Category C
Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Example drugs: tramadol, gabapentin, amlodipine, trazodone, prednisone

Category D
There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Example drugs: topiramate (Topamax), divalproex sodium (Depakote), lisinopril, alprazolam, losartan, clonazepam, lorazepam

Category X
Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

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Sumatriptan (Imitrex) and similar drugs (so called triptans) are “designer” drugs that were specifically developed for the treatment of migraine headaches. They are very effective, but do not help all migraine sufferers. Anti-inflammatory pain killers, such as aspirin and ibuprofen work well for some people and sometimes these drugs are combined with triptans to achieve better relief.

Many migraineurs experience nausea and sometimes vomiting as part of their migraine, which prevents or delays the absorption of medicine, making it ineffective or less effective. To address this problem, two of the triptans, sumatriptan and zolmitriptan (Zomig) are available in a nasal spray form. Sumatriptan can be also self-administered as an injection and recently a skin patch of sumatriptan (Zecuity) became available. An anti-inflammatory pain medicine, ketorolac is also available as a nasal spray, as does a narcotic pain killer, Stadol (butorphanol). While Stadol is addictive and has other serious side effects, intranasal ketorolac (Sprix) is a very good pain medication. Sprix works much better than the ketorolac tablet, but not as well as an injection of ketorolac (Toradol).

Intranasal ketorolac was compared with intranasal sumatriptan in a study that was recently published in the journal Headache. The study showed that ketorolac and sumatriptan nasal sprays were equally effective and both were better than placebo spray. Both drugs caused nasal irritation and unpleasant taste in some patients, but these were not severe.

The main problem with intranasal ketorolac is its cost. On GoodRx.com the price of 5 vials of Sprix (with a coupon) is about $1,000. Each vial is good for one day of use; it contains 8 sprays (15 mg each) and the usual dose is one spray into each nostril, repeated every 6 hours as needed. However, there is a way around the cost of this medication. Ten 30 mg vials of generic ketorolac for injections cost $15. You just need to buy a nasal spray bottle, empty the contents of the vial into it and use it as needed.

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The FDA approved Botox injections for the treatment of chronic migraine headaches more than five years ago. I just discovered that in this period of time only 100,000 chronic migraine sufferers received this treatment. According to the Migraine Research Foundation, 14 million Americans suffer from chronic migraines, so less than 1% of them have recieved this potentially life-changing treatment.

There are several possible explanations.
1. Botox is expensive and many insurance companies make it difficult for patients to get it. They require that the patient first try 2 or 3 preventive drugs, such as a blood pressure medicine, (propranolol, atenolol, etc.), an epilepsy drug (gabapentin, Depakote, Topamax), or an antidepressant (amitriptyline, nortriptyline, Cymbalta). Patients also have to have 15 or more headache days (not all of them have to be migraines) in each of the three preceding months. If these requirements are met, the doctor has to submit a request for prior authorization. Once this prior authorization is granted, the insurer will usually send Botox to the doctor’s office. After the procedure is done, the doctor has to submit a bill to get paid for administering Botox. This bill does not always automatically get paid, even if a prior authorization was properly obtained. The insurer can ask for a copy of office notes that show that the procedure was indeed performed. All this obviously serves as a deterrent for many doctors. Some of them find that the amount of paperwork is so great and that the payment is so low and uncertain, that they actually lose money doing it.

2. There are not enough doctors trained in administering Botox. This is becoming less of a problem as more and more neurologists join large groups or hospitals where at least one of the neurologists is trained to give Botox and gets patients referred to him or her. However, doctors in solo practices or small groups without a trained injector can be reluctant to refer their patients out for the fear of losing a patient. They may suggest that this treatment is not really that effective or that it can cause serious side effects.
The majority of doctors who inject Botox are neurologists, but there are only 15,000 neurologists in the US and many specialize in the treatment of strokes, Alzheimer’s, epilepsy, MS, and other conditions. This leaves only a couple of thousand who treat headache patients. Considering that there are 14 million chronic migraine sufferers, primary care doctors will hopefully begin to provide this service.

3. Chronic migraine patients are underdiagnosed. Many patients will tell the doctor that they have 2 migraines a week and will not mention that they also have a mild headache every day. The mild headaches they can live with and sometimes my patients will even call them “normal headaches”, which they don’t think are worth mentioning. Good history taking on the part of the doctor solves this problem. However, once doctors join a large group or a hospital, they are pressured to see more patients in shorter periods of time, making it difficult to obtain a thorough history.

4. Some patients are afraid of Botox because it is a poison. In fact, by weight it is the deadliest poison known to man. However, it is safer than Tylenol (acetaminophen) because it all depends on the amount and too much of almost any drug can kill you. Fifty 500 mg tablets of Tylenol kills most people by causing irreversible liver damage. Hundreds of people die every year because of an accidental Tylenol poisoning, while it is extremely rare for someone to die from Botox. Tens of millions of people have been exposed to Botox since its introduction in 1989. It is mostly young children who have gotten into trouble from Botox because the dose was not properly calculated. Kids get Botox injected into their leg muscles for spasticity due to cerebral palsy, although children with chronic migraines also receive it (the youngest child with chronic migraines I treated with Botox was 8).

In summary, if you have headaches on more than half of the days (not necessarily all migraines) and you’ve tried two or three preventive drugs (and exercise, meditation, magnesium, CoQ10, etc), try to find a doctor who will give you Botox injections. Botox is more effective and safer than preventive medications because it does not affect your liver, kidneys, brain, or any other organ.

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