Propranolol was first introduced as a blood pressure drug 50 years ago and about 40 years ago it was discovered to be effective for the prevention of migraines. This is quite a remarkable drug because it is also used for rapid heart beat, heart attacks, tremor, and performance anxiety. Public speakers, musicians, and others take a small dose before performances and the drug reduces the physical stress responses such as sweating, tremulousness, weakness, and other. Blinded studies showed that musicians perform better when given a beta blocker compared to musicians who are given a placebo pill.

Since the introduction of propranolol, another two dozen beta blockers have been developed. The newer, so called selective beta blockers (they attach to only one type of stress receptor) tend to have fewer side effects than propranolol and other non-selective beta blockers. Selective beta blockers can be given to patients with well-controlled asthma, while non-selective ones can cause an asthma attack.

Recent studies have shown that chronic stress promotes the growth and spread of cancers. Researchers at MD Anderson Cancer Center decided to review the records of 1,425 patients who were treated for ovarian cancer at four hospitals between 2000 and 2010. Of these, 268 had been treated with a beta blocker while receiving chemotherapy for their ovarian cancer. The average survival of those who were on a beta blocker was 48 months compared to 42 months for those who were not. A more dramatic difference was found between those who were taking a non-selective beta blocker (propranolol in almost all cases): they lived 95 months – twice as long as women not on a beta blocker.

Considering these findings, if I decide to prescribe a beta blocker, I may start prescribing propranolol as the first-line drug for the prevention of migraines. And only if the patient has side effects, will I switch them to a selective beta blocker, such as atenolol or nebivolol (Bystolic). Common side effects of beta blockers are fatigue and dizziness from a drop in blood pressure and difficulty exercising because the heart rate cannot increase high enough to provide for the increase in demand for oxygen. Because regular aerobic exercise is my first recommendation for the prevention of migraines, I tend to reserve beta blockers for patients whose blood pressure is high or at the high end of normal range, whose pulse is fast, and for those who fail other preventive drugs and Botox (however, most insurers approve Botox for chronic migraines only if the patient fails 2 or 3 preventive drugs, including a beta blocker).

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New onset of headaches is always worrisome, but even more so in a pregnant woman. Neurologists at the Montefiore Headache clinic in the Bronx conducted a 5-year retrospective study of pregnant women who presented with an acute headache, were hospitalized, and received a neurologic consultation. The study was published in Neurology.

The researchers identified 140 women with a mean age of 29 years. About 56% of these women presented in the third trimester. Primary headaches was present in 65% and secondary (due to an underlying disease) was found in 35% of women. The most common primary headache disorder was migraine and it was found in 91%, while the most common secondary headache disorder present in 51% was high blood pressure.

Primary headaches included migraine without aura, seen in 37%, migraine with aura, in 24%, chronic migraine, in 6%, episodic tension-type headache, in 3%, chronic tension-type headache, in 1%, and primary stabbing headache, in 2% (this adds up to more than 65% because some had more than one type of headaches). Besides hypertensive disorders such as preeclampsia and eclampsia (18%), secondary headache diagnoses included pituitary adenoma or apoplexy in 4%, infections in 2%, stroke in 3%. Pregnant women with secondary headaches were less likely to have had headaches in the past (37% in secondary vs 13% in primary) and were more likely to have seizures (12% vs 0%), elevated blood pressure (55% vs 9%), fever (8% vs 0%), and an abnormal neurologic examination (35% vs 17%). Psychiatric comorbidity (presence of depression, anxiety, bipolar, etc) and phonophobia (sensitivity to light) were less likely with secondary headache.

The authors concluded that among pregnant women receiving inpatient neurologic consultation, more than one-third have secondary headache. Doctors should be particularly vigilant in the absence of a headache history and if seizures, hypertension, or fever are present. On the other hand, specific headache features such as location of the pain, throbbing character, sensitivity to light and noise are less helpful in distinguish primary vs secondary headaches. The neurologists who conducted this review recommend low thresholds for neuroimaging (CT or MRI scan) and monitoring for preeclampsia and eclampsia. Preeclampsia and eclampsia are complications of pregnancy with elevated blood pressure, sometimes seizures, and kidney problems, which can be life-threatening and which are treated with intravenous infusions of magnesium.

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Migraine with aura is believed to increase the risk of strokes and possibly heart attacks, although the risk estimates vary from study to study.

A recent study demonstrated no increase in the risk of strokes in people who suffered from migraine with and without aura, unless they were active smokers. The findings were published last month in the journal Neurology. Among the 1292 participants with an average age of 68 years there were 262 with migraine. There was no relationship between migraine (with or without aura) and stroke or heart attacks during the 11 year follow up period. However, among the 198 current smokers, there was a 3-fold increased risk for stroke.

The lack of relationship between migraine with aura and stroke seen in previous studies is probably due to a relatively small sample size.

I personally have seen two young women with migraine with aura who suffered a stroke. Both of them were smokers and were taking oral contraceptives. Estrogen contraceptives (even newer ones with lower estrogen content) further increase the risk of strokes in women who have migraine with aura. Progesterone-only pill does not increase the risk of strokes. Some women with severe endometriosis, heavy menstrual blood loss, and severe PMS sometimes have to accept a slight increase in the risk of strokes and take an estrogen-based contraceptive. However, if they smoke, they must stop smoking and also try to reduce other risk factors for strokes, if they are present. These include keeping hypertension and diabetes under control, lower high cholesterol, maintain normal weight and exercise regularly.

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Fluctuations in the female hormone estrogen have been proven to be involved in triggering menstrual and perimenopausal migraine headaches. Testosterone levels have been reported to be low in men and women with cluster headaches. Testosterone replacement therapy seems to help these patients, when other standard treatments for cluster headaches do not.

A study presented at the recent annual meeting of the American Headache Society reported on testosterone levels in men with chronic migraine headaches. A significant percentage of men with chronic migraines also have low testosterone levels. This study did not look at the effect of testosterone replacement therapy, but it is possible that it may help chronic migraine sufferers as it does those with cluster headaches. It seems prudent to check testosterone level in men with chronic migraine headaches who do not respond to standard approaches such as medications, Botox injections, magnesium, and other treatments. And if the level is low, replacement therapy should be tried.

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Ayurvedic medicine has many healthy aspects. However, a recent story on NPR described the risks involved with the traditional Ayurvedic medicines from India. A very high percentage of Ayurvedic supplements in the category called bhasmas sold in the US contains large amounts of lead and other toxic elements. There is a lot more to Ayurvedic medicine than these supplements, so it is important to separate dangerous parts from things like healthy diet, yoga, and other.

Unfortunately, the US government does not regulate supplements, so there is always a question of safety of these products, especially those made outside the US. The one exception is products made in Germany, where supplements are as strictly regulated as drugs (please note that Petadolex, a butterbur product is made in Germany, but is not allowed for sale there). Many patients ask me about not only Indian but also Chinese herbal medicines, which are often combined with acupuncture and other treatment methods. As a rule, I recommend avoiding products made in China or India, where quality controls are very poor. Instead, you should buy products made by major US manufacturers, although they do not make many traditional Chinese and Indian products. However, you cannot always count on products sold in major US store chains either – recently, herbal products sold at Walgreens, WalMart, Target and GNC were found to have no active ingredients. Thankfully, there were no toxic ingredients in those products.

The largest mass poisoning with a Chinese herbal dietary weight loss product occurred in Europe where 18 patients developed kidney failure and urinary cancer.

In summary, no matter how promising a Chinese or an Indian herbal product may sound, it is not worth the risk.

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Ehlers-Danlos syndrome is a group of inherited disorders that are notable for excessive joint mobility with some people also having lax or stretchy skin, at times heart problems, and other symptoms. Headaches appear to be also very common.

We see Ehlers-Danlos syndrome in many of our migraine patients and most of our headache specialist colleagues also notice this association. However, there are very few studies that confirm this observation. One such study was recently presented at the annual scientific meeting of the American Headache Society in Washington, DC. The research was performed at a cardiology clinic in Texas. They looked at the records of 139 patients who were referred to this clinic in a period of one year. Of these 139 patients with Ehlers-Danlos syndrome, 90% were women and the average age was 32. Out of 139 patients, 70% suffered from headaches – 32% had tension-type, 26% had migraines, 9% had chronic migraines and 2% had sinus headaches. These numbers are much higher than what is seen in the general population, confirming clinical observations by headache specialists.

One form of Ehlers-Danlos syndrome affects not only joints and ligaments, but also the heart. So, when see a migraine patients who also appears to have Ehlers-Danlos syndrome, we also ask about symptoms related to the heart and if they are present refer such patients to a cardiologist.

Another presentation at the same meeting described a 23-year-old woman with Ehlers-Danlos syndrome who suddenly developed headaches that would worsen on standing up and improve on lying down. This is typical of headaches due to low cerebrospinal fluid (CSF) pressure, which was confirmed by a spinal tap. The most common causes of low CSF pressure are a leak caused by a spinal tap done to diagnose a neurological disease or caused by a complication of epidural anesthesia. Spontaneous unprovoked leaks have also been reported. In this patient with Ehlers-Danlos syndrome the leak probably occurred because of the lax ligaments that surround the spinal canal and contain the CSF. The report describes the most accurate test to document such leaks, which is an MRI myelogram.

The treatment of CSF leaks begins with a blood patch procedure, but if it is ineffective, surgery is sometimes done to repair the leak. A recent report suggested that Botox could be effective for low spinal fluid pressure headaches.

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I recently gave Botox injections to my oldest patient – an 96-year-old man who is otherwise in excellent mental and physical health has been suffering from daily severe cervicogenic (neck-related) headaches for many years. He had tried pain killers, nerve blocks, radiofrequency ablation (destruction) of nerves in his neck, all with no relief. A month after being treated with Botox he reported having almost no headaches. I have also given Botox to a number of patients with chronic migraines in their 70s and 80s.

At the last scientific meeting of the American Headache Society Cleveland Clinic neurologists presented a report entitled, Safety and Efficacy of OnabotulinumtoxinA (Botox) for Chronic Migraines in the Elderly. They described 28 patients who were older than 65, had an average age of 73 and who were treated with Botox injections for their chronic migraine headaches. They compared the safety and efficacy of Botox injections in this group with that of 700 patients aged 18 to 65 who participated in PREEMPT II study of Botox for chronic migraine (one of the two studies that led to the FDA approval of Botox for chronic migraines, in which we also participated). There was no significant difference in side effects between the younger and the older groups, except for a slightly higher incidence of neck pain after the injections in the elderly. The improvement was also comparable – after Botox the elderly had 11 fewer headache days a month compared with 9 fewer days in the younger group.

In conclusion, while many migraine medications are more likely to cause side effects in the elderly, this is not the case with Botox. Also, Botox appears to be as effective in the elderly with chronic migraines as in younger patients.

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Looking for health advice is one of the most common reason people search the web. Many websites provide health information and some even offer self-diagnosis using a symptom checker. After entering all of the symptoms the website suggests a possible diagnosis and advises to take some home remedies or see a doctor. A study recently mentioned on this blog showed that Wikipedia had errors in 9 out of 10 articles on different medical conditions.

Another recent study by Harvard researchers examined the accuracy of the sites that offer self-diagnosis. Not surprisingly, this study also found that the online programs are often wrong. The results were published in the British Medical Journal.

The lead author Ateev Mehrotra, commented that “These tools may be useful in patients who are trying to decide whether they should get to a doctor quickly, but in many cases, users should be cautious and not take the information they receive from online symptom checkers as gospel.”

Some of these symptom checkers were developed by prestigious institutions, including Harvard and other medical schools, major hospital groups, insurance companies, and some government agencies (including the United Kingdom’s National Health Service).

The researchers presented 45 hypothetical cases (including headaches) to test 23 different symptom checkers. Only 34% listed the correct diagnosis first and the correct diagnosis was in the top three possibilities in 51% of cases.

Dr. Mehrotra said that “It’s not nearly as important for a patient with fever, headache, stiff neck, and confusion to know whether they have meningitis or encephalitis as it is for them to know that they should get to an ER quickly.”

Of the 23 symptom checkers 58% provided correct advice and in more serious conditions, it correctly recommended emergency room visit in 80 percent of cases.

To complicate matters, the checkers with the most accurate diagnoses (Isabel, iTriage, Mayo Clinic, and Symcat) were not the ones that were best at recommending the appropriate level of care (Healthychildren.org, Steps2Care, and Symptify).

The researchers compared the online symptom checkers with a live telephone triage nurse offered by many insurance companies. The accuracy of live nurses is between 61% and 69%, so these are more accurate accurate, but also leave a lot of room for improvement. Hopefully, these online programs will continue to evolve, but at this point, you should not rely on them.

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The Food and Drug Administration (FDA) has just released a new strengthened warning about NSAIDs. Prescription and over-the-counter NSAIDs (ibuprofen, naproxen, nabumetone, diclofenac, and other) are widely used for the treatment of pain including different types of headaches. They are fairly safe, especially in young healthy people who take NSAIDs for an occasional headache. However, the risk of strokes and heart attacks and heart failure is higher in older people, especially those with risk factors such as smoking, diabetes, hypertension, high cholesterol, and other. These risks are present with all NSAIDs, except for aspirin, which in fact can sometimes lower these risks. So, when in doubt, take aspirin, which is the main ingredient of my product, Migralex. Migralex is fast acting and is less likely to upset your stomach because of the buffering effect of magnesium. You can buy Migralex on Migralex.com, Amazon.com, and CVS stores.

Here is the full text of FDA’s announcement:

Safety Announcement
The U.S. Food and Drug Administration (FDA) is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on our comprehensive review of new safety information, we are requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. We will also request updates to the OTC non-aspirin NSAID Drug Facts labels.
Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.

NSAIDs are widely used to treat pain and fever from many different long- and short-term medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu. NSAIDs are available by prescription and OTC. Examples of NSAIDs include ibuprofen, naproxen, diclofenac, and celecoxib (see Table 1 for a list of NSAIDs).

The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, we have reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies,1 a large combined analysis of clinical trials,2 and other scientific publications.1 These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.

Based on our review and the advisory committees’ recommendations, the prescription NSAID labels will be revised to reflect the following information:

The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.
The risk appears greater at higher doses.
It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.
NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.
Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.
There is an increased risk of heart failure with NSAID use.
We will request similar updates to the existing heart attack and stroke risk information in the Drug Facts labels of OTC non-aspirin NSAIDs.
In addition, the format and language contained throughout the labels of prescription NSAIDs will be updated to reflect the newest information available about the NSAID class.

Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken.

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Hopefully, your doctor has given you many treatment options, so that you can manage even the most severe attacks at home (including Compazine or Phenergan anti-nausea suppositories for when you are very nauseated or vomit and Imitrex or sumatriptan injection pen for severe pain). However, many people end up in an ER, where they are usually given an injection or intravenous medications. Unfortunately, there is no standard protocol for the best way to treat an acute migraine that does not respond to oral medications. Ideally, the first step should be an infusion of magnesium, which can provide fast relief for up to 50% of patients. Some ER doctors give an injection of sumatriptan or a non-narcotic pain killer ketorolac (Toradol). Others will give a nausea drug which can also help pain such as metoclopramide (Reglan) or prochlorperazine (Compazine). An allergy medicine, diphenhydramine (Benadryl) is also a popular choice.

A study by Dr. Benjamin Friedman and his colleagues at the Albert Einstein COllege of Medicine in the Bronx compared the efficacy of intravenous Reglan combined with Benadryl and Reglan without Benadryl. This was a double-blind study, meaning that neither the doctor giving the medicine nor the patient knew what was being given. They recruited 208 patients, which is a high enough number to produce reliable results. And the results showed that Reglan without Benadryl provided as much relief as with Benadryl.

Benadryl is not a dangerous drug, but can make you drowsy, so if you can, ask the doctor not to give it to you. It is not easy to tell a doctor what to do, especially during a severe migraine attack. But if doctor is agreeable, ask for intravenous magnesium followed by either sumatriptan or ketorolac injection as well as metoclopramide for nausea.

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