Botox is a very effective treatment for chronic migraines and possibly other types of headaches and pain. However, Botox is an expensive and somewhat unpleasant treatment. Even though Botox helps a high percentage of patients (about 70%) it would be useful if we could predict who is going to respond and who is not.

One of the predictors seems to be the directionality of pain. That is, if patients with migraine who have constricting (imploding) pain or pain localized to the eye seem to respond better than those who have pain that seems to be pushing from inside out (exploding). This is not a very reliable predictor because some people have difficulty categorizing their pain in that way and because even if they do describe it clearly one way or another, this predictor is far from 100% accurate.

In a study just published in the journal Headache a group of Spanish neurologists claim that they have found a predictor with 95% accuracy. They measured blood levels of calcitonin gene-related peptide (CGRP) and found that those with levels of CGRP above a certain number were 28 times more likely to respond to Botox than those with levels below that level.

CGRP has been shown to be very involved in the process of migraine and several drugs and antibodies which block the CGRP receptor appear to be very promising (see my recent blog post on such antibodies). So, it is not very surprising that this correlation between the response to Botox and blood level of CGRP was found. However, this finding needs to be confirmed in a larger group of patients (this study involved 81 patients) and this test needs to become available commercially since now it can be done only in research laboratories.

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Besides many other mental and physical problems, bullying in school causes headaches. This is the conclusion of a group of psychologists at the University of Padua in Italy who published their findings in the last issue of the journal Headache. They looked at 20 published studies on bullying, which included 173,775 children, and found that 14 of these studies recorded the presence of headaches. While 19% of kids who were not bullied suffered from headaches, this number was 33% in those who were. There was no difference in the incidence of headaches between kids in Europe compared to other countries.

This study confirms what has been reported for health problems in bullied kids in general. It is well known that psychological stress causes physical symptoms. Social pain is a term that psychologists use to describe the effect of peer rejection, ostracism, or loss. Recent studies have shown that physical and social pain share many physiological mechanisms in the brain. The authors also speculate that lack of coping skills, low self-esteem or lack of assertiveness may lead to more psychological and physical problems. They also call on pediatricians, school nurses and others to become more aware of the physical symptoms, such as headache, as a manifestation of bullying.

I have seen a number of children with severe persistent headaches, which required home schooling. In some of these kids bullying was a definite contributing factor, although many children are reluctant to admit this even to their parents.

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The introduction of Levadex has been delayed again, this time for a year. It seems like deja vu all over again – I wrote the same thing on this blog in April of last year. Levadex, which the manufacturer (Allergan) just renamed as Semprana, is an inhaler containing DHE. DHE, or dihydroergotamine is one of the most effective injectable drugs for migraine. It should be even better in an inhaled form because it works faster and causes much less nausea than the injection. The FDA is again delaying the launch because of manufacturing problems. Apparently, the particle size of the drug when it comes out of the inhaler is not uniform enough. Many patients are unhappy, but I am sure that the Allergan is very unhappy too since they spent almost a billion dollars to acquire this drug from a small company that developed it.

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Migraine aura precedes the headache in about 20% of patients. The most common type of aura is visual. It consists of flashing lights, sparkles, partial loss of vision, and other visual distortions, which can move across the visual field. Typical duration of the aura is 20 to 60 minutes and it can occur without a headache. Many people get frightened when experiencing an aura for the first time. Thoughts of a brain tumor spring to their minds. Although auras rarely indicate a serious problem, an MRI scan is usually indicated when an aura occurs for the first time.

MRI scans are considered to be safe in pregnancy, but the current guidelines of the FDA require labeling of the MRI devices to indicate that the safety of MRI with respect to the fetus “has not been established”. Not surprisingly, most expecting mothers instinctively try to avoid any testing. So, what to do if a pregnant woman develops an aura? A study by headache specialists at the Montefiore Headache Center in the Bronx suggests that this is not an uncommon occurrence. Of 121 pregnant women presenting with an acute headache, 76 had migraines and a third of these had an aura for the first time in their lives. Two thirds of auras occurred in the third trimester. This report should be reassuring and may help avoid unnecessary MRI scans. However, MRI may still be needed if there are other signs of a more serious neurological problem on examination or by history.

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“Visual snow” is a continuous TV-static-like visual disturbance experienced by some people who suffer from migraines and by some without migraines. A group of British doctors examined 120 patients with persistent “visual snow” and found that 70 of them also suffered from migraines. Of these 70, 37 had migraine with aura and 33 had migraine without aura. Many of these patient had other visual complaints: some had a trailing after-image when shifting their gaze, saw sparkles, were always sensitive to light, and had poor night vision. Fifty two of them also complained of noise in their ears (tinnitus).

Seventeen of these patients underwent PET scans of their brain, which were compared to PET scans of 17 normal control subjects. Those with “visual snow” had increase brain activity in two parts of the brain, indicating that this is not a psychological or an eye problem, but a brain disorder.

Unfortunately, the authors did not provide any ideas as to how to treat these patients. However, the fact that some areas of the brain were overactive, suggests that using epilepsy drugs, which suppress excessive brain cell activation and are proven to help migraines, may help. These drugs include gabapentin (Neurontin), topiramate (Topamax), and divalproate (Depakote). Before using drugs though, I would suggest trying magnesium orally or intravenously because magnesium also reduces excitability of the nervous system and because half of migraine sufferers have low magnesium levels. See an article on magnesium and migraines here.

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The benign nature of white matter lesions (WML) on MRI scans of patients with migraine was noted in a post last year. While they appear to be benign, they are disconcerting nevertheless. It is possible that we haven’t yet discovered the negative effects they may have.

A study by Chinese researchers published in the Journal of Neurology reported on MRI scans in 141 people, including 45 healthy controls without migraines, 38 chronic migraine sufferers who were not overusing acute migraine medications and 58 patients with chronic migraines who were overusing these medications. They found that women, but not men, who were not overusing acute medications had more WML compared with controls and those who were overusing medications. As reported by other researchers, the number of WML increased with age. Interestingly, most patients who overused medications were taking non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen and naproxen. The authors concluded that taking NSAIDs may have a preventive effect on the development of WMLs, possibly because of their anti-inflammatory properties. Previous studies have shown that aspirin does not even cause medication overuse headaches, unlike drugs with caffeine (Excedrin, Fiorinal, Fioricet), opioid analgesics (Vicodin, Percocet, codeine, etc), and to a lesser extent NSAIDs.

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Idiopathic intracranial hypertension is also called pseudotumor cerebri because just like with a brain tumor, the
pressure is increased inside the skull. This condition usually presents with a headache and sometimes with visual symptoms. Increased intracranial pressure is not only a very painful condition, but also, if left untreated, can cause loss of vision and strokes.

An observational study just published in JAMA Neurology reports on 165 patients with pseudotumor seen by a group of neurologists and ophthalmologists across the country. The mean age of these patients was 29 and only 4 were men. The vast majority of them were obese with an average body mass index of 40, while normal is below 25. Headache was present in 84% of patients and 68% reported transient loss of vision. Half of them had back pains and pulse-like noise in the ears (pulsatile tinnitus) was reported by 52%. Visual loss was found in 32% and it was usually loss of the peripheral vision with an enlarged blind spot in the middle.

The authors concluded that pseudotumor cerebri mostly occurs in young obese women. The importance of this report is in reminding physicians to consider this diagnosis in young obese women with headaches. The diagnosis is confirmed by performing a lumbar puncture (spinal tap), which is the only way to measure intracranial pressure. An MRI scan is also always done (before the spinal tap), to make sure that it is not a real tumor that is causing increased pressure and to visualize ventricles (fluid-filled spaces) inside the brain. These ventricles are usually small in patients with pseudotumor. Performing the lumbar puncture involves draining of the cerebrospinal fluid, which can immediately relieve the headache and also improve vision. Some patients require regular spinal taps or placement of a draining shunt (usually from one of the brain’s ventricle or spinal canal to the abdominal cavity).

However, many patients respond to medications, such as acetazolamide (Diamox) or topiramate (Topamax). Weight loss is the most effective, albeit difficult treatment. The same group of physicians reported that acetazolamide combined with weight loss was somewhat more effective than weight loss alone. Only rarely, when vision is acutely threatened, a surgical procedure to relieve pressure inside the optic nerve is performed by an ophthalmologist (the procedure is called optic nerve sheath fenestration).

In summary, increased intracranial pressure is often mistaken for chronic migraine and should be considered in every young female obese headache sufferer.

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Don’t use Wikipedia for medical information and tell your doctor not to either. It is the most popular reference site not only for the lay public, but also for doctors – anywhere from 47% to 70% of physicians and medical students admit to using it as a reference.

A study just published in a medical journal shows that Wikipedia very often offers erroneous information.The researchers looked at articles on 10 common conditions: coronary artery disease, lung cancer, major depression, concussion, osteoarthritis, chronic obstructive lung disease, hypertension,diabetes, back pain, and hyperlipidemia.

Articles on each condition were evaluated independently by two physicians to make sure that the evaluations were not biased and were consistent between two doctors. The information on Wikipedia was compared to the up-to-date information on these diseases published in scientific medical journals. Shockingly, only information on concussion was accurate, while information on the other nine conditions contained serious errors. This study did not include migraines or other headaches, but it is very likely that at least some information on these conditions are also incorrect.

Tell your doctor about this study, just to make sure that he or she knows about it. For consumers, the best sources of information are medlineplus.com, mayoclinic.org/diseases-conditions, and WebMD.com.

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Cluster headache patients have been coming to our office in increasing numbers in the past few weeks. We seem to be in a cluster season – many patients with cluster headaches come within the same month or two and then, for several months we see very few cluster patients. Many cluster headache sufferers ask about the efficacy of LSD, hallucinogenic mushrooms and seeds.

The use of hallucinogens for cluster headaches was first reported by a Scottish man in 1998. He started using LSD for recreation and for the first time in many years had a year without cluster headaches. The first report in scientific literature appeared in 2006 in the journal Neurology. Dr. Sewell and his colleagues surveyed 53 cluster headache sufferers, of whom 21 had chronic cluster headaches. Half of those who tried LSD reported complete relief.

Researchers are trying to study a version of LSD (brominated LSD) that does not cause hallucinations. This form of LSD was reported in the journal Cephalalgia to stop cluster attacks in all five patients it was given to. It is not clear if any additional studies are underway, but one American doctor, John Halpern is trying to bring this product to the market in the US.

Trying to obtain LSD or hallucinogenic mushrooms carries legal risks, including incarceration. According to Dr. McGeeney, who is an Assistant Professor at Boston University School of Medicine, it is legal to buy, cultivate, and sell seeds of certain hallucinogenic plants, such as Rivea Corymbosa, Hawaiian baby woodrose, and certain strains of morning glory seeds. However, it is not legal to ingest them.

The bottom line is that I urge my patients not to try hallucinogens because their safety has not been established. This is especially true for illicit products, which may contain additional toxic substances.

Fortunately, we do not need to resort to these agent because we have such a variety of safer and legal products. These include preventive medications, such as verapamil in high doses, topiramate, lithium, and for chronic cluster headaches, Botox injections. None of these drugs are approved by the FDA and are not likely to be approved because this is a relatively rare condition, which makes performing large studies very difficult. The only FDA-approved drug for cluster headaches is an abortive drug, injectable sumatriptan (Imitrex).

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Two new migraine drugs are about to be released on the market. They were mentioned in this blog in their earlier stages of development. Another two drugs are more interesting, but are several years away from becoming available (if at all).

Zecuity is a patch that delivers sumatriptan (active ingredient in Imitrex) through the skin. The patch contains a small battery and the electric current it generates helps the medicine penetrate through the skin. The patch is particularly useful when migraine is accompanied by nausea and vomiting. The main side effect of the patch, compared to the tablet, is that it causes irritation of the skin in one third of patients. This product was already approved by the FDA and will be soon available in pharmacies from its manufacturer, Teva Pharmaceuticals.

Levadex is a drug inhaled into the lungs using a device similar to those used for asthma drugs. It contains dihydroergotamine – a very old and very effective injectable drug. Dihydroergotamine does not work well in a nasal spray (Migranal) or when taken by mouth. Levadex causes less side effects, such as nausea, than the injection of this drug. The main target population for this drug is also migraine sufferers who experience nausea and vomiting and for whom tablets do not work. Because it works very fast it may be also very effective for those whose headache starts and escalates to a severe intensity very quickly, which includes not only migraine, but also cluster headache sufferers. Levadex is manufactured by Allergan, the company that also makes Botox. It should be available in the next few months.

Lasmitidan is a new drug being developed by CoLucid. It is in phase III trials, which is the final phase, which if successful, can lead to the FDA approval. Lasmitidan is a new type of drug – it targets a specific serotonin receptor subtype – 1F, while triptans (sumatriptan, rizatriptan, and other) target 1B and 1D serotonin receptors. It may have the advantage of not constricting arteries at all and may be allowed in patients with coronary artery disease. Triptans are contraidicated in such patients.

Merck is developing a drug, which does not have a name yet, only a number – MK-1602. It is a CGRP receptor antagonist – a blocker of a neurotransmitter in the brain that is involved in migraine origination. It is in phase II trials. MK-1602 also has the advantage of not constricting arteries. At least two other companies are developing CGRP antibodies (different from CGRP antagonists) and they were mentioned in a recent post here.

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