We are again in a cluster season. We do not see any cluster headache patients for months and then dozens come in within weeks. It is not allergies, barometric pressure or any other earth phenomena that trigger cluster headaches in so many people at once. It has been speculated that solar activity may be the trigger and I just checked the NASAs Solar Dynamics Observatory website and found that the sun has “active regions galore”. I wrote about solar activity as a possible culprit last October when we had another wave of cluster patients. Unfortunately, there is not much we can do about the sun, but we do have many effective treatments for cluster headaches, including intravenous magnesium, occipital nerve blocks, oxygen, injectable sumatriptan, verapamil, and for chronic cluster headaches, Botox injection.

A recent study by British neurologists in the journal Headache described the severe impact of cluster headaches on quality of life and neuro-psychological symptoms. The researchers found that cluster headache patients had normal intelligence and executive functions, but had worse working memory, disturbance of mood, and poorer quality of life compared with healthy controls. Similar findings have been found in patients with other chronic pain conditions as well. It is most likely that cognitive impairment and mood changes can be reversed with effective treatment of pain.

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Another supplement to consider for the preventive treatment of migraine headaches is diamine oxidase (DAO). It is an enzyme that breaks down histamine.

Histamine is released during an allergic reaction and is present in many foods. It is one of the neurotransmitters that is involved in the process of migraine. A quarter of the population has insufficient amounts of DAO, which leads to inefficient metabolism of histamine. The largest amounts of DAO in the body are found in the intestines and the kidneys.

A group of Spanish neurologists published a study that showed that of 137 patients with migraines, 119 (87%) showed impaired activity of the enzyme.

The normal enzyme activity is a score of at least 80 histamine-degrading units [HDU]/mL. In a survey which was conducted in 2006 and again in 2012, migraine symptom scores correlated with enzyme activity. Symptom scores rose progressively as enzyme activity dropped below 80 HDU/mL, with scores almost twice as high in the 30-40 HDU/mL range compared with enzyme activity >80 HDU/mL.

Dr. Izquierdo and his colleagues in Barcelona conducted a double-blind, placebo-controlled trial of DAO oral supplementation, for the prevention of migraines in patients with DAO activity less than 80 HDU/mL.

Participants were men or women age 18 to 60 years old with an attack within the previous 6 months. Most of the patients were women, with only 8 men in each group.

The supplement contained 4.2 mg of DAO which participants took with a glass of water before breakfast, lunch, and dinner. The supplement was associated with a similar reduction in the mean number of attacks per month in the placebo and DAO groups, but the group that took DAO used significantly fewer triptan drugs (such as sumatriptan, Imitrex). These results are not overwhelming, but they possibly hide the fact that some of these patients had a very good response while others had none, which averaged out to a modest benefit. Considering that this a very benign supplement with no potential for serious side effects (unlike prescription drugs), it may be worth trying.

Histamine intolerance is defined by an imbalance of histamine and the histamine degrading enzyme diamine oxidase (DAO), which is mainly produced in the small intestine. Excessive amounts of histamine in the body can cause not only migraine and other types of headaches, but also diarrhea, nasal congestion, asthma, rashes, and other symptoms. People who are prone to severe allergic reactions with anaphylactic shock often have lower DAO activity. Diamine oxidase activity can be measured in blood, but the test is expensive and not very reliable. Instead of doing this test, try a low histamine diet or taking a DAO supplement. This is particularly worthwhile for people who in addition to migraines suffer from colitis (such as Crohn’s), allergic conditions, asthma, and celiac disease.

Here is an informative post on this topic on The Daily Headache blog.

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Tension headaches can be prevented, or at least made milder by strength training, according to a new Danish study just published in the journal of the International Headache Society, Cephalalgia.

Tension-type headache is the most common type of headaches and it is usually accompanied by increased muscle tenderness.

The researchers compared muscle strength in neck and shoulder muscles in 60 patients with tension-type headaches and 30 healthy controls, using rigorous strength measurement techniques. Patients were included if they had tension-type headaches on more than 8 days per month and had no more than 3 migraines a month. Compared to controls headache patients had significantly weaker muscle strength in neck extension, which helps keep the head straight. Headache patients also showed a tendency toward significantly lower muscle strength in shoulder muscles. Among the 60 headache patients, 25 had frequent headaches and 35 had chronic tension-type headaches (defined as occurring on 15 or more days each month).

The use of computers, laptops, tablets, and smart phones has increased in recent years and this may increase the time people are sitting with a forward leaning head posture, which contributes to neck muscle weakness.

Neck pain and tenderness is a common symptom in both tension-type and migraine headache sufferers.

This is not the first study to show that muscle strength and weakness were associated with tension-type headaches, but it is still not clear whether the muscle weakness is the cause or the effect of headaches. Neck and shoulder strengthening exercises have been shown to reduce neck pain in previous studies and in my experience strengthening neck muscles will often relieve not only tension-type headaches, but also migraines. So it is most likely that there is not a clear cause-and-effect relationship, but a vicious cycle of neck pain causing headaches and headaches causing worsening of neck pain and neck muscle weakness.

Physical therapy can help, but the mainstay of treatment is strengthening neck exercises. Here is a YouTube video showing how to do them. The exercise takes less than a minute, but needs to be repeated many times throughout the day (10 or more). Many people have difficulty remembering to do them, so using your cell phone alarm can help. Other treatment measures include being aware of your posture when sitting in front of a computer or when using your smart phone, wearing a head set if you spend long periods of time on the phone, doing yoga or other upper body exercises, in addition to the isometrics.

Sometimes pain medications or muscle relaxants are necessary, while for very severe pain, nerve blocks and trigger point injections can help. Persistent neck pain can respond to Botox injections. When treating chronic migraines with Botox, the standard protocol includes injections of neck and shoulder/upper back muscles. Here is a video of a typical Botox treatment procedure for chronic migraines.

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While Botox (OnabotulinumtoxinA) has been shown to be effective in treating chronic migraines, its exact mechanism of action is not clear. Initially, we thought that it works by relaxing muscles in the forehead, temples and the back of the head and neck. However, this is not likely for several reasons. One reason is that some people have pain at the top of their heads, where there are no muscle, and injecting those areas leads relief of pain. Another reason is that Botox seems to be effective in relieving different nerve pains, such as that of shingles (post-herpetic neuralgia), trigeminal neuralgia, and other.

Botox blocks the release of acetylcholine, a neurotrasmitter that is normally released into the space between the nerve ending and the muscle (synapse), making the muscle contract. We also know that Botox blocks the release of other neurotransmitters, which may be responsible for its pain-relieving properties. One of these chemical messengers is CGRP (calcitonin gene-related peptide).

A study just published in the journal Pain by Spanish researchers showed that CGRP level is increased in blood of patients with chronic migraine even when they are not having a migraine attack. CGRP levels were determined in 83 patients with chronic migraines (average age 44 years; 94% females) before and 1 month after treatment with 155 to 195 units of Botox. CGRP levels after Botox treatment were significantly lower as compared with CGRP levels obtained before Botox treatment. Pretreatment CGRP levels in responders were significantly higher than those seen in nonresponders. One month after treatment, the CGRP levels did not change in nonresponders, but significantly decreased in responders. Demographic factors, clinical features, and comorbidities (co-existing medical conditions) were not different in responders as compared with those of nonresponders. The authors concluded that “These results confirmed that CGRP levels can be of help in predicting the response to Botox and suggest that the mechanism of action of Botox in chronic migraine is the reversal of sensitization as a result of the inhibition of CGRP release.”

Unfortunately, the test to measure CGRP levels is not yet available outside research laboratories and because this was a small study we do not know how accurate this test will be. It has to tells us with greater than 90% which migraine sufferer will respond. If it is less than 90% accurate, we’d be denying over 10% of patients a very effective and often life-altering treatment. Some studies also suggested that we can predict who will respond and who will not by the description of pain. That is, if the pain is squeezing, crushing from outside in, or involves the eye, then the chances of response are better than if the pain is exploding, or from inside out. The accuracy of this predictor is less than 70%, so it should not be used to screen for potential non-responders.

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A topical cream seems to be effective in treating migraine headaches. Achelios Therapeutics announced results from a Phase IIa placebo-controlled clinical trial in moderate and severe migraine sufferers treated with Topofen, the company’s proprietary topical anti-migraine therapy. This is a well-known non-steroidal anti-inflammatory drug (NSAID) ketoprofen, which is applied to the face and seems to provide relief for patients suffering from acute migraine.

The results of the clinical trial were presented at the American Academy of Neurology annual meeting in Washington, D.C. Surprisingly, this study showed that it may be possible to relieve severe migraine with a topical application to facial nerve endings. Topical application avoids potentially serious side effects of NSAIDs, such as stomach bleeding and ulcers. The randomized, crossover, double-blind, placebo-controlled study involved only 48 adults with a history of episodic migraine with and without aura. Of the severe migraine patients, 77 percent experienced relief of pain and migraine-associated symptoms and 45 percent had sustained pain relief from two to 24 hours compared to 15 percent on placebo. Also, 50 percent of patients who treated their severe pain with Topofen were pain free at 24 hours compared to 25 percent of placebo-treated patients. Some patients experienced application-site irritation, which was mild or moderate in severity. That was the only reported side effect, which resolved quickly.

Such a small study does not prove that this treatment is in fact effective. A typical drug trial required for an FDA approval usually involves hundreds of patients. However, you do not need to wait for this cream to appear on the market because there are creams containing an NSAID already available by prescription (Voltaren Gel) and over-the-counter (Aspercreme). It is possible that the cream tested in the study may be better because it is a different NSAID, but Voltaren Gel is already approved and you can ask your doctor for a prescription. It is possible that insurance companies will not pay for it since it is not approved for migraines. A tube of Voltaren Gel will cost you about $55 (go to GoodRx.com to get the lowest price).

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The FDA-approved protocol for Botox injections for chronic migraines calls for 31 injections with 155 units of Botox. This is the protocol we teach young doctors and new injectors.

However, just like with any other medication, doctors are allowed to go “off label”, meaning that we can inject Botox for headache types and pain conditions other than chronic migraine (in which case insurance will usually not pay) and we can also adjust the number of injection sites and the total dose of Botox when treating patients with chronic migraines. I have a fair number of patients who need up to 200 units and on a very rare occasion even 300. The maximum dose allowed during a single treatment is 400 units, which is usually needed when injecting large muscles in arms and legs, like in cerebral palsy or spasticity due to strokes.

This YouTube video shows injections for chronic migraines with additional injections into the masseter muscles (at the corner of the jaw) to treat TMJ syndrome, which is also called temporomandibular disorder. Injections of the temporalis muscles in the temples, which are also involved in chewing and which are always injected for chronic migraines, also helps relieve TMJ syndrome.

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Low vitamin D level predicts larger stroke size and poor outcome, according to a new study by University of Massachusetts researchers. They examined data on 96 consecutive patients with stroke and found a strong inverse correlation between the level of vitamin D and the size of the stroke. This is not surprising since vitamin D seems to be very important for the normal functioning of the nervous system. In a previous post I mentioned a study that showed an inverse correlation between vitamin D level and relapses of multiple sclerosis. Such correlation has been also found with migraine headaches and other major diseases.

Yes, all these studies are correlational and do not prove that taking vitamin D will prevent any of these conditions. But there is no evidence at all that taking vitamin D to maintain your blood level in the normal range has any side effects.

The stroke study was done only in caucasian patients and we know that blacks may need lower levels of vitamin D than caucasians, at least as measured by the standard blood test. This test is not very reliable since it measures the total level of vitamin D, while only the free portion of it is biologically active. To be safe, try to aim to have vitamin D level at least in the middle of normal range, which is from 30 to 100. Many people take the recommended 400 unit dose of vitamin D, but still have low levels in their blood. It is important to check your vitamin D level even if you are taking a supplement. Some patients require 2,000 and even 5,000 units daily to get their blood level to the middle of normal range.

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Topiramate (Topamax) is a drug used for the prevention of migraine headaches (and epilepsy) in adults and last year it was also approved for adolescent migraine sufferers. This drug is notorious for causing cognitive side effects, kidney stones,osteoporosis, overheating, and many other side effects. It is contraindicated (just like another migraine drug, Depakote) in pregnancy because of the risk of birth defects.

A new report published in the journal Pediatrics documents an increased risk of eating disorders in adolescents who take Topamax. This report describes 7 female teenagers who developed an eating disorder or whose eating disorder got worse on topiramate.

Considering that we have many other effective preventive drugs for migraine headaches, topiramate should be used only when several other treatments fail.

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Chronic migraine sufferers appear to be more likely to have dryness of their eyes, according to a study by ophthalmologists at the University of Utah, which was published in the journal Headache. The researchers used sophisticated techniques to measure tear production, corneal sensitivity, dry eye questionnaire, and other tests. The results of these tests were compared in migraine sufferers and healthy control subjects.

A total of 19 chronic migraine patients and 30 control participants completed the study. The nerve fiber density was significantly lower in the corneas of migraine patients compared with controls. All migraine sufferers had symptoms consistent with a diagnosis of dry eye syndrome. The researchers plan to continue studying the interrelationships between migraine, corneal nerve architecture, and dry eye.

Similar findings in patients with episodic migraine were published by a group of Turkish doctors in the journal Cornea in 2012.

Migraine sufferers and their doctors should be aware of this correlation since irritation caused by dry eyes could potentially trigger a migraine. It is possible that some migraines can be prevented by using over-the-counter and prescription eye drops or, in severe cases, eye inserts (Lacrisert). High doses of omega-3 fatty acids have been reported to help dry eyes and omega-3 fatty acids have also been reported to relieve migraines.

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Cluster headaches cause more severe pain than any other type of headaches. Some patients even call them suicide headaches because they provoke thoughts of suicide. The name comes from the fact that they occur in clusters – every day for a couple of months and then they go away for a year or longer. In those with chronic cluster headaches they never go away. The headaches are brief – anywhere from 30 minutes to 3 hours. They are always one-sided, with pain usually around the eye, and are accompanied by tearing, nasal congestion, and sometimes restlessness. More men than women suffer from them.

Treatment of cluster headaches can be very effective. A 10-day course of prednisone or an occipital nerve block can abort the entire cluster. We also have preventive drugs, such as a blood pressure medicine, verapamil (used in high doses), epilepsy drugs, and lithium. These are taken daily to prevent headaches. To treat individual attacks, inhalation of 100% oxygen under high flow, zolmitriptan nasal spray (Zomig NS), and sumatriptan (Imitrex) injections can be true life savers.

Some of the alternative therapies that have been reported to help include melatonin, intranasal capsaicin (hot pepper extract), and an herbal product, Boswellia (Nature’s Way is a good brand for herbals).

Unfortunately, there are some cluster headache sufferers who do not respond to any of these treatments. We even treated some patients with intravenous histamine, which requires hospital admission and two of my patients were implanted with a vagus nerve stimulator (with good relief).

Some cluster patients have been found to have low testosterone levels and treating them with testosterone seems to help.

This testosterone connection led to trials of a fertility drug, clomiphene citrate (Clomid). Clomiphene enhances testosterone production and binds to hypothalamic estrogen receptors, which is why it was considered as a treatment for cluster headaches. A second case of successful treatment of cluster headaches with Clomid has just appeared in the journal Headache. This was a case of a 65-year-old man with a 17-year history of chronic cluster headaches who did not respond or had significant side effects to many cluster headache preventive medications including verapamil, lithium, valproic acid, topiramate, baclofen as well as greater occipital nerve blocks and inpatient hospitalization.

The patient experienced 3-5 headaches per day. On Clomid (100 mg/day) he became 100% pain-free and remained so for three and half years with only mild fatigue as a side effect. He then had cluster headache recurrence and did well on gabapentin for another 3 years, but then his headaches returned. Clomiphene was restarted, and he became pain-free once again.

Clomid should be considered when the usual preventive drugs for cluster headaches are ineffective.

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