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Headaches

Opportunities & Challenges in the Management of Headache is one of the two annual courses organized by the Diamond Headache Clinic Research & Educational Foundation. This year, it will be held in San Diego from February 16th through February 19th.

The other annual event, Headache Update 2023 will be held in Orlando, Fl from July 13th through July 16th. Both courses have been always well attended and have been receiving very high marks from the attendees.

It’s been my privilege to participate in these annual courses over the past 25 years. This year I will be speaking on February 17th on Nutritional Approaches and Alternative Therapies in Migraine.

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Multiple posts on this blog have described clinical trials that prove the benefit of exercise for the prevention of migraine headaches.

In a recent paper published in The Journal of Headache and Pain Stanford researchers compared the efficacy of aerobic and strength training exercises. They conducted a meta-analysis of 21 clinical trials that involved a total of 1,195 migraine patients.

Simplifying the statistics, compared to no exercise, strength training was 3.55 times more effective, high-intensity aerobic exercise was 3.13 times more effective, and moderate-intensity aerobic exercise was 2.18 times more effective.

For general health and for the prevention of migraines, 2-3 weekly sessions of strength training and 2-3 sessions of aerobic exercise would be an ideal regimen. As I mentioned in a recent post, an additional benefit of exercise is a larger brain volume. The only other intervention that has been shown to expand the brain and prevent its shrinkage with age is meditation.

Exercise and meditation are the first two recommendations on my list of top 10 treatments described in my latest book, The End of Migraines: 150 Ways to Stop Your Pain.

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According to a new report by Spanish researchers published in The Journal of Headaches and Pain, effective preventive treatment of migraines can improve cognitive impairment in patients with frequent attacks.

Patients with migraines often complain that their memory is not as good as it used to be, that they have difficulty concentrating, or can’t think clearly.

There are many possible causes of such symptoms. Stress is probably the most common reason people have trouble with memory and concentration. There is just too much on their mind. Certain drugs, most notably topiramate (Topamax), can cause pronounced cognitive impairment.  Nutritional deficiencies, particularly of vitamin B12 and other B vitamins, magnesium and vitamin D can cause brain fog and other cognitive problems. Alzheimer’s disease, which is what people fear most, thankfully is rare at the age when most people suffer from migraines.

I also see patients who do not have any of the above reasons. There are several possible explanations for why migraines alone can cause cognitive problems. We know that if a patient has only a few attacks a month, the brain remains hyperexcitable even between attacks. Some patients have a prodrome – one or two days of brain dysfunction prior to an attack. Others have post-drome – a feeling of exhaustion as if being hungover for a day or two after the attack. There is also a likely contributing effect of anticipatory anxiety – living in fear of the next attack.

Christina Gonzalez-Mingot and her colleagues in Lleida, Spain, compared 50 control subjects and 46 patients with chronic migraine. These patients were evaluated using a battery of tests prior to the use of preventive treatment based on botulinum toxin (Botox) or oral drugs and after 3 months of this treatment.

Compared with controls, patients with chronic migraine had lower scores on three standard tests of cognitive performance and had lower quality of life. Three months after the use of preventive treatment, improvement was observed in all but one cognitive parameters and in the quality of life.

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Psychedelics are being actively studied for depression and post-traumatic stress disorder (PTSD). These trials usually involve hallucinogenic doses. Microdosing psychedelic substances such as psilocybin, lysergic acid diethylamide (LSD), and methylenedioxymethamphetamine (MDMA) has become a popular treatment for depression. Microdosing means that the amount of a psychedelic is too low to cause hallucinations or other overt sensory experiences.

There is an accumulation of evidence that psychedelics can provide pain relief. A case series just published in the journal Pain describes three patients with chronic pain who obtained significant relief from microdosing psilocybin-containing mushrooms.

The first patient was a 37-year-old man with severe pain due to traumatic quadriplegia. He had almost complete relief of pain and was able to stop taking tramadol, an opioid analgesic, diazepam (Valium), and marijuana. The relief was ongoing for six months when he was last seen by the doctors.

The second patient was a 69-year-old woman with complex regional pain syndrome (also known as reflex sympathetic dystrophy) secondary to left leg trauma. She had tried nerve blocks, other invasive procedures, stem cell injections, acupuncture, opioid analgesics, and many other medications, all with no relief. At the time of the published report, microdosing was providing continued significant relief for over a year.

The third patient was a 40-year-old woman with pain in her leg due to degenerative disk disease in her spine. Her pain did not improve with epidural injections, back surgery, muscle relaxants, opioid drugs, and physical therapy. Psychedelic mushrooms had a profound effect on her pain.

Psychedelic mushrooms have been reported by many patients to be effective in the treatment of cluster headaches (see ClusterBusters.org). A small double-blind study by Yale researchers showed a beneficial effect of synthetic psilocybin in treating migraine headaches.

It remains to be proven that sub-hallucinogenic doses of psychedelic drugs provide relief of painful conditions. If proven effective, however, such drugs will offer a much safer option than any opioid and NSAID analgesics, epilepsy drugs, antidepressants, or any other prescription drug. They are very safe even at hallucinogenic doses.

I am often asked about the practical side of using psychedelic mushrooms – where to buy them, how much to take, and for how long. Since the state of NY, unlike some other states, has not legalized or decriminalized the use of psychedelic mushrooms, I cannot answer these questions. Even if it was legal for me to do, I would not have reliable answers until clinical trials give us good data.

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A recent study by Chinese researchers showed that acupuncture is an effective treatment for tension-type headaches. The results were published in a leading neurology journal, Neurology. Being published in such a journal suggests that the study was scientifically rigorous and the results are likely to be reliable.

The study included 218 patients with half receiving true acupuncture and the other half, sham acupuncture. In the first group, after inserting each needle, the acupuncturist induced a specific deqi sensation. Patients describe it as a sensation of fullness, aching, or tingling. You can experience this sensation without needles – try squeezing hard the thick muscle between your thumb and the index finger. Needling or pressing on this acupuncture spot can provide relief of a headache and facial pain. The second, control group, had needles inserted without any further manipulation.

The main outcome measure in this trial was the number of patients who achieved at least a 50% reduction in the number of monthly headache days. In the true acupuncture group, 68% achieved this result compared to 48% in the control group. The difference was statistically highly significant.

These results are not surprising. Hundreds of clinical trials (admittedly, of varying quality) have shown that acupuncture can relieve migraine headaches and other painful conditions.

I am a licensed acupuncturist but use this treatment very infrequently. It is time-consuming (it should be done at least once a week) and expensive, especially if done by an MD (it is not covered by most insurance plans). For patients who are interested in trying it, I recommend finding a conveniently located non-physician acupuncturist whose fees are usually more affordable.

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Nummular (coin-shaped) headache is an uncommon condition.  It is defined as intermittent or continuous pain in a small circumscribed area of the scalp with the following four characteristics: sharply-contoured, fixed in size and shape, round or elliptical and 1-6 cm in diameter. The pain is usually mild or moderate in intensity, but some patients have severe pain. These headaches often occur in patients who also have migraines.

Nummular headaches often respond to ibuprofen, naproxen, and other NSAIDs. Botox injections are also very effective. They provide relief for 3 months, obviating the need for daily medications which are more likely to cause side effects. A very small amount of Botox is needed to treat nummular headaches, so the cost is much lower than when treating migraine headaches.

A case report just published in the journal Headache describes a patient who suffered from migraines and nummular headaches. His nummular headaches did not respond to medications and Botox injections but he had complete elimination of his nummular headaches along with improvement of his migraines after he received an injection of galcanezumab (Emgality).

Galcanezumab and other CGRP monoclonal antibodies have been also reported to help trigeminal neuralgia as has rimegepant (Nurtec ODT), an oral CGRP receptor blocker. It is possible that nummular headache is the result of damage or irritation of a small terminal branch of a nerve. This is suggested by the fact that the pain is invariably superficial. And we know that CGRP is involved in pain messaging along the nerves. So it is not surprising that anti-CGRP drugs can help relieve nummular headaches.

 

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Regular exercise has been proven to prevent migraine headaches in many studies. A Swedish study of 91 patients established that exercising for 40 minutes 3 times a week is as effective as relaxation training or taking a preventive migraine drug topiramate. Topiramate, however, caused significant side effects. Another study by the same group of researchers of 46,648 people found a strong inverse correlation between physical activity and the frequency of headaches.

A report by German researchers in the September 13 issue of the journal Neurology provides strong evidence that physical activity leads to larger brain volumes. This was a rigorous study that included 2,550 participants. The physical activity was measured using an accelerometer, a device similar to a fitness tracker.

The authors discovered that “Physical activity dose and intensity were independently associated with larger brain volumes, gray matter density, and cortical thickness of several brain regions.” The most notable change occurred in people who went from a sedentary lifestyle to a modest amount of low-intensity exercise when compared with those who already engaged in at least moderate amounts of physical activity. And this trend continued – very high frequency and intensity of training did not offer any additional benefits.

Two other reports of various benefits of exercise were published this month.

One was a study published in JAMA Neurology. This study also used accelerometers to count the steps made by 78,430 people. The researchers found that a higher number of steps prevented the development of dementia. The optimal dose was just under 10,000 steps and a higher speed had an additional benefit.

The second report in JAMA Internal Medicine analyzed the same group of 78,430 people and discovered that accumulating more steps per day (up to 10,000) may be associated with a lower risk of all-cause, cancer, and cerebrovascular disease mortality and incidence of cancer and cerebrovascular disease. Here they also found that a higher step intensity may provide additional benefits.

 

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No, Daxxify is not really a competitor in the treatment of chronic migraines or any other medical condition. Daxxify, a new botulinum toxin, was just approved by the FDA only for cosmetic use. Daxxify does stand out from five other botulinum toxin brands in that its effect lasts longer. The other toxins are Xeomin, Dysport, Jeuveau, and Myobloc. Myobloc is approved only for medical conditions, Jeuveau only for cosmetics, and Xeomin and Dysport are approved for both cosmetics and a few medical conditions.

Initially, Botox was approved by the FDA in 1989 to treat eye problems. Since then, it has been approved for many medical and cosmetic indications, including chronic migraine. None of the other toxins are approved for such a wide range of indications. It remains by far the most widely used type of botulinum toxin with tens of millions of people treated for medical and cosmetic reasons.

Yes, having a longer-acting botulinum toxin is an advantage. You will need to have less frequent treatments. However, if you have any side effects, they will also take longer to go away. We are talking mostly about cosmetic side effects, such as droopy eyelids. When treating headaches, with proper technique, side effects are uncommon. These may include weakness of the neck muscles or, if treating TMJ syndrome, difficulty chewing.

Since Botox is approved by the FDA for chronic migraines, Botox is the drug insurance companies cover. Allergan (a division of Abbvie), the manufacturer of Botox, has many more years left on their patent to treat chronic migraines. Botulinum toxin is a biological product (made by bacteria rather than synthesized from chemicals) and every version of it is slightly different. This is why when Allergan’s patent to treat migraines expires, the competitors will have to conduct large trials to prove that their product is also effective for migraines.

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Headache is a common symptom of any infectious illness, including COVID. A group of Spanish researchers analyzed six published studies of headaches in adult Spanish COVID patients.

According to their review, headache is an early symptom of COVID. It typically lasts two weeks. Patients in these studies were followed for up to a year. One out of five patients had developed a headache that persisted for at least a year. Women and older patients were more likely to be affected. This persistent headache most often resembled chronic migraine. The pain was throbbing with associated sensitivity to light and noise, and worsening with physical activity.  The authors did not observe a difference between patients with and without prior history of headache. Patients with more intense headaches were more likely to develop a chronic headaches.

The published studies reviewed by the authors did not address the treatment of headaches. Considering that the persistent headaches resembled migraines, we tend to treat them as we do chronic migraines. This means the use of antidepressants, epilepsy drugs, blood pressure medications, Botox, triptans, and CGRP drugs (both oral and injectable). It is likely that with early and aggressive treatment, many patients would not have headaches persist for such a long time. Doctors in Europe are less likely to prescribe medications and use Botox in headache patients than we are in the US.

COVID vaccination also carries a risk of developing persistent headaches. As mentioned in a previous post, people who received Pfizer or Oxford-AstraZeneca vaccine were twice as likely to develop a headache as those who received the placebo. The headache in these patients also tended to resemble migraine.

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Dr. Brian Loftus, a Texas neurologist, alerted me to the possibility that the shortening of the effect of Botox can be reversed by taking a zinc supplement. Dr. Loftus shared an unpublished report by Houston physicians who showed that zinc supplementation can extend the effect of Botox.

There is a good theoretical reason to suggest that for Botox to work, you need to have sufficient amounts of zinc. You can read about this connection in a review article by one of the leading movement disorders specialist, Dr. Mark Hallet.  He concludes that “Toxins are zinc dependent proteases, and supplemental zinc may produce a greater effect.”

It is very likely that taking zinc will benefit mostly people who are deficient. I just saw a patient in whom Botox provides relief for only 2 months and whose blood test showed a low zinc level. I suggested that he takes 50 mg of zinc every day.

Zinc is necessary for the activity of over 100 different enzymes that are involved in vital chemical processes of the body. Zinc is involved in the immune system, growth of cells, building proteins, and many other functions.

We might consider adding zinc to the usual battery of tests done on the first visit to our clinic. These include RBC magnesium, vitamins B12 and D, and routine blood tests.

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The 6th Annual International Headache Symposium in Israel will be held at Daniel Hotel, Herzliya (8 miles from Tel Aviv), on October 27, 2022. THe symposium is organized by the President of the Israeli Headache Association, Dr. Oved Daniel and by Dr. Arieh Kuritzky.

I am honored to have been invited to speak alongside the President of the International Headache Society Dr. Messoud Ashina, Dr. Rami Burstein of the Harvard Medical School, and other leading headache experts. The topic of my presentation will be “What to do when nothing works”. Other topics to be discussed include, Molecular signaling pathway in migraine: update, (Messoud Ashina), Connecting the line between dizziness, occipital headache, muscle tenderness and the cerebellum (Sait Ashina), Open-label studies: do they have any value? (Cristina Tassorelli), and others.

You can see the full program and registration information on this website.

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With tens of millions of Americans suffering from migraines, access to care is a major problem. Cove, a telemedicine startup, offers a practical and affordable solution. They deliver evidence-based therapies to patients in need. To prove that their approach works, Cove collects and analyzes vast amounts of data. The study I just presented at the annual scientific meeting of the American Headache Society shows that with Cove underserved minorities obtain excellent outcomes that are equal to those of whites.
Disclosure: I am a paid consultant to Cove.

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