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Migraine

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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Riboflavin (vitamin B2) has been a popular supplement for the prevention of migraine headaches. The evidence for its efficacy is limited. Only one small double-blind, placebo-controlled trial showed that a very high dose of riboflavin (400 mg daily) is better than a placebo. The study included only 55 patients, which makes the results not very reliable. Besides, the difference between the riboflavin and the placebo groups appeared only in the third month. There was no difference during the first two months. This study was published over 20 years ago and my clinical impression over this long period of time has been fairly negative.

A study just published in the journal Headache examined dietary intake of riboflavin and thiamine (vitamin B1) and correlated it with the occurrence of migraines or severe headaches. The researchers used the data from 13,439 adult participants in the National Health and Nutrition Examination Survey conducted between 1999 and 2004 in the United States. They found that people with a high intake of thiamine were significantly less likely to suffer from severe headaches or migraines. This was more pronounced in women. They found no such association for riboflavin.

Supplements with the most evidence in treating migraines are magnesium and CoQ10. I recommend riboflavin, folate (vitamin B9) and vitamin B12, to patients with an elevated homocysteine level. Excessive amounts of this amino acid are damaging to blood vessels and may be responsible for the increased risk of strokes in patients who have migraine with aura. It is worth checking homocysteine levels in all patients who have migraine auras, even if the auras occur infrequently.

“B complex” is a popular combination of various B vitamins. This latest paper is making me consider adding B complex rather than individual B vitamins to magnesium and CoQ10 in all of my migraine patients.

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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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It was an honor to speak in Israel at the 6th Annual International Headache Symposium along with past presidents of the International Headache Society, Drs. Messoud Ashina and Alan Rapaport, the current IHS president, Cristina Tassorelli, the president-elect, Dr. Rami Burstein, and other leading headache experts. The symposium was organized by the President of the Israeli Headache Association, Dr. Oved Daniel, and by Dr. Arieh Kuritzky.

 

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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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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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Patients with chronic migraine who were started on Botox were significantly more likely to continue to be treated with Botox after one year than patients who were started on a CGRP monoclonal antibody (mAb). mAbs are given monthly by injection. This category includes erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality).

The results of this large retrospective study that included 1,974 patients were presented at the last meeting of the American Headache Society held in June of this year. The lead authors were Dr. Todd Schwedt of the Mayo Clinic and Dr. Andrew Blumenfeld.

The study was sponsored by the manufacturer of Botox which makes it inherently biased. However, the difference between the two groups was striking. Of patients who were started on Botox, 66% continued the treatment at the end of the year. Less than a third of patients who were started on a mAb were still getting it at the end of the year.

The researchers looked at differences in outcomes in patients enrolled before and during COVID. The results were similar before and during the pandemic. This is surprising because, during the pandemic, many patients were reluctant to come to the office for Botox injections. Many preferred to self-inject mAbs at home. Despite this obstacle, Botox patients were twice as likely to continue treatment at the end of the year.

Besides efficacy, the major reason I recommend Botox ahead of mAbs and other drugs is its proven long-term safety. Botox was first approved by the FDA in 1989. Botox is my preferred treatment for chronic migraines even in pregnant women.

Both mAbs and Botox are fairly expensive. The same group of researchers presented a second study that evaluated all-cause and migraine-related costs in these two groups of patients. They found no difference in total healthcare costs and migraine-related costs, including emergency department expenses.

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Last week I spoke to Dr. Amelia Scott Barrett, a neurologist and headache specialist based in Denver. She shares my interest in combining medications with various non-drug therapies. In our first conversation, we discussed the role of magnesium in treating migraines.

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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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Regular intravenous infusions of magnesium prevented migraines in five children, according to a report presented at the annual meeting of the American Headache Society by A.J. Freed and S. Sahai-Srivastava. The children were between the ages of 11 and 16. Four of them had the diagnosis of chronic migraines and one, episodic. Two of them continued to have daily headaches but they were mild with the infusions. The other three also had a significant drop in the number of headache days.

Over the past 30 years, we’ve given monthly infusions to thousands of patients, including children as young as 6. Genetic factors play a role in some patients with magnesium deficiency. We’ve had three generations of a family coming for monthly infusions. Besides genetics, other reasons for magnesium deficiency include stress, alcohol, gastrointestinal disorders, poor diet, and others.

About half of migraine sufferers are deficient. They are likely to respond to oral magnesium supplementation. Many, however, do not absorb magnesium taken by mouth. If we know that a patient is deficient because they have other symptoms of magnesium deficiency (cold extremities, muscle cramping, PMS, palpitations, brain fog, and others) or because their blood level (RBC magnesium) is low or is at the bottom of the normal range, we give magnesium intravenously.

If you cannot find a doctor who gives infusions of magnesium, you may want to search for an infusion center or an urgent care facility that would do it. In many large cities, magnesium and vitamin infusions are done at some spas. There are also companies that offer home visits by a nurse.

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Two out of three women stop having migraines during pregnancy, especially in the second and third trimester. The difficult question is how to treat migraines in the first trimester and in women whose migraines do not improve or get worse in pregnancy.

Acetaminophen (Tylenol, paracetamol) is considered safe in pregnancy and that is what many women take for migraines and other pains. Unfortunately, acetaminophen is usually ineffective for severe migraines. It is also not as safe as many physicians and the general public thinks. Several studies indicate that acetaminophen increases the risk of attention-deficit hyperactivity disorder (ADHD) and with heavy use, possibly even autism spectrum disorder.

Some obstetricians strongly advise against taking any migraine medications. However, the stress of an acute migraine attack with severe pain, vomiting, and dehydration is likely to have a deleterious effect on the fetus. A Danish study of 22,841 pregnancies among women with migraine showed that untreated migraine leads to an increased risk of low birth weight, preterm birth, and cesarean delivery.

A report just published in the journal of the American Medical Association (JAMA) examined “Association of Maternal Use of Triptans During Pregnancy With Risk of Attention-Deficit/Hyperactivity Disorder in Offspring”.

The study used the data from the Norwegian Mother, Father and Child Cohort Study, linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry, and the Norwegian Prescription Database using the mother’s personal identification number. The conclusion of this large and rigorous study was: “This cohort study found no association between prenatal triptan exposure and ADHD diagnosis or ADHD symptoms at 5 years of age. This study adds to the growing literature on the safety of triptan use during pregnancy and expands it to an important neurobehavioral outcome.”

Triptans have been available without a prescription in all European countries for over a decade. In the US, triptans are available only by prescription. This is one of the reasons for the perception of acetaminophen as being more benign than sumatriptan and other triptans. The opposite is likely to be true. If you are a pregnant woman suffering from severe migraines, ask your doctor for a prescription for sumatriptan.

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