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Chronic migraine

I am once again honored to participate in the annual meeting of the Headache Cooperative of the Northeast to be held March 7-9 at the Stamford Marriott Hotel and Spa in Stamford, CT.

You will get a chance to learn about the latest scientific breakthroughs from Rami Burstein, president of the International Headache Society. You will also hear from other prominent figures in the field, renowned for their pioneering work and extensive contributions over several decades – Drs. Steven Baskin, Elizabeth Loder, Thomas Ward, Morris Levin, Richard Lipton, Steven Silberstein, Allan Purdy, Alan Rapaport, Paul Rizzoli, Sait Ashina, and others.

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We use a neuronavigation system from Soterix (on the left) for precise targeting of transcranial magnetic stimulation (TMS). And we use the most advanced TMS machine from MagVenture (on the right) to treat chronic pain, migraines, fibromyalgia, and other neurological conditions.

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Medication overuse or rebound headaches can occur as the result of excessive intake of caffeine, opioid analgesics, and short-acting barbiturate drug, butalbital (contained in Fioricet, Esgic and similar drugs). These three substances not only worsen migraine headaches, they are also addictive.  Two of my patients with medication overuse headaches were able to stop the offending drugs with the help of repetitive transcranial magnetic stimulation (rTMS).

One patient, a 51-year-old man, had his migraines under control with Botox and infusions of eptinezumab (Vyepti) until he sustained a head injury with a skull fracture. His migraines worsened and he became disabled. A variety of therapies failed to reduce his pain. His pain was partially relieved by 60 mg of oxycodone a day, although he still was unable to work. After six weekly sessions of rTMS he was able to start reducing his oxycodone intake and after eight, he completely stopped it. He was able to return to work with the help of injections of fremanezumab (Ajovy).

Another patient, a 50-year-old woman, had been taking butalbital with caffeine and acetaminophen (Fioricet) for 20 years. The number of pills increased over time and for the previous several years, she had been taking 10 to 12 tablets every day. She was also receiving Botox injections, infusions of eptinezumab, and taking rizatriptan (Maxalt), 10 mg three times a day as well as 60 mg of nortriptyline, 12 mg of tizanidine nightly and atogepant, 60 mg. She had tried a wide variety of other treatments but was unable to reduce her Fioricet intake. Despite her persistent migraines, she was able to take care of her family. After three weekly sessions of rTMS she reduced her Fioricet intake to 3-4 a day, by the third month she was taking one a day, and after 6 months she was completely off it. She was also able to stop atogepant and tizanidine and reduced her nortriptyline to 25 mg.

In addition to helping relieve pain and migraines, rTMS has shown promise in the treatment of addiction, particularly in addressing withdrawal symptoms, depression, and cravings. While the use of rTMS for addiction is still relatively recent and not yet FDA-approved, some studies have demonstrated positive outcomes. For instance, a double-blind study showed that individuals receiving rTMS therapy for cocaine addiction had a higher rate of abstinence compared to those who received standard treatment. rTMS for addiction is still considered experimental, and more research is needed to fully understand its long-term effects and optimal treatment parameters.

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Neurologists frequently find themselves managing patients resistant to standard treatments due to limited proven therapies for many neurological conditions. Some patients cannot tolerate or have contraindications to medications, particularly for such common disabling conditions like migraine and chronic pain. 

One promising treatment is transcranial magnetic stimulation (TMS). It is a proven procedure for anxiety, depression, obsessive-compulsive disorder (OCD), smoking cessation, and acute migraines. TMS utilizes magnetic fields to stimulate nerve cells in the brain that are underactive or reduce the excitability of overactive cells. TMS can change the flow of information between different parts of the brain in various neurological conditions. Published reports show the potential benefit of TMS in fibromyalgia, neuropathic pain, cluster headaches, facial pain, trigeminal and other neuralgias, back pain, insomnia, memory disorders, tinnitus, post-concussion syndrome, post-traumatic stress disorder (PTSD), restless leg syndrome, and long COVID. The evidence for the efficacy of TMS for these neurological disorders, however, is still limited.

Single-pulse TMS is approved by the FDA for the acute treatment of migraines with aura. The patient uses a portable device during the aura phase to self-administer a single pulse of TMS to the back of the head. This can abort the attack. Repetitive TMS (rTMS) has been studied for the prevention of migraines and other types of pain. It appears effective, but compared to depression trials, migraine studies were relatively small and the FDA has not cleared rTMS for the treatment of migraines. This means that insurance companies are not likely to pay for this “off-label” use of TMS.

rTMS is generally considered safe and well-tolerated, with side effects typically mild and temporary, including scalp discomfort, headaches, and facial twitching. More serious side effects like seizures and mania are very rare. 

Before starting TMS, patients undergo a physical and mental health evaluation. The coil placement and dose are determined in the first session. During a TMS session, patients sit in a comfortable chair with earplugs. An electromagnetic coil is positioned near the scalp, delivering short magnetic pulses to specific brain regions involved in processing pain and other information. Patients feel and hear rapid tapping on their scalp that continues, on and off. Patients are awake and alert during the entire procedure. There are no limitations to activities before or after the treatment.

Treatment length varies from 20 to 45 minutes, depending on the stimulation pattern and number of sites stimulated. The frequency of treatments also varies – anywhere from daily for several weeks, to once a week. After the initial period of more frequent sessions, some patients require weekly or monthly sessions to maintain the effect. It may take a few weeks to see noticeable effects. 

TMS is a good choice for people who have not responded to multiple standard therapies, people who do not want to take drugs, those who also suffer from depression and anxiety, and pregnant women. Sufficient evidence suggests that TMS is as safe in children as it is in adults, with studies indicating its effectiveness in treating depression in adolescents.

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Proton Pump Inhibitors (PPIs) are a class of medications commonly used to treat conditions such as acid reflux, ulcers, and heartburn. They include omeprazole (Prilosec, Zegerid), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (AcipHex), Dexlansoprazole (Dexilant), and pantoprazole (Protonix). Several of these are available without a prescription.

While PPIs are generally considered safe and effective, several studies have suggested a potential association between PPI use and several medical and neurological problems. These include osteoporosis, kidney problems, impaired hearing, vision, memory, and an increased risk of conditions such as migraines, dementia, peripheral neuropathies, and seizures. The evidence is circumstantial and not definitive. However, considering the large number of studies and a large number of conditions, PPIs are probably not safe for long-term use.

In the case of migraines, one study found that past and current use of PPI increased the odds of migraine by 2.56-fold and 4.66-fold, respectively. The exact reason for this link is still a mystery, but researchers are exploring several possibilities:

Nutrient deficiencies: PPIs can interfere with the absorption of important nutrients like vitamin B12, other B vitamins, and magnesium, which can contribute to headaches.

Gut microbiome changes: PPIs can alter the gut microbiome, which may indirectly impact brain function and migraine susceptibility.

Inflammation: Some studies suggest PPIs might trigger low-grade inflammation, a potential factor in migraine development.

This post was prompted by a recent study showing an association between PPI intake and the risk of dementia. Those who used PPIs for a cumulative four and a half years or longer had a 33% higher risk of developing dementia.

Stopping a PPI can cause severe rebound acidity. This is why people get stuck taking them for years. The way to try is by replacing the PPI with an H2 blocker such as famotidine (Pepcid, Zantac 360) along with an antacid such as Rolaids (it’s better than Tums because it contains not only calcium but also magnesium) or Gaviscon. After a few weeks, people can often stop famotidine and after another few weeks, stop the antacid. Famotidine does not cause problems associated with PPIs.

If you cannot stop or have a condition that requires long-term intake of a PPI (e.g. Barrett’s esophagitis), make sure to take a variety of vitamins and minerals. However, the lack of acidity can prevent the absorption of supplements. We usually do a blood test to check vitamin B12, RBC magnesium, vitamin D, and others. Some of our patients come in for monthly infusions of magnesium and other nutrients they are deficient in.

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The annual course, “The Shifting Migraine Paradigm 2024” will be held February 15-17, 2024 at the Plaza San Antonio Hotel & Spa. This three-day conference offers an excellent update on the treatment of migraine and other headaches.

It is always an honor to be invited to speak at this event. The topic of my presentation is Supplements and Medical Foods.

 

 

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Homocysteine, an amino acid crucial for cellular metabolism and protein synthesis, is naturally produced by the body. However, either too low or too high levels in the body can lead to significant health issues.

Insufficient homocysteine levels impair the production of glutathione, a vital substance for detoxifying the liver and the entire body. In some cases, patients are given glutathione infusions for its additional benefits.

Having too much homocysteine is also a problem. High levels are associated with an increased risk of cardiovascular disease, cancer, and migraine with aura. High homocysteine levels may also mean you have a Replacing these vitamins often helps return the homocysteine level to normal.

Some drugs may lead to increased homocysteine levels. These include cholestyramine, metformin, methotrexate,  nicotinic acid (niacin), and fibric acid derivatives (drugs that are used to lower lipids).

Besides migraine with aura, other symptoms of high homocysteine and low vitamin B12 levels may include memory difficulties, weakness, fatigue, tingling sensations in the hands, arms, legs, or feet, dizziness, mouth sores, and mood changes.

White matter lesions seen on the MRI scans of migraine patients are more common in those with high homocysteine levels.  High homocysteine levels may be responsible for the increased risk of strokes in migraine patients.

A recent large study of the role of pollution in the development of dementia revealed that pollution increases this risk only in those with high homocysteine levels.

The good news is that taking vitamins B12, folate, and B6 (pyridoxine) can lower homocysteine levels. Methylated forms of vitamin B12 and folate, methylcobalamin and methylfolate are better absorbed than cyanocobalamin or folic acid.

If you suffer from migraines, especially migraine auras (with or without headaches) you may want to have your homocysteine levels checked. In all of our migraine patients, we also check vitamin B12, folate, RBC magnesium, vitamin D, TSH (thyroid), and routine tests – CBC and CMP.

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Lack of sleep is a common migraine trigger. A less common trigger is getting too much sleep. I always recommend that patients try to go to sleep at the same time and get up at the same time. Even on weekends. Instead of sleeping in on the weekend, take a 30-minute nap in the afternoon.

A new study by Australian researchers published in Neurology reports another important reason for sleep regularity. This was a large and rigorous study involving 88,094 UK subjects. All subjects wore an accelerometer that detected their sleep patterns. The researchers controlled for variables that are known to predispose to dementia –  age, sex, ethnicity, material deprivation, retirement status, current shift work status, household income, highest level of education, smoking status, use of sedative, antidepressant, or antipsychotic medication, and genetics (APOE ?4 carrier status).

They “identified a nonlinear relationship between day-to-day sleep regularity and dementia risk such that dementia rates were highest in those with the most irregular sleep, dipped as sleep regularity approached the median, and then marginally increased at the highest estimates of sleep regularity.” In subjects who underwent brain MRI (n = 15,263), gray matter and hippocampal volume (area of the brain critical to memory) similarly tended to be lowest at the extremes of the sleep regularity index. This was surprising – subjects whose sleep patterns were extremely chaotic did slightly better than those with moderately irregular sleep.

Other sleep disorders that can contribute to migraines and increase the risk of dementia are restless leg syndrome, sleep apnea, and sleeping too much or not enough.

 

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My recent blog post on supplement combinations mentioned one that contains magnesium, riboflavin, and feverfew. I did not mention its name to avoid the appearance of a conflict of interest. I am a paid consultant to the manufacturer. However, many readers of this blog want to know the name of this mystery product. It is called MigreLief.

Akeso, the manufacturer, also makes several related products. One is MigreLief NOW, which contains magnesium, feverfew, ginger, and boswellia. Both ginger and boswellia have proven anti-inflammatory properties.

Another product is a daily MigreLief supplement for children. It also contains magnesium, riboflavin and feverfew but at a lower dose and in smaller caplets.

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The thyroid function test is in the initial battery of blood tests we order on all our headache patients (along with RBC magnesium, vitamins D, B12, folate, and others). Having either an overactive or underactive thyroid is known to worsen migraine headaches.
A new study published by Indian researchers confirmed that treating an underactive thyroid improves headaches. The researchers studied 87 headache patients with a mild decrease in thyroid function. Half of them were prescribed thyroid medicine and the other half received a placebo. Correcting thyroid deficiency improved headache frequency, severity, and disability (MIDAS score) at three months of follow-up in the treatment group compared to the placebo group.
The conclusion was that it is logical to check thyroid function status in patients presenting with migraine headaches.
Thyroid function can sometimes decline precipitously and cause worsening of headaches without any other symptoms. This can happen after delivering a baby and the cause is often misinterpreted. Lack of sleep, stress, hormonal changes (female hormones, not thyroid hormone), occlusion of veins inside the head, and even stroke are suspected.  All those conditions can cause headaches after the delivery. But we should not forget to check the thyroid.
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Neurologists diagnose migraine by the description of symptoms provided by the patient. We have not had an objective test to confirm that a person suffers from migraines.

A group of researchers led by Dr. Yiheng Tu in the department of psychiatry at Harvard Medical School developed an AI program that can diagnose migraine using fMRI (functional MRI) scanning. The AI program was first fed information on fMRIs of 116 individuals with migraines and then had this data compared to healthy controls.

The AI program had 93% sensitivity and 89% specificity. This means that it missed the diagnosis of migraine in only 7 out of 1oo patients and diagnosed migraine in 11% of patients who did not have it. These are very good numbers, but clearly, the method is not error-proof.

When they compared people with migraines to those with other types of pain, the sensitivity dropped to 78% and specificity, to 76%. This can be explained by the fact that similar functional changes in the brain probably occur with any type of pain.

A major obstacle to the wide use of fMRI scans is the cost. They are more expensive to perform than a regular MRI. Insurance companies are not likely to cover it since this is an experimental procedure. Another potential difficulty is that fMRI takes much longer to do than a regular MRI – an hour vs 20 minutes. During this time you have to lie inside a tube while trying not to move and hearing loud banging noises.

 

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I tell most of my patients that after physical exercise, meditation is the second-best preventive treatment for migraine headaches.

It turns out that meditation is not an unalloyed good. In a recent podcast, Tim Ferris interviews a psychologist, Dr. Willoughby Britton whose research is devoted to the negative effects of meditation. Tim Ferris describes his experience of going on a week-long silent meditation retreat, while also fasting and taking psychedelic mushrooms. It is not too surprising that Tim Ferris ended up needing professional help. However, even meditation alone, if taken to an extreme can cause psychological problems. In California, the joke is that meditation is a competitive sport.

Dr. Britton and her colleagues identified a staggering 59 different symptoms that can be triggered by meditation. Cheetah House, an organization led by Dr. Britton, is dedicated to assisting individuals who have experienced negative effects from meditation. According to one study, the most common adverse effects are anxiety, traumatic re-experiencing, and heightened emotional sensitivity. Those with a history of adverse childhood experiences are at a higher risk. But surprisingly, even individuals with adverse effects reported being glad they had meditated.

Dr. Britton suggests that meditating for less than 30 minutes is not likely to result in negative effects.

I have been meditating for years, and it was only when I extended my meditation time to 45 minutes about a year ago that my migraines completely stopped. Fortunately, I have not encountered any side effects.

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