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New treatments

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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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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Cluster headaches arguably cause the worst imaginable pain, hence the moniker, suicide headaches.  Fortunately, there are many treatments for this condition, including two FDA-approved drugs. One is sumatriptan injections taken as needed to stop an attack. The other is a preventive monthly injection of galcanezumab (Emgality). We also use Botox injections, oxygen and a variety of medications. Nevertheless, some people do not respond to these treatments.

A report by Japanese neurologists from Tokyo suggests a new treatment. One theory of the origin of cluster headaches is the reactivation of the varicella-zoster virus that causes chickenpox and shingles.

The study included over 160 patients with episodic cluster headaches who received a shingles vaccine. The response to the vaccine was measured by the amount of antibodies in the blood. Those patients who had more antibodies had a longer delay to the next cluster episode than those with low antibody counts. They also found that those who had a COVID infection and received multiple COVID vaccines, tended to do worse.

It is premature to recommend shingles vaccine to patients with cluster headaches unless they are over 50, the age when everyone is advised to get it.

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There is growing evidence that vitamin D is important in the development and treatment of migraines. In the past 15 years, I have written a dozen posts on the role of vitamin D in migraines.

At the last meeting of the International Headache Society, Maria Papasavva and her Greek colleagues presented a study entitled, Genetic variability in vitamin D receptor and migraine susceptibility: a case-control study.

Their study aimed to investigate an association of three genetic variants of vitamin D receptor with the susceptibility to develop migraine. DNA sample was collected and extracted from 191 patients diagnosed with migraine and 265 headache-free subjects. According to their statistical analysis, a significant association between migraine susceptibility and abnormal variants of vitamin D receptors was found.  They also showed a significant association of two variants with migraine without aura. Their conclusion was that there is a clear association between migraine susceptibility and two vitamin D receptor variants. This further supports the role of vitamin D and its receptor in migraine.

Vitamin D is important not only for migraines but also for your immune system. Vitamin D deficiency increases the risk of COVID and other viral infections. Lower levels of vitamin D are associated with a higher risk of attacks of multiple sclerosis even if the level is still within normal range. There are many other reasons to maintain your blood vitamin D level at least in the middle of the normal range. The normal range is 30 to 100, so keep it well above 40. If your doctor tells you that your level is normal, ask for the actual number.

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Since the legalization of medical marijuana in New York in 2014, I have prescribed it to several hundred patients. My experience suggests that approximately one-third of my patients benefit from its use and continue to rely on it for their medical needs. Some have reported relief from symptoms such as nausea and anxiety, often associated with migraines, while others find it highly effective in aiding sleep. Additionally, there are patients who have reported significant pain relief.

It is possible that the relatively low response rate I see in my patients is due to the fact that I reserve medical marijuana for those patients who do not respond to multiple drugs.

At the recent meeting of the International Headache Society, Dr. Nathaniel Schuster and his colleagues presented a study titled “Vaporized cannabis versus placebo for the acute treatment of migraine: a randomized, double-blind, placebo-controlled, crossover trial.” This study aimed to investigate the potential of medical marijuana in alleviating pain and associated migraine symptoms.

In this study, participants were instructed to treat moderate-to-severe migraine attacks within four hours of onset using vaporized cannabis flower. They were asked to treat up to four separate migraine attacks, using vaporized cannabis with different compositions: 1) THC-dominant (6% THC), 2) CBD-dominant (11% CBD), 3) THC/CBD mix (6% THC/11% CBD), and 4) placebo cannabis, with the order randomized and double-blinded.

Out of the 92 participants enrolled, 71 treated at least one migraine attack. Two hours after vaporization, the THC/CBD mix outperformed the placebo in achieving pain relief (69% vs. 48%), pain freedom (36% vs. 16%), and freedom from the most bothersome symptoms, such as nausea, photophobia, or phonophobia (62% vs. 36%). The THC-dominant option was superior to the placebo for pain relief at 2 hours (71% vs. 48%) but was not significantly different from the placebo regarding pain freedom or freedom from the most bothersome symptoms. The CBD-dominant option did not significantly differ from the placebo in terms of pain relief, pain freedom, or freedom from the most bothersome symptoms. The most common side effects reported were sleepiness, followed by euphoria, with no serious adverse events observed.

In conclusion, the authors of the study found that the acute treatment of migraine with a vaporized THC/CBD mix (6% THC/11% CBD) was superior to the placebo in terms of pain relief, pain freedom, and freedom from the most bothersome symptoms at the 2-hour mark.

This study has significant practical implications. In the past, I would leave the choice of products to the licensed pharmacist at the dispensary, while advising patients that finding the right combination is often a trial-and-error process. However, now, I will be better equipped to advise my patients on the most suitable type of medical marijuana for their specific needs based on the findings of this study.

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New daily persistent headache (NDPH) is condition that is defined solely by the fact that the headache begins suddenly one day and does not go away. There are no scientific studies to suggest possible underlying mechanisms or treatments. Some patients develop it after a viral infection while others, after a period of stress and many with no apparent trigger.

In my latest book, I mentioned how a seemingly benign idea of classifying medical conditions can cause harm. In case of NDPH, many anecdotal reports in medical journals indicate that this condition is not responsive to treatment. However, there are no controlled double-blind studies, only anecdotal reports. Many patients with this condition will look up this literature and conclude that there is no hope of getting better. I have seen many such devastated people. But this bleak picture is clearly wrong.

I have seen many patients with NDPH who responded to various treatments. In my 30 years of using Botox, I have found it to be one of the safest and most effective treatments for NDPH as well as migraine and other types of headaches.

At the recent meeting of the International Headache Society held in Seoul, two presentations described good responses of NDPH to Botox injections.

The first report was by S. Cheema and colleagues of Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK. They compared patients with NDPH (58) and those with chronic migraine (CM) with daily attacks (153) and chronic migraines without daily attacks (85). There was a 30% reduction in mean moderate and severe headache days in 33% of patients with NDPH, 43% with daily CM and 55% with non-daily CM.

The second report was by Shuu-Jiun Wang and colleagues of the Neurological Institute, Taipei Veterans General Hospital. They looked at the response of patients with NDPH who had predominately migraine features and those who had predominantly features of tension-type headaches. Of 228 patients diagnosed with NDPH, 199 patients (87%) had migrainous features and 29 patients (13%) had tension-type features. Their conclusion: “Through a mean follow-up duration of 2.5 years, around 40% patients with NDPH showed a favorable outcome at our headache center. Our results suggest NDPH might not be as grave as previously reported.”

Yes, these were also anecdotal reports rather than controlled trials, but they clearly show what I have also observed in my practice – NDPH is a very treatable condition. Hopefully, the next, fourth edition of the International Classification of Headache Disorders will no longer list NDPH as a diagnosis since it has no scientific basis.

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Most people have heard about the gut-brain connection. Research published in The Journal of Headache and Pain examined this connection in relation to migraine headaches. The researchers looked at whether the collection of microorganisms living in our guts (called the gut microbiome) could be linked to the development of migraine headaches and its different types – migraine with and without aura.

To do this, the scientists used information from a big genetic study that looked at the genes related to the gut microbiome. They also used data from studies that explored the genetics of migraine headaches. They employed sophisticated methods to analyze this data, and they also checked for other factors that could affect the results.

In the analysis, they found that certain types of bacteria in the gut were connected to migraine headaches, including ones with and without aura. They also found that some specific types of bacteria were more likely to be associated with certain types of migraines. Even after doing some statistical adjustments, these connections still held up.

So, this study suggests that the mix of bacteria in our guts might actually influence whether we get migraines and what kind they are. It shows that there might be a link between our gut and our brain when it comes to migraines.

They found that while some bacteria seemed to contribute to migraines, one type appeared to be protective. This protective effect was linked to the Bifidobacterium family. You can find Bifidobacterium in many probiotics, including a well-known brand called Align. Additionally, various fermented foods like milk kefir, sourdough bread, sauerkraut, kimchi, and other fermented vegetables contain Bifidobacterium.

However, it’s important to note that this research doesn’t mean other types of bacteria aren’t helpful too. A healthy human gut microbiome consists of many different types of bacteria. When there is an imbalance of these healthy bacteria, it can lead to various health problems, not just migraines. This imbalance can come in many different forms and may require different probiotics to correct it. That is why I recommend that patients try different types of probiotics for a few months at a time. Besides Bifidobacteria, some patients respond well to Saccharomyces, Lactobacillus, or other types, or even a combination of several.

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People who suffer from migraines are twice as likely to develop benign paroxysmal positional vertigo (BPPV) than individuals without a history of migraines. BPPV, though benign, can be a terrifying experience, especially for those experiencing it for the first time. It has a sudden onset and is often accompanied by nausea and vomiting. The first thought that enters people’s mind is a stroke or a brain tumor.

The cause of BPPV is a loose crystal in one of the semicircular canals of the inner ear. Epley maneuver usually succeeds in trapping and immobilizing this crystal. I’ve had a patient who emailed me with a typical description of BPPV. I emailed her this link to a YouTube video with the instructions on how to perform the Epley maneuver. She emailed back 30 minutes later reporting that her vertigo stopped.

A new study by Dr. Michael Strup, a neurologist at the Hospital of the Ludwig-Maximilians University in Munich and his European colleagues compared two different maneuvers to relieve BPPV. They showed that Semont-Plus maneuver is more effective than the Epley maneuver.

Of the 195 participants 64% were women and the mean age was 63. Initially, the procedure was administered by a physician. Subsequently, patients were instructed to perform the maneuver independently—three times each in the morning, noon, and evening. The Epley group stopped having vertigo after an average of 3.3 days, while the Semont-Plus group, after an average of 2 days.

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Zavegepant (Zavzpret), the first CGRP nasal spray for the treatment of acute migraine attacks, was approved by the FDA in March and is now readily available in all US pharmacies..

Zavegepant belongs to the family of CGRP antagonists, which work by blocking excessive amounts of the neurotransmitter CGRP. Elevated levels of CGRP are known to contribute to the development of migraines. By inhibiting its action, zavegepant can effectively stop an ongoing migraine attack. While there are already two oral CGRP medications for the acute treatment of migraines (Nurtec and Ubrelvy), zavegepant is the first nasal spray option. Nasal sprays offer several advantages, including faster onset of action compared to tablets and the ability to bypass the stomach. These benefits are particularly valuable for individuals experiencing migraines accompanied by nausea and vomiting.

Clinical studies have demonstrated that zavegepant is superior to placebo in promptly eliminating all pain and the most bothersome symptom within two hours of administration. The most commonly reported bothersome symptoms associated with migraines are nausea, sensitivity to light (photophobia), and sensitivity to noise (phonophobia).

Side effects of zavegepant were generally mild and infrequent. Participants in clinical trials noted an unpleasant taste in 18% of cases, compared to 4% in the placebo group. Additional side effects included nausea (4% vs. 1%), nasal discomfort (3% vs. 1%), and vomiting (2% vs. 1%). Taste-related issues have been observed with other nasal sprays used for migraines, particularly among patients who experience nausea. However, this can be easily addressed by sucking on a hard candy while using the nasal spray.

Interestingly, even individuals who did not respond to other CGRP drugs may potentially benefit from zavegepant. While these drugs are similar in their mechanism of action, they are not identical, and patients often exhibit strong preferences for a particular medication within the same category. This preference phenomenon is common in other migraine drug categories such as triptans, NSAIDs, and oral CGRP drugs.

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Our research at the New York Headache Center and that of many of our colleagues, as well as the clinical experience of doctors and thousands of patients, have proven the role of magnesium in treating migraine headaches. I’ve written many blog posts on the role of magnesium in a wide variety of other medical conditions.

A new report in the European Journal of Nutrition suggests that dietary intake of magnesium is related to the size of the brain.

This study looked at how the amount of magnesium in people’s diets is related to the size of their brains and the presence of white matter lesions (which are abnormalities in the brain seen on the MRI scan) as they get older. The researchers used data from 6,000 middle-aged to older adults in the UK. They measured magnesium intake through a questionnaire and used statistical models to analyze the data.

The results showed that people who had higher magnesium intake generally had larger brain volumes, including the gray matter and specific areas called the left and right hippocampus. When they looked at different patterns of magnesium intake over time, they found three groups: one with high magnesium intake that decreased over time, one with low magnesium intake that increased, and one with stable and normal magnesium intake. In women, those in the high-decreasing group had larger brain volumes compared to the normal-stable group. On the other hand, women in the low-increasing group had smaller brain volumes and more white matter lesions.

The researchers also looked at the relationship between magnesium intake and blood pressure, but the results were not significant. Additionally, they found that the positive effect of higher magnesium intake on brain health was more pronounced in women who had gone through menopause.

In conclusion, having a higher intake of magnesium in the diet is associated with larger brain volumes.

Omega-3 fatty acids have also been shown to have a positive effect on brain volume in older adults.  

Vitamin B12 is another nutrient that is probably involved in preserving brain volume. 

Multiple studies have shown that meditation is associated with larger brain volumes. 

Exercise is also a proven way  to prevent cognitive decline.

All these interventions have no side effects and I would recommend them to everyone regardles of age.

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Thank you, Lisa Robin Benson for a kind review of my book. This is a video review on the Migraine.com website.

Many of my colleagues have written very positively about my book. It is even more gratyfing to hear that patients and patient advocates also find it useful.

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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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