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Brain disorders

In a recent blog post, I wrote about the benefit of different types of exercises for the relief of migraines and other types of headaches. It mentioned that strength training may be more beneficial than aerobic (cardio) exercise. A study just published in Nature Communications suggests that the time of day when you exercise also matters. Not specifically for headaches but for “all-cause and cardiovascular disease mortality”.

This was a very rigorous study of 92,139 UK participants over an average of 7 years of follow-up which added up to 638,825 person-years. The timing of exercise was recorded by an activity tracker (accelerometer). Moderate-to-vigorous intensity physical activity at any time of day was associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. However, the morning group (5:00 – 11:00), midday-afternoon (11:00 – 17:00), and mixed timing groups, but not the evening group (17:00-24:00), had lower risks of all-cause and cardiovascular disease mortality.

This study suggests that exercising before 5 PM has more health benefits than exercising after 5. It is likely that this may also apply to the relief of migraines and other headaches.

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In a post last August, I mentioned that zinc could possibly extend the duration of the effect of Botox. A new report by Chinese neurologists in Headache describes their findings of an inverse association between dietary zinc intake and the occurrence of migraine in American adults.

The researchers used the data from a five-year study conducted by the CDC to assess the health and nutritional status of Americans. Data were collected using a computer-assisted dietary interview system which proved to be very reliable. Over 11,000 adults were included in the analysis of zinc intake. These subjects were divided into quintiles, according to their zinc intake. The data were adjusted for various confounding factors. These included age, sex, race, ethnicity, smoking status, body mass index, and others.

People in the lowest quintile were at least 30% more likely to suffer from migraine compared to people in the other four quintiles. Associaion does not mean causation and this study does not prove that taking zinc will prevents migraines. However, a few small studies did show the benefit of taking a zinc supplement in migraine patients.

Checking your blood for zinc levels before taking a supplement would be ideal. However, there is very little downside to taking 10-25 mg of zinc daily even if you don’t know your zinc level.

Zinc is very important for the normal functioning of the immune system, it possibly prevents macular degeneration, and has many other benefits.  Taking too much zinc can cause serious side effects. The effects of zinc toxicity are mostly due to the lowering of copper levels.

 

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Insomnia is a very common problem. Sleep aids, over-the-counter and prescription have been proven to be harmful if taken long-term. They even raise the risk of Alzheimer’s.

A small dose of melatonin (300 mcg, or 0.3 mg) can help better than the usual 3 mg dose sold in most stores. You can also try valerian root and definitely adhere to sleep hygiene. This includes no reading or watching TV in bed, no screens for at least an hour before bedtime, no eating or exercising within two hours of going to bed, and sleeping in a cold room (65 to 68 degrees). Going to bed at the same time also helps.

If you still can’t fall asleep, try visualization. Actually, you don’t just use your visual memory but engage all the senses. This post was prompted by a WSJ article on this topic, A Happy Memory Can Help You Fall Asleep, if You Know How to Use It.

I usually imagine myself on a beach in a hammock under a tree, feeling a warm breeze on my body, seeing a beautiful view of the beach and the ocean, smelling fragrant flowers, and hearing the sound of waves lapping at the shore.

Once you find your happy place and can vividly recreate it, always use the same setting without variation. This way you will fall asleep within minutes.

 

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Daily multivitamin use was compared to cocoa extract in more than 2,200 people over 65. After three years, taking a cocoa extract had no benefit while taking a multivitamin led to a significantly slower age-related cognitive decline. This included measures of global cognition, memory, and executive function.

Many physicians discourage their patients from taking a multivitamin. They should stop. There is little downside to taking a multivitamin. It is very inexpensive and safe. Many people also feel that if they eat a well-balanced healthy diet they should not need to take vitamins. Unfortunately, that is not the case. Even foods that are considered healthy are often processed, stored for a long time, or grown in depleted soil. Another problem is that as we age our body loses its ability to absorb vitamins and minerals (as well as protein, which is a different topic).

Taking a multivitamin should be a standard recommendation for those over 65. Many younger individuals need supplements as well. Ironically, a healthy diet (especially vegan or vegetarian) is often deficient in vitamin B12. Many young people whom I see for migraine headaches are deficient in vitamin D and magnesium. The role of vitamin D is also often underappreciated by primary care doctors. Multiple studies have shown that your vitamin D level should be not only within the normal range but in the upper half of the normal range for your brain to function normally. Most people who died of COVID had low vitamin D levels. And I’ve written many times about the importance of magnesium – just search this blog.

Ideally, to approach this problem scientifically, you should have your vitamin and mineral levels checked. This will allow you to take only those vitamins that you are deficient in. the difficulty is that there are too many vitamins to check and the insurance companies often refuse to pay for these tests. Taking at least a multivitamin is a reasonable alternative.

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Botox has been shown to relieve the pain of trigeminal neuralgia (TN). TN is an excruciatingly painful and debilitating condition. The most common cause of TN is compression of the trigeminal nerve by a blood vessel. This tends to occur in older people in whom blood vessels may harden with age. The definitive treatment of TN is surgical decompression of the trigeminal nerve. This is done by opening the skull and placing a Teflon patch between the nerve and the blood vessel. Several medications and invasive procedures directed at the peripheral nerve have been also proven effective. They are usually tried before surgery because of the risk of complications from surgery.

Besides the elderly, younger people with multiple sclerosis (MS) are also predisposed to developing TN. The mechanism is somewhat different. There is less or no compression of the nerve but rather there is damage to myelin, a sheath that covers the nerve inside the brainstem. Myelin prevents cross-talk between nerve fibers, which is the cause of the pain.

According to a report by Turkish neurologists that was recently published in Headache, Botox can relieve the pain of TN in MS patients as well. They compared the response to Botox in 22 patients with primary TN and 31 with MS-related TN. Ten patients of 22 in the first group and 16 out of 31 in the second group improved with Botox. Patients who had interventional treatments in the past did not respond as well. Those who had mild continuous pain between bouts of severe pain were more likely to respond to Botox.

Botox is not the first-line treatment for TN. Medications such as carbamazepine and oxcarbazepine are. However, Botox is a very safe treatment and should be tried before considering surgery and other invasive procedures.

 

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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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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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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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A case report presented at the annual meeting of the American Headache Society described a patient with trigeminal neuralgia (TN) whose pain responded well to rimegepant (Nurtec). Rimegepant is a drug approved for the acute and preventive treatment of migraines. This patient did not obtain relief from surgery and several medications. He was taking 300 mg of oxcarbazepine, buprenorphine (narcotic) patch, and up to 120 mg of oxycodone with partial relief. Within 12 hours of starting rimegepant he was pain-free. In the six months of taking rimegepant he experienced very infrequent and mild pain.

There have been several reports indicating that injections of CGRP monoclonal antibodies such as erenumab can relieve the pain of TN. So it is not surprising that an oral CGRP drug helped this patient.

I’ve treated several TN patients with CGRP antibodies. One such patient has been receiving injections of galacanezumab for over 3 years. He requires injections of 240 mg every 3 weeks and also has to take daily medications. This combination has allowed him to be fully functional and to keep his job. I may now try him on an oral CGRP drug.

In addition to rimegepant, there are two other oral CGRP drugs – ubrogepant (Ubrelvy) and atogepant (Qulipta). They are very similar but many patients have a clear preference for one over the others. It may be worth trying them all if the first drug is not fully effective. A major obstacle to using these medications “off label” for TN is their high cost.

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Primary stabbing headache is a rare disorder. Because it is rare, it is often misdiagnosed and not treated properly. This post was prompted by a patient with this condition I saw last week. She went undiagnosed for 45 years.

This 57-year-old woman has been having intermittent headaches since age 12. Her headaches would occur in bouts lasting anywhere from a few days to a couple of weeks. She’s had periods of up to a year without any headaches. Her latest period of daily headaches has been the longest – it has lasted almost 4 weeks and was still ongoing. Her headaches were left-sided and localized to the temple. The pain was very severe in intensity (9 on a 1 to 10 scale), sharp and stabbing in character. The pain lasted only a second but occurred 1-2 times an hour. She was having difficulty working as her work involved being in a videoconference all day long. She had no associated tearing, nasal congestion, nausea, or sensitivity to light or noise. She was taking 400 to 800 mg of ibuprofen with modest relief. During one of her previous bouts, she had tried gabapentin, 100 mg three times a day, which helped initially, but then became ineffective and she stopped it.

As is the case with all rare conditions, controlled treatment trials are very difficult to do. Anecdotally though, indomethacin, a strong anti-inflammatory drug, seems to be very effective. Gabapentin, which the patient tried in a small dose, has been also reported to help. I prescribed indomethacin as her first treatment.

If headaches persist or if indomethacin causes stomach upset or other side effects, I will start her on gabapentin, 300 mg three times a day. There are two other rare indomethacin-sensitive headache types – hemicrania continua and chronic paroxysmal hemicrania. A few reports suggested that an herbal supplement, Boswellia can be effective for patients who cannot tolerate indomethacin. After that, another reasonable option would be to try Botox injections. Botox has been reported to help hemicrania continua, chronic paroxysmal hemicrania, cluster, and other types of headaches. Because the area where she experiences pain is small and circumscribed, she will need a very small amount of Botox, making it relatively inexpensive.

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I’ve been prescribing medical marijuana (MM) since 2016 when it became legal in New York. We still lack controlled clinical trials of MM for the treatment of migraines. Most of my patients who find MM useful report that it relieves nausea or anxiety, helps them go to sleep and sometimes relieves pain. Others find that taking it daily prevents migraines. CBD alone can be also helpful, but most patients need a combination of CBD and THC as well in order to obtain a therapeutic effect.

Like any other drug, MM can have side effects. One of them is cognitive impairment. A study just published in the New England Journal of Medicine describes the effect of recreational marijuana legalization in Canada on injuries to car drivers. The researchers studied drivers treated after a motor vehicle collision in four British Columbia trauma centers from 2013 through 2022. They discovered that after legalization, the number of moderately injured drivers with a THC level above the legal limit doubled. The largest increase was seen in older and male drivers.

This is relevant to the users of MM as well. From now on, I will caution my patients not to drive after taking any THC-containing products. Just like with alcohol, you don’t need to have a blood level above the legal limit to slow your reflexes.

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