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Brain disorders

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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Worsening of headaches in children is one of many deleterious effects of the pandemic and measures to control it. A survey of children in a headache clinic at the Children’s National Hospital in Washington DC by Dr. DiSabella and his colleagues showed that 46% of children had worsening of their migraine headaches during the pandemic.

They also reported much higher rates of anxiety, depression, and stress. Two-thirds of children reported that they exercised less. This could be one of the contributing factors since exercise has been shown to reduce the frequency and the severity of headaches.

What this survey did not explore is the effect of family stress and the presence of child abuse. Reports of child abuse have actually declined during the pandemic because most of these reports come from teachers. Chronic migraines and chronic pain are much more common in patients with a history of being physically, emotionally, or physically abused. PTSD from other causes has a similar predisposing effect and many children and adults have been traumatized by the pandemic.

Some children (as well as adults) report improvement of their headaches during the pandemic. My patients tell me that because they do not have to commute, they have more time to exercise, meditate, cook healthy meals, and get more sleep. I see this in a small proportion of patients. A larger group did worse with additional factors being worsening of headaches due to COVID and in a very small number, COVID vaccines.

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There is a new and surprising connection between postoperative nausea and vomiting (PONV) and migraines. It offers a very effective treatment that will relieve the suffering of tens of thousands of patients.

Many migraine patients tell me that they develop a severe migraine following surgery. Possible reasons include the stress of the operation, fasting before surgery, the effect of anesthetic drugs, pain medicines given after surgery, an awkward head position, and caffeine withdrawal. But some patients report severe nausea and vomiting that occurs without a headache.

PONV affects about 30% of all patients undergoing surgery under general anesthesia. Some patients develop intractable vomiting that does not respond to typical nausea medications even though there are more than a dozen such medications. This often requires hospital admission when surgery is done in an ambulatory (outpatient) setting. Admissions for PONV are more common than for surgical or cardiovascular complications. Intractable PONV can cause opening of the sutured wound, aspiration pneumonia, bleeding, and other complications.

It appears that patients who suffer from migraines or have had migraines in the past are more prone to develop intractable PONV. I learned about this last month while participating in a headache conference in Zurich. Dr. Leander Sakellaris, a Swiss anesthesiologist and pain specialist, told me about his Masters degree thesis on this topic. He allowed me to share its full text – MasterThesis-PONV.

His thesis describes ways to reduce the risk of PONV. If possible, ask for surgery to be done under regional and not general anesthesia. Ask if total intravenous anesthesia is an option. Avoid nitrous oxide, etomidate, thiopental and after surgery, opioid drugs. Good hydration during the operation is also helpful. I would also add a request for an intravenous (IV) infusion of magnesium. IV magnesium is a standard procedure after open heart surgery because it prevents irregular heart beats (arrhythmias), but it is not given after other types of surgery. Magnesium is depleted by physical and emotional stress and surgery induces a major stress response.

The most fascinating part of Dr. Sakellaris’ thesis is the description of eight patients he has encountered in his practice. They all developed intractable PONV but did not have a headache. However, they all had a history of migraines or headaches suggestive of migraines. After they failed to respond to the usual nausea medications, Dr. Skellaris gave them either an injection of sumatriptan or intranasal zolmitriptan. They all had a prompt and dramatic relief of their vomiting and were able to go home.

This should not be very surprising because abdominal migraines and cyclic vomiting syndrome, conditions without a headache that are considered to be migraine variants, also respond to triptans.

Dr. Sakellaris made an important discovery that deserves to be widely disseminated. Forty million Americans suffer from migraines, millions of Americans undergo surgery under general anesthesia, of whom 30% suffer from PONV. It is very likely that many thousands of patients with PONV who do not respond to standard therapies could be helped by triptans.

If you suffer from migraines or have had them in the past and are having an operation, you may want to bring with you an injection of sumatriptan. Outpatient surgery clinics may not have it while hospitals may take a long time to get it to you. I would discuss this with your surgeon and the anesthesiologist before surgery.

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The influence of estrogen on migraines in women is well established – women often experience migraines before or during menstruation and ovulation and their migraines usually subside during pregnancy and menopause.

According to a new study published this month by Dutch researchers, men who suffer from migraines often have a deficiency of male hormones.

Gisela Terwindt and her collaborators evaluated a possible deficiency of androgens or male hormones in 534 men with migraine and 437 men with cluster headaches. These men were compared to 152 healthy controls. Two validated questionnaires were used to measure androgen deficiency scores. The researchers controlled for age, weight (BMI), smoking, and lifetime depression. They also measured four sexual symptoms (beard growth, morning erections, libido, and sexual potency). These four symptoms have been shown to differentiate between hormonal deficiency from anxiety and depression. They did not perform blood tests to measure hormone levels.

Patients reported more severe symptoms of clinical androgen deficiency compared with controls. Both patient groups were more likely to suffer from any of the specific sexual symptoms compared to controls (18% migraine, 21% cluster headache, 7% controls).

The findings in men with cluster headaches are not surprising. Prior reports have documented low testosterone levels in this population. A small study by Dr. Mark Stillman suggested that those cluster patients who have low testosterone levels could benefit from hormone replacement therapy.

There are also reports of low testosterone levels in men with chronic migraines but the connection is less established.

This study may prompt me to pay more attention to sexual dysfunction in men with chronic migraines. I may also start checking testosterone levels in such patients.

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To gain FDA approval a drug has to be shown to be better than a placebo. The placebo effect is a well-established psychological contributor to the efficacy of most treatments.

A group of Italian researchers just published an interesting study looking at other psychological factors that might influence the response to treatment.

They evaluated chronic migraine patients who were treated with erenumab (Aimovig). Erenumab is a monoclonal antibody that targets CGRP, a neurotransmitter involved in the development of migraine attacks.

Monthly erenumab injections were given for one year to 75 patients with chronic migraine who had already failed at least three other oral preventive drugs. A full psychological evaluation assessed personality disturbances, mood and anxiety disorders, as well as childhood traumas, and ongoing stressors.

After 12 months of treatment, 53 patients had at least a 50% drop in the number of headache days per month. The other 22 did not. When compared to responders, non-responders were more likely to have personality disorders with anxious-fearful, avoidant, dependent, and obsessive-compulsive features. Non-responders were also more likely to suffer anxiety disorders and had a higher number of current major stressors.

A very practical application of these findings is that doctors need to address anxiety when treating migraine and chronic pain patients. I’ve seen a number of patients whose migraines improved with an SSRI antidepressant such as fluoxetine (Prozac) or escitalopram (Lexapro). SSRIs do not possess pain-reliving properties. However, they are good at relieving anxiety and so can indirectly improve migraines. Most of the time, I prescribe SNRIs such as duloxetine (Cymbalta) or a tricyclic antidepressant such as nortriptyline (Pamelor) because they relieve anxiety and can have a direct pain-relieving effect.

The old dogma in psychology was that you cannot change your personality. We now know that such change is possible. Different types of cognitive-behavioral therapy (CBT) can be very helpful. Swedish researchers showed that even a brief internet-based CBT can produce long-term changes in personality traits.

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Many patients with headaches are concerned about having a brain aneurysm. It is rare for an aneurysm to cause ongoing headaches. An aneurysm usually causes one very severe headache when it ruptures and causes a brain hemorrhage. Half of the patients with a ruptured aneurysm die and many of those who survive have persistent neurological problems. This is why detecting and treating an aneurysm before it ruptures is the goal. Because aneurysms have a genetic component we do angiograms in close relatives of someone with a ruptured or unruptured brain aneurysm. About 2% of the population has brain aneurysms. It would be prohibitively expensive to subject everyone to a screening angiogram.

Aneurysms are the result of an outpouching of a weak spot in an artery. This process is very gradual and aneurysms tend to get bigger with age. People with small aneurysms and high blood pressure are advised to control their blood pressure in the hope that this will prevent or slow down the growth of the aneurysm. Small aneurysms rarely rupture. If an aneurysm is larger than 5 millimeters in diameter, however, the risk of rupture becomes significant and surgery or non-surgical obliteration is recommended.

Until now, there have been no interventions proven to reduce the risk of aneurysm formation and rupture.

In the current issue of Neurology, a group of Swedish researchers published a rigorous study entitled, Association of Serum Magnesium Levels With Risk of Intracranial Aneurysm.

They provided evidence showing that higher serum magnesium concentrations reduce the risk of intracranial aneurysm and aneurysmal rupture. This was only partly due to the blood pressure-lowering effect of magnesium. They speculated that the additional effects were due to the improved function of the blood vessel lining (endothelium) and a reduction in oxidative stress – proven actions of magnesium.

They concluded: “These findings add to the growing body of evidence highlighting a beneficial role of higher magnesium for preventing cerebrovascular and cardiovascular diseases.” These diseases include strokes, heart attacks, cardiac arrhythmias, and certainly, migraines. Besides these diseases, magnesium is very helpful in a host of other conditions such as asthma, diabetes, osteoporosis, obesity, and many others.

In 2012, I wrote an article, Why all migraine patients should be treated with magnesium. Considering that one-third of the population is deficient in magnesium, it would not be inappropriate to say that everybody should be taking a magnesium supplement.

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Many patients with chronic migraines complain of memory, word-finding, and other cognitive difficulties. I tell them that once we find an effective treatment for their migraines, their cognitive abilities should improve. I explain that the barrage of pain messages disrupts the normal flow of information in the brain.

“Association between chronic pain and long-term cognitive decline in a population-based cohort of elderly participants” is the title of a study published in a recent issue of the journal Pain. The French researchers followed elderly chronic pain patients for up to 15 years.

They concluded that “Chronic pain is associated with a higher cognitive decline, particularly in processing speed. This result reinforces the importance of actively treating chronic pain with pharmacological and nonpharmacological strategies to prevent its consequences, including cognitive consequences.”

This also applies to chronic migraines. Fortunately, we have many new and not so new highly effective pharmacological and non-drug therapies that can provide relief to well over 90% of chronic migraine suffers. Check out my new book, The End of Migraines: 150 Ways to Stop Your Pain.

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Trigeminal neuralgia (TN) is an extremely painful condition. Patients describe the pain as electric shocks going through the face. The most common or classic form of TN is caused by the compression of the trigeminal nerve as it exits the brainstem by a blood vessel. TN can also be caused by multiple sclerosis (MS).

The pain of TN can be debilitating. Some people are unable to eat because of pain and become malnourished. The pain can interfere with speech. In some, it occurs unprovoked. In many, it leads to depression.

The first-line treatment is epilepsy drugs. These include carbamazepine (Tegretol) and oxcarbazepine (Trileptal). We also use Botox injections and the new preventive migraine drugs – CGRP monoclonal antibodies. If drugs and Botox fail, radiofrequency destruction of the nerve can be of help. When none of this helps, surgery can be very effective.

The so-called microvascular decompression surgery involves opening the skull and placing a Teflon patch between the nerve and the blood vessel which presses on the nerve. Since TN in people with MS is not caused by the compression of the nerve, surgery is rarely undertaken.

This is a very delicate surgery and should be performed by a neurosurgeon who has done many of such operations (yes, it’s a conundrum – how do surgeons become experienced if nobody wants to be one of their early cases). Sometimes, even if surgery is performed well, the pain persists.

Fortunately, a group of Canadian researchers found a way of predicting who is likely to respond to decompression surgery. In a study just published in the journal Pain, they described a special MRI scanning technique that predicted the success of surgery with high accuracy. They discovered that if the trigeminal nerve fibers are disrupted inside the brainstem rather than after they exit the brainstem, surgery was much less likely to help. This applied to both patients with classic TN and TN due to MS.

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