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Brain disorders

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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The opioid epidemic has claimed many lives. Overprescribing by doctors has certainly played a role. The push to use opioids more liberally started in the late 1980s. This promotion by many pain experts even led to pain being adopted as the fifth vital sign. One impetus for this push was the mistaken belief in the low rates of addiction when opioids are used to treat pain. Another was the results of surveys of patients being discharged from hospitals. Poor pain control was the main complaint of 40% of such patients. Centers for Medicare & Medicaid Services (CMS) got into the act as well and included good pain control as one of the measures required for the recertification of hospitals. In January 2018, however, the three survey questions about pain management were replaced by three questions about communication about pain. In October of 2019, even these three items about communication about pain were completely removed from the CMS’ HCAHPS Survey. So hospitals and doctors no longer need to worry about relieving pain and the suffering that goes with it. Doctors have to worry more about losing their license or even being put into jail. I’ve testified in front of a disciplinary panel on behalf of a doctor who was at risk of losing his license. An adult patient’s mother complained to the state health department about her son getting prescriptions for opioid drugs. In this case, the doctor was exonerated but the financial and the emotional toll will certainly make him very unlikely to continue prescribing opioids drugs.

These drugs, despite their potential for causing addiction and other side effects, are life-savers for many people. When used judiciously and as part of a multidisciplinary approach, they can provide not only improved quality of life but can make a difference between disability and normal functioning.

A study just published in the journal Pain looked at the difficulties patients taking opioid drugs have in finding a primary care doctor.

This study examined if primary care clinics “are more or less willing to accept and prescribe opioids to patients depending on whether their history is more or less suggestive of aberrant opioid use”. They conducted an audit survey of primary care clinics in 9 states from May to July 2019. They had simulated patients call the clinics and give one of two scenarios for needing a new provider: their previous physician had either (1) retired or (2) stopped prescribing opioids for unspecified reasons. Of 452 clinics responding to both scenarios (904 calls), 193 (43%) said their providers would not prescribe opioids in either scenario, 146 (32%) said their providers might prescribe in both, and 113 (25%) responded differently to each scenario. Clinics responding differently had greater odds of willingness to prescribe when the previous doctor retired than when the doctor had stopped prescribing.

The authors concluded that “…primary care access is limited for patients taking opioids for chronic pain.” and that “This denial of care could lead to unintended harms such as worsened pain or conversion to illicit substances.”

Hopefully, the pendulum will soon begin moving closer to the middle. Another hope is that the researchers will finally discover the holy grail of pain management – a non-addictive pain medicine with few other side effects.

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Almost 1.5 million Americans visit emergency rooms every year for the treatment of head trauma. Headache, not surprisingly, is one of the most common symptoms of head trauma. What is very surprising is that until now, there have been no controlled studies of acute therapies for posttraumatic headaches.

Dr. Benjamin Friedman and his colleagues at the Montefiore Hospital in the Bronx just published a “Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache” in the journal Neurology. Emergency rooms often use metoclopramide (Reglan) as the first-line drug for the treatment of migraines. Diphenhydramine (Benadryl) was added to reduce the chance of side effects from metoclopramide. These side effects of restlessness and involuntary movements can be very unpleasant.

The study involved 160 patients. Their pain severity was measured on a 0 to 10 verbal scale. Patients who received a placebo reported a mean improvement of 3.8, while those receiving two medications improved by 5.2 points. Side effects occurred in 43% of patients who received medications and 28% of patients who received placebo.

My recent post was devoted to a study that showed dramatic similarities between migraines and posttraumatic headaches. The outcome of Friedman’s study, therefore, is not unexpected.

The overall efficacy of metoclopramide is fairly modest. It provides only partial relief that often does not last. And some patients get no relief at all. It also causes unpleasant side effects.

It is puzzling why emergency room doctors are not using a migraine-specific drug, sumatriptan for both migraines and posttraumatic headaches. An injection of sumatriptan works well within an hour for 70% of migraine patients. It has significantly fewer side effects than metoclopramide. Vials of sumatriptan (but not autoinjectors) are relatively inexpensive.

As far as the use of sumatriptan for posttraumatic headaches, we have only a few anecdotal reports. One of the reports, however, describes seven patients who did not respond to other drugs and had very good relief of their posttraumatic headaches with sumatriptan.

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Post-traumatic headaches (PTH) are classified as a distinct category of headaches. There is growing evidence, however, that headaches that develop after a head injury are migraines.

A study just published in Cephalalgia by Dr. Ann Scher, her colleagues at the Uniformed Services University, and other researchers, showed that PTH and migraines are very similar. The only difference they found was that headaches occurring after a head injury tend to be more severe.

They studied 1,094 soldiers with headaches. 198 were classified as having PTH. These headaches were compared to those in the other soldiers. They looked for the presence of 12 migraine features: Unilateral location, photophobia, phonophobia, nausea, exacerbation of headache by routine physical activity, pulsatility, visual aura, sensory aura, pain level, continuous headache, allodynia (sensitivity to touch), and monthly headache days.

Soldiers with post-traumatic headache had a greater endorsement of all 12 headache features compared to the soldiers with non-concussive headaches. The authors concluded that post-traumatic headaches differ from non-concussive headaches only by severity and not by any other symptoms.

Another study published in 2020 by Dr. Håkan Ashina and his Danish colleagues showed similar results. They performed a detailed evaluation of 100 individuals with persistent PTH following a mild traumatic brain injury. They found that 90 of the 100 patients had migraines or migraines as well as tension-type headaches. The rest had only tension-type headaches.

These findings have important treatment implications. These patients should be treated like other patients with chronic migraine. Assigning these patients the diagnosis of chronic migraine allows them access to treatments such as Botox injections and CGRP drugs. Insurance companies will not pay for any of the expensive migraine therapies if a patient carries only the diagnosis of PTH.

Our experience and that of our colleagues suggest that Botox is indeed very effective for PTH.

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The goal of personalized medicine will be achieved through the exponential growth of computing power. Epigenetics, pharmacogenomics, and machine learning are some of the approaches that are being driven by our ability to process massive amounts of data. Unfortunately, it may take another decade or two before we can offer our patients truly personalized medicine.

Until then, we still have to rely on clinical skills. In a study just published in the journal Pain, D. Bouhassira and his colleagues were able to predict the response of neuropathic pain to Botox injections. The prediction was based on a specific combination of symptoms and signs. They used the Neuropathic Pain Symptom Inventory (NPSI) in 628 patients to identify three distinct clusters of patients. The first group had a more severe pinpointed pain, the second one had more evoked pain, and the third had a higher score for deep pain.

The study included adult patients who had experienced pain for at least three months with a mean pain intensity three or greater on a 0 to 10 numerical rating scale. In more than 85% of the patients, neuropathic pain was due to a traumatic or surgical nerve injury. In the rest, it was due to postherpetic neuralgia (shingles).

The researchers used these three groupings to predicting treatment response through the analysis of their two previous controlled trials of Botox. They found significant effects of Botox compared to placebo in clusters 2 and 3, but not in cluster 1. They also developed and performed a preliminary validation of a web-based version of the NPSI and algorithm for the stratification of patients in both research and daily practice.

Botox is not yet approved by the FDA for the treatment of neuropathic pain. This means that insurance companies are unlikely to pay for it. Besides the pain of shingles, neuropathy, injured nerves (I’ve treated two patients with post-amputation pain), we use Botox “off label” to treat trigeminal neuralgia, cluster headaches, hemicrania continua, numular headaches, and other painful conditions. In one of my patients, even headache due to a large but benign brain tumor responded to Botox.

Botox helps such a wide variety of headaches and other painful conditions probably due to its proven effect on sensory nerve endings.

In treating migraine headaches with Botox, there were several attempts to find clinical predictors of response. More recent onset of chronic migraine and fewer days with migraine have been identified as predictors of a better response. . There have been also suggestions that eye pain was a good predictor of response to Botox. Patients with”exploding” (pressure from inside-out) headache may be less responsive than those with “imploding” (pressure from outside-in, or constricting pain) headache.

When studied in large groups, these features might have some predictive value. But it is not anywhere close to 100% or even 70%. Therefore, when dealing with an individual patient we would try Botox in patients with chronic migraines regardless of the presence or the absence of any of these symptoms.

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COVID-related lockdowns have saved many lives. We don’t yet fully appreciate, however, the other side of the ledger – the harms the lockdowns have caused. These include delays in diagnosing cancers, alcohol and drug abuse, depression, anxiety, deprivation of schooling and socialization in children, and worsening of pain and headaches. The latter not only because of lack of access to care but also due to the effect of loneliness.

Prior studies have shown that loneliness is consistently associated with pain. A study by British researchers published in the current issue of the journal Pain examined the question of whether loneliness worsens pain or pain leads to loneliness.

Drs. Anna Loeffler and Andrew Steptoe studied 4,906 men and women (mean age was 65) over a period of four years. They also looked at the role of inflammation in these people. Pain was defined by reports of being often troubled by pain at a moderate or severe intensity. Loneliness was measured using a standard scale. The researchers took into account age, sex, ethnicity, educational attainment, wealth as a marker of socioeconomic resources, marital status, physical activity, degree of mobility, and depressive symptoms.

They found that baseline loneliness was associated with pain four years later. Similarly, baseline pain independently predicted loneliness four years later. The likelihood of pain was increased when at the baseline loneliness was accompanied by an increase in an inflammation marker, C-reactive protein (CRP). On the other hand, inflammation did not predict future loneliness. Both pain and loneliness are distressing experiences that impact well-being and quality of life. The researchers concluded that the relationships between pain and loneliness are bidirectional.

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