Chronic migraine | Headache NewsBlog

More science to support the use of cannabis for pain

By: Dr. Mauskop

01-10-2018

Alternative Therapies, Chronic migraine, Pain, Pain Research

We’ve been prescribing medical marijuana for migraines and other painful conditions since it was legalized in the state of New York four years ago. While it does not seem to help most of our patients, it does benefit a significant minority. The benefits may include relief of pain, nausea, anxiety, and improved sleep. Various ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD) produce different effects and often neither one alone is as effective as a combination of the two (so called entourage effect). Although marijuana is a very effective medicine for some patients, there is no good science to explain how it works, in what combination of ingredients and for what types of pain.

A very interesting study that sheds some light on the possible mechanism of action of THC was just published in a leading neurology journal, Neurology by Israeli researchers. They enrolled fifteen patients with chronic neuropathic pain in the leg (like sciatica) in a double-blind placebo-controlled crossover study. Nine patients were given THC in the first part of the study and placebo in the second and six were given placebo first and then THC. In addition to measuring the effect of THC on pain the researchers performed functional MRI (fMRI) scans before and after administering THC or placebo.

THC was significantly better than placebo at relieving pain and the fMRI scans showed THC-induced changes in the way pain may be processed in our brains. They found that THC produced a reduction in functional connectivity between the anterior cingulate cortex (ACC), a major pain-processing region that is rich in cannabinoid receptors and the sensorimotor cortex. This reduction correlated with the reduction in the subjective pain ratings after THC treatment, meaning that patients who did not have pain relief usually did not have a decrease in the connectivity between the two regions.

The study also showed that pretreatment functional connectivity between the ACC and the sensorimotor cortex positively correlated with the improvement in pain scores induced by THC, that is, the higher the positive functional connectivity at baseline, the more benefit was gained from THC administration.

The authors also commented that THC combined with CBD may have stronger pain-relieving properties. Hopefully, the researchers will figure out the best combination of THC and CBD, but it is possible that other ingredients in marijuana contribute to the therapeutic effects. This could be why some of our patients prefer products from one dispensary and not the other and why some find that the whole plant is more effective than THC with CBD in any ratio. Most patients also find that products made from different strains of marijuana plant (sativa vs indica) have different effects.

Botox relieves hemiplegic migraine and migraine with aura

By: Dr. Mauskop

22-09-2018

Botox, Chronic migraine, injections, Migraine

A recent report by neurologists from the Mayo Clinic suggests that onabotulinumtoxinA (Botox) injections can relieve not only headache pain, but associated neurological symptoms, such as visual aura, numbness and weakness, which can precede or accompany a migraine attack. This article describes 11 patients with hemiplegic migraine, which means that these patients developed weakness on one side of their body prior and during an attack. From the description of these cases, it appears that at least a couple of patients had migraine with sensory-motor aura rather than true hemiplegic migraine. But regardless of the precise nature of their symptoms, Botox was effective in reducing these symptoms, along with headaches in 9 out of 11 patients. Ten of the 11 patients had chronic migraine and on average they failed five preventive drugs before starting Botox.

Two of the physicians who wrote the report have already presented some of these cases in 2013. As mentioned in the blog post describing this older report, I have also successfully treated many patients with visual, sensory and motor aura with Botox injections. Just like with patients in the current article, many of my patient responded to Botox after failing several preventive drugs.

We seem to understand how Botox relieves pain, but it is less clear how it helps neurological symptoms such as weakness, numbness and visual impairment. One possible explanation is that Botox reduces painful messages from the surface of the skull to the brain, which reduces excitability of the brain and this in turn prevents the brain from generating a migraine attack, including its associated symptoms.

Allergan Announces Positive Results for Ubrogepant – an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine

By: Dr. Mauskop

21-03-2018

Chronic migraine, Headache medications, Migraine, New treatments

The first of the four CGRP monoclonal antibodies developed for the prevention of migraines is expected to be approved by the FDA in the next 2-3 months. The other three should be approved within a year. All four will be given by an injection (three subcutaneously and one, intravenously).

Most people prefer tablets to injections and two companies are developing three drugs with the same mechanism of action as the monoclonal antibodies (blocking CGRP), but in a tablet form. The original CGRP drug in a tablet form was developed by Merck and it was very effective for the prevention and acute treatment of migraines, but a few patients developed liver side effects. The side effects were not serious, just abnormal blood tests, which returned to normal once the drug was stopped, but nevertheless Merck stopped the development of telcagepant in 2009. This led pharma companies to shift to the development of monoclonal antibodies, which bypass the liver, but can be given only by injection.

Allergan and Biohaven are two companies that are developing oral CGRP drugs in the hope that they can achieve good efficacy without the side effects. Allergan just released the results of the first phase 3 study of ubrogepant. The study included 1327 U.S. adult patients who were given placebo, ubrogepant 50 mg or 100 mg. They treated a single migraine attack of moderate to severe headache intensity. Both doses were significantly better than placebo in achieving pain freedom at 2 hours after the initial dose. Sensitivity to light, noise, and nausea also significantly improved with the drug, but not placebo. The side effect profile of ubrogepant was similar to placebo without serious liver problems.

Results of the second phase 3 trial are expected in the first half of 2018. Allergan plans to file these results with the FDA in 2019, after which the FDA has a year to review the data and will hopefully approve the drug.

FDA approves the first blood test to diagnose concussion

By: Dr. Mauskop

11-03-2018

Chronic migraine, Head trauma, post-traumatic headache

The news headlines are filled with stories of professional football players suffering from brain damage, but you do not to have to participate in sports to sustain a concussion – it is an everyday occurrence. In the US, in 2013 there were 2.8 million concussion-related emergency room visits and hospitalizations with 50,000 people dying from brain injuries. Three out of four concussions are mild. However, even mild concussion can cause impaired thinking or memory, poor concentration and emotional problems.

The U.S. Food and Drug Administration has recently approved the first blood test to evaluate concussion in adults. The diagnosis of concussion or in medical lingo, mild traumatic brain injury (mTBI), has been based purely on the description of symptoms by the patient, neurological examination, including the 15-point Glasgow Coma Scale, and brain imaging, such as CT scan to detect brain damage or bleeding. The majority of patients with a concussion have normal MRI and CT scans. This new blood test will help health care providers decide if a CT scan is necessary. This will avoid unnecessary scans which expose patients to radiation. It should also save money.

The Brain Trauma Indicator developed by Banyan Biomarkers, Inc. works by measuring levels of proteins, known as UCH-L1 and GFAP, that are released from the brain into blood and measured within 12 hours of head injury. Levels of these blood proteins after mTBI can help predict which patients may have brain lesions visible by CT scan and which won’t. Test results can be available within 3 to 4 hours.

The FDA based their approval on the data from a study of 1,947 patients with a suspected concussion. The Brain Trauma Indicator was able to predict the presence of intracranial lesions on a CT scan 97.5 percent of the time and those who did not have intracranial lesions on a CT scan 99.6 percent of the time.

It is not clear how this test will be used in the real world. If someone is sick enough to be brought to an ER, they are likely to get a CT scan, which is faster and avoids the 3-4 hour wait for the blood test results and the added cost of the blood test. People with a mild concussion who are not taken to an ER will not need the test because they are very unlikely to have visible brain injury on the CT scan. If symptoms persist for a while and the patient comes to our headache clinic, we obtain an MRI scan, which is more informative and avoids radiation, although it is more expensive.

Terrorism and headaches

By: Dr. Mauskop

22-01-2018

Chronic migraine, Headaches, Headaches in children, Psychology of headaches

Survivors of terrorist attacks are four times more likely to suffer from migraines and three times more likely to suffer from tension-type headaches, according to a study just published in Neurology. The researchers evaluated 213 of 358 adolescent survivors of the 2011 massacre at a summer camp in Norway that resulted in deaths of 69 people. These survivors were compared to over 1,700 adolescents of the same sex and age who were not exposed to terrorism. The survivors were not only much more likely to suffer from migraines and tension-type headaches, but were also much more likely to have daily or weekly attacks.

Many previous studies have shown that physical, sexual, and emotional abuse in childhood and posttraumatic stress disorder (PTSD) are strong risk factors for the development of migraines and chronic pain in many previous studies. Having a family history of migraines further increases this risk, as does head trauma, and having other painful or psychological disorders. Headache is also one of the first symptoms reported by adolescent girls and women who were raped.

The authors of the current report cite evidence that “Childhood maltreatment during periods of high developmental plasticity seems to trigger modifications in genetic expression, neural circuits, immunologic functioning, and related physiologic stress responses. It is plausible that exposure to interpersonal violence could induce functional, neuroendoimmunologic alterations, affecting central sensitization and pain modulation and perception. Central sensitization, expressed as hypersensitivity to visual, auditory, olfactory, and somatosensory stimuli, has long been thought to play a key role in the pathogenesis and chronification of migraine.”

It is likely that early intervention after a traumatic event will result not only in better psychological outcomes, but also in fewer and milder headaches. One such intervention is cognitive-behavioral therapy. However, there are several different types of such therapy and a study just published in JAMA Psychiatry compared 12 sessions of cognitive processing therapy (CPT) with 5 sessions of written exposure therapy (WET) for the treatment of posttraumatic stress disorder. WET was shown to be at least as good as CPT with fewer treatment sessions required. This makes WET more efficient and affordable and patients are more likely to complete it.

My previous blog posts mention online self-administered courses of cognitive-behavioral therapy for PTSD, anxiety, depression, OCD, insomnia, chronic pain, and other conditions. The site is ThisWayUp.org.au and the researchers behind it have published scientific data indicating that their approach is very effective. It is also very inexpensive – some courses are free and some cost about $50.

Botox for kids with chronic migraines

By: Dr. Mauskop

27-12-2017

Botox, Chronic migraine, Headaches in children

A new report by doctors at UC Irvine describes successful treatment of 9 children aged 8 to 17 with migraine headaches using Botox injections. It may sound surprising, but unfortunately children also suffer from chronic migraines. Chronic migraine is defined as headaches that occur on 15 or more days each month and on at least 8 of those days headaches have migraine features. In children with episodic and chronic migraines, migraine features, such as throbbing, unilateral location, sensitivity to light and noise are less common than in adults.

There are only 5 treatments that are approved by the FDA for the prevention of migraine attacks. Four are drugs – 2 blood pressure medications, propranolol (Inderal) and timolol (Blocadren) and 2 epilepsy drugs, topiramate (Topamax) and divalproex sodium (Depakote). The fifth treatment is Botox injections. While Botox is not approved for kids with migraines, it is approved to treat eye conditions in children 12 years of age and older. Botox is also widely used to treat younger children with cerebral palsy (CP), although there is no official FDA clearance for such use. For a child with CP, Botox injections can make a difference between being wheelchair-bound and walking unassisted. However, very young children with CP are at the highest risk of serious complications and even death because they have small bodies and very stiff muscles, which require relatively large doses of Botox.

The dose to treat migraines is much smaller and therefore a lot safer. My youngest child with chronic migraines was a boy of 8 who weighed 50 lbs. He had excellent relief of his migraines after receiving 15 units of Botox into his forehead. He underwent a total of five treatments over a period of two years and for the last treatment, I gave him 50 units (forehead and temples). By then his weight was 65 lbs. The standard adult dose for migraines is 155 units. The dose for cerebral palsy in an adult goes up to 400 units.

The main difficulty in using Botox in children with migraines is that insurance companies often deny coverage, which they justify by the lack of FDA approval. However, Botox injections at low doses used to treat migraines in children are safer than drugs for epilepsy, high blood pressure, or depression.

Psychological factors in chronic migraine

By: Dr. Mauskop

24-11-2017

Alternative Therapies, Chronic migraine, Pain, Pain Research, Psychology of headaches

Psychological factors play a major role in migraines. This is not to say that migraine is a psychological disorder – we have good genetic and brain imaging studies confirming its strong biological underpinnings. The divide between biological and psychological is very artificial since we know that physical illness leads to psychological problems and the other way around. Stress is obviously one of the major triggers of migraines and we know that people with migraines are at least twice as likely to develop anxiety, depression, and other mental disorders. These are not cause-and-effect relationships because anxiety and depression can precede the onset of migraines. The connection is probably due to shared underlying problems with serotonin, dopamine, and other neurotransmitters.

We have strong evidence that addressing psychological factors involved in migraines through biofeedback, meditation, and cognitive therapy can lead to the reduction of migraine frequency, severity, and disability. Studies in chronic pain patients have shown that people with external locus of control (thinking that uncontrollable outside chance events are major contributors to pain) have more disability than people with internal locus of control (those who feel that their actions are contributing to pain and that active involvement in treatment can relieve pain).

Chronic migraine sufferers (defined as those with 15 or more headache days each month) are known to have greater disability than those with episodic migraines. In a recent study by researchers at the Yeshiva University and Albert Einstein College of Medicine, 90 chronic migraine patients were evaluated for psychological symptoms. Of these 90 patients, 85% were women, their mean age was 45, and half reported severe migraine-related disability. They were twice as likely to be depressed and to have external locus of control. The half with severe migraine-related disability were 3.5 times more likely to have anxiety and depression and were twice as likely to have a symptom described as catastrophizing. Catastrophizing is defined as having irrational thoughts about pain being uncontrollable, leading to disability, loss of a job, partner, ruined life, etc.

The good news is that many studies show that with cognitive therapy locus of control can be shifted from external to internal, catastrophizing can be reduced or eliminated, and disability diminished. This may not eliminate migraines or chronic pain, but can make you less anxious and depressed, and much more functional. Cost and access to therapy can be a problem, but studies suggest that even online therapy can be very effective.

Besides psychological approaches, regular aerobic exercise (stationary bike is easiest for migraine sufferers), certain supplements and prescription drugs can also help. Supplements that can relieve anxiety and depression include SAMe, omega-3 fatty acids (fish oil), methylfolate, and other. Some antidepressant medications relieve not only anxiety and depression, but also provide relief of migraines even when psychological factors are absent. These include so called SNRIs (duloxetine or Cymbalta, venlafaxin, or Effexor, and other) and tricyclics (amitriptyline, or Elavil, protriptyline, or Vivactil, and other). The most popular group of antidepressants, the SSRIs (fluoxetine, or Prozac, escitalopram, or Lexapro, and other) do help anxiety and depression, but have no pain or headache-relieving properties. Obviously, all drugs have potential side effects and for most patients it makes sense to try non-drug treatments first.

Curcumin helps improve memory, possibly migraines.

By: Dr. Mauskop

13-11-2017

Alternative Therapies, Brain disorders, Chronic migraine, Migraine

Curcumin, which is one of the ingredients in turmeric, has long been touted for many of its anti-inflammatory and anti-cancer properties. A study presented at the 2017 Alzheimer’s Association International Conference showed that curcumin improves memory in healthy adults without Alzheimer’s disease.

This double-blind study was performerd by Dr. Gary Small and his colleagues at UCLA and it involved 40 men and women with a mean age of 63. Half of these subjects received 90 mg of Theracurmin brand of cucurmin twice a day, while the other half was given placebo for a period of 18 months. Researchers administered both verbal and visual memory tests and also measured brain deposits of amyloid plaques and tau tangles using special imaging methods (PET scans). These deposits are found in the brains of patients with Alzheimer’s.

The scores for both types of memory improved in the curcumin group, but not in the placebo group. Curcumin also prevented buildup of amyloid plaques and tau tangles in the brains. Daily curcumin also improved attention and mood.

Four patients in the curcumin group and two in the placebo group had stomach pains and nausea. These were the only side effects.

The authors concluded that “This relatively inexpensive and nontoxic treatment may have a potential for not only improving age-related memory decline, but also as a prevention therapy, possibly staving off progression, and eventually future symptoms of Alzheimer’s disease.”

There is less clinical evidence for the use of curcumin for the prevention of migraines. A recent study, published in the journal Immunogenetics, Iranian researchers reported that a combination of omega-3 fatty acids and curcumin reduced the production of TNF. TNF is a protein that is involved in sending messages between cells, which leads to increased excitability of neurons, neuroinflammation, and pain. The study involved 74 patients with migraines, who were divided into 4 groups – placebo, curcuming, omega-3, and combination of omega-3 and curcumin. The combination produced not only a reduction in TNF levels, but also fewer migraine attacks than seen in the other 3 groups.

Curcumin is not very well absorbed and several companies have tried to improve its absorption using various methods. The UCLA study utilized Theracurmin, which is an ingredient in several brands of curcumin. Another type, Longvida also seems to be better absorbed and is also used by several manufacturers.

Stem cells help stroke victims, will revolutionize medicine

By: Dr. Mauskop

30-10-2017

Alternative Therapies, Brain disorders, Chronic migraine, Head trauma

There is little doubt that stem cells, along with genetics and computer science will revolutionize medicine. There are more than a dozen journals devoted to stem cell research and many general and speciality medical journals also publish research on stem cells, which means that a couple of hundred articles are published every month. At first, the research was stymied by the controversy about the fetal sources of stem cells. For the most part this problem has been circumvented by the discovery of other sources, such as umbilical cord, placenta, fat tissue, and other.

In neurology, multiple sclerosis, spinal cord injuries, and strokes have been the main targets of stem cell research. The latest study of stem cells for stroke victims conducted at Stanford by Gary Steinberg and his colleagues produced very encouraging results. This trial included only 18 patients, but they all had their stroke anywhere between 6 months and 3 years before the study – past the usual time where further recovery is expected. Improvement occurred in the majority of patients and the improvement was not affected by the age of the patient or the severity of the stroke. Although stem cells were injected directly into the brain through a small hole that was drilled in the skull, there were no serious complications or side effects. The researchers also noted that stem cells did not replace damaged cells but rather stimulated patients’ own repair mechanisms. This is at odds with the original idea that stem cells by their nature could turn into nerve cells or any other cells in the body to replaced damaged cells.

This stimulating (and anti-inflammatory) effect of stem cells was our reason for conducting a small pilot study of stem cells in patients with refractory chronic migraines, which was described in a previous post. We did not inject cells into the brain, but into the muscles around the head and neck. Three out of 9 patients showed some improvement. We used patients’ own cells extracted from their fat tissue, while the stroke study used cells derived from the bone marrow of a donor. The future of stem cell research clearly lies in the use of such off-the-shelf cells, which have been shown to be safe and are probably more effective than fat-derived cells.

Stem cell lines are being developed to treat different medical conditions – Asterias for spinal cord injury, Pluristem for radiation damage, and many other.

The same team of researchers and SanBio, Inc. the Japanese company that developed these stem cells are conducting another larger controlled trial. You can email stemcellstudy@stanford.edu for information about participating in this trial.

The effect of post-traumatic headaches on the brain

By: Dr. Mauskop

21-10-2017

Alternative Therapies, Botox, Chronic migraine, Head trauma, post-traumatic headache

Chronic pain is known to alter the structure of the brain. Mayo Clinic researchers used MRI scans to examine brains of 29 patients with post-traumatic headaches and compared their scans to those of 31 age-matched healthy volunteers. The average frequency of headaches was 22 days a month. Patients with post-traumatic headaches were found to have thinning of several areas of their cerebral cortex which are responsible for pain processing in the frontal lobes. Cortex covers the surface of the brain and contains bodies of brain neurons. Drs. Chiang, Schwedt, and Chong, who presented their findings at the annual meeting of the International Headache Society held last month in Vancouver, also discovered that the thinning was correlated with the frequency of headaches.

This study did not address possible treatments, but it would make sense that with better control of headaches, this brain atrophy might be reversible. To treat post-traumatic headaches we often use Botox injections, which have been shown to help posttraumatic headaches. Even though Botox is approved only for chronic migraines, many patients with post-traumatic headaches do have symptoms of migraines and can be diagnosed as having post-traumatic chronic migraines (without such a designation insurance companies may not pay for Botox). We also check RBC magnesium, CoQ10 and other vitamin levels, which are often low in chronic headache sufferers and if corrected, can lead to a significant improvement. Epilepsy drugs and anti-depressants can also help.

While the above mentioned treatments can help headaches and potentially could reverse brain atrophy, there is only one intervention that has been shown to increase the thickness of the brain cortex on the MRI scan. This intervention is meditation. And this effect was demonstrated in several studies. An 8-week course of mindfulness-based stress reduction led to a measurable increase in the gray matter concentration of certain parts of the brain cortex. A pilot study of migraine sufferers showed that meditation has a potential not only to restore thickness of the brain, but also to relieve migraines.

In one of my previous blog posts that described a sceintific study of meditation, I mentioned several ways to learn meditation: Free podcasts by a psychologist Tara Brach an excellent book, Mindfulness in Plain English by B. Gunaratana, and several apps – Headspace, 10% Happier, and Calm. You can also take an individual or a group class, which are widely available.

Gut bacteria can cause big holes in the brain

By: Dr. Mauskop

16-10-2017

Alternative Therapies, Chronic migraine, Headaches, Migraine

Biome, or the collection of bacteria living in our bodies has been receiving belated and well deserved attention. The discovery that bacteria living in our intestines can cause cerebral cavernous malformations or CCM (see photo) is quite dramatic. But there is no need to panic since this is a rare condition. However, it does indicate that gut bacteria can have a major impact on our brains.

It was a serendipitous discovery by Dr. Mark Kahn, professor of medicine at U. Penn, who studied mice with CCM. He noticed that mutant mice prone to CCM stopped developing holes in their brains after being moved to a new building. The exception was mice who developed an abscess after having their intestines accidentally stuck with a needle during a routine injection. Dr. Kahn and his colleagues identified a specific bacterium, Bacteroides fragilis, which was responsible for the development of brain caverns.

This finding may explain why there is such a wide variety of presentations in people who have the familial form of CCM. Some have no lesions even when they are 70, while others have hundreds of them at age 10. Just like mutant mice, humans seem to need an additional trigger to start developing CCMs. This finding provides a clear path to developing an effective treatment and perhaps, just a simple probiotic could keep such patients healthy.

In fact, a probiotic containing 14 different strains of bacteria (Bio-Kult, made in UK) is effective in preventing migraine headaches, according to a study presented by Iranian doctors at the recent International Headache Congress in Vancouver. Fifty patients were recruited into this study with half taking the probiotic and the other half, placebo. After 8 weeks, patients on the probiotic had fewer days with migraine and the pain was milder when compared to those taking placebo.

The big question is, what other brain disorders are triggered or worsened by our gut bacteria. We have more bacterial cells living in our bodies (about 39 trillion) than we have of our own cells (about 30 trillion) and scientists are finally beginning to study them. I Contain Multitudes: The Microbes Within Us and a Grander View of Life, is a fascinating and well-written book by Ed Yong on this subject.

What to do when Botox stops working

By: Dr. Mauskop

07-10-2017

Botox, Chronic migraine, Cluster headaches, Migraine

Botox is the most effective and the safest preventive treatment for migraine headaches. However, in a very small number of patients, Botox loses its effectiveness over time. This happens for two main reasons – the person develops antibodies as a defense mechanism to block the effect of Botox or headaches change in character and stop responding to Botox.

It is easy to tell these two reasons apart. If Botox fails to stop movement of the forehead muscles and the patient can frown and raise her eyebrows, it is most likely because of antibodies. On a very rare occasion this is due to a defective vial of Botox, so to confirm that antibodies have formed, we give a small test dose amount of Botox into the forehead. If again there is no paralysis, we know that antibodies have developed. This can happen after one or two treatments or after 10, but in my experience over the past 25 years, significantly fewer than 1% of patients develop this problem.

Fortunately, some patients who develop antibodies to Botox, known as type A toxin, may respond to a similar product Myobloc, which is a type B toxin. Myobloc is not approved by the FDA to treat chronic migraine headaches, but it has a similar mechanism of action and has been shown to relieve migraines in several studies. Injections of Myobloc can be a little more painful, it begins to work a little faster than Botox, but the effect may last for a slightly shorter period of time.

An even smaller number of patients have naturally occurring antibodies to Botox, which is most likely due to an exposure to botulinum toxin in food. I’ve encountered 4 or 5 such patients and a couple of them who did go on to try Myobloc, did not respond to it either.

When Botox stops working despite providing good muscle relaxing effect, it could be because the headaches have changed in character, severity or are being caused by a new problem. It could be due a sudden increase in stress level, lack of sleep, hormonal changes, drop in magnesium level due to a gastro-intestinal problem, or another new illness, such as thyroid disease, diabetes, multiple sclerosis, or increased pressure in the brain. Such patients need to be re-evaluated with a neurological examination, blood tests, and usually an MRI scan. One of my patients who was doing well on Botox for several years, did not have any relief from her last regular treatment. Since she had no obvious reasons why her migraines should stop responding to Botox, I ordered an MRI scan. Unfortunately, she turned out to have brain metastases from breast cancer which had not yet been diagnosed.