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Brain disorders

A large study confirms previous reports of the beneficial effect of onabotulinumtoxinA (Botox) injections on depression as well as anxiety. In my two previous blog posts from 2011 and 2014 I mentioned reports of cosmetic Botox injections relieving depression but those involved a relatively small number of patients.

A study published in the Journal of Neurology, Neurosurgery, & Psychiatry under the title Effects of onabotulinumtoxinA treatment for chronic migraine on common comorbidities including depression and anxiety ,described the COMPEL trial (Chronic Migraine OnabotulinumtoxinA Prolonged Efficacy Open-Label). It was a multicenter, open-label, prospective study assessing the long-term safety and efficacy of 155 units of onabotulinumtoxinA (Botox) over nine treatments (108 weeks) in adults with chronic migraines.

OnabotulinumtoxinA treatment was associated with sustained reduction in headache days and depression and anxiety scores in the 715 patients over 108 weeks. The anxiety and depression scores were significantly reduced at all time points in patients with clinically significant symptoms of depression and/or anxiety at baseline. By week 108, 78% and 82% had clinically meaningful improvement in depression and anxiety symptoms, respectively. Sleep quality and symptoms of fatigue also improved.

In an earlier poster presentation of this data at a scientific conference the authors reported that the improvement in anxiety and depression was seen even in patients whose migraines did not improve with Botox. Even if that were true, we need a separate large study of Botox for anxiety and depression. The one study that treated patients with major depression in a double-blind, placebo-controlled trial involved only 74 patients.

In my practice, I’ve treated one young woman with severe bipolar disorder which did not respond to multiple drugs and who had a dramatic response to Botox. She has been receiving injections for over two years with sustained improvement. Another young man with depression had a very significant response as well, but has had only one treatment so far. I came to treat them accidentally – both were adopted children of my migraine patient who read about this possible effect of Botox and asked me to try it.

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An alarming study entitled Association Between Migraine Headaches and Dementia in More than 7,400 Patients Followed in General Practices in the United Kingdom was just published in the Journal of Alzheimer’s Disease. The researchers found that the risk for ALzheimer’s and other dementias is increased only in women with migraines and not in men.

The first large study to discover an association between migraines and dementia was done in Taiwan. Interestingly, a follow-up study in Taiwan discovered that people who used traditional Chinese medicine (mostly herbal products Jia-Wei-Xiao-Yao-San and Yan-Hu-Suo) had lower risk of dementia than those who did not.

There is no need to panic since other studies have found no such association and there is a wide range of preventive measures that are proven effective.

Controlling ones blood pressure, blood glucose, cholesterol level, and avoiding smoking are extremely important in lowering the risk of Alzheimer’s.

The single most effective preventive measure is regular physical exercise, which is more effective than mental exercise. Engaging in mental activities, such as learning languages, solving crossword puzzles, and playing bridge (which adds the benefit of social contacts) can also help. Dancing and tai chi combine physical and social benefits. Meditation appears to be effective in preventing shrinkage of the brain, which used to be thought a normal part of aging. This was confirmed in more than one study.

In addition to Chinese herbal products mentioned above, there are several other supplements that are also less proven but are safe and may help prevent Alzheimer’s. These include vitamins B12 and D, magnesium, curcurmin, nicotinamide, and possibly other.

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Migraine with and without aura carries an increased risk of strokes and heart attacks, according to several large studies. Most migraine sufferers are young women and until now there have been no studies looking at postmenopausal women.

At the last annual scientific meeting of the American Headache Society, Dr. Pavlovic and her colleagues at the Albert Einstein College of Medicine in the Bronx presented data of their study of over 70,000 postmenopausal women who were followed annually for 22 years. Ten percent of them had a history of migraines (compared to 18% seen in surveys of all women). Surprisingly, those with a history of migraine did not have a higher risk for strokes or heart attacks.

This somewhat contradicts another study mentioned on this blog last year. Doctors in South Carolina established that people with migraine with aura who were 60 or older, were more likely to have atrial fibrillation (a type of arrhythmia, or irregular heart beat), a condition that increases the risk of strokes.

Despite some inconsistencies in various studies, the practical implications are that those with migraines (and those without) should try to control modifiable risk factors. These include smoking, high blood pressure, diabetes, high cholesterol. If atrial fibrillation is present, a blood thinner is usually indicated as it may prevent strokes. Control of modifiable risk factors includes not only medications, but also regular exercise, healthy diet, stress management, and good sleep habits.

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Researchers at SUNY Buffalo and University of Manitoba studied the effect of exercise on recovery from a sports-related concussion in 103 adolescents. The results were published in JAMA Pediatrics.

The participants were enrolled within 10 days of a concussion. Half of the kids were given a stretching program and the other half, aerobic exercise on a treadmill. The intensity of aerobic exercise was subthreshold, or just below the level where it caused any post-concussion symptoms and was determined individually for each participant. Both stretching and aerobic exercise were performed for 20 minutes every day for a month. Those who did aerobic exercise recovered in 13 days, while those who did stretching exercise, in 17 days. There were no complications in either group.

This was the first randomized controlled trial of exercise, although prior observational studies also showed that early return to physical activity is beneficial for recovery from a concussion.

Cognitive rest is also not necessary after a concussion, but the activities should be also subthreshold and not too strenuous, which can worsen symptoms and delay recovery.

Other useful strategies include intravenous magnesium, cognitive-behavioral therapy, and Botox injections.

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Patients suffering from migraine with aura (MA) are at a higher risk of strokes. It is not clear what leads to this problem. Elevated homocysteine level increases the risk of strokes and heart attacks and patients with MA are more likely to have this abnormality. Another possible explanation is reported in a recent study mentioned on this blog in December, This study convincingly argues that the risk of stroke is increased because of the higher incidence of a certain type of cardiac arrhythmia, atrial fibrillation in patients with MA.

Researchers at the University of South Carolina recently discovered that the risk of strokes is higher only in migraine sufferers who started having migraines after the age of 50.

The findings were a part of the Atherosclerosis Risk in Communities (ARIC) study. Among 11,592 black and white participants, 447 had MA and 1,128 MO. The risk of stroke in those whose MA began after the age of 50 was double that of those with no headaches. MA that started before 50 was not associated with stroke. MO was not associated with increased stroke regardless of the age of onset. The absolute risk for stroke in migraine with aura is 8% and migraine without aura is 4%.

To reduce the risk of strokes (whether you have migraine with aura or not) you need to keep your cholesterol under control, not smoke, exercise regularly, maintain good blood pressure and weight.

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A study just published in Neurology by the MEGASTROKE project of the International Stroke Genetics Consortium found that “genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke…” It is an open access article, so you can download the full text. The study looked at 34,217 cases of strokes and 404,630 noncases, which makes the data highly reliable.

Here are some quotes (some modified) from the paper.

Several observational prospective studies have reported that low circulating magnesium concentrations and low magnesium intake are associated with increased risk of stroke. In the Nurses’ Health Study, low plasma magnesium concentrations were associated with an approximately 70% to 80% increased risk of embolic and thrombotic stroke.

Magnesium may in part reduce the risk of cardioembolic stroke through its antiarrhythmic effects and via atrial fibrillation. Low serum magnesium concentrations are associated with increased risk of atrial fibrillation, which is a strong risk factor for cardioembolic stroke. (My recent post mentioned that the increased risk of strokes in patients with migraines with aura is possibly related to the higher incidence of atrial fibrillation) Two of the magnesium-associated SNPs (genetic variants) were significantly associated with atrial fibrillation, with higher serum magnesium concentrations being associated with lower risk of atrial fibrillation.

Magnesium also has anticoagulant and antiplatelet properties (platelet aggregation is also implicated in migraine). Magnesium is considered to be nature’s calcium blocker as it suppresses many of the physiologic actions of calcium. For example, calcium promotes blood coagulation, whereas magnesium suppresses blood clotting and thrombus formation and reduces platelet aggregation. Antithrombotic effects may lead to reduction in risk of both cardioembolic and large artery stroke.

Other possible mechanisms whereby high serum magnesium concentrations may reduce ischemic stroke risk include improvement of endothelial function and reduction in blood pressure, atherosclerotic calcification, arterial stiffness, oxidative stress, fasting glucose concentration, insulin resistance, and risk of type 2 diabetes. Some of those beneficial e?ects may also lead to a reduction in small vessel stroke, which was not observed in this study.

Magnesium also reduces the size of a hemorrhagic stroke (bleeding into the brain), according a another recent study.

Magnesium has been my main area of research and because I never tire of promoting the role of magnesium in the treatment of migraines some colleagues call me Dr. Magnesium. The evidence is overwhelming – many studies have shown that magnesium deficiency is common in migraine sufferers and that taking magnesium can help. The American Academy of Neurology and the American Headache Society guidelines for the treatment of migraines include magnesium, but it is still underappreciated and underutilized. This is in part because there have been no large-scale (i.e. expensive) trials of magnesium which are done by pharmaceutical companies for new drugs. Another reason is that the trials that have been conducted supplemented migraine patient regardless of their magnesium status – both deficient and non-deficient patients were given magnesium, thus obscuring the great benefit obtained by the deficient cohort.

As mentioned in several previous posts, magnesium also helps asthma, palpitations, feeling cold or having cold hands and feet, muscle twitching, cramps or diffuse muscle aches (fibromyalgia), premenstrual symptoms (PMS), brain fog, and many other symptoms. If you have any of these symptoms you may want to have a blood test for magnesium. And even if you don’t have symptoms, the next time you have any kind of a routine blood test, ask your doctor to add a test for “RBC magnesium”, which is more accurate than the usual “serum magnesium”.

If you have any of the above symptoms, you can also just start taking 400 mg of magnesium glycinate, which is the daily recommended allowance for magnesium. If oral magnesium does not help and the RBC magnesium level is low we usually give monthly infusions of magnesium. They take 10 minutes to do, have no side effects and are covered by most insurance plans.

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A group of American and Israeli researchers published a study in the journal Brain, suggesting that hits to the head, even those that do not cause an overt concussion, contribute to the chronic traumatic encephalopathy (CTE). CTE has been found in many football players, combat veterans, and other athletes who suffer from repeated head injuries.

The current study examined brains of four teenage athletes who had sustained repetitive hits to the head in the days and weeks before their death. They did not have typical symptoms of concussion – headaches, dizziness, confusion, memory difficulties, or vision problems. One of them had an early-stage CE and two had accumulation of tau protein that is implicated in CTE and Alzheimer’s disease.

These researchers proceeded to create a mouse model of repetitive and subconcussive head trauma, which also showed that relatively mild repetitive head injuries lead to degenerative changes in the brain.

These findings are not very surprising – repeatedly hitting your head cannot be good for your brain, regardless of the severity of each injury. However, many questions remain unanswered – what is the role of certain genetic traits that are known to predispose to CTE, could magnesium, which is depleted by trauma, or other supplements help reduce the damage, and what other interventions could possibly protect the brain.

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Several drugs are often used to treat symptoms of concussion, including an epilepsy drug, gabapentin (Neurontin), amitriptyline (Elavil) and other antidepressants.

A recent study by doctors at the University of Utah in Salt Lake City examined the role of medications in the treatment of concussions. They studied 277 patients who suffered a concussion and were seen at the local sports medicine clinic. Patients were evaluated for 22 symptoms including headaches. The patients were divided into three groups: those prescribed amitriptyline or nortriptyline, those who were prescribed gabapentin, and those who were not prescribed any medication at all.

Patients who were prescribed medications tended to have more severe headaches and other symptoms. However, headaches and other symptoms decreased significantly within days after the initial visit equally in all three groups.

This study does not prove that all treatments for postconcussion syndrome are ineffective. A recent presentation by Dr. Bert Vargas of the Sports Neurology and Concussion Program at the University of Texas Southwestern Medical Center in Dallas stressed that many migraine treatments can be very effective for postconcussion headaches and other symptoms. The features of postconcussion headaches often resemble migraines and migraine medications, such as triptans (sumatriptan, or Imitrex, and other) can be very effective. Unfortunately, only 2% – 5% of patients with posttraumatic headaches receive migraine drugs. The vast majority are treated with acetaminophen or NSAIDs, such as ibuprofen or naproxen.

Botox injections have also been reported to be very effective for postconcussion headaches, which has been my experience as well. Botox injections are approved by the FDA only for the treatment of chronic migraines. However, if headaches are accompanied by migraine features a diagnosis of posttraumatic chronic migraine can validly be made and then many insurance companies will pay for this treatment.

Dr. Vargas also noted that topiramate (Topamax), which is an epilepsy drug approved for the prevention of migraines, is not a good choice for posttraumatic headaches. Topiramate often causes cognitive side effects which can worsen the concussion-related cognitive problems, including impaired memory and concentration.

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A recent article in the New York Times by the health columnist, Jane Brody, Trying the Feldenkrais Method for Chronic Pain, described her very positive experience with the Feldenkrais method. Then, at about the same time a patient told me that Feldenkrais lessons made a big difference in her neck and back pain. I started to read about Feldenkrais (download an article from the Smithsonian Magazine), took a lesson with my patient’s teacher, and then invited this teacher to work in our office.

This method was developed by a Russian-born Israeli engineer Dr. Moshe Feldenkrais (1904-1984). He was a physicist who was educated at Sorbonne and worked with Frédéric Joliot-Curie, then worked in the British survey office and during the war, as a science officer in the Admiralty. In 1936, while in France, he became one of the first Europeans to earn a black belt in judo.

A knee injury led Feldenkrais to develop a movement method named after him. He did not call it therapy and always insisted that he did not treat patients, but rather taught lessons on how to move naturally. At the same time, his lessons often led to a dramatic relief of pain, improved movement and functioning in individuals who suffered from cerebral palsy, strokes, multiple sclerosis, back, and neck pains. He felt that the key to healing was to become aware of what one is doing. Dancers, artists, and athletes have been using Feldenkrais lessons to improve their performance and to heal and avoid injuries. In the early 1950s Feldenkrais worked with the first Prime Minister of Israel, David Ben-Gurion, whose decades-long chronic back pain dramatically improved. Feldenkrais quit his position as the first director of the electronics department of the Israeli Defense Force and decided to devote all of his time to teaching his movement method. He had trained hundreds of practitioners all around the world and they in turn trained the next generation of teachers.

Feldenkrais emphasizes gentle and often small movements that re-educate and re-establish the connection between the body and the brain. It also makes you do movements that do not come naturally and that we never do, such as turning your head to one side and moving your eyes in the opposite direction. It is difficult to describe this method in words, but even a single lesson can show its dramatic potential. Try this simple exercise. Check the range of movements in your neck – how far can you turn your head to one side, then the other without straining. Then, put palms of your hands on your cheeks and attach your arms to the body. Now, turn your body at the waist from the midline to the left and back to the midline, again only as far as you can comfortably do it. Repeat this 10 times and then 10 times from the midline to the right. Now, put down your arms and test your range of movements again. Most people, including those who have very tight neck muscles, will noticed a significant and a very surprising improvement. Surprising, because it happened without moving your neck. You can watch me doing this exercise on youtube; I also show another exercise that improves the lateral flexion of your neck.

A possible explanation is that our brains get visual cues indicating that our head moved far to one side, but the brain cannot tell if the movement came from turning the torso or the neck. Repeating the move 5-10 times trains our brain to allow such movement even when we only move the neck. This explanation has some scientific support. When vision and proprioception were incongruent, participants were less accurate and initially relied on vision and then proprioception over time.

This explanation has some scientific support. The authors of an article in the Experimental Brain Research, Untangling visual and proprioceptive contributions to hand localisation over time, conclude that “When vision and proprioception were incongruent, participants were less accurate and initially relied on vision and then proprioception over time” (proprioception is our sense of the relative position of our body parts).

Another fascinating phenomenon that provides Feldenkrais method additional scientific support is the observation that when we cross our hands, we feel less pain in the hand. The Journal of Pain published an article “Seeing One’s Own Painful Hand Positioned in the Contralateral Space Reduces Subjective Reports of Pain…” Scientific research using functional MRI images of the brain led to the publication of another article in the same journal: Crossing the line of pain: FMRI correlates of crossed-hands analgesia.

It appears that our visual cues are very important to our ability to move and feel pain and this may be one of the ways the Feldenkrais method improves movement and relieves pain.

Individual lessons can be expensive ($100-$200 an hour), but Feldenkrais is often taught in groups, which makes it more affordable. You can also learn it by reading books, such as Awareness Heals: The Feldenkrais Method For Dynamic Health , audio recordings – The Feldenkrais Lessons: Awareness Through Movement by Bruce Holmes , and youtube videos

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People who have experienced “visual snow” know what it means. Their vision tends to be distorted by white spots that resemble what you see on the television when there is no signal.

At the latest meeting of the International Headache Society, the topic of visual snow was addressed in four presentations. The first presentation by British and Swiss researchers attempted to give a definition, so that this phenomenon can be studied scientifically. They collected data on 636 subjects by using an online survey of patients. 636 is a surprisingly high number because this is thought to be a relatively uncommon symptom. I certainly do not see more than a handful of patients each year. They found this phenomenon to be present with equal frequency in men and women and 39% reported to have it all their lives. The majority (56%) saw black and white static, 44% saw colored spots, while 45% experienced flashing, and 52% described it as transparent. The most common non-visual symptom was tinnitus, or ringing in the ears, which was present in 74%. Only 226 patients gave information on headaches and 83% of them suffered at least one attack of migraine. They concluded that visual snow is an unrecognized symptom, which can be very disabling and which deserves further research.

The second presentation reported on 90 patients of the original 636 who agreed to keep a diary of their symptoms for 30 days. The results showed that the visual snow was least noticeable outdoors, in bright sun. It was most pronounced at night. The amount of distraction that was caused by visual snow was correlated to the size and density of the static.

The third study by German and Swiss doctors showed that visual snow is a phenomenon that is common in migraine sufferers, but it is distinct in its character. They came to this conclusion by testing the excitability of the visual cortex of the brain.

The fourth paper described the effectiveness of various treatments. The data was collected by reviewing questionnaires that were returned by 204 patients. The effect of 112 drugs was reported. Unfortunately, less than half (92) of the responders had any relief from medications. Antidepressants and anti-epilepsy drugs were most commonly used. Only 29% improved from benzodiazepine drugs (Valium or diazepam, Klonopin or clonazepam, and other). Recreational drug use was reported 117 times and in 32% produced worsening and in 61% there was no change.

We clearly do not know how to treat this condition, but if you have it, have your doctor check your RBC magnesium level since magnesium deficiency increases the excitability of the nervous system. I would also check vitamin B12, D, and CoQ10 levels, thyroid function, and routine blood tests, looking for an underlying medical condition (for example, anemia) which can worsen many symptoms. Regular and sufficient amounts of sleep, exercise and meditation can also reduce the excitability of nervous system.

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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.

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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.

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