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Botox

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.

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Sleep disturbances and fatigue are more common in patients with chronic migraine headaches than in people without migraines. Sometimes it is not clear what came first, migraines or the sleep problem with secondary fatigue.

A multicenter study performed in Australia, South Korea, and the US examined the effect of Botox injections given for chronic migraines on sleep and fatigue. This was a 108-week study of 715 adult patients who received Botox injections every 12 weeks. Their sleep quality was assessed by the Pittsburgh Sleep Quality Index and fatigue was measured by the Fatigue Severity Scale, both standard and proven measures of sleep and fatigue.

The authors presented their findings at the American Headache Society meeting held two months ago in Boston. While sleep quality was poor before injections were started, significant improvement was noted 24 weeks later and the improvement persisted for the rest of the study. The same was true for fatigue. These findings suggest that sleep difficulty and fatigue are more often the result of chronic migraine, rather than the other way around.

This does not mean that sleep issues should not be addressed while chronic migraine is being treated. Patients are advised to adhere to sleep hygiene, which consists of going to sleep and getting up at the same time, not reading or looking at any screens in bed, sleeping in a cool and quiet environment, exercising and eating at least 2 hours before bedtime, and avoiding caffeine after 1 PM. Regular practice of progressive relaxation and meditation can be very effective for sleep, migraines, and stress. Natural supplements for sleep, such as melatonin and valerian root are also worth trying.

As far as fatigue, we always check vitamin B12 levels, along with vitamin D, RBC magnesium, thyroid, and other blood tests.

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Cluster headache is one of the most painful conditions that has lead some patients call it a suicide headache. A new observational study done by researchers at the Eli Lilly company and Stanford University was presented at the recent annual scientific meeting of the American Headache Society.

Considering that cluster headaches are relatively rare, the major strength of this study is its size – 7589 patients. These patients were compared to over 30,000 control subjects without headaches. We’ve always known that cluster headaches are more common in men with previous studies indicating that male to female ratio is between 5:1 and 3:1. However, only 57% of patients in this new report were males. This does not reflect my experience – I see at least five times as many men as women. It is possible that I underdiagnose cluster headaches in women or the study used unreliable data. In fact, the study data was collected from insurance claims, so I suspect that the truth is closer to my experience and to the older published data.

The study did find that thoughts of suicide were 2.5 times more common in patients with cluster headaches compared to controls, while depression, anxiety and sleep disorders were twice as common. Cluster headache patients also were 3 times more likely to have drug dependence. The most commonly prescribed drugs were opiates (narcotics) in 41%, which partially explains high drug dependence rates, steroids, such as prednisone (34%), triptans, such as sumatriptan (32%), antidepressants (31%), NSAIDs (29%), epilepsy drugs (28%), blood pressure drugs, such as verapamil (27%), and benzodiazepines, such as Valium or Xanax (22%).

It is very unfortunate that over a period of one year only 30% of patients were prescribed drugs recommended for cluster headaches. We know that narcotics and benzodiazepine tranquilizers are not very effective and can lead to dependence and addiction. Drugs that are effective include a short course of steroids (prednisone), sumatriptan injections, blood pressure drug verapamil (often at a high dose), some epilepsy drugs and occasionally certain antidepressants. The report did not mention oxygen, which can stop individual attacks in up to 60% of cluster headache sufferers. Nerve blocks and to a lesser extent, Botox injections can also provide lasting relief. It is possible that the data on oxygen, nerve blocks and Botox was not available.

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Trigeminal neuralgia is a rare, but an extremely painful conditions. Patients compare the quality and the severity of pain to an electric shock. The underlying cause is usually compression of the trigeminal nerve by a blood vessel inside the skull and underneath the brain. Surgery to place a teflon pad between the nerve and the blood vessel is curative, but many patients can avoid surgery by using drugs such as carbamazepine, oxcarbazepine, baclofen, and other. Botox, which is approved only for one pain condition – chronic migraines, appears to help other painful conditions, including trigeminal neuralgia (TN). A single previous double-blind placebo-controlled study by Chinese doctors confirmed our clinical observation that Botox does indeed help TN.

A new report presented at the annual meeting of the American Headache Society, also by Chinese researchers describes another positive study. This study compared a single injection of Botox with two injections separated by two weeks. It is not clear what was the logic in giving a second treatment so soon after the first one since Botox effect lasts 3 months. They followed 81 patients for 6 months and both groups had more than 80% success in the first 3 months and somewhat less of an effect in the last 3 months of the study. This was not a blinded study, but placebo response is relatively low in TN, probably because of the high pain intensity. While this study was not as scientific as the first one, it does offer some additional evidence of the efficacy of Botox for TN. Botox is certainly much safer than medications, although facial asymmetry can be an unpleasant cosmetic side effect, especially if pain involves the second branch of the TN (middle of the face).

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Concussion, even when it is mild, can result in a post-concussion syndrome. The main symptom is a headache and it is present in 60% of people within the first year after a mild traumatic brain injury. In people with personal or family history of migraines these headaches are often post-traumatic chronic migraines. Post-traumatic headaches and other symptoms such as dizziness and difficulty with vision, concentration and memory are often difficult to treat. However, an effective treatment of headaches often leads to an improvement in other symptoms as well.

Treatment with epilepsy drugs (Topamax, Depakote, Neurontin), blood pressure medications (propranolol), or antidepressants (Elavil, Cymbalta) can be effective in some, but not in all and not without side effects. Botox injections have been very effective without any serious side effects in many of my patients and similar results have been published by other doctors (see here and here).

Dr. Sylvia Lucas of University of Washington in Seattle presented her experience with the treatment of posttraumatic headaches with Botox at the annual meeting of the American Headache Society held in Boston last month. She described 15 patients who sustained a mild traumatic brain injury and suffered from chronic migraines for an average of 8 months prior to being treated with Botox. After a series of three Botox treatments given every 3 months most patients had a significant improvement in the number of headache days, as well as improved physical and social functioning, emotional well-being, energy level and a reduction in pain. As expected, no patient experienced any serious side effects.

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Searching on Amazon for books on migraines yields over 2,291 items. Do we need another book? Having just read the latest book on migraines, Understanding Your Migraines, the answer is a definite yes.

The book is written by two colleagues who for many years co-directed the Dartmouth Headache Clinic. Dr. Morris Levin is now the Director of the Headache Center and a Professor of Neurology at UCSF, while Dr. Thomas Ward is Professor of Neurology Emeritus at the Geiser School of Medicine at Dartmouth and the editor of the journal Headache. They are clearly highly qualified to write such a book, but qualifications are not enough – you need to be a good writer as well. And in fact, excellent writing style and case-based discussion are two of the major strengths of the book.

The book consists of 17 chapters, which cover diagnosis and our understanding of the underlying causes of this condition. What the readers will find most useful is the treatment approaches. Drs. Levin and Ward go into great detail about various non-drug options, including nutrition, exercise, meditation, acupressure, herbal products, vitamins and minerals. They also present pros and cons of various medications, nerve blocks and describe in detail the most effective and the safest preventive treatment for chronic migraines, Botox injections.

One chapter is devoted to specifics of migraines in pregnancy and another one to children and adolescents. The book also includes individual chapters on tension-type headaches, cluster and other less common headache types, and postconcussion headaches.

The authors also mention an exciting new treatment option, which we expect to be approved by the end of 2018. Four companies are racing to bring to the market CGRP monoclonal antibodies, which act like vaccines against migraines. A single injection will provide 1 to 3 months of relief with very few side effects. It is likely that this treatment will help about 60% of patients with both episodic and chronic migraines. Cluster headache patients might also benefit from these biologic drugs.

Reading so much information can make it difficult to understand how to actually use it and how to talk to your doctor about all these options. The authors successfully tackle this problem by providing many real-life cases and by including a chapter, How to Communicate with Your Medical Team.

I am sure that this book will help many migraine sufferers find relief. You can buy it on Amazon.

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Botox is by far the safest and the most effective preventive treatment for chronic and frequent episodic migraine headaches. The only downside is the cost. A 200-unit vial of Botox costs about $1,200. Most insurance companies cover Botox if you have chronic migraines (15 or more headache days each month) and if you’ve tried and failed (it did not help or caused side effects) 2 or 3 preventive medications. The copay for a vial of Botox is often as high as $400 or more. If your insurance does not cover Botox at all, or you have “only” 10 to 14 headache days each month, or you do not want to take daily drugs because of potential side effects, you may have to pay the entire cost. To reduce this cost, you may want to ask the doctor to start with 100 units instead of the standard dose of 155 units. Since the manufacturer makes only 100 and 200 unit vilas, the remaining 45 units are discarded. Some doctors are very accommodating, but I’ve heard of many that will not deviate from the FDA-approved protocol of 155 units injected into 31 spots. I discussed some of this in a recent post.

Another way to avoid excessive costs when paying out of pocket for Botox is to avoid large hospitals. A few years ago, while giving lectures at the Mayo Clinic, Cleveland Clinic, and Beth Israel Hospital in Boston, I discovered that they all charged $6,000 for one Botox treatment. What prompted this post is that I recently saw a patient who had Botox injections at the Cedars-Sinai Hospital in Los Angeles and had to pay $11,000. Every charge for a procedure done in a hospital or even at a doctor practice that is owned by the hospital, includes a hefty “facility fee”. This is why hospitals often buy doctor practices – they can triple the charges and even insurers such as Medicare and Medicaid will pay at an inflated rate.

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One of the most common problems with Botox injections given for chronic migraines is that doctors use the standard protocol without adjusting the dose. One of my patients is an 83 year old woman with chronic migraines who has done exceptionally well with Botox injections with no side effects for the past 16 years. She recently started living in Florida during the winter and had Botox injections given by a local doctor. I provided her with a copy of the injection sites and the total dose, which was 65 units given into 20 sites in the forehead and temples. Her Florida neurologist insisted on giving her the standard 31 injections with 155 units all around the head, neck and shoulders. The result was that she developed drooping of her eyelids and pain and weakness of her neck. It defies common sense to inject a small woman who weighs 90 lbs with the same amount of Botox as a 200-lbs man.

Sticking strictly to the protocol prevents many doctors from addressing clenching and grinding of the teeth (TMJ syndrome), which often worsens migraines. Injecting Botox into the masseter muscles (chewing muscles at the corner of the lower jaw) can have a dramatic effect on TMJ pain and migraines. Other patients may need additional injections into the scalp or upper back, depending on where the pain is felt. Since Botox comes only in 100 and 200 unit vials, if the insurance company approves Botox, it sends us 200 units. Instead of discarding the remaining 45 units, we usually give additional injections into the areas of pain that may not be included in the standard protocol.

Giving injections every 3 months or even every 12 weeks works well for many patients. However, about a quarter of my migraine patients find that the effect of Botox lasts only 10 weeks and in a small number , even less than 10 weeks. Fortunately, some insurance companies allow Botox to be administered every 10 weeks, but many do not. Some even limit injections to every 3 months, and not a day earlier, even though the clinical trials that led to the FDA approval involved giving injections every 12 weeks. Having a week or two of worsening migraines can eliminate the cumulative effect we see with repeated treatments. That is, each subsequent Botox treatment provides better relief than the previous one. This may not the case if headaches worsen before the next treatment is given.

Cosmetic concerns are not trivial since Botox injections can make you look strange – as if you are always surprised or look sinister with the ends of your eyebrows always lifted. This can be easily avoided by injecting a very small amount of Botox into the appropriate muscles above the ends of the eyebrows or a little beyond them. In some patients this can be predicted before the first treatment by looking at the lines seen with lifting of the eyebrows. In others, it becomes apparent only after the first treatment. If the appearance is very unappealing, we ask the patient to return to get two small additional injections for which we do not charge.

To minimize bruising and pain we use very thin needles. A 30-gauge needle is used most often, however an even thinner, 33-gauge needle is also available, but is rarely used (higher number indicates a thinner needle). We recommend using a 33-gauge needles, at least for the forehead, where injections tend to be more painful and where bruising, if it happens, is very visible.

Many dermatologists and plastic surgeons tell their patients not to bend down or do anything strenuous to avoid movement of Botox which may lead to drooping of the eyelids. There is no theoretical or practical evidence for this restriction. Once injected, Botox does not move around freely but stays in the injected area. In my 22 years of injecting Botox, I’ve treated thousands of headache sufferers and fewer than 1% of patients developed drooping eyelids and none were related to bending or any other activities. Drooping is more common in older patients, is always reversible within days or weeks, and sometimes can be relieved by eye drops (aproclonidine).

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Several of my patients with trigeminal neuralgia (TN) responded to Botox injection (although some have not). My previous post on this topic four years ago discussed a study involving 40 patients with TN, of whom 68% responded to Botox. Recently, two new cases of TN successfully treated with Botox have been reported and in the past month I’ve treated three additional patients. Two of my patients had excellent relief and one had none.

One of the case reports was presented at the recent meeting of the American Headache Society in San Diego. This was a 65-year-old woman who suffered from very severe electric shock-like pain typical of TN. She did not respond to a variety of medications, including carbamazepine (Tegretol), but did respond to Botox injections. Botox did not eliminate her pain, but the severity of it was reduced by 50% and this significantly improved the quality of her life.

The current issue of Headache contains a report of a 60-year-old man with severe TN who also did not respond to any medications. He did obtain complete relief from Botox injections and Botox has remained effective for over 2 years.

With any new treatment we usually hope to see large double-blind controlled clinical trials and eventually an FDA approval. FDA approval usually compels insurance companies pay for the treatment. Botox injections have received approval for chronic migraines, excessive sweating, twitching of muscles around the eyes (blepharospasm), and several other conditions. Unfortunately, it is not likely that Botox will receive approval for the treatment of TN because it is a relatively rare condition, which will make it difficult to conduct a large blinded trial. Fortunately, the amount of Botox needed to treat TN is much smaller than what is used for migraines, making a little more affordable. We use 100 to 200 units of Botox for chronic migraines (the FDA-approved protocol calls for 155 units injected over 31 sites) and only 20 to 50 units for TN.

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The FDA approved Botox injections for the treatment of chronic migraine headaches more than five years ago. I just discovered that in this period of time only 100,000 chronic migraine sufferers received this treatment. According to the Migraine Research Foundation, 14 million Americans suffer from chronic migraines, so less than 1% of them have recieved this potentially life-changing treatment.

There are several possible explanations.
1. Botox is expensive and many insurance companies make it difficult for patients to get it. They require that the patient first try 2 or 3 preventive drugs, such as a blood pressure medicine, (propranolol, atenolol, etc.), an epilepsy drug (gabapentin, Depakote, Topamax), or an antidepressant (amitriptyline, nortriptyline, Cymbalta). Patients also have to have 15 or more headache days (not all of them have to be migraines) in each of the three preceding months. If these requirements are met, the doctor has to submit a request for prior authorization. Once this prior authorization is granted, the insurer will usually send Botox to the doctor’s office. After the procedure is done, the doctor has to submit a bill to get paid for administering Botox. This bill does not always automatically get paid, even if a prior authorization was properly obtained. The insurer can ask for a copy of office notes that show that the procedure was indeed performed. All this obviously serves as a deterrent for many doctors. Some of them find that the amount of paperwork is so great and that the payment is so low and uncertain, that they actually lose money doing it.

2. There are not enough doctors trained in administering Botox. This is becoming less of a problem as more and more neurologists join large groups or hospitals where at least one of the neurologists is trained to give Botox and gets patients referred to him or her. However, doctors in solo practices or small groups without a trained injector can be reluctant to refer their patients out for the fear of losing a patient. They may suggest that this treatment is not really that effective or that it can cause serious side effects.
The majority of doctors who inject Botox are neurologists, but there are only 15,000 neurologists in the US and many specialize in the treatment of strokes, Alzheimer’s, epilepsy, MS, and other conditions. This leaves only a couple of thousand who treat headache patients. Considering that there are 14 million chronic migraine sufferers, primary care doctors will hopefully begin to provide this service.

3. Chronic migraine patients are underdiagnosed. Many patients will tell the doctor that they have 2 migraines a week and will not mention that they also have a mild headache every day. The mild headaches they can live with and sometimes my patients will even call them “normal headaches”, which they don’t think are worth mentioning. Good history taking on the part of the doctor solves this problem. However, once doctors join a large group or a hospital, they are pressured to see more patients in shorter periods of time, making it difficult to obtain a thorough history.

4. Some patients are afraid of Botox because it is a poison. In fact, by weight it is the deadliest poison known to man. However, it is safer than Tylenol (acetaminophen) because it all depends on the amount and too much of almost any drug can kill you. Fifty 500 mg tablets of Tylenol kills most people by causing irreversible liver damage. Hundreds of people die every year because of an accidental Tylenol poisoning, while it is extremely rare for someone to die from Botox. Tens of millions of people have been exposed to Botox since its introduction in 1989. It is mostly young children who have gotten into trouble from Botox because the dose was not properly calculated. Kids get Botox injected into their leg muscles for spasticity due to cerebral palsy, although children with chronic migraines also receive it (the youngest child with chronic migraines I treated with Botox was 8).

In summary, if you have headaches on more than half of the days (not necessarily all migraines) and you’ve tried two or three preventive drugs (and exercise, meditation, magnesium, CoQ10, etc), try to find a doctor who will give you Botox injections. Botox is more effective and safer than preventive medications because it does not affect your liver, kidneys, brain, or any other organ.

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I recently gave Botox injections to my oldest patient – an 96-year-old man who is otherwise in excellent mental and physical health has been suffering from daily severe cervicogenic (neck-related) headaches for many years. He had tried pain killers, nerve blocks, radiofrequency ablation (destruction) of nerves in his neck, all with no relief. A month after being treated with Botox he reported having almost no headaches. I have also given Botox to a number of patients with chronic migraines in their 70s and 80s.

At the last scientific meeting of the American Headache Society Cleveland Clinic neurologists presented a report entitled, Safety and Efficacy of OnabotulinumtoxinA (Botox) for Chronic Migraines in the Elderly. They described 28 patients who were older than 65, had an average age of 73 and who were treated with Botox injections for their chronic migraine headaches. They compared the safety and efficacy of Botox injections in this group with that of 700 patients aged 18 to 65 who participated in PREEMPT II study of Botox for chronic migraine (one of the two studies that led to the FDA approval of Botox for chronic migraines, in which we also participated). There was no significant difference in side effects between the younger and the older groups, except for a slightly higher incidence of neck pain after the injections in the elderly. The improvement was also comparable – after Botox the elderly had 11 fewer headache days a month compared with 9 fewer days in the younger group.

In conclusion, while many migraine medications are more likely to cause side effects in the elderly, this is not the case with Botox. Also, Botox appears to be as effective in the elderly with chronic migraines as in younger patients.

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Several presentations at the annual meeting of the American Headache Society held in Washington DC last weekend discussed the treatment of post-concussion symptoms in children (everything below also applies to adults). Among many topics, the speakers addressed the question of aerobic exercise after the concussion. Most experts agree that starting physical exercise too early can worsen the symptoms and delay recovery. At the same time, because aerobic exercise has so many benefits for the brain, it is prudent to begin aerobic exercise 2 to 4 weeks after the concussion. The child should begin exercising for short periods of time and at low intensity. Exercise should be stopped as soon as symptoms, such as headache or dizziness worsen. Brisk walking could be the first activity to be tried. The ideal duration is about 30 minutes and when this goal is achieved, the intensity of exercise can be gradually increased.

As far as the very common cognitive problems after a concussion, the experts also agreed that complete cognitive rest is not helpful. Just like with physical exercise, it is best to begin mild activities, such as reading for pleasure, and then slowly increase the load, as tolerated.

Several scientific presentations reported that the most common type of headaches that occurs after a concussion is migraine. When these post-concussion migraines last for more than 3 months and occur on more than 15 days each month, they are considered to be chronic migraines.

The treatment of post-concussion chronic migraines is the same as the treatment of chronic migraines that occur without a concussion. These treatments may include cognitive behavioral therapy, biofeedback, magnesium and other supplements (magnesium deficiency is found in up to 50% of migraine sufferers and magnesium is depleted by trauma), various preventive medications, and Botox injections.

Although the FDA has not yet approved Botox injections for the treatment of chronic migraines in children, Botox is safer than most drugs. We know about the safety of Botox in children because it has been widely used even in very young children who suffer from cerebral palsy and are unable to walk unless their stiff leg muscles are relaxed by Botox. Botox was approved by the FDA 26 years ago and some kids have been getting injections for over 20 years and so far there have been no long-term side effects observed.

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