adverse drug reaction

Adverse Drug Reactions (ADRs): We’re ALL at Risk

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adverse drug reactions

I’m lying in my bed, with my arms and legs straight out. I figured out pretty fast that any stress whatsoever on the tendons, makes things worse for days, weeks even. “Stress” includes not only trying to walk or use my arms or legs for any reason at all, but also simply bending my arms, or my knees, or my fingers, in one position for too long. What’s “too long”?  Maybe 3-5 minutes or so. I can’t use crutches or a wheelchair, because both of those involve use of my arms and shoulders and hands, which are also out of commission. I can’t type or use the computer, because every tendon in my fingers, hands, wrists, and arms are affected and severely painful. I can’t hold up a book to read, because the weight of the book is too much and I can’t bend my arms, without increasing the tendon pain. The weight of the sheets on my toes causes severe pain in the tendons there. There must be tendons around the eye muscles too, because it hurts simply to move my eyes. So I lay there in my bed, with my arms and legs flat out, with my head still and my eyes closed, waiting. Waiting for what, I’m not sure. It’s hard to believe that I went jogging and bike riding and swimming only a few days ago. I’m also in shock. How in the world could a simple antibiotic that I took for a simple UTI do this to me?

My Journey into the Frustrating World of ADR’s Begins

In March 2010 I took the antibiotic Ciprofloxacin for a simple UTI, and within days became one of the millions of people in this country who experience an Adverse Drug Reaction (ADR) every year to a pharmaceutical drug that is deemed “safe” for use. My adverse reaction, as extreme as it was, unfortunately is not as “rare” as the public is led to believe. It turns out there were tens of thousands of other people, and possibly many times more that, also suffering from the same and similar reactions as I was as a result of this class of very popular antibiotics. There were no “Black Box Warnings” on my drug insert, and the warnings that were listed on the insert didn’t even remotely accurately describe what I was going through then, and continue to go through today.

I’ve been disabled ever since, often times going months without leaving the house, or even getting out of bed, as a result of those few pills. As I lay there waiting, I didn’t know if I was waiting to die or to live. With no known treatment, cure, or detox, or even any idea of why this happens in the first place to some of us, there was nothing left to do but wait.  Whatever was known about these reactions came from the victims themselves, observations painstakingly accumulated over time, sharing information that was now available on the internet. Pharma, the FDA, and the medical and pharmacy professions were noticeably and conveniently absent in having any knowledge, concern, clue, or curiosity about these reactions and why this happens in some people, or what to do about it. Their role in all this apparently ended the minute I took the drug.

I’ve had plenty of time to lay around and think about things in the past five years, given that I can’t do much else.  And understandably, I’m not too happy about this situation. It didn’t take me too long to figure out that my life, or what was left of it, was simply going to be a nameless, faceless, long lost forgotten statistic when it came to my ADR. There was no help on the way for me from the medical profession, the FDA, or Pharma to help me with my ADR, and as far as I could tell, absolutely no interest in learning anything from it by any of these parties either. And if there was one thing that became quite clear, it’s that everything was skewed in everyone else’s favor but mine when it came to my ADR. My physicians, pharmacists, the FDA, and of course Pharma, didn’t want to even acknowledge my ADR due to culpability and liability issues – which meant none of the numerous physicians I saw even bothered to report my ADR to anyone anywhere or the FDA. Without this acknowledgement, insurance companies didn’t want to pay for any “excessive testing” outside of the basic “Top 40 Diagnoses” screening tests for a non-existent problem. With “nothing wrong” on paper, I was denied any form of disability payments and probably considered to be a hypochondriac and/or malingerer trying to commit disability fraud. Even the legal profession, as hungry as they are for business, wasn’t interested in me once they found out I took the generic, since there is no legal recourse available with generic drugs. Everyone else in this chain of events walked away from my ADR unscathed, except, of course, me. I’m the one stuck living with it every minute of every day, with no assistance, and no end in sight. I’m the one scouring the internet, reading everything I can about my symptoms, reviewing the available research, paying for my own medical testing, looking for something, anything that will give a clue as to what this drug did to me and how to fix it.

The only other thing I can say about this scenario is that I’m actually not alone in my frustration and anger about this. There are millions of people out there who have been harmed by a pharmaceutical drug, vaccine, or medical device, in the same boat I am. Most of us have felt this same sense of abandonment by “the system”. Each one of us does the best we can, trying to figure out how to pick up the pieces of a life destroyed by a pharmaceutical prescribed to us by the medical profession, and deemed “safe” for use by Pharma and the FDA.

We’re All Sitting Ducks, Sacrificial Lambs, and Play Russian Roulette When it Comes to ADR’s

Several issues have become quite clear to me since I got hit with my ADR. First, is that for the most part, everyone, from Pharma to physicians and pharmacists, to end consumers like you and me, accept that ADR’s are a part of the deal. A lot of rules and regulations are in place in a supposed effort to ensure that a pharmaceutical is safe for “most” of the population. And therein lies the unspoken fact. At the end of the day, no matter how much effort has been put into safety, it’s accepted that there will always be some people that will react negatively to a drug. There’s an implicit acceptance, regardless of how unpalatable it might be, that “some always have to be sacrificed for the greater good”. We just hope that sacrificial lamb won’t be us or those we love.

Secondly, is that pharmaceutical use, and their ADR’s, are here to stay. In the US, nearly 70% of the population is on one prescription drug, more than 50% are on two, and 20% are actually on five or more prescription medications.  Between 1990 and 2008, U.S. spending on prescription drugs increased from $40 billion to $234 billion. And this doesn’t even include all the over the counter meds. As a society, “Just Say No” has never worked for any drug, and that includes legal pharmaceuticals. Increasing right along with this pharmaceutical epidemic, are the “serious and fatal event” ADR’s, which have quadrupled in the past decade, even by the woefully inaccurate and under reported FDA records. Every single person reading this is at risk for experiencing one or more ADR’s in their lifetime. These ADR’s may be mild and transient, or severe, disabling, and long term or lifelong. They might even be those “fatal events” the fast talking monologues on the drug commercials always warn you about. The point is, no one reading this is safe or exempt from them.  Even people who are very “anti-Pharma” may find themselves on the operating table in the ER someday, being given any number of pharmaceuticals without the opportunity for “informed consent”. We are all at risk, and basically sitting ducks when it comes to ADR’s. I rarely took any medications or supplements, and had only taken antibiotics a few times in the first 50 years of my life. Despite that, I let my guard down once — it only took a few pills, and there was no going back from that mistake. I read the drug insert carefully, which talked about how a little transient mild nausea or GI upset might be the worst ADR, and further on down, mentioned “if you develop a pain in your Achilles tendon, call your doctor”. There was no hint in these warnings that these symptoms could be so extreme, permanent, disabling, and that “my doctor” had never heard of it and had no clue what to do about it either.

Third, is that pharmaceutical companies of course want to minimize, downplay, and outright deny ADR’s because they don’t want to open themselves up to culpability and liability issues and lose profits. From the limited “safety studies” that Pharma does on a drug pre-market, to “publishing bias” of only publishing research studies with data in their favor, to minimizing and hiding the adverse effects as they sell their products to the medical profession and us, Pharma does all they can to get a drug to market and profit from it. Once the drug gets to market, the big experiment occurs, as the drug is unleashed en masse on the general population. For those taking the drug, it’s essentially a game of Russian Roulette, no matter how “informed” you are. At that point in time, if things go wrong, it usually takes tens of thousands, hundreds of thousands, or millions of people suffering severe ADR’s before any action, if any, is taken (think Thalidomide, DES, and more recently, Vioxx). YOUR life may be wrecked, but it’s no big deal to Pharma, the FDA, or even your doctors. If you experience a severe ADR, their lives will continue on, while your life becomes just another long lost statistic, simply considered the “cost of doing business”.

Pharma: The Untouchable Behemoth

It can seem pretty hopeless at times. Physicians and pharmacists get their extremely biased information on the drugs they prescribe directly from Pharma via Pharmaceutical Sales Representatives. These reps get more training in marketing and selling, than in knowing anything about the products they’re selling. If the more curious and ethical physicians actually do take the time to look up the research, they will see biased research studies funded by Pharma, all minimizing the risks while highlighting the benefits. The FDA, who relies on Pharma to do the research studies and present the findings on safety and efficacy of drugs, as well as relies on Pharma as a large source of funding for their own organization, is equally in the dark and basically impotent, as they now see Pharma as their main client to serve, and not the public. And we, the people?  We’re the sacrificial lambs, the sitting ducks, and the true massive post surveillant “research study” when we play Russian Roulette with safety and efficacy of any drug Pharma puts out. The icing on the cake for Pharma is that they can laugh all the way to the bank, no matter how many people are harmed, in the meantime. If, despite Pharma’s best attempts, a drug indeed is found to be unsafe, their main goal is to sell the hell out of it to keep bringing in profits until they are absolutely and overwhelmingly forced to remove it from the market.

This is nothing really new. If you live long enough, or read history, you will see the same old story over and over again, whether in the pharmaceutical industry or any other industry. And if you think your doctor or the medical profession is any smarter than the rest of us, think again. As I discussed here, in another writing:

“My own mother was “prescribed” cigarettes – yes, that’s right – as part of her “prenatal care”, she was told to start smoking by her doctor while pregnant with my younger sister “to prevent hemorrhoids”.  We can laugh, or be aghast now at such a notion, but an entire generation, including the medical profession at the time, was repeatedly brainwashed by the corporations manufacturing these products, and they would leave no stone unturned in promoting the “health and safety” of their products for the sole interest of their own profits.”  (See:  here, and here.  And for anyone wondering, the ‘science’ behind this is that nicotine constricts blood vessels.  And yes, this is exactly how my mother started smoking at age 32).

I provide this example simply to highlight the fact that medical professionals are subject to the same corporate and cultural forces that we all are.  Drugs that would never be blithely and indiscriminately prescribed today, such as Thalidomide, DES, Vioxx, and many others were routinely prescribed by physicians in the not too distant past, and this apparently includes “cigarettes” as well. The point being, is the drug your doctor prescribing you today the result of a judicious, prudent, and well thought out approach deemed absolutely necessary for your health?  Or is it simply the latest fad promoted by Pharma, the next big blockbuster drug for their coffers, being offered you even when safer, less expensive, or better alternatives may exist?

“Your doctor” is subject to the same forces everyone else is, and they happen to be a very important target for Pharma in particular.  Most physicians are honorable, trying to do the best they can with the information they have, but the fact is, they might not know any more than you do if what they’re selling (prescribing) you is a necessary and lifesaving drug, or a ‘cigarette’ of a drug. It turns out, when it came to my particular ADR, plenty of medical professionals have been hit and suffer from the same ADR’s. I sure wish I had known that before I took the drug, because now I’m one of them.

The odds are overwhelmingly in Pharma’s favor and against us.  And despite everything I’ve written, I’m not really “anti-pharmaceutical”.  I’m well aware pharmaceuticals and modern medicine have helped and saved many lives. I happen to love both science and medicine, and I’m a big believer in using the fruits of ethical, curiosity-driven science and medicine in its truest, most honorable and noble form — to improve the health and welfare of individuals and society as a whole. The problem is, that’s not a description of current day Pharma. Phrases more apt to come to mind with the word “Pharma” now include:  Corporate Greed, Profits at All Costs, America’s legal Drug Cartel, White Collar Drug Dealers, and  “Pharmageddon”. The medical profession is allowing themselves to be reduced to Pharma’s “drug pushers”, pushing pills for everything and everybody even if they’re not necessary or downright dangerous, with drugs as the first and sole option offered even when other options such as healthy lifestyle changes can help.

Given these odds, is there anything we can do to protect ourselves? Is there anything we can do to demand change?

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This article was first published on June 8, 2015.

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Metronidazole: The New Mitochondrial Nightmare

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Metronidazole toxicity

When “Rare” Happens to You

On June 13, 2015, I lost the ability to walk and speak. These symptoms came on suddenly, and were accompanied by hand tremors, shortness of breath, weakness, difficulty concentrating, and dizziness. My mother drove me to the ER, but despite my deteriorating condition, I was confident the problem had a simple solution.

I’d been taking the antibiotic, metronidazole (Flagyl), for c diff (a gut infection). When my symptoms abruptly manifested, I looked the drug up online and, sure enough, all of my symptoms were listed as side effects of the medication. So my mother and I thought this would be easy, that the trip to the ER was a mere “technicality” for me to be put on an alternative antibiotic.

When it comes to having an adverse drug reaction, I would learn the hard way that things are never easy. What followed were six weeks where I could not care for myself. While a few symptoms diminished after discontinuing the medication, others randomly popped up to take the stage, this jumble of problems that didn’t seem to connect to one another:

  • Difficulty swallowing
  • Frequent urination
  • Constipation
  • Asthma-like respiratory issues
  • Complete loss of appetite (twenty pound weight loss)
  • Inability to stand up straight
  • Difficulty walking
  • Shortness of breath when talking
  • Chest pressure
  • Heart palpitations
  • Face flushing
  • Dry mouth
  • Cough
  • Headache
  • Pressure at the back of the head
  • Neck pain and stiffness
  • Constant adrenaline rushes
  • Anxiety
  • Depression
  • Crying spells
  • Insomnia
  • Extreme fatigue

I was the medical version of a Picasso painting. Nonetheless, there was one connection between these symptoms; they’re listed as side effects of metronidazole.

The Google Patient

During those first two months, I went from the patient who sees her doctor once or twice a year, to the compulsive consumer, calling several times a week, setting up appointments, and being put through the ringer of medical exams.

In total, I saw eight general practitioners, including my primary care physician, and almost every specialist known to medicine: a cardiologist, an immunologist, a pulmonologist, an ENT doctor, a psychiatrist, and a psychologist. There were tests, from multiple CT scans to X-rays, EKGs, an upper GI, an echocardiogram, a heart monitor, a laryngoscopy, several lung function tests, and about 30 vials of blood taken.

I insisted the cause of my symptoms was the metronidazole, but no one listened. After two months and no answers, my primary care physician handed down the diagnosis of depression and an anxiety disorder. That was the moment I lost faith in the medical community.

So I did the thing that doctors hate—I Googled. A lot. Medical literature is a language all its own—a new version of Pig Latin, MD edition—and I didn’t know what to search for, what the magical keywords were to unlock the “prize.”

Eventually, I ran across another group of people suffering from an adverse drug reaction—the floxies.  This group of patients had suffered an adverse reaction to another type of antibiotics called fluoroquinolones and, as I read their stories, I was horrified how their experiences mirrored my own, including their doctors usually dismissing their claims about the drugs. There were numerous blogs, YouTube videos, local media coverage, books and medical literature about their condition.  Fluoroquinolone antibiotics can directly damage mitochondrial DNA (the energy source of our cells), and people who suffer from this can become permanently disabled or even die. The effects are systemic, with certain regions of the body like the tendons, the heart, and the brain especially affected.

They called it “getting floxed,” and said they suffered from “fluoroquinolone toxicity.”  Reading this phrase, I plugged the words “metronidazole toxicity” into Google.  The answer I’d been searching for flashed on the screen.  What I had, it had a name:

Metronidazole-induced Central Nervous System Toxicity

If you lose the ability to walk and speak while taking metronidazole, there’s a 93% chance lesions have formed on the back of your brain, specifically the cerebellum, followed closely by the brain stem and then the basal ganglia. The effects cause motor control issues, seizures and an “altered mental state.”

From Patient to Blogger

Upon finding numerous pieces of medical literature to back up my claim about metronidazole toxicity, I presented the information to my primary care physician. When I tried to set up another appointment a short time later, she banned me from her clinic. It took a meeting with her supervisor and the clinic’s Risk Management to receive the proper diagnoses on my records—cerebellar dysfunction and altered mental state.

My ban from the clinic was never retracted.

At this point, it became clear that, not only did the medical community not have a way to treat an adverse drug reaction like metronidazole toxicity, they refused to even acknowledge it existed.

Nonetheless, the diagnoses didn’t fully explain my symptoms. There were others, like heart palpitations (including irregular blood pressure), constipation, dry mouth, loss of appetite, difficulty swallowing, and breathing issues that just didn’t match with cerebellar dysfunction.

Over nine months, my condition had greatly improved. I was able to work and enjoy social activities again, but some lingering symptoms would still randomly “flare up,” either due to over-exerting myself, an illness, allergies, or for no reason at all. I used to be an avid biker and that was no longer possible.  There were times, when a flare up would be too great, that I’d end up back in bed.

I decided to take the medical literature on metronidazole and create an online blog for others who might need answers. In addition, I started a support group on Facebook for metronidazole victims; when it began, there were three of us.  A year and a half later, there’s over a hundred, and counting.

Each of us have different issues, but almost all of them fall into four categories:

  • Cerebellar dysfunction (dysfunction of the cerebellum)
  • Autonomic dysfunction (dysfunction of the brain stem)
  • Altered Mental State (neuropsychiatric issues)
  • Polyneuropathy (damage to the nerves throughout the body)

Despite metronidazole’s ability to damage the brain stem, there’s little medical literature connecting metronidazole to autonomic dysfunction. The autonomic nervous system controls all the “automatic” operations of the body, like heart rate, breathing and digestion. As I listened to various stories from other patients that matched my own about uncontrollable heart palpitations, irregular blood pressure, dry mouth (dysfunction of the salivary glands), digestive issues, asthma-like respiratory issues, irregular sleep patterns, swallowing issues and the like…it became clear that this was the final puzzle piece to the metronidazole mystery.

Some patients have recovered as well as I have or better; others are disabled and housebound.  Almost everyone has flare up’s, months or years after taking the drug. Some people have full relapses and worsening symptoms long after they took metronidazole.

So the question keeps being asked—why? Why are these symptoms still here so far out from taking this drug?

Metronidazole and Thiamine

It was November of 2017 that I had the biggest flare up in two years. I had begun a second job on the weekends to get some extra cash for the holidays. My symptoms had remained steady for well over a year at that point, with only mild flare up’s. By the second weekend of work, my condition worsened, with symptoms that I thought were long-gone returning in full force. Heart palpitations, weakness in my legs, difficulty breathing, dizziness, brain fog, chest pressure, and even the anxiety came roaring back. On top of these, two new symptoms developed—pain in my hands and feet, and ringing in my ears. I had to quit the seasonable job, and, with the exception of going to my full-time work, I stayed mostly in bed for weeks.

At this time, I happened upon Dr. Lonsdale and Dr. Marrs’ new medical textbook, “Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition.”  The title caught my eye because I vaguely recalled, through my metronidazole research, the word “thiamine” had popped up multiple times. So I bought the book.

Everything I had experienced was listed within its pages. Thiamine (aka vitamin B1) is essential for oxidative metabolism. It is the gatekeeper of our mitochondria and, without it, the cells cannot properly convert food into fuel. In addition to this, without thiamine, oxygen cannot be properly utilized, causing our cells to—for lack of a better word—suffocate.

This suffocation (called “pseudohypoxia”) leads to our autonomic nervous system to activate its “fight-or-flight” response, which causes extreme anxiety, insomnia, emotional instability, a heightened sensitivity to stimuli, and an overall lowering of our stress threshold. In addition to these symptoms, there is a paradoxical one; the body is not designed to run on its fight-or-flight response for days or weeks on end. This over-use of the body’s energy reserves results in extreme fatigue.

Thiamine is found all over the body, but there are places where its use is concentrated, the brain being the most crucial, followed by the heart and our nerves. When there’s a deficiency, dysfunction typically hits the back of the brain the hardest—specifically the cerebellum and brain stem. Lack of thiamine causes:

  • Cerebellar Dysfunction
  • Autonomic Dysfunction
  • Altered Mental State
  • Polyneuropathy

After reading Dr. Lonsdale and Dr. Marrs’ textbook, I went back to all the medical literature I had pulled about metronidazole toxicity (and then some). It turns out, metronidazole and thiamine are antagonists; the drug inhibits thiamine from being absorbed into the body, which can plummet the victim into deficiency. The chemical structure of metronidazole is similar to that of the third ring within thiamine’s chemical structure; when the body mistakes metronidazole as this third ring, it turns thiamine into “thiaminase”—an inhibitor of thiamine.  This is called “thiaminase poisoning,” and it plummets the body into deficiency.

The symptoms of thiamine deficiency and metronidazole toxicity are identical.

Theoretically, the reason patients cannot recover from metronidazole toxicity adequately is because they never restore their thiamine after discontinuing the drug. The deficiency is too great to recover from by simply eating thiamine-rich foods; it requires high-dose supplementation over months to resolve the underlying problem. Therefore, victims of this toxicity are, at best, skating on the edge of this deficiency, and when a stressor enters our lives—illness, work, exercise—we exhaust the limited thiamine we have.  We plunge back into deficiency and the neurological symptoms manifest once again.

To conventional medicine, thiamine deficiency is considered a relic of the past—something that belongs in history books like scurvy—and rarely happens in the industrialized world. But there is one modern-day condition that is still being recognized by the medical community—Wernicke’s encephalopathy. This is an alcohol-induced thiamine deficiency that causes lesions to form on the back of the brain, specifically the cerebellum and brain stem.

In medical literature, metronidazole toxicity and Wernicke’s encephalopathy are constantly being compared because their symptoms and presentation of brain lesions are almost exactly the same.

Metronidazole and the Floxies

It all comes down to the mitochondria. For two years, I’ve read various stories and spoken directly with dozens of victims of metronidazole toxicity. Many times, they have commented about their symptoms being similar to that of the floxies, with several of them even stating that they’ve been “floxed.”  I’ve corrected them, explaining that metronidazole is in a different class of antibiotics and, while it causes damage to the brain, there’s no significant medical literature proving that it causes mitochondrial damage.

Nonetheless, as I’ve read numerous accounts from the fluoroquinolone community, I couldn’t help but note the similarities in our neurological symptoms.  Metronidazole victims don’t have the ruptured tendons…but the polyneuropathy and central nervous system effects (including psychiatric effects) are indistinguishable.

One website I focused on during my metronidazole toxicity research was askapatient.com. It houses one of the largest collections of customer reviews on the internet for medications, and metronidazole/Flagyl is the most reviewed drug on the site.  It also has the 5th highest number of 1-star reviews (Cipro and Levaquin are 1st and 2nd).

I compared metronidazole and its central nervous system side effects to that of those two popular fluoroquinolone medications from reviews between 2000 and 2015, totaling the number of reviews complaining about CNS symptoms:

Reviews Metronidazole Cipro Levaquin
Total # of Reviews 3312 1828 2032
Total # 1-star Reviews 1246 1352 1432
Dizziness 733 200 246
Fatigue 471 206 144
Anxiety 556 281 229
Panic Attack 180 95 65
Depression 641 185 152
Confusion 155 53 69
Disorientation 96 20 19
Paranoia 76 26 38
Headaches/Migraines 837 263 209
Suicidal Ideation 33 47 36
Numbness 157 121 119
Burning Sensation 51 151 133
Tingling Sensation 225 130 120

If metronidazole toxicity is caused by thiamine deficiency, then this deficiency is causing mitochondrial dysfunction and possible damage. And since thiamine concentrations are highest in the brain—specifically ,the cerebellum and brain stem, which is also the highest in mitochondria—this means that metronidazole is ultimately causing the same CNS issues as the fluoroquinolones.

Essentially, people with metronidazole toxicity are getting brain-floxed.

Can Something Be Done for Victims of Metronidazole? What I Have Learned

Unlike those who suffer from fluoroquinolone toxicity, those with metronidazole toxicity might have one advantage—our mitochondria haven’t been damaged directly by the antibiotic. Because it is a thiamine deficiency that is, in theory, the true culprit in this crime, it might be possible for victims of metronidazole toxicity to have a relatively clean-cut treatment plan.

Dr. Lonsdale and Dr. Marrs explain in detail about thiamine deficiency in their textbook, including the condition’s history, its symptoms and how they’ve implemented this information into action for various patients with documented case studies. If you believe you’re suffering from thiamine deficiency, reading this text would be the first big step in your treatment plan.

Depending on your level of deficiency, you will need to decide what works best for you. To sum up, there are several versions of thiamine to pick from; thiamine mononitrate and thiamine HCL are readily available at pharmacies and health food stores. Because they are water-soluble versions of thiamine, it is difficult to overdose on them; however, if you have severe or chronic thiamine deficiency, their benefits might be limited due to their short time span in the body and their inability to penetrate the cell without a protein transporter (making the absorption a little more complex).

Other versions may only be available for purchase online, but they cut out that “middle man.”  Allithiamine is naturally derived from garlic and is a fat-soluble version of thiamine. Because it is fat-soluble, the body stores it longer and it works better on the central nervous system and nerves.  Benfotiamine is another fat-soluble version, synthetically made, and works well on nerves but not the brain.  Lipothiamine has similar effects as Allithiamine, but is synthetically made.

You must supplement magnesium with thiamine. These two nutrients go hand-in-hand; thiamine supplementation will not work without magnesium. One option is Natural Calm Magnesium Powder that dissolves in water; you can control your dose of magnesium easily. If you notice loose stools, cut back. It’s available at several health food stores like The Vitamin Shoppe and online.

As the book details, patients who are severely and/or chronically deficient might need to “megadose” on thiamine before they notice improvements. If you feel you need to megadose, it would be a good idea to be monitored by a physician. Integrative physicians are more likely to support nutritional therapy than conventional doctors. Because this is new medical knowledge, you will probably have a lot of “trial and error” before finding the right type of thiamine and dosage that helps your condition and it could take months before treatment starts to work if you have a severe or chronic case. Do not begin by megadosing, however—start small and work your way up.

Thiamine has limited side effects, but they can happen, as can allergic reactions at high doses. If you are severely deficient in thiamine, there’s a good chance you’re deficient in other nutrients and taking thiamine might make those deficiencies more apparent. You could also have a “paradoxical” effect at first, as your cells have adapted to not having adequate thiamine (this is actually a good sign, as it confirms your body is no longer well-adapted to thiamine due to deficiency).  The paradoxical effect is temporary, but if you feel uncomfortable, scale back to a smaller dose and then work up from there.

One issue that could arise with high doses of thiamine over time is an imbalance of the other B-vitamins. However, this works both ways. If you are deficient in thiamine, then taking high doses of other B-vitamins right now could further imbalance your thiamine. After speaking with patients suffering from metronidazole toxicity, one misdirection is to take high doses of vitamin B12 (some even get injections).  This seems to result in worsening of the toxicity symptoms. Eventually, you’ll want to supplement other B-vitamins to keep everything in balance, especially if you wish to megadose on thiamine for a longer duration.

Unfortunately, there is no clinical trial for me to point when it comes to metronidazole toxicity and thiamine. It is taking medical literature from one side of the spectrum and connecting it to the other side.

I started taking thiamine mononitrate about two weeks after my major flare up began, 100 mg’s.  It did nothing, so I doubled it to 200mg. After two days, I started to feel better. I switched to thiamine HCL, 300mg, after another week and, again, noticed improvement. After reaching 600mg, I switched to Allithiamine at 50mg. I had a slight “paradoxical reaction” the first day, with anxiety and shortness of breath that dissipated quickly. Now, I’m at 200mg of Allithiamine, and my flare up has gone from debilitating to mild.

I still have a long way to go, but for the first time in two and a half years, it finally feels like my health is curving in the right direction.  There is a light at the end of this very long tunnel. Just like me, if you feel you suffer from metronidazole toxicity, then there might be something you can do about it.  There might be hope in treating your symptoms. Please be advised, however, I am not a physician and this post does not constitute medical advice. It is simply what I have learned over the course of my illness. To treat your illness, you will need to educate yourself, learn everything you can, and work with a physician.

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5 Things Not to Say to a Stroke Survivor

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Stroke

Before I had a stroke at 28 from hormonal birth control (you can read my story here), I didn’t really know what a stroke was. And I certainly didn’t understand the implications or ramifications of what it meant to have an “insult to the brain.”

I knew I had physical and mental limitations, that I needed to learn how to walk again, to put on my socks, to bathe myself. But they also told my family that I may have an entirely different personality. Can you imagine? You wake up one day, have a brain injury, and your personality is completely different? And would you be able to recognize how your own personality had changed or would it be something people would whisper about when they thought you weren’t listening? My sister must have been particularly worried about my personality. I remember one morning she had to butter my biscuit for me after I had tried unsuccessfully several times. “I’ll butter your biscuit for you for the rest of your life,” she said. “I’m just so glad you’re still in there.” At least most of me was. That is to say, I still had my struggles with who I was and who I had been. But really, who doesn’t?

The interesting thing about surviving a stroke is learning what you can and cannot do. To others, even others that are informed about brain injuries, you may look so similar to your pre-stroke self that they take for granted you are the same. But you may not be.

So as a public service announcement for Stroke Awareness Month, here is a list of 5 things not to say to a person who has had a stroke (or any brain injury).

1. “Hold this.”

The disconnect between mind and body when you have a traumatic brain injury is a constant surprise. The first time they handed me the receiver to talk on the telephone, I held it backwards. One time I put a Cheeto in my ear instead of my mouth. When my mother asked me if I wanted to put on some lipstick, I took the tube from her, put it on my lips (or near them), then put the cap back on the raised stick of lipstick, crushing it. In the ICU, when they had me brush my teeth and rinse with a paper cup of water, the nurse instructed me to spit the dirty water back in the cup. I nodded. “Of course,” I thought. Then I promptly swallowed it. One of the most surprising things, and this was long after I’d been discharged from the hospital (and if I’m being completely honest, even now sometimes), is how things get lost in my left hand. I can literally be holding my keys in my left hand and be looking around the house for them.

But it’s not just the things in my left hand. Sometimes I will stand before a trash can with a pen in one hand and a tissue in the other and tell myself, “throw away the tissue, throw away the tissue, throw away the tissue.” Then I always have to bend down and pick the pen out of the trash.

2. “Lift your leg.”

During my rehabilitation, I was a bit of a challenge for my therapists. Most stroke survivors have damage to either the right or the left side of the body. But the damage from my stroke went down both sides of my brain and consequently affected my left arm and my right leg. One of the exercises the physical therapist asked me to do was to raise my left arm while all on all fours. I did. Then he asked me to raise my right leg. I did. “Raise your right leg,” he said again. So I raised it again. “Kerry, raise your right leg,” he said, like I might not have realized he was talking to me. “Right leg. Right leg,” my mom added. “I am raising my right leg,” I said, exasperated. What is wrong with them? I wondered. I looked behind me with complete certainty that I would see my leg raised. Of course I didn’t, but I did catch an expression on my mom’s face. It was the same expression she was wearing when we played Boggle in recreational therapy and I only found a few words. It was the same expression she wore when I smashed her tube of lipstick. It was an expression that seemed to say she wasn’t quite sure who I was.

3. “Write this down.”

A day or two after I got out of ICU, my mom asked me if I thought I could still write. You would think after the sock incident, I might have had my doubts. But I’m clearly a slow learner, because I said, “Sure, I can.” She handed me a notebook and a pen. I recently found that notebook, the picture is above. (My mom would continue to lovingly document these little milestones, just like she had when I was a baby.) When I wrote that, I thought I had done a pretty good job. And considering what my brain had been through, it was amazing I could even hold a pen. But when I look at it now, it breaks my heart a little bit. I’m so lucky that I write flawlessly now. Just kidding! My writing, while mostly legible and mostly on the lines of the paper, is still a mess. Until a few weeks ago, I didn’t even realize that messing up every third word, leaving letters out, adding letters where they don’t belong—that isn’t just how everyone writes. After a highly scientific study of asking a few of my friends, it seems that’s not normal. The first paper I wrote in graduate school, I typed the words male and female as “mail” and “femail.” Every. Single. Time. Even when I would remind myself, it still came out wrong. To this day, I have trouble with homonyms but I usually catch the mistake before I send the email or publish the story. But sometimes I don’t. I hope you’ll bare with me… haha.

4. Glare at them when they park in a handicapped spot.

In fairness, glaring at someone is not saying anything to them, but so much of communication is nonverbal that I had to include it. After my stroke, they gave me a temporary handicapped decal for my car. And while I may have looked relatively normal, I assure you I was not. I couldn’t walk long distances. I found any remotely crowded place to be extremely stressful. I had to sit down halfway through a trip to the grocery store. Day-to-day things that used to be easy were difficult and frustrating. But even more frustrating were the looks that people would give me when we parked in handicapped parking. One woman glared at me in such obvious disgust as we got into our car. She waited to comment until we had closed our doors so I didn’t hear what she said, but I’m pretty sure she heard me when I rolled down my window. As my husband sped quickly out of the parking lot, I hung my head out of the car and yelled, “I had a stroke!” at the top of my lungs. Not one of my finer moments, to be sure. The lesson that remains, and one even I frequently have to remind myself of, is that you really never know what a person is going through just by looking at them.

5. “My (insert friend or relative)’s experience was much worse than yours.”

A few months after I got out of the hospital, I was at dinner with friends when a woman I had just met (a friend of a friend) was surprised to learn that I had recently had a stroke. “My grandfather just had a stroke,” she said excitedly. “But his was way worse than yours. He’s still in the hospital.” Of course, what she meant was that I looked like I was fully recovered while he was still having visible problems. And of course, she probably didn’t mean to be dismissive. But it really bothered me. I had a massive stroke. I didn’t just have blood clots in my brain (an ischemic stroke, which accounts for 87% of all strokes). I also had bleeding in my brain (a hemorrhagic stroke—a much less common and far more deadly stroke). In my mind, I had actually survived two strokes. Yes, I was extremely lucky and I know my recovery was nothing short of miraculous. But that didn’t negate what happened to me nor what I was continuing to deal with. This woman knew nothing of my struggle to get to dinner that night, nor the struggle of the months before (and certainly not of the subsequent years), yet she made a value judgment on what had happened to me based on her grandfather’s experience. As human beings, it’s natural for us to draw comparisons and to find patterns. After all, common experiences and sharing stories are the major ways we connect to one another. And when you are interacting with someone who has had a traumatic brain injury, or any health crisis, it is completely fine to ask questions. But then just try to listen.

If you’ve ever had a health crisis, and many of us have, what have people unwittingly said to you? Or have you ever put your foot in your mouth when dealing with a friend or loved one’s health crisis? I know I have! Leave your answers in the comment section below.

Real Risk Study: Birth Control and Blood Clots

Lucine Health Sciences and Hormones Matter are conducting research to investigate the relationship between hormonal birth control and blood clots. If you or a loved one have suffered from a blood clot while using hormonal birth control, please consider participating. We are also looking for participants who have been using hormonal birth control for at least one year and have NOT had a blood clot, as well as women who have NEVER used hormonal birth control. For more information or to participate, click here.

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Triptans ± SSRIs ± Migraines ± Depression: Flip a Coin!

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Angela Stanton, PhD

Migraines and depression are understood to be neurological diseases though many consider them to be mental illnesses [1, 2]. Recent research sheds light on both conditions and shows us how much they have in common. Both migraines and depression can be stopped by voltage applied to the brain. In the case of depression, voltage has only been applied via open-brain surgical procedures as deep brain stimulation of the specific brain region, shown in the scanner as dark region [3-6]. For migraines the stimulation has been tried both outside of the brain [7, 8] and internally via deep brain electrical stimulation [9]. The cause inn both migraine and depression is seen in scanners [1, 10] as cortically depressed areas. These are dormant regions that have no observable electrical activity. When electrical stimulation is applied to a dormant brain region, it regains its function. Crucially for migraines, it has been demonstrated that a dormant area be shocked by a wave of electricity generated by the brain itself, called cortical spreading depression, energizing the dormant area to be able to create action potential again [11-14]. This is quite similar to a cardiac arrest patient receiving an electrical shock to the heart which restarts electrical activity. The difference is that in the case of the heart the electricity is applied externally by others, whereas in the case of the brain the electric shock is applied by the brain itself by using its functioning brain regions to energize nonperforming regions. Because neurons communicate to each other via neurotransmitters and are connected to each other, neurons that do not manufacture neurotransmitters and do not participate in communication exchange cannot hide. The healthy, energized regions send a wave of energy within the brain. However, this wave reaches the meninges where all pain sensory neurons are located [14] and hence migraine pain.

Similarly to how a cardiac arrest does not always get the heart to continue beating again, the electric shock of the spreading cortical depression may not awaken the dormant regions either. Energy for proper functioning of either the heart or the brain – or indeed for any living tissue – cannot be created from nothing. To continue to generate voltage after the initial shock, the proper minerals have to be available. One can only drive a car on fumes for so long. Interestingly we understand this very well when it comes to our cars but we tend to forget it when it comes to our body. Our body uses energy it receives from what we eat and drink. The energy is carried to the cells by electrolytes. Electrolytes are water mixed with vital nutrients. Electrolytes take up 55%-70% of our body per gender and age with salt about 9 grams per liter. Those brain regions that lack important nutrients will not function.

We now understand that brain regions that are starved of energy and that are not able to generate action potential cause abnormal synaptic transmissions [15, 16]. Yet rather than replenishing the brain by restocking it with nutrients, the current favorite treatment method is some form of serotonin medicine, such as triptans for aborting an ongoing migraine, or serotonin reuptake inhibitors (SSRIs or SNRIs) for prevention for both migraines and depression. Many unlucky migraineurs and depression patients also receive a voltage dependent calcium channel blocker, one of which I discussed in my last article. Given that these medications are so often prescribed, one would think that they actually work. But do they?

They actually don’t work for depression over 70% of the time. And for migraines? Well, that is another story as I am about to discuss.  It is also important to note that where energy is needed, medicines that block energization via electrolytes actually work against recovery and dull the brain, using symptom management instead.

Why Triptans and SSRIs/SNRIs are Hit or Miss for Migraines

Serotonin for migraines only works sometimes and even then with tremendous side effects, often causing depression (see adverse reaction tables below), violence, and fatalities. Based on my migraine group where thousands of migraineurs have passed through over the years, the statistics show that 80% of those who join the group take some serotonin preventive, usually an SSRI or SNRI but they still need to take abortives, such as triptans, and yet they still have migraines! Not only does this show that serotonin does not work but also that there is a very dangerous practice of “more is better,” which may be followed by fatal consequences, such as serotonin syndrome. The dangerous practice is common because of five critical reasons:

  1. Doctors should know better than to prescribe multiple serotonin medications to the same patient and if they don’t know what their patients take, they owe the courtesy to ask before they prescribe!
  2. Pharmacies have records of all medicines a patient takes. If a doctor makes a mistake, it is the responsibility of the pharmacist to catch the mistake and warn the doctor and the patient. This has never happened in the entire history of my migraine group! I usually analyze their medicines and point out the pharmacological interactions and duplication that they print out and hand to their doctors. Only after the patient’s intervention will doctors initiate removal of dangerous medicines. Last time I checked: The patients are not responsible for the medicines they are being prescribed.
  3. 85% of the doctors do not recognize serotonin syndrome. The sad truth is that while 100% of the doctors can prescribe SSRIs and similar medications with a few scribbles, 85% of them do not recognize if it reaches toxic levels in their patients. I estimate that the majority of doctors are not familiar with the mechanisms of the medicines they prescribe; they cannot tell if one is a voltage dependent calcium channel blocker or a voltage dependent sodium channel blocker or both or neither.
  4. This is the saddest of them all: financial incentives actually cause many doctors to be angry with patients who wish to reduce their medicines. Many members in my migraine group faced rude and angry doctors who placed them on such quick reduction from these highly “discontinuations syndrome” (politically correct for addictive) medicines that they were forced back on the medicines and of course that increased again the lunches and dinners or straight cash flow of the prescribing doctors—search out your doctor’s name and see what she/he has been earning on your medicines in 2014!
  5. The side effects of many of these serotonin medicines are worse than the initial problem they are prescribed for; reduction is slow and painful. While the adverse effects hit all at once when starting a medicine, the very same adverse effects return in slow motion as the patients reduce. For example, they may not even realize that they had increased blood pressure, nausea, dizziness, and diarrhea all at once for a few days or weeks while starting the medication since these adverse effects showed up at once. But in reversing and stopping the medicine, each of these effects can last for weeks and is highly pronounced, frightening the patient. Furthermore, adverse effects are updated on the go by the FDA. Most users are not informed about these by their prescribing physicians.

I randomly picked two very common medications I see prescribed all the time. Zoloft, used for depression, is a selective serotonin reuptake inhibitor (SSRI), and Elavil, a tricyclic antidepressant (TCA), prescribed for migraines frequently. The list of side effects for Zoloft (Sertraline) is huge (Wikipedia). I must say that if I were not depressed before taking this medicine, I most certainly would be after reading this list:

Adverse effects: Fatigue, Insomnia, Somnolence (sleepiness), Nausea, Dry mouth, Diarrhea, Headache, Ejaculation disorder, Dizziness, Agitation, Anorexia, Constipation, Dyspepsia (indigestion), Decreased libido, Sweating, Tremor, Vomiting, Impaired concentration, Nervousness, Paroniria (i.e., depraved or morbid dreaming/nightmares), Yawning, Palpitations, Increased sweating, Hot flushes, Weight decrease, Weight increase, Myoclonus, Hypertonia, Bruxism (teeth grinding), Hypoesthesia, Menstrual irregularities, Sexual dysfunction, Rash, Vision abnormal, Asthenia, Chest pain, Paranesthesia, Tinnitus (hearing ringing in the ears), Hypertension (high blood pressure), Hyperkinesia, Bronchospasm, Esophagitis (swollen esophagus), Dysphagia, Hemorrhoids, Periorbital Edema, Purpura, Cold Sweat, Dry skin, Nocturia, Urinary Retention, Polyuria (excessive urination), Vaginal Hemorrhage, Malaise, Chills, Pyrexia (fever), Thirst, Pollakiuria, Micturition disorder, Salivary Hypersecretion, Tongue Disorder, Osteoarthritis, Muscular Weakness, Back Pain, Muscle Twitching, Eructation (belching), Dyspnea (air hunger), Epistaxis (nose bleed), Edema peripheral, Periorbital edema, Syncope, Postural dizziness, Tachycardia (high heart rate), Urticaria (hives), Migraine, Abnormal bleeding (esp. in the GI tract), Muscle cramps, Arthralgia, Depressive symptoms, Euphoria, Hallucination, Alopecia (hair loss), Urinary Retention (being unable to pass urine), Pruritus, Amnesia memory loss., Urinary incontinence, Eye pain, Asymptomatic elevations in serum transaminases, Abnormal semen, Melena (black feces due to a bleed in the stomach), Coffee ground vomiting, Hematochezia, Stomatitis (swollen mouth), Tongue ulceration, Tooth Disorder, Glossitis (soreness/swelling of the tongue), Mouth Ulceration, Laryngospasm, Hyperventilation (breathing more often than required to keep one’s blood sufficiently oxygenated), Hypoventilation (breathing less often than required to keep one’s blood sufficiently oxygenated), Stridor, Dysphonia (voice disorder), Upper Respiratory Tract Infection, Rhinitis (irritation/inflammation inside the nose), Hiccups, Apathy, Thinking Abnormal, Allergic reaction, Allergy, Anaphylactoid reaction, Face edema, Priapism, Atrial arrhythmia, AV block, Coma, Peripheral Ischemia, Injury, Vasodilation Procedure, Lymphadenopathy, Involuntary muscle contractions, Galactorrhea (lactation that is unrelated to pregnancy or breastfeeding), Gynecomastia (swelling of breast tissue in men), Hyperprolactinemia (high blood prolactin levels), Hypothyroidism (underactive thyroid gland), Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), Pancreatitis (swollen pancreas), Altered platelet function, Hematuria (blood in the urine), Leukopenia (low white blood cell count), Thrombocytopenia (low blood platelet count), Increased coagulation times, Abnormal clinical laboratory results, Hyponatremia (low blood sodium), Conversion Disorder, Drug Dependence, Paranoia, Myocardial Infarction (heart attack), Bradycardia, Cardiac Disorder, Suicidal Ideation/behavior, Sleep Walking, Premature Ejaculation, Hyperglycemia (high blood sugar), Hypoglycemia (low blood sugar), Hypercholesterolemia (high blood cholesterol), Vasculitis, Aggressive reaction, Psychosis (hallucinations and delusions), Mania (a dangerously elated mood), Menorrhagia (an abnormally excessive amount of menstrual bleeding), Atrophic Vulvovaginitis, Balanoposthitis, Genital Discharge, Angioedema, Photosensitivity skin reaction, Enuresis, Visual field defect, Abnormal liver function, Dermatitis, Dermatitis Bullous, Rash Follicular, Glaucoma, Lacrimal Disorder, Scotoma, Diplopia, Photophobia, Hyphemia, Mydriasis, Hair Texture Abnormal, Neoplasm, Diverticulitis, Choreoathetosis, Dyskinesia, Hyperesthesia, Sensory Disturbance, Gastroenteritis, Otitis Media, Skin Odour Abnormal, QTc prolongation, Anaphylactoid Reaction, Allergic Reaction, Allergy, Neuroleptic malignant syndrome. A potentially fatal reaction that most often occurs as a result of the use of antipsychotic drugs. It is characterized by fever, muscle rigidity, rhabdomyolysis (muscle breakdown), profuse sweating, tachycardia, tachypnoea (rapid breathing), agitation, Stevens-Johnson syndrome a potentially fatal skin reaction, Toxic epidermal necrolysis another potentially fatal skin reaction, Torsades de pointes a potentially fatal change in the heart’s rhythm., Cerebrovascular spasm, Serotonin syndrome similar to neuroleptic malignant syndrome but develops more rapidly (over a period of hours instead of days/weeks for neuroleptic malignant syndrome), Bone fracture, Movement disorders, Diabetes mellitus, Dyspnea, Jaundice yellowing of the skin, mucous membranes and eyes due to an impaired ability of the liver to clear the haem breakdown by product, bilirubin, Hepatitis, Liver failure. This medicine can cause serotonin syndrome on its own.

For migraine I picked Elavil (Amitriptyline) which is a TCA. While it has fewer side effects (Wikipedia) than Sertraline (SSRI), one of its major side effects is headache. Why would a competent doctor prescribe a known headache causer to a migraineur?

Here are some of the other adverse effects: dizziness, headache, weight gain, delirium, confusion, anxiety, agitation, orthostatic hypotension (low blood pressure), sinus tachycardia, loss of libido, impotence, sleep disturbances such as drowsiness and insomnia. Most importantly, Amitriptyline inhibits sodium channels, L-type calcium channels, and voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.

Recall my argument of a car only able to go on fumes for so long? This drug, by blocking all possible energizing channels, blocks the inflow of nutrients and the outflow of toxins. This car is not going anywhere!

Yet many migraineurs who join my group have been taking Elavil, which of course doesn’t work, so then they end up having to take several other medicines to replace activities the brain cannot do: they often receive prescriptions for other types of SSRIs, sometimes voltage dependent calcium blockers, barbiturates, NSADs, muscle relaxers, steroids and even triptans to come full circle, and add the very ingredient they blocked from being released the first place!

Does Serotonin Use Make Any Sense At All?

When a brain region is not able to generate action potential, as shown, lack of serotonin is not the cause. It is entirely possible that the particular neurons that cannot generate enough energy happen to be responsible for serotonin production, in which case adding serotonin will indeed take the pain away. However, it will not treat the underlying cause of not having enough energy for generating action potential. The fact that it is energy shortage rather than serotonin shortage that causes depression is clearly demonstrated by the deep brain stimulation experiments on live humans, where the voltage stimulation lifted their depression right there during the experiment without any serotonin. The patients were able to explain what they felt and how their depression lifted during the procedure [4-6, 17]. It all sounds very simple actually since we know what generates action potential in the brain: salt.

So why do migraine and depression sufferers keep on getting serotonin medications knowing that serotonin has absolutely nothing to do with migraines? This is a great question that I would like to ask many physicians! Habits are hard to break but eventually they must!

Concluding Thoughts

There is only a small chance that triptans or SSRIs will work for your migraines or depression but it is 100%  certain that adverse effects will prevent your brain from working properly. In the long run, these drugs cause permanent damage. Do yourself a favor and learn what migraines are and how to prevent them. Since migraines and depression have the same cause as seen in the scanners, why not try the same solution? Many who joined my migraine group with depression and migraine are now free of both, as well as all their medicines! Join the movement for healthy life without medicines.

Sources

  1. Gasparini, C.F., H.G. Sutherland, and L.R. Griffiths, Studies on the Pathophysiology and Genetic Basis of Migraine. Current Genomics, 2013. 14(5): p. 300-315.
  2. Young, W.B., et al., The Stigma of Migraine. PLoS ONE, 2013. 8(1): p. e54074.
  3. Holtzheimer, P.E., et al., Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Unipolar and Bipolar Depression. Jama Psychiatry, 2012: p. 150-158.
  4. Lozano, A.M., et al., A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg, 2012: p. 315-322.
  5. Mayberg, H.S., et al., Deep brain stimulation for treatment-resistant depression, in Neuron. 2005. p. 651-60.
  6. Taghva, A.S., D.A. Malone, and A.R. Rezai, Deep brain stimulation for treatment-resistant depression. World Neurosurg., 2013: p. 826-831.
  7. Aurora, S.K., et al., Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine, in Neurology. 1998. p. 1111-4.
  8. DaSilva, A.F., et al., tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine. Headache: The Journal of Head and Face Pain, 2012. 52(8): p. 1283-1295.
  9. Tepper, S.J., et al., Acute Treatment of Intractable Migraine With Sphenopalatine Ganglion Electrical Stimulation. Headache: The Journal of Head and Face Pain, 2009. 49(7): p. 983-989.
  10. Hadjikhani, N., et al., Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proceedings of the National Academy of Sciences, 2001. 98(8): p. 4687-4692.
  11. Charles, A.C. and S.M. Baca, Cortical spreading depression and migraine. Nat Rev Neurol, 2013: p. 637-44.
  12. James, M.F., et al., Cortical spreading depression and migraine: new insights from imaging? TRENDS In Neuroscience, 2001: p. 226-271.
  13. Lauritzen, et al., Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury, in J Cereb Blood Flow Metab. 2011. p. 17-35.
  14. Bolay, H., et al., Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med, 2002. 8(2): p. 136-142.
  15. Pietrobon, D., Insights into migraine mechanisms and Ca(V)2.1 calcium channel function from mouse models of familial hemiplegic migraine. The Journal of Physiology, 2010. 588(Pt 11): p. 1871-1878.
  16. Vecchia, D., et al., Abnormal cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans. Front. Cell. Neurosci., 2015: p. epub ahead of print.
  17. Lozano, M. and N. Lipsman, Probing and regulating dysfunctional circuits using deep brain stimulation, in Neuron. 2013. p. 406-24.

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