# New research about Botox and your brain



## SparklingWaves (Jul 25, 2008)

*A New Reason to Frown*

                    Does Botox get into the brain? Troubling research contradicts earlier findings about the treatment.

                    By Sharon Begley | NEWSWEEK

             From the magazine issue dated Apr 21, 2008


                            The way it usually works is, the rats and mice die first. Or at least get sick first. Or at the very least, show some adverse effect first—as in, before people do. The reason countless lab animals have given their lives during the testing of experimental drugs is to allow manufacturers and regulators to see that a compound might be toxic, even deadly, before millions of people use it. And if the compound does look a little dodgy, the lab-animal tests uncover the reason—how the compound affects the liver, say, or reaches the brain. Not surprisingly, these "preclinical tests" (that is, those performed before testing on humans) were especially rigorous for botulinum. One of the deadliest poisons in nature and a possible bioterrorism agent, this neurotoxin reached the market, in very dilute doses, starting in 1989 as Botox. A big reason Botox and its cousins, such as Myobloc, were OK'd was that preclinical testing showed that after being injected, they did not travel along the body's highways—nerve cells—to the brain and spinal cord. Yes, there was some evidence the toxin slipped into the bloodstream or the lymph system, but Botox in the bloodstream cannot enter the brain, says its manufacturer.


           Oops. In a reversal of the usual sequence in science, researchers have discovered, after millions of people have received the drug, something fundamental about how Botox can act. Contrary to what turned up in preclinical testing, botulinum toxin can travel along neurons from the injection site into the brain, at least in lab animals. Researchers at Italy's Institute of Neuroscience injected rats and mice with botulinum neurotoxin A in doses comparable to those used in people. (Strains are named A, B and E, depending on where the common soil bacteria that produce them live; A is Botox, B is Myobloc, which is used for severe back pain.) Neurons at the injection site—the whisker muscles—absorbed some of the toxin and passed it along to other neurons they connected to, the researchers report this month in The Journal of Neuroscience. Within three days, the toxin had migrated from the whisker muscles to the brainstem, where it disrupted neuronal activity. "The discovery was quite serendipitous ... and surprising," Matteo Caleo, who led the study, told the journal Science. "A significant portion of the toxin is active where it's not intended to be."


           That stands in contrast to the findings of earlier studies, which suggested that the neurotoxin is completely broken down at the injection site into innocuous compounds and does not migrate beyond it—or if it does, only into the bloodstream or lymph system. Botox's manufacturer, Allergan, thinks those older studies are more credible. "This study is not conclusive," says spokesperson Cathy Taylor, "and other published studies using botulinum toxin type A contradict these findings." Contrary to Allergan's statement that the Italian scientists "injected the material directly into the brain," however, they injected the neurotoxin into facial muscles—and from there it found its way to the brainstem. "This is a new pathway, and we need to think about the implications of this," says Edgar Salazar-Grueso, chief medical officer of Solstice Neurosciences, which makes Myobloc. The new study, he says, means the original preclinical testing of Botox and its cousins "can be interpreted in a different light."
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      Something else that can be seen in a different light is the hospitalizations and deaths that have been reported following Botox injections. In 2005 scientists at the U.S. Food and Drug Administration analyzed 1,437 such "adverse events" between 1989, when Botox was approved for eye spasms, and 2003. Most came from people who got Botox to erase their wrinkles, but the 28 deaths occurred in people who had received it for medical purposes. The FDA didn't do much in response, but since then it has been getting new reports of serious adverse reactions in people receiving Botox, and launched a safety review. An analysis of the FDA's database by the advocacy group Public Citizen found 16 deaths from Botox or Myobloc. Most involved children with serious diseases like cerebral palsy, who got the injections for muscle spasms (an unapproved, though legal, use). But the agency has "evidence that [serious reactions and even death] can happen in a broader population," said the FDA's Russell Katz. "Is it possible with cosmetic use? Possibly."


           Those unapproved uses are another concern of the agency. Last month Allergan revealed that federal prosecutors were investigating it for promoting the non-FDA-approved use of Botox for headaches, though doctors are free to prescribe a drug as they see fit. Allergan says it's cooperating.


           Botox and Myobloc carry labels warning of possible adverse reactions near the injection site such as drooping eyelids, and of severe difficulty swallowing in patients with neuromuscular disorders. The FDA's Katz said that people getting Botox for cosmetic reasons should "make their own personal best judgment about this" and "be aware that there's the potential for" the neurotoxin to spread. With the new evidence that Botox can spread to the brain in ways that preclinical tests failed to turn up, it's enough to bring back those Botox-erased frown lines.
_With Matthew Philips_ 
_ 2008

Comment: I can't say that I really put a lot of faith in drug companies.
_


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## redambition (Jul 25, 2008)

Quote:

   Originally Posted by *SparklingWaves* 

 
_Those unapproved uses are another concern of the agency. Last month Allergan revealed that federal prosecutors were investigating it for *promoting the non-FDA-approved use of Botox for headaches*, though doctors are free to prescribe a drug as they see fit. Allergan says it's cooperating._

 





botox for headaches? 

i'm a bit stunned here.


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## Lissa (Jul 25, 2008)

Quote:

   Originally Posted by *SparklingWaves* 

 
_ One of the deadliest poisons in nature and a possible bioterrorism agent_

 
That alone is enough to put me off having it injected into my face


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## SparklingWaves (Jul 25, 2008)

Botox is being tested out  and used on so many conditions.  The amount of research being done is staggering.    If anyone is interested in reading research abstracts, I hope you may find these of interest.

*Botulinum Toxin Type A (BOTOX®) for the Prophylactic Treatment of Chronic Daily Headache: A Randomized, Double-Blind, Placebo-Controlled Trial*

Wiley InterScience :: Session Cookies


*Botox for the brain: enhancement of cognition, mood and pro-social behavior and blunting of unwanted memories
*
ScienceDirect - Neuroscience & Biobehavioral Reviews : Botox for the brain: enhancement of cognition, mood and pro-social behavior and blunting of unwanted memories


*Botulinum toxin in urinary incontinence*. 

Current Opinion in Urology - Abstract: Volume 16(4) July 2006 p 255-260 Botulinum toxin in urinary incontinence.

*Botulinum toxin A and chronic low back pain* 
A randomized, double-blind study 

Botulinum toxin A and chronic low back pain: A randomized, double-blind study -- Foster et al. 56 (10): 1290 -- Neurology


**One article that I really wanted to read was titled - “*Botox induced muscle paralysis rapidly degrades bone*”.  I couldn’t pull it up.  I had to be a registered member.  

However, I did find this article informative in regard to bone loss from Botox.

*Bone Loss after Temporarily Induced Muscle Paralysis by Botox Is Not Fully Recovered After 12 Weeks
*
Wiley InterScience :: Session Cookies


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## SparklingWaves (Jul 25, 2008)

Quote:

   Originally Posted by *redambition* 

 
_





botox for headaches? 

i'm a bit stunned here._

 

I had heard it rumored to be used for it, but I had to look it up in the research to be certain.


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## rbella (Jul 26, 2008)

I'm actually kind of shocked at the surprise that this is used for headaches. It was originally approved to prevent sweating by injecting it into the armpits, hands, etc. 

The next logical step was to use it to try and prevent tension headaches since it paralyses the muscles in which it is injected. Therefore, injecting it into the head helps keep the patient from tensing the muscles in their forehead and hence alleviates tension headaches. 

I know quite a few people who have had a significant decrease in tension headaches after botox therapy. I don't have a problem with it. My neurologist has used on me before and it has helped quite a bit. The odds of it connecting to a neuro-pathway are so slim. You are at risk with any procedure that is done or any medication that you take. Even having dental work is risky. You just have to decide what is important to you. JMO.


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## redambition (Jul 26, 2008)

i was shocked because i wasn't aware of that use. i can see how it could help prevent chronic tension headaches, but i'm still a bit uneasy about it being used at all... purely because it is essentially a dilute form of a very dangerous toxin.


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## ratmist (Jul 26, 2008)

Last time I went to the maternity ward at the hospital to get some tests done, I went to the toilet and found a flyer for new tests that are being undertaken to assess whether Botox can help incontinence issues.  The flyer was asking for participants who have incontinence to take part in the study, which is supposed to last over a six month period.  It said it'd involve a minor surgery and follow-up checkups.  I don't think they'd be getting Botox injections, but maybe an implant of some kind.

I thought it was funny and interesting.


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## SparklingWaves (Jul 26, 2008)

Youtube video from the FDA

YouTube - Early Communication on Adverse Events from Botox and Myobloc

Botox is big business for some doctors.  Here is a paragraph from one source.

“Dr. Klein had his own humbling moments on the stand. He admitted he had not changed his patient consent form to include new reports in the literature of ''life-altering headaches'' associated with Botox injections in cosmetic uses. And he confirmed what a gold mine Botox can be for some doctors. Up to a quarter of the $20,000 his practice generates a day comes from Botox treatments, he said, and Allergan paid him more than $100,000 a year.”

Source:  New York Times 
_*Botox Lawsuit Is Raising Eyebrows*_ 
By MIREYA NAVARRO Published: October 3, 2004




Here are more details about those “adverse events”.  

_*Allergan failed to warn of dangerous Botox side effects, lawsuit claims*_​ Adverse reactions to the popular wrinkle-erasing drug have been rare, its Irvine-based manufacturer says. By Lisa Girion, Los Angeles Times Staff Writer 
July 10, 2008 

More than a dozen Botox users and relatives filed a lawsuit Wednesday contending that the blockbuster wrinkle-buster injured them or killed their relatives, and they blamed maker Allergan Inc. for failing to warn them of the dangers.

The suit, filed in Orange County Superior Court near Allergan's Irvine headquarters, links the toxin-based drug to three deaths, including one in March of a 69-year-old Texas nurse who received injections for neck and shoulder pain.

The second death was that of a 7-year-old girl with cerebral palsy, also from Texas, who died in 2004, allegedly after receiving injections to control limb spasticity.

The third death occurred earlier this week in Arizona. In that case, a 71-year-old woman allegedly got Botox injections for wrinkles around her mouth at a mall clinic a year ago. After that, the suit says, she had trouble swallowing and breathing, was unable to speak and lost weight until she died. All three deaths involved uses of Botox that were not approved by federal regulators.

The suit also contends that Botox injections both for approved uses, such as smoothing frown lines, and unapproved uses, such as treating migraines, left 12 other plaintiffs with a range of disabilities, including blurred vision, numbness, allergic reactions, flu-like symptoms, muscle weakness and difficulty breathing.

Allergan spokeswoman Caroline VanHove said she could not discuss the suit in particular. But, she said, "_It is important to recognize that Botox has a remarkable safety record. The product was first approved nearly 20 years ago and today benefits 21 different patient populations across more than 75 countries."_

Botox is often administered to patients who are suffering from chronic, debilitating neurological conditions and are already at increased risk from underlying diseases, she said.

VanHove said Botox's safety record had been validated by the distribution of more than 18 million vials of the drug over 19 years, with more than 15 million treatments performed around the world. Serious adverse events have rarely been reported, she said.

Several of the plaintiffs in the suit were hospitalized and suffer from chronic, life-altering conditions. The most-common side effect cited in the suit is a loss of the ability to swallow, which causes a slow death from starvation or asphyxiation.

"_Botox is causing major injuries and death, and it's well-documented but not widely known_," said Ray Chester, a Texas lawyer who leads a nationwide team of lawyers involved in the suit. "_So thousands of people are getting these injections with no warnings to speak of. Then they fall ill with serious illnesses and, in some cases, they are not even aware that it's the Botox that caused it_."

VanHove said that Allergan had been the target of other Botox suits, but she declined to detail them.

One suit resulted in a high-profile Los Angeles trial that cleared Botox in 2004. In that case, Irena Medavoy, the wife of a movie studio founder, claimed she got terrible headaches from the injections a Beverly Hills dermatologist gave her to keep her wrinkles at bay. Medavoy lost her claim against her dermatologist, and the case against Allergan was dismissed.

Botox is derived from botulinum toxin Type A, a form of one of the deadliest known poisons. In its raw form, the toxin kills by interrupting the communication between nerves and muscles, causing them to relax and leaving the victim paralyzed and susceptible to suffocation.

Allergan maintains that the toxin, as sold as Botox, is purified, highly diluted, safe and effective. Injected locally, it smooths wrinkles by relaxing muscles. The effect is temporary, wearing off in a few months if injections are not repeated, the company says.

Originally developed to treat people with crossed eyes, Botox became a worldwide cosmetic juggernaut after it won approval several years ago as a treatment for vertical frown lines between eyebrows. Sales surpassed $1.2 billion last year.

Botox also is used for a variety of maladies, including migraines -- uses that have not been approved by the Food and Drug Administration. Such off-label prescribing is a legal practice for physicians. But manufacturers are not allowed to promote off-label uses.

In February, the FDA warned that it was reviewing reports of at least one death and other serious reactions among patients to botulinum-based drugs, including Botox and competitor Myobloc.

FDA officials said at the time that they were unaware of any deaths among cosmetic users.

The most serious of the reported problems occurred in children with cerebral palsy who were treated for arm and leg spasms with doses many times those recommended for cosmetic treatments.

The FDA warning followed the consumer group Public Citizen's announcement in January that it found reports linking 16 deaths to the use of Botox or Myobloc from 1997 to 2006.

The group also found that 180 patients had developed life-threatening conditions after being injected, leading to 87 hospitalizations.

In March, Allergan disclosed that the U.S. Department of Justice was looking at the company's promotion of its best-selling drug. Allergan, which received a subpoena for information from the U.S. attorney in the Northern District of Georgia, said it understood the inquiry involved questions about the use of Botox for headaches.

The suit filed Wednesday contends that the injuries arose from both approved and non-approved cosmetic and therapeutic uses of Botox. The three deaths allegedly occurred as a result of off-label uses -- two as therapeutic treatments for muscle problems and the third for smile lines, a non-approved cosmetic use.

"_Allergan emphasizes that Botox is a miracle drug and has often compared it to 'penicillin,'_ " the suit says. "_Meanwhile, Allergan obscures that Botox is a highly lethal toxin with serious and life-threatening side effects."
_
Allergan continuously monitors the safety of Botox in clinical practice, spokeswoman VanHove said.

"_This means, we evaluate any adverse event report that we receive following treatment with Botox or Botox Cosmetic, even though often times there is only limited information available and causality is not established_," she said. "_Given its high profile, it is not surprising that Botox might eventually attract an attempt of this kind."
_ 
"_In fact, we are aware that the plaintiff lawyers in this case have been soliciting claims regarding Botox over the Internet for months_," VanHove said. "_However, it still remains disappointing to see irresponsible allegations about a product that has done so much good for so many patients suffering from debilitating conditions_."


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## Kuuipo (Jul 27, 2008)

When I was working in brain/spine rehab, the physiatrists (doctors of movement) were frequently injecting botox into patients who were very rigid.  I have yet to see this work on anyone at all......


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## snowflakelashes (Aug 1, 2008)

I don't know, I hope I never have to consider this for tension headaches, I'd rather get therapy to deal with the stresses that are causing the tensions in the first place. EI mental stress and/or address whatever physical issues.  Then again talk to me in another 5 years and I might say getting rid of the wrinkles is worth the risks.  Interesting... and I'm reading/thinking about this instead of sleeping... Oops


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## KikiB (Aug 1, 2008)

If I were to get Botox, I would just get it for my already-atrocious wrinkles, but this is kind of scary.


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## SparklingWaves (Aug 1, 2008)

Yes, this latest information is scary.


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