Two centuries ago, Clostridium botulinum was identified as a deadly bacterium that caused a life-threatening type of food poisoning called botulism. Today, a toxin produced from that dangerous bacterium has been harnessed to treat many neurologic diseases, including chronic migraine, cerebral palsy, and dystonia. Botulinum toxin type A, commonly known as Botox (onabotulinumtoxinA) but also manufactured as Dysport (abobotulinumtoxinA) and Xeomin (incobotulinumtoxinA), has changed the course of how neurologists treat many conditions, including spasticity and dystonia, says Steven Frucht, MD, professor of neurology and director of the division of Parkinson's and movement disorders at NYU Langone Medical Center. (Dr. Frucht has received grant support from Merck for a trial of Xeomin to treat musicians' dystonia as well as grant support for an upcoming trial on task-specific tremor. He is a former consultant for Merck, Allergan, and Ipsen but has no stock options and is not currently an advisor for any company.)

There are two types of botulinum toxin—type A and B, based on different strains of the bacteria—available for clinical use. In addition to type A, which is approved by the US Food and Drug Administration (FDA) to treat various conditions, type B, rimabotulinumtoxinB (Myobloc), is FDA approved to treat adult cervical dystonia.

From Toxin to Tonic

After uncovering Clostridium botulinum as the cause of food poisoning due to improper canning or sausage making in the late 1800s, researchers began studying its use for other purposes, including as a chemical weapon during World War II. Then in the 1950s, physician Vernon Brooks discovered that injecting small amounts of botulinum toxin A into the hyperactive muscles of cats and guinea pigs blocked the release of a chemical called acetylcholine from nerve endings. The result? The muscle relaxed.

In the 1970s, ophthalmologist Alan B. Scott, a founding member of the Smith-Kettlewell Eye Research Institute in San Francisco, tested the toxin on monkeys, and in 1977 injected it for the first time into a human eye muscle to correct strabismus, also known as crossed or lazy eye. A little more than a decade later, in 1989, the FDA approved botulinum toxin A (Botox) for the treatment of strabismus, blepharospasm (uncontrolled muscle spasms in the eyelid), and hemifacial spasm (involuntary muscle spasms on one side of the face due to irritation of the facial nerve) in children under 12.

Muscle Relaxer

Botulinum toxin blocks the chemical signal between the nerves and the muscles that makes a muscle contract or tighten, says David Simpson, MD, FAAN, director of the neuromuscular diseases division at the Icahn School of Medicine at Mount Sinai in New York. (Dr. Simpson does consulting for and has grant support from Allergan, Merck, and Ipsen.) "In order for your muscles to contract, your nerves have to release the neurotransmitter acetylcholine, which attaches to receptors on your muscle cells and causes them to contract," he explains. "Injecting botulinum toxin prevents the release of acetylcholine, which in turn prevents muscle cells from moving." As a result, you get relief from symptoms like pain and muscle stiffness.

The treatment usually starts working a few days after the injection and lasts for about three months. "The effect is always reversible, even after years of repeated injections into the same muscles," Dr. Simpson says. While its effectiveness is mainly due to paralyzing muscles, it may also alter pain signaling and reduce nerve inflammation that's causing tightness and pain, says Alan Rapoport, MD, FAAN, clinical professor of neurology at the David Geffen School of Medicine at UCLA. (Dr. Rapoport has no associations with any pharmaceutical companies that manufacture botulinum toxin.)

Evidence Guidelines

A review of existing evidence conducted by the American Academy of Neurology (AAN) and published in Neurology in 2016 concluded that botulinum toxin is effective or probably effective in the following four areas: chronic migraine, cervical dystonia, blepharospasm, and spasticity.

Bear in mind, Dr. Simpson says, that botulinum toxin is not a cure, and may not offer relief for everyone.

Chronic Migraine

Botox was approved by the FDA for chronic migraine in 2010. "Botox injections are for people who get headaches at least 15 days out of each month," says Dr. Rapoport. One study published this past February in The Journal of Headache and Pain found that people with chronic migraine (with an average of 22 headache days a month) reported about nine fewer headache days after about one year and 10.7 fewer days after two years of injections.

The toxin can prevent migraine, but it takes time to work and isn't effective for all patients, says Stephen Silberstein, MD, FAAN, director of the Jefferson Headache Center of Thomas Jefferson University in Philadelphia and a member of the advisory board for Allergan. "In my experience, among people who do respond, about 60 percent see improvement after the first injection, another 20 percent after the second round, and another 20 percent after the third," Dr. Silberstein says. If you don't respond after three rounds of injections, he says, it's unlikely the toxin will do anything for your migraines.

Cervical Dystonia

Since 2000, all four versions of botulinum toxin—Botox, Dysport, Myobloc, and Xeomin—have been approved by the FDA to treat cervical dystonia, a frequently painful condition in which the neck muscles involuntarily contract, causing the head to twist to one side or tilt forward or backward. "It's really the first choice for treating this condition-nothing else comes close to helping relieve symptoms," says Dr. Frucht.

In the AAN review, Dysport and Myobloc were considered effective while Botox and Xeomin were labeled "probably effective."

Blepharospasm and Hemifacial Spasm

In 1989, the FDA approved the use of botulinum toxin to treat blepharospasm, an abnormal contraction of the eyelid muscles, and hemifacial spasm. Again, it's the treatment of choice for the condition, says Dr. Simpson. It takes about two to three days to work, with peak effect occurring at around seven to 10 days. Side effects include bruising around the eye, dry eye, and blurred vision. The AAN review recommends type A toxins. The evidence as to whether the B form is as effective is mixed, according to the review.

Spasticity

Stroke survivors and people with diseases such as cerebral palsy or multiple sclerosis often experience spasticity, in which certain muscles are continuously contracted, causing tightness and stiffness that interferes with day-to-day movement, speech, and walking. This is caused by a signal imbalance from the brain and spinal cord to the muscles. But botulinum toxin has been proven to help.

"The toxin essentially acts as a muscle relaxant," explains Quyen Luc, MD, assistant director of the pediatric movement disorders program at Children's Hospital in Los Angeles. (Dr. Luc has no conflicts of interest.) "We generally use it if a patient has muscle tightness in only one or two areas—for example, for children whose parents are having trouble changing their diapers because they are scissoring and crossing their legs a lot, we might inject it into their hip area. But if there are more than a couple areas, then we're better off using an oral medication such as tizanidine (Zanaflex) first."

A number of studies support the effectiveness of Dysport and Botox for treating lower limb spasticity (in the ankle and toe muscles) while Dysport, Botox, and Xeomin have been found to help treat upper limb spasticity (in the elbows, wrists, and fingers).

Other Conditions

A 2016 study published in The Lancet Neurology found that botulinum toxin A injections could help treat neuropathic pain by acting as an analgesic. And other studies and trials are exploring botulinum toxin for focal dystonia, another neurologic disorder that involves spasms in small muscles such as the hands and fingers. "We see it a lot in musicians who get the so-called violinist or pianist cramp," says Dr. Simpson. Results are promising, but more research is needed.

It may even help people stop grinding their teeth at night, according to a small randomized placebo-controlled study published in Neurology in February. The group that received injections of botulinum toxin A had greater improvements, including significantly less pain and teeth grinding, than those who received a placebo injection.

What to Expect from Botulinum Toxin Injections

1. PREPARATION. Before undergoing injections, ask your doctor which toxin he or she plans to use—Botox, Dysport, Xeomin, or Myobloc—and how to prepare, says Allan Wu, MD, associate professor of neurology at the David Geffen School of Medicine at UCLA. In general, it's wise to refrain from drinking alcohol the week before. Avoiding aspirin and anti-inflammatory drugs for two weeks before will help reduce the risk of bruising. If you take blood thinners, talk to your doctor about stopping them a few days before the procedure to reduce the risk of bleeding or bruising.

   

2. PROCEDURE. When getting an injection, your doctor may use topical anesthesia beforehand to numb the area. A thin needle is used to inject tiny amounts of botulinum toxin into the skin. The number of injections depends on many factors, including the size of the area being treated, says David Simpson, MD, FAAN, director of the neuromuscular diseases division at the Icahn School of Medicine at Mount Sinai in New York.
3. DOSAGE. Dosage varies considerably, depending on the type of toxin and the condition being treated, says Dr. Wu. In general, he says, each type has its own starting and maximum recommended doses, and patients should ask about these ranges beforehand. "Patients should inform their doctors if they are receiving botulinum toxin injections for any other purpose, including cosmetic, so the total dose can be estimated by their physicians," advises Dr. Wu.
4. EFFECT. It generally takes about three to seven days, but sometimes as long as two weeks, for the toxin to take full effect. To maintain its benefits, you'll need repeat treatments every three to four months, says Dr. Simpson.
5. SIDE EFFECTS. Since this toxin is injected, most side effects are around the injection site and include redness, bruising, pain, and possible infection. The most common side effect when using it for migraines is neck pain, says Alan Rapoport, MD, FAAN, clinical professor of neurology at the David Geffen School of Medicine at UCLA. Although it's extremely rare, the toxin can spread to other parts of the body, causing symptoms like muscle weakness, vision problems, or trouble speaking, swallowing, or breathing, says Quyen Luc, MD, assistant director of the pediatric movement disorders program at Children's Hospital in Los Angeles. If you notice any of these symptoms, call your doctor immediately or head to the emergency department.
6. RECOVERY. You can expect to return to your daily activities right after the procedure, says Dr. Simpson.