WHAT IS BOTOX?

Botox is made from the highly poisonous toxin produced from the bacteria Clostridium Botulinum, the same bacteria that causes botulism or food poisoning. This bacteria is usually found on plants, in soil, water and the intestines of animals. It works by blocking the release of chemicals from the nerve endings and causes the muscles or glands to become temporarily inactive. Its first medical use was in 1980 to treat strabismus or crossed eyes.

9 years later the decrease in wrinkles and the cosmetic benefit was noted. Clostridium Botulinum is composed of 8 different toxins. Type A is the most potent of the toxins and the most likely to cause disease in humans and is the type that is approved for medical use and is known as Botox. When Botox is injected into a muscle at the neuromuscular junction, it causes the muscle to become paralyzed when the nerve terminals are blocked.

3 to 7 days after the injection is when the peak paralysis occurs. The nerve terminals are not damaged but they can no longer release the neurotransmitter chemicals. This means that new nerve terminals must grow around the paralyzed ones. The growth of the new terminals takes between 2 – 3 months. Once the new terminals are in action the muscle paralysis eases and the injections need repeated for muscle paralysis to continue.

HOW IS IT SUPPLIED AND GIVEN?

Botox is supplied as Serotype A preparation and is either listed as Dysport or Botox. Dysport is most commonly used in European Countries and Botox in the United States. Each vial of Botox contains 100 units of Type A Clostridium Botulinum, 0.5 milligrams of human albumin, and 0.9 milligrams of sodium chloride to dilute and mix the solution. There is no preservative in the vial so it must be thrown away after each use. Once the vial has been mixed with the sodium chloride, it must be stored in the refrigerator and should be used within 4 hours of mixing.

Botox is given as an intramuscular (IM) injection into the affected muscle areas or groups. Doses are individual to each patient based on body weight, level of weakness and sex. Females are normally given lower doses. People receiving the injection may be carefully monitored using Electromyography (EMG) monitoring to make sure the injection is given in the part of the muscle where it will have the most beneficial effect.

It is recommended that patients go home after the injection and rest, avoiding any strenuous activity and exercise for 1 – 2 days. This helps prevent the Botox from breaking away from the injected muscle and entering the blood stream or reaching other muscles.

Injections will need to be repeated every 3 months as the beneficial effects of the Botox wears off and the muscle becomes unparalyzed. These injections can go on for years, especially if they are working well. Repeated injections over a long period of time can lead to patients developing antibodies to the toxin making it an ineffective treatment. Using the least number of injections and the lowest dose possible can help prevent the patient from developing antibodies.

WHAT TYPE OF DISEASES AND CONDITIONS DOES BOTOX HELP TREAT?

There are a number of nerves and muscle disorders that Botox has been approved to treat. These include:

• Severe uncontrollable underarm sweating.
• Severe nerve and muscle contractions in the neck and shoulders known as Cervical Dystonia.
• Uncontrollable Blinking or Blepharospasm
• Strabismus or cross-eyes
• Dystonia or involuntary contractions of the muscles that cause twisting and unusual posturing and positioning of the muscles, especially of the limbs.
• Torticollis or twisted neck
• Contractions of the larynx that causes laryngospasms including chronic hoarseness and involuntary speech breaks.
• Stuttering or stammering
• Tardive dyskinesia or difficulty chewing and swallowing or repetitive movements of the mouth and tongue that cannot be controlled.
• Facial spasms and palsy
• Tourette’s syndrome
• Involuntary tremors such as Parkinson’s disease.
• Conditions that cause muscle spasticity including Multiple Sclerosis, stroke, traumatic brain injury, Cerebral Palsy, Spinal cord injury.
• Frey’s syndrome. This happens when people become flushed and sweat while eating
• Chronic Migraines
• Over Active Bladder

HOW DOES BOTOX WORK ON CHRONIC MIGRAINES?

Before talking about how Botox works on Chronic Migraines it is important to know what a chronic migraine is. Migraine headaches are considered to be a neurobiological disorder that involves increased brain activity and sensitivity to stimuli.

Migraines can present themselves in a variety of ways. Some people will experience one or more symptoms such as a sensitivity to light, sound and or have nausea, vomiting with symptoms increasing with movements. Migraines can be triggered by certain types of food, stress, certain odors, caffeine withdrawal and menstrual cycles. Migraines are classified as either Episodic or Chronic.

• Episodic Migraines are defined as occurring as 15 days or less per month.
• Chronic Migraines are defined as headaches that occur for at least 15 days a month for 3 or more months. 8 or more of those days must have the symptoms of migraines.

Statistics show that at least 36 million Americans report having migraine headaches. Migraine headaches are more common in women than men with the peak of Chronic Migraine Headaches occurring in midlife.

Some migraine can be managed without medications such as staying in a quiet, dark room, using cold compresses at the sites of the worst pain and avoiding anything that triggers a migraine. Some patients can take Non-steroidal anti-inflammatory medications and remain functional. If none of the above work, patients may be described medications such as Propranolol, Timolol, or Topamax. If none of these medications work for 3 or more months then Botox injections can be used.

IS BOTOX SAFE AND EFFECTIVE TO USE IN CHRONIC MIGRAINES?

The safe use and effectiveness of Botox as a preventative treatment for Chronic Migraines has been studied in Phase III Clinical Trials and shown to reduce the impact of migraine headaches as well as help with improvements in quality of life.

There was at least a 50% reduction in headache and migraine days reported in the patients receiving Botox and a reduction in acute headache medication usage. Using Botox as a treatment to prevent migraines is recommended for patients who fail to get relief from migraines with 3 other treatment options.

HOW IS BOTOX GIVEN FOR MIGRAINE PREVENTION?

Botox is given every 12 weeks as a series of IM injections given at 31 sites on the head and neck. The recommended dose is 5 units per injection site for a total of 155 units. The pain decreases in a short period of time following the injection as neurotransmitters are blocked and stopped from being released.

The number of doses and injections done at the every 3 month treatment session is invidualized to each patient based on symptoms, height, weight and tolerance to previous injections.

WHAT IS OVERACTIVE BLADDER?

Overactive bladder (OAB) is defined by the International Continence Society as an urgency to urinate and may or may not be accompanied by incontinence, causing people to urinate frequently even at night. This disorder can happen to anyone, although it is more common in older people. As people age, the bladders ability to hold urine gets smaller and the ability to stop urine from leaving the bladder weakens.

For some people, the bladder may suddenly and for no apparent reason contract to release urine, causing leakage. This is because the Detrusor muscle becomes overactive. This muscle over activity may be caused by an injury to the spinal cord or other neuromuscular injury such as Multiple Sclerosis.

OAB are often taught how to do muscle strengthening exercises called Kegel exercises, follow a bladder training schedule such as emptying their bladder at regular times and take medications to help stop the urgency. This is not always effective because the medications often have side effects and patients get frustrated when the exercises and bladder training makes little or no difference. For these patients, Botox Treatments can be a good option to control urgency and leakage.

HOW DOES BOTOX TREAT OVERACTIVE BLADDER?

Botox is currently accepted as a treatment for OAB because of its ability to decrease the muscle contractions and spasticity caused by the overactive detrusor muscle. The effectiveness of Botox injections into the detrusor muscle was first reported in 1999.

Injecting Botox into the bladder muscle has several effects:

• The bladder muscle relaxes and does not spasm as much because the neurotransmitter release is blocked so fewer signals are received.
• The bladder holding capacity increases because the bladder muscle is not contracting as much
• Episodes of urinary incontinence decrease because the bladder muscle is not as active as before.

HOW IS BOTOX INJECTED INTO THE DETRUSOR (BLADDER MUSCLE)?

A cystoscopy is performed by the doctor to examine the bladder and urethra, by placing a tube in the urethra and bladder so the doctor can see how the muscles and bladder lining looks. The doctor then uses the cystoscope to guide the placement of the injections so that only certain parts of the muscle are affected. If the injections have been successful in controlling the symptoms, injections can be repeated every 12 weeks. The dose used is either 200 units or 300 units based on patient height, weight and symptoms.

ARE THERE ANY SIDE EFFECTS TO THE INJECTION INTO THE BLADDER?

As with any medication, there are potential side effects to injecting the bladder muscle. These include:

• Urinary Tract infections
• Pain on urination
• Incomplete emptying of the bladder also known as Urinary Retention

It is important for patients who have had Botox injections in the bladder to talk to their healthcare provider if they notice any unusual symptoms such as blood in the urine, urine that is darker than normal, cloudy urine, or any pain/burning when urinates. These can all be signs of a urinary tract infection and require prompt treatment.

HOW SAFE AND EFFECTIVE IS BOTOX FOR OVERACTIVE BLADDER?

The FDA based its approval for use in OAB on 2 clinical trials that contained 1105 patients with history of overactive bladder. Patients either received the Botox injections or a placebo. Results were reviewed after 12 weeks and showed:

• Patients who received Botox injections had episodes of urinary incontinence 1.6 to 1.9 times less than patients treated with placebo injections.
• Patients injected with Botox had the urge to urinate an average of 1.0 to 1.7 times less in a 24 hour period and put out about 30 milliliters of urine more than patients who received the placebo.
• Side effects such as urinary tract infections, blood in the urine and urine retention were reported more frequently by patients receiving Botox than patients who received the placebo.

Long term effects are still being monitored and studied, but at the present time studies show that Botox injections for OAB are safe and effective.

WHAT ELSE IS THERE TO KNOW ABOUT BOTOX INJECTIONS?

There are ongoing research studies in using Botox to treat a variety of conditions. One in particular is in Arthritis treatment. Several small research studies have been conducted looking at pain relief for arthritis in the shoulders, knees and hips. People who have participated in these various small studies have reported improvement both in arthritis pain and movement and usage of the joints.

These studies have used small numbers of patients and many did not have a control group of patients who received a placebo to use a comparison of effectiveness. It is a small but important start in learning if Botox can help those with arthritis.
There is still a great deal to learn about Botox and what other disorders and diseases it may be able to treat. For patients who suffer from Dystonia, Spasticity, Strabismus, Chronic Migraines and Overactive Bladder, it has offered an improved quality of life and reduction in symptoms.

REFERENCES:

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