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Botulinum: A Deeper Dive

Botulinum is a simple, nonsurgical, physician-administered treatment that can temporarily smooth moderate to severe frown lines and wrinkles throughout the face. It is typical to treat patients between the ages of 18 to 80 years of age. It is the only treatment of its type approved by the Food and Drug Administration (FDA).

What Creates Wrinkles?

Wrinkles are caused by facial creases resulting from our facial expressions, activated hundreds of thousands of times (perhaps more) over the course of a lifetime. Some of the most significant creases are typically located at the outer eyelid area (crow’s feet) and in the forehead (frown lines). Other areas include marionette lines and nasolabial folds that accompany our smiles. Bunny lines, along the side of our noses, are also created over time. Below, we see vertical wrinkles, or frown lines, can lead to an angry look.

How Can They be Treated?

To reduce the appearance of fine lines and wrinkles, the muscle creating those unwanted creases can be surgically damaged or temporally paralyzed with botulinum injections (area in red for frown lines). Botulinum toxin injections work by disrupting the communication between nerve and muscle, thereby relaxing the wrinkles and fine lines. At Idaho Eyelid and Facial Plastic Surgery, our Botox/Dysport injectors are supervised by a physician-led medical director. This assures our patients have both guidance and supervision should complications arise.

Does the Injection Hurt?

At Idaho Eyelid and Facial Plastic Surgery, our Botox/Dysport injections are performed by using the smallest possible needle. These hurt less than larger needles. While there can be initial sting, the pain is mitigated by higher gauge needles and numbing cream, as needed.

Background of Botulinum Toxin

Botulinum toxin is a biological substance and neurotoxin produced by clostridium botulinum. It has been called “miracle poison” because of its variety of uses despite being a poisonous substance. Botulinum toxin is being increasingly used in clinical practice over the past two decades across all fields of medicine. It was originally approved by the US Food and Drug Administration (FDA) in 1989 as a possible therapeutic modality in the management of strabismus and blepharospasm. I At Idaho Eyelid and Facial Plastic Surgery, we have been using it to treat blepharospasm since the late 1980s. Since then, our practice has used it for both functional and cosmetic indications in ophthalmology and oculofacial plastic surgery cases. There has been a steady rise in the use of botulinum toxin for various cosmetic and neurological disorders over the past couple of decades such that it is now the most commonly performed nonsurgical cosmetic procedure. Some of the other applications of botulinum toxin over the past two decades include:

  • 1989 – management of strabismus and blepharospasm.
  • 1992 – management of facial rhytids with significant clinical improvement
  • 2002 – FDA approval for the aesthetic management of glabellar furrows
  • Modern Day – used as an efficient and reliable option in minimally invasive facial rejuvenation, facial and cervical dystonias, achalasia cardia, bruxism, hemifacial spasm, headaches, hypersalivation, hyperhidrosis, correction of lines, creases, and wrinkles over the face, chin, neck and chest.

Botulinum toxin is available in a variety of preparations, each with its distinct chemical and therapeutic characteristics. The most commonly available preparations are Botox, Dysport, and Xeomin and have been extensively studied for various cosmetic and neurological uses.

Source of Botulinum Toxin

Botulinum toxin is a product of the gram-positive anaerobic, spore-forming rod, Clostridium botulinum. It is commonly found on plants, soil, water and gastrointestinal tract of animals. It is a potent neurotoxin which inhibits the release of acetylcholine at the neuromuscular junction of the peripheral nervous system blocking neural transmission after acting on the presynaptic terminal. When injected into any muscle, it leads to muscle paralysis thereby causing its therapeutic effect.

Botulinum toxin has 7 different serotypes, serotypes A through G, each derived from a different strain of the bacteria. However, only types A and B are found to be clinically useful and approved by the FDA for intramuscular injections. The most potent of them, type A botulinum toxin is approved for both aesthetic and functional use while type B botulinum toxin is approved only for the management of cervical dystonia.

Mechanism of Action of Botulinum Toxin

Botulinum toxin acts by blocking neural transmission at four different sites in the body – the neuromuscular junction, autonomic ganglia, postganglionic parasympathetic nerve endings and postganglionic sympathetic nerve endings that release acetylcholine. It irreversibly blocks the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, without causing degeneration of the nerve terminals. The botulinum-induced irreversible paralytic effect starts in 24 to 72 hours and is complete in four to seven days after injection. There is recovery of muscle function only with the formation of new nerve terminals and new synaptic contacts which takes about two to three months.

Hence, Idaho Eyelid and Facial Plastic Surgery recommends repeating injections every three or four months based on individual response to therapy. It should be kept in mind that tolerance to the drug develops with repeated injections due to antibody formation. Therefore, it is advised that the lowest effective dose be given as infrequently as possible.

Available Preparations of Botulinum Toxin

Botulinum toxin serotype A was the only commercially available form of botulinum toxin for clinical use for quite some time. Recently, Myobloc, a botulinum toxin type B preparation has been used with some success in cervical dystonia. Following is a list of available preparations of Botulinum toxin with their clinical uses:

  • OnabotulinumtoxinA (Botox, Botox Cosmetic): This was the first commercially available preparation of Botulinum toxin. It is highly potent and has a well-established safety profile. Botox is stored in a freezer at or below -5°C and has to be used within 4 hours of reconstitution with 0.9% saline. Treats excessive, abnormal contractions in blepharospasm by binding to receptor sites on motor nerve terminals and inhibiting release of ACh, which, in turn, inhibits transmission of impulses in neuromuscular tissue. Botox is used to treat cervical dystonia, severe primary axillary hyperhidrosis, strabismus, and blepharospasm while Botox Cosmetic is used to treat moderate-to-severe glabellar lines.
  • Abobotulinumtoxin A (Dysport): Botox is four times more potent than Dysport. Dysport is also used to treat cervical dystonia, and moderate-to-severe glabellar lines.
  • Incobotulinumtoxin A (Xeomin): Xeomin is a highly purified Botulinum Type A formulation containing pure 150 kD neurotoxin, free from complexing proteins of the natural toxin. Hence it does not induce antibody formation. Its potency is equal to that of Botox. It is an acetylcholine release inhibitor and neuromuscular blocking agent. It is used in cervical dystonia and blepharospasm previously treated with Botox.
  • Rimabotulinumtoxin B (Myobloc or Neurobloc): Myobloc/Neurobloc has a shelf life of more than a year after reconstitution but is less potent than Botox. It is used to treat cervical dystonia.

Technique of Administration

Botulinum toxin is administered by injecting an appropriate dose into the affected muscle or gland using a 30-gauge 1-inch needle. Lower doses are preferred in females and those with pre-existing weakness. The injections are administered through hollow teflon coated needles directly into affected or overactive muscles and are occasionally guided by electromyography.

Precautions After Botulinum Toxin Injection

To prevent toxins from affecting neighboring muscles, patients should avoid any strenuous physical activity for one to two days, and refrain from laser or intense pulse light (IPL) treatments, facials and facial massage for one to two weeks after injections. Patient selection and the proper choice of dose and administration site are the most important determinants for a favorable response to botulinum toxin injections.

Indications for Botulinum Toxin

Botulinum toxins have found veritable applications in the management of various medical, neurological, dermatological, ophthalmic and cosmetic conditions with good response to treatment. Clinical applications include:

  • Strabismus
  • Focal dystonias
  • Hemifacial spasms
  • Pastic movement disorders
  • Headaches (migraines for example)
  • Hypersalivation
  • Hyperhidrosis
  • Alternative to surgery in chronic anal fissures
  • Achalasia cardia
  • Ptyalism
  • Gustatory sweating after parotid gland surgery

Dermatological and cosmetological applications include:

  • Glabellar lines
  • Correction of lines, creases and wrinkles all over the face, chin, neck, and chest
  • Depressor anguli oris, nasolabial folds, mentalis, medial and lateral brow lifts
  • Lessen shadows on one’s face
  • Maintain a smooth outline of the jaw and cheeks from all directions
  • Localized axillary or palmar hyperhidrosis nonresponsive to conventional therapy

Adverse Effects of Botulinum Toxin

Botulinum toxin injections are generally well-tolerated and cause relatively few side-effects which are divided into two groups, paralysis of the wrong muscle group and allergic reaction. Unwanted weakness or paralysis of the wrong muscle group is temporary and lasts from a few weeks to several months and can cause: upper lid or brow ptosis, double vision, uneven smile, weakness of the lower eyelid or lateral rectus resulting in exposure keratitis, dysphagia due to toxin reaching the oropharynx, and/or neck weakness due to weakening of the sternocleidomastoid muscles. Allergic reaction to Botulinum toxin is rare but can occur due to hypersensitivity towards any of the components of the injections. Systemic but uncommon side effects can include headaches, flu-like syndromes, immune-mediated plexopathy, blurred vision, dry mouth, fatigue, swelling and redness at injection site.

Contraindications to Botulinum Toxin Injection

The following conditions are contraindications to Botulinum toxin injections:

  • Preexisting motor neuron disease
  • Myasthenia gravis
  • Eaton-Lambert syndrome
  • Neuropathies
  • Psychological unstability
  • History of allergy to toxin or albumin
  • Pregnancy and lactating mothers infection at the injection site
  • Aminoglycosides accentuate the effect of botulinum toxin
  • Penicillamine, quinine, chloroquine, and hydroxychloroquine reduce the effect of botulinum toxin
  • Calcium channel blockers and blood thinning agents such as warfarin and aspirin might cause bruising

Why would Botulinum Toxin Injection fail often?

There are a number of reasons why Botulinum toxin might not work for a patient:

  • Photodamage and age-related changes which are not dynamic in origin
  • Improper injection technique
  • Denatured toxin used for injection
  • Neutralizing antibodies due to repeated exposure or individual variation
  • Overuse of botulinum toxin may result in poor results over time (some patients find switching back and forth from Botox to Dysport makes injections more effective)

Future of Botulinum Toxin

The future of botulinum toxin is bright as it has revolutionized the treatment of various ophthalmic spastic disorders, facial dystonias and periocular wrinkles. As we gain more insight into the uses of various toxins for chemodenervation (to target muscles affected by dystonia and spasms), there is hope for better uses of botulinum toxin.

BEFORE & AFTER

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