Botulinum toxin is a potent neurotoxin that is produced from the bacteria Clostridium botulinum.
Clostridium botulinum is a spore-forming, gram-positive, anaerobic bacterium.
Botulinum neurotoxins are a group of seven serotypes A-G.
There are three forms of serotype A and one form of serotype B.
All four types are approved globally for treating spasmodic torticollis.
The three serotype A products have approval for focal dystonia that can affect the eye, causing abnormal eyelid twitching or closure.
Botulinum toxin is approved to treat migraines, which to date, is the only chronic condition approved for its use.
Approved for prophylactic treatment of chronic migraine headaches.
A meta-analysis comparing Botulinum toxin A with placebo for chronic tension headaches and chronic migraines is associated with a small to modest benefit, but is not associated with fewer episodic migraine or chronic tension type headaches per month (Jackson JL et al).
Botulinum toxin minimize muscle tension and enhance muscle relaxation.
Oabotulinumtoxin A is a popular cosmetic procedure practiced in America.
All three serotypes A forms are used for wrinkles and facial lines.
Botulinum toxin effective in other medical conditions, such as strabismus and hypersalivation.
FDA-approved uses:
Chronic migraine
Cervical Dystonia
Blepharospasm
Strabismus
Hyperhidrosis
Cosmetics
Urinary incontinence from detrusor overactivity
Hemifacial Spasms
Other uses:
Neurogenic thoracic outlet syndrome
Epicondylitis
Post-stroke pain
Post-herpetic neuralgia
Diabetic neuropathy
Trigeminal neuralgia
Neuropathic pain
Spinal cord injury
Myofascial pain
Bladder pain
It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis.
It is a potent zinc proteinase neurotoxin that binds to extracellular receptors on cholinergic nerve terminals.
It cleaves one of the three attachment receptor proteins, causing reversible inhibition of the release of acetylcholine by presynaptic vesicles intracellularly.
Botulinum toxin leads to a transient restraint of neurotransmitter release at the neuromuscular junction.
The toxin cleaves SNARE proteins, which are proteins that mediate vesicle fusion, with their target membrane bound compartments: acetylcholine vesicles cannot bind to the intracellular cell membrane, and prevent the cell from releasing acetylcholine.
SNARE proteins also have a role in neurons that release glutamate, and substance R, and bradykinin, prostaglandins, histamine, and serotonin, which are proinflammatory mediators.
The inhibition of these substances may account for its possible treatment in chronic pain disorders, migraines, and neuralgias.
Botulinum toxin has a long duration of action.
Its efficacy in cosmetics may take two weeks to develop and it may last three to five months.
Its use on the autonomic neurons for hyperhidrosis or overactive bladder have range from six to nine months.
FDA-approved botulinum toxins:
OnabotulinumtoxinA
AbobotulinumtoxinA
IncobotulinumtoxinA
When injected into distinct muscles, it causes flaccid paralysis and muscle relaxation: diminishes wrinkles by muscle relaxation and smoothing the overlying dermis.
Adverse effects are usually moderate and self-limited: bruising, edema, or pain at the injection site can develop during aesthetic use, and flu-like symptoms can also occur.
Uncommon complications include blepharoptosis and eyebrow ptosis when introduction of botulinum toxin is introduced into the glabella and associated muscles.
Allergic reactions are rare.
Other complications include:
Headache
Infection
Cocked eyebrow
Ectropion
Decreased strength of eye closure
Xerophthalmia
Botulinum toxin contraindications include:
Keloidal scarring
Neuromuscular disorders
Botulinum toxin allergies
Body dysmorphic disorder
Pregnancy
Breastfeeding
Amyotrophic lateralizing sclerosis
Continued paralysis and muscle relaxation is related to the temporary restrictive neurotransmitter release.
Botulinum neurotoxin serotype A has the most prolonged half-life.
The human LD50 for inhalation botulism is 1 to 3 ng/kg body mass.
Can be used as a bioweapon, and be transmitted in airborne or foodborne methods.
Antitoxin Vaccine F(ab’)2 immune fragment therapies are available.
May be associated with the spread from the injection site distant parts of the body and cause botulinum-like symptoms, including muscle weakness, difficulty speaking, loss of bladder control, impaired breathing and swallowing, blurred or double vision and drooping eyelids.
Most adverse events have been noted in children with cerebral palsy that have received treatment for muscle spasticity.
The majority of adverse events in adults involved patients treated for cervical dystonia or for use in patients with muscle spasticity.
The injection of botulinum toxin into the splenius capitis muscle is more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks, but not at 24 weeks, and is associated with adverse effects, including head and neck pain, posterior cervical weakness, and dysphagia (Marqvues A).