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Neuromodulation

Botulinum toxin treatment

Botulinum Toxin Therapy

Botulinum toxin therapy is a treatment that controls muscle hyperactivity, pain, and hypersecretion of autonomic nerves by blocking the secretion of acetylcholine at the neuromuscular junction using neurotoxins produced by Clostridium botulinum bacteria.

AT A GLANCE

At a glance

Botulinum toxin is used as a standard treatment in the field of neurology for chronic migraine (PREEMPT protocol), cervical dystonia, blepharospasm, and hemifacial spasm [1]. In chronic migraine, the effect of injecting 31 sites every 12 weeks was reported to reduce monthly headache days by about 8 to 9 days [2]. There are also approved indications for hyperhidrosis and neurogenic bladder, and the effect lasts for about 3 to 6 months [3].

Definition and Overview

Botulinum neurotoxin (BoNT) is a neurotoxin produced by Clostridium botulinum. Among the seven serotypes (A to G), types A and B are used for clinical treatment.

It blocks acetylcholine secretion by cutting SNARE protein, which is essential for membrane fusion of synaptic vesicles at the neuromuscular junction, thereby producing muscle relaxation, secretion inhibition, and pain control effects. Since the FDA first approved the treatment of blepharospasm in 1989, indications have continued to expand in neurology, rehabilitation medicine, and urology.

Mechanism of Action

Neuromuscular blockade

Botulinum toxin type A cleaves SNAP-25 protein, and type B cleaves synaptobrevin (VAMP). If synaptic vesicles fail to fuse with the nerve terminal cell membrane, acetylcholine is not secreted, resulting in relaxation of the target muscle.

Pain suppression mechanism

The effect in migraine cannot be explained solely by the muscle relaxant effect. Botulinum toxin inhibits the secretion of pain-related neuropeptides such as CGRP and substance P from the terminals of the trigeminal nerve and blocks peripheral sensitization by interfering with the membrane insertion of TRPV1 receptors.

secretion inhibition

It suppresses sweating by blocking the secretion of acetylcholine from the sympathetic cholinergic sweat nerve. It also blocks the secretion of acetylcholine from the bladder detrusor muscle to control detrusor overactivity.

Neurological indications

chronic migraine

In PREEMPT I and II studies, onabotulinumtoxinA (Botox) showed significant effectiveness compared to placebo in chronic migraine (headaches more than 15 days per month, of which migraines more than 8 days), and was approved by the FDA in 2010.

The procedure (PREEMPT protocol) is as follows.

  • A total of 155 units (maximum 195 units) are injected into 31 areas.
  • Injection site: frontalis (4 sites), corrugator (2 sites), gastrocnemius (1 site), temporalis (8 sites), occipital muscle (6 sites), cervical paraspinal muscle (4 sites), trapezius (6 sites)
  • Repeat every 12 weeks
  • Effect onset: 2-4 weeks after the first cycle, maximum effect after 2-3 cycles

A Cochrane systematic review confirmed the effect of reducing headache days by approximately 3.5 additional days per month (compared to placebo).

Cervical dystonia (torticollis)

Cervical dystonia is one of the most established indications for botulinum toxin. It is injected directly into the affected muscle to relieve abnormal contraction. It is effective in approximately 85-90% of patients and is repeated at 12-16 week intervals.

Blepharospasm and hemifacial spasm

In blepharospasm and hemifacial spasm, small amounts are injected into the orbicularis oculi and adjacent facial muscles to control involuntary eye closure. The effectiveness of the Level A level of evidence is recognized.

Spasticity

For spasticity after stroke, cerebral palsy, multiple sclerosis, and spinal cord injury, it is injected into target muscles to relieve spasticity and promote functional recovery.

Hyperhidrosis (excessive sweating)

Intradermal injection significantly suppresses sweating in axillary (armpit), palmar (palm), and plantar (soles) hyperhidrosis. In axillary hyperhidrosis, the duration of effect is about 6 to 12 months, and sweating is reduced by about 80 to 90%.

neurogenic bladder

For urinary incontinence caused by detrusor overactivity, intravesical injection (onabotulinumtoxinA 200 units) reduces the frequency of urinary incontinence by about 50 to 70%, and the effect lasts for about 6 to 9 months.

Chronic salivary hypersecretion

It is injected into the parotid and submandibular glands to control saliva secretion in response to excessive salivation (sialorrhea) in Parkinson's disease, amyotrophic lateral sclerosis (ALS), etc.

side effects

local side effects

  • Injection site pain, bruising, and swelling (most common)
  • Ptosis: Approximately 2-4% in facial injections
  • Temporary muscle weakness: spread of toxins to muscles adjacent to injection site

Systemic side effects (rare)

  • Whole body muscle weakness due to remote spread of toxins
  • Difficulty swallowing, difficulty breathing (when injecting high doses into the cervical muscle)
  • Flu-like symptoms (fatigue, muscle pain)

Formation of neutralizing antibodies

Neutralizing antibodies may form in about 3-5% of patients who receive repeated injections, reducing the effectiveness of treatment. Using the lowest effective dose and maintaining appropriate injection intervals (at least 12 weeks) are important to reduce antibody formation.

Available formulations

  • OnabotulinumtoxinA (Botox): Most widely used, indicated for chronic migraine
  • AbobotulinumtoxinA (Dysport): Cervical dystonia, stiffness
  • IncobotulinumtoxinA (Xeomin): Complex protein-clearing agent, low risk of antibody formation.
  • RimabotulinumtoxinB (Myobloc/NeuroBloc): Alternative for Type B Toxin, Type A antibody formation

Since the potency is different between each agent, caution is required when changing dosage.

QUESTIONS

Frequently asked questions

Q01Is Botox effective for migraines?

It is an FDA-approved treatment for chronic migraines (headaches more than 15 days per month). In the PREEMPT study, the effect of injecting a total of 155 to 195 units into 31 areas of the skull and neck every 12 weeks was proven to reduce monthly headache days by about 8 to 9 days [2]. Effectiveness has not been proven for episodic migraine (less than 15 days per month).

Q02Does botulinum toxin injection hurt?

Because a very thin needle (30-32 gauge) is used, the pain is mild. You may feel a slight tingling sensation when injecting into the scalp and forehead area. Apply a cooling spray or local anesthetic cream if necessary. The procedure time is approximately 10 to 15 minutes.

Q03How long do the effects last?

It varies depending on the indication, but generally lasts about 3 to 4 months (12 to 16 weeks). For chronic migraine, the injection is repeated at 12-week intervals, and for cervical dystonia, the injection is repeated at 12-16 week intervals. In hyperhidrosis, the effect can last for about 6 to 12 months [3].

Q04What are the side effects of botulinum toxin treatment?

Pain at the injection site, bruising, and temporary muscle weakness are most common. In migraine treatment, drooping of the eyelids (ptosis) may occur in approximately 2-4% of cases, but is mostly temporary [2]. Very rarely, difficulty swallowing or breathing due to spread of toxin throughout the body is reported.

Q05Is it safe to repeat injections over a long period of time?

Long-term safety data did not identify cumulative toxicity following repeated injections. However, in some patients, the effectiveness may be reduced due to the formation of neutralizing antibodies (approximately 3-5%), in which case switching to a different serotype toxin should be considered [1].

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This article provides general medical information and does not replace an individual diagnosis or treatment plan. Please seek a medical assessment if symptoms persist.

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