Neurolysis

Author(s): Supreet Deshpande, MD, Mark E. Gormley Jr.

Originally published:09/20/2013

Last updated:09/20/2013

1. OVERVIEW AND DESCRIPTION

Definition

Chemical neurolysis is the destruction of a motor nerve achieved by injecting an agent, typically phenol, onto the nerve. Chemodenervation is the blockade of neuronal signaling using botulinum toxin (BTX). Appropriate procedures will result in significant functional improvement in conjunction with other treatments to treat generalized tone reduction. They can be utilized safely in children older than infants and may be used indefinitely if continued functional gains are seen. Optimum management of hypertonia may prevent contractures, increase tolerance of braces, and improve function, cares, comfort, and positioning.

Mechanism of Action

  1. Phenol (or carbolic acid): phenol denatures proteins at concentrations of 5% or more. When phenol is injected onto a motor nerve, either before or after it enters the target muscle, the nerve undergoes demyelination. Phenol is not commonly used to treat cervical dystonia because of concerns of diffusion to other vital structures in the neck, including the phrenic nerve and vascularity.
  2. BTX: BTX blocks the release of acetylcholine at the distal axon causing blockade of both alpha and gamma motor neurons and decreases spasticity by both weakening the extrafusal muscle and decreasing the excitability of the muscle spindle. BTX is an exotoxin produced by Clostridium botulinum; it has 8 serotypes, A through G. Only BTX types A and B are used therapeutically. BTX is available in several different forms, with different dosing guidelines and similar adverse event profiles. The following types of BTX are available: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB.

Summary of Food and Drug Administration-Approved BTX Products

OnabotulinumtoxinA AbobotulinumtoxinA IncobotulinumtoxinA RimabotulinumtoxinB
Cervical dystonia Yes Yes Yes Yes
Glabellar lines Yes Yes Yes
Blepharospasms Yes Yes
Strabismus Yes
Axillary hyperhidrosis Yes
Upper extremity spasticity Yes
Chronic headaches Yes
Overactive bladder Yes

BTX injections used for other indications and in children are considered off-label.

Side Effects or Complications

  1. Phenol
    • Dysesthesias if a sensory nerve is infiltrated, local infection, injection site pain, and edema can occur. Intravascular injections can lead to seizures and central nervous system or cardiovascular depression.
  2. BTX
    • Pain at injection site, systemic spread (more probable with higher doses and in vulnerable patients), excessive focal weakness, and flu-like symptoms.
    • BTX type B more frequently cause autonomic adverse effects.

Both phenol and BTX reduce hypertonia temporarily and need to be repeated periodically. Phenol is more technically difficult to perform, and the effects typically last longer.

2. RELEVANCE TO CLINICAL PRACTICE

Available or Current Treatment Guidelines

  1. Selection of BTX only, phenol only, or a combination of BTX and phenol is dependent on the number of muscle groups to be injected. BTX is preferred in smaller, deeper muscles and also muscles innervated by highly mixed sensorimotor nerves. Phenol is selected for treatment of nerves, which are primarily motor neurons. Phenol is often used in conjunction with BTX when a large number of muscle groups needs treatment for spasticity.

Phenol

  1. Motor point stimulation, using needle electrostimulation, is used to identify the peripheral or intramuscular nerve to a spastic muscle. The electric stimulation is decreased, and the needle is reoriented until the minimum current required to obtain a muscle twitch is reached. This technique facilitates a close approximation to the nerve. A 5% to 7% aqueous phenol solution is then injected.
  2. Dosing is less than 1 g per treatment session in adults and less than 30 mg/kg in children.
  3. Results last 3 to 12 months.
  4. Incidence of dysesthesias is 2% to 32% in adults and less than 5% in children; dysesthesias can last a few weeks.
  5. Compressive garments and systemic analgesic treatment are sometimes needed to treat dysesthesias.
  6. Inexpensive and widely approved.

BTX

  1. Dose depends on commercial formulation of BTX, age, weight, and target muscles.
  2. Most efficacious when injected close to the motor points. Localization techniques used include anatomic localization using palpation (which may not yield injection close to the motorpoint), electromyography (EMG) guidance, electric stimulation (ES), sonography, and computerized tomography guidance.
    • Palpation: after palpating the target muscle, the needle is inserted in the midbelly of the muscle with the goal of injecting into the target muscle, even if this may not be as close as possible to the neuromuscular junctions. Needle movement seen with passive movement of the distal joint is used to aid in confirmation of needle placement in the target muscle, but once again does not necessarily place the injection near the motor point.
    • EMG guidance: motor unit potentials (MUPs) that are close to the needle tip are identified either by morphology or acoustic properties. Crisp, full-sized MUPs confirm needle tip near the contracting muscle fibers. EMG guidance only indicates the needle being in an active muscle and not a specific muscle.
    • ES: When ES is used for guidance, the needle electrode is introduced into the desired muscle, and the muscle is stimulated. BTX is injected once contraction of only the desired muscle is noted. With ES, proximity of the needle tip to the motor endplate zones is confirmed, and the ability of BTX to diffuse in the muscle is relied on.
    • Sonography or ultrasound (U/S) guidance: real-time visualization of the target muscle makes U/S a very helpful guide when targeting muscles. It does require proficiency with using the U/S machine to identify muscles and the needle. The needle, although in the muscle, may not be close to the motor endplates.
    • Computerized tomography: rarely used for identifying muscles because of cost and time limitations.
  3. Dosing: BTX type A: onabotulinumtoxinA and incobotulinumtoxinA dosing is comparable (1:1), whereas onabotulinumtoxinA compared with abobotulinumtoxinA has a reported 1:3 to 1:6 dosing ratio. Dosing guidelines in children are up to 12 U/kg to a maximum of 400 U; in adults, a maximum dose is 400 to 600 U, with more limited dosing for an individual muscle or limb.
  4. Effects of abobotulinumtoxinA may last a little longer than onabotulinumtoxinA and incobotulinumtoxinA. Effects last between 12 and 30 weeks.
  5. Side-effects secondary to systemic spread are possible when higher doses are used. Molecular size of BTX prevents it from crossing the blood brain barrier. The side-effect profile for onabotulinumtoxinA and incobotulinumtoxinA are similar; although, abobotulinumtoxinA seems to produce more local side-effects, which could be because of more diffusion or conversion factors being incorrect. BTX type B has a lower pH value compared with the BTX type A formulations, which could cause more injection site pain. BTX type B also has a relatively stronger autonomic effect, such as dry mouth, corneal irritation, and accommodation difficulties.
    • Safety of use during pregnancy has not been established. Caution should be rendered when using BTX in patients with neuromuscular conditions or neuromuscular junction disorders. Aminoglycosides may potentiate the efficacy of BTX and should be avoided.
  6. Antigenicity: because BTX consists of foreign proteins, antibodies can be formed against these proteins. Risk factors for antibody production include the amount of toxin used at each visit and short treatment intervals. Antibodies can be detected serologically or by assessing paralysis after unilateral frontalis or extensor digitorum brevis injections.
  7. If treatments are insufficient, consider increasing dose and dilution, changing injection technique, or adding phenol blocks. If these measures are ineffective, then surgical interventions should be considered, such as iliotibial band, orthopedic procedures, and partial peripheral neurectomies.

3. CUTTING EDGE/UNIQUE CONCEPTS/EMERGING ISSUES

BTX is now being used to treat the following:
  1. Neurogenic detrusor overactivity, which is involuntary detrusor contractions during the filling phase observed in urodynamic studies and neurogenic overactive bladder, which is a symptom complex, including urgency, frequency, and nocturia with or without urge incontinence, can be treated with BTX. Doses of a maximum of 300 U (10 to 12 U/kg in children) injected into 30 detrusor sites has been efficacious.
  2. Bruxism: injecting the masseters and/or the temporalis with up to 100 U of BTX type A helps reduce pain and discomfort.
  3. Sialorrhea: treated with BTX type A by injecting the parotid and submandibular glands with the recommended maximum total dose of 100 U. Ultrasound guidance is recommended.
  4. Spasm of rectal sphincter: BTX type A injected into both the internal and external sphincters helps reduce rectal sphincter spasms. Doses up to 80 U are safe, and fewer side-effects are seen when eliminating injections into the external sphincter.
  5. Hyperhidrosis: axillary, palmar, and plantar hyperhidrosis requires multiple injections, commonly injected in aliquots of 2 to 3 U per site. Commonly, 50 U is used for each axilla. Palmar and plantar injections are more painful. Doses of 120 to 220 U have been used. Best responses are seen with concentrations of 20 U/mL.
  6. Facial wrinkles: BTX has been used to treat facial wrinkles since 1992. BTX type B may produce a greater area of diffusion and a more rapid onset of action than BTX type A.
  7. Pain: the ablility of BTX to inhibit neuropeptide release from nociceptors, thereby blocking central and peripheral pain sensitization processes, is utilized to treat chronic headaches and myofascial pain.

4. GAPS IN KNOWLEDGE/EVIDENCE BASE

Although BTX has been approved for the use of focal spasticity, cervical dystonia, hyperhidrosis, and glabellar wrinkles in adults, more class I studies are needed to determine safety and efficacy in children and other off-label uses. Also, further studies are needed to optimize dosing, injection guidance, injection distribution, and dilution.

REFERENCES

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