Chemical denervation of constrictor pharyngeus muscles with Botulinum toxin
Introduction and physiologic effects:
Botulinum toxin is an endotoxin produced by the microorganism clostridium botulinum. The disease Botulism is known since the 18th century and the bacteria causing it is isolated in the beginning of the 20th century.
The endotoxin blocks the acetylcholine release at the neuromuscular junction and is rapidly (in 30-60 minutes) taken up by contracting muscles. Clinical onset of the symptoms begins in 24-48 hours. The endotoxin causes a permanent denervation of the muscles with atrophy starting after 2 weeks. The nerve endings, however, always regenerate, a process that takes several months. Therefore, the duration of the effect is mostly not more than 3-6 months.
Botulinum toxin has a wide range of clinical applications in the head and neck region, such as blephorospasm, cervical and laryngeal dystonia, hemifacial spasm, strabismus, and more recently also for hypertonicity/spasm of the PE segment. Botulinum toxin is commercially available in 2 products: Botox (Allergan) and Dysport (Speywood) (the latter is 4 times less active). The effect is measured in MU (mouse units), where 1 MU = LD50 for Swiss Webster female mice. The LD50 for humans is approximately 2500-3000 MU. The single dose limit is 400 MU, and no serious reactions or adverse events are reported with this dose, but in clinical practice much lower doses are applied. Contraindications are: pregnancy, lactation, pre-existing neuromuscular diseases (myasthenia gravis, Easton-Lambert syndrome, ALS), and simultaneous use of drugs, affecting neuromuscular junctions, such as amino-glycosides.
Application in PE segment hypertonicity (2-5)
The dose of Botox advised mostly is 50-100 MU (4 times as much in case Dysport is used), which is considerably higher than in most other indications in the head and neck region. The toxin is easily inactivated, which means that the vial, which contains 100 MU, should be kept in the refrigerator until use. The toxin is reconstituted in 2 to 4 cc normal saline and should be used within 6 hours after reconstitution.
First, the position of the hypertonic bar of the PE segment should be determined. This can be achieved best by videofluoroscopy, which should be carried out in the same body posture wherein the injection will be performed afterwards. The upper and lower border of the hypertonic bar of the PE segment is marked in a resting position, using lead beads, taped on the skin.25
Next, the Botox solution can be injected unilaterally at the upper and lower marking site and halfway. We use 100 MU in a tuberculin syringe, injecting carefully between the carotid artery and the pharyngeal wall (it should be kept in mind that the carotid artery often is displaced medially after total laryngectomy). The needle is advanced onto the prevertebral fascia and then withdrawn 1 cm and Botox is injected at the 3 spots already mentioned. Alternatively, the procedure is carried out under EMG guidance, using a hollow 27 gauge EMG needle. However, it is advisable also in this case to mark the hypertonic bar of the PE segment in order to be more certain of the correct injection site.
The effect of the Botox treatment can be noticed in 24 hours, and, interestingly enough, if a positive effect is obtained, it can last much longer than the normal physiologic effect, which persists, as already mentioned, between 3 and 6 months. It is not unusual that a single injection is sufficient to achieve a permanent effect.
Botulinum toxin is an endotoxin produced by the microorganism clostridium botulinum. The disease Botulism is known since the 18th century and the bacteria causing it is isolated in the beginning of the 20th century.
The endotoxin blocks the acetylcholine release at the neuromuscular junction and is rapidly (in 30-60 minutes) taken up by contracting muscles. Clinical onset of the symptoms begins in 24-48 hours. The endotoxin causes a permanent denervation of the muscles with atrophy starting after 2 weeks. The nerve endings, however, always regenerate, a process that takes several months. Therefore, the duration of the effect is mostly not more than 3-6 months.
Botulinum toxin has a wide range of clinical applications in the head and neck region, such as blephorospasm, cervical and laryngeal dystonia, hemifacial spasm, strabismus, and more recently also for hypertonicity/spasm of the PE segment. Botulinum toxin is commercially available in 2 products: Botox (Allergan) and Dysport (Speywood) (the latter is 4 times less active). The effect is measured in MU (mouse units), where 1 MU = LD50 for Swiss Webster female mice. The LD50 for humans is approximately 2500-3000 MU. The single dose limit is 400 MU, and no serious reactions or adverse events are reported with this dose, but in clinical practice much lower doses are applied. Contraindications are: pregnancy, lactation, pre-existing neuromuscular diseases (myasthenia gravis, Easton-Lambert syndrome, ALS), and simultaneous use of drugs, affecting neuromuscular junctions, such as amino-glycosides.
Application in PE segment hypertonicity (2-5)
The dose of Botox advised mostly is 50-100 MU (4 times as much in case Dysport is used), which is considerably higher than in most other indications in the head and neck region. The toxin is easily inactivated, which means that the vial, which contains 100 MU, should be kept in the refrigerator until use. The toxin is reconstituted in 2 to 4 cc normal saline and should be used within 6 hours after reconstitution.
First, the position of the hypertonic bar of the PE segment should be determined. This can be achieved best by videofluoroscopy, which should be carried out in the same body posture wherein the injection will be performed afterwards. The upper and lower border of the hypertonic bar of the PE segment is marked in a resting position, using lead beads, taped on the skin.25
Next, the Botox solution can be injected unilaterally at the upper and lower marking site and halfway. We use 100 MU in a tuberculin syringe, injecting carefully between the carotid artery and the pharyngeal wall (it should be kept in mind that the carotid artery often is displaced medially after total laryngectomy). The needle is advanced onto the prevertebral fascia and then withdrawn 1 cm and Botox is injected at the 3 spots already mentioned. Alternatively, the procedure is carried out under EMG guidance, using a hollow 27 gauge EMG needle. However, it is advisable also in this case to mark the hypertonic bar of the PE segment in order to be more certain of the correct injection site.
The effect of the Botox treatment can be noticed in 24 hours, and, interestingly enough, if a positive effect is obtained, it can last much longer than the normal physiologic effect, which persists, as already mentioned, between 3 and 6 months. It is not unusual that a single injection is sufficient to achieve a permanent effect.
Example of a hypertonic voice and videofluoroscopy before and after Botox treatment
