Craniofacial Muscles

300 J. Park et al.
Botox ® in humans is estimated as 39 units/kg and 2,500–3,000 units for a person
weighing 70 kg (Osako and Keltner 1991 ; Harrison 2003 ; Cather and Menter 2002 ) .
Based on several studies and our own personal experience, it seems that 100 units
of Botox ® or Xeomin ® are bioequivalent to 300 units of Dysport ® with a conversion
factor of 1 Botox ® or Xeomin ® unit to 3 Dysport ® unit and 50–100 Myobloc ® (Jost
et al. 2007 ; Odergren et al. 1998 ; Ranoux et al. 2002 ; Dressler 2009 ) .
BoNTs act on the peripheral nervous system where they interrupt calcium-mediated
exocytosis of acetylcholine-containing vesicles at the motor endplate within
the neuromuscular junction. It is mediated by inhibition of the proteolytic cleavage
of different proteins of the acetylcholine transport protein cascade (soluble
N -ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) proteins).
BoNT/A hydrolyses synaptosomal-associated protein 25 (SNAP-25), which is
located on the presynaptic cell membrane, whereas BoNT/B acts on synaptobrevin
or vesicle-associated membrane protein (VAMP), which is embedded in the
membrane of the acetylcholine vesicles. By cleaving these target proteins, BoNT
prevents the fusion of the synaptic vesicle with the presynaptic membrane, thereby
blocking the release of acetylcholine into the synaptic cleft (chemodenervation).
BoNT/A consists of a heavy chain (100 kDa) and a light chain (50 kDa) of neurotoxin,
but only the light chain is responsible for the pharmacological action of BoNT
(Daniele Ranoux 2007 ; Dressler 2010 ) .
The neurotoxin acts on individual motor neuron terminals, and its effects occur
within hours of binding to the nerve cell membrane. The onset of action is gradual
and continues until the end-plate potential is reduced to an extremely low level.
Muscle weakness might become clinically evident in 2–7 days after the injection
because of the continued release of acetylcholine from vesicles that have not been
blocked by the toxin. Some reports indicate that Dysport ® has a quicker onset of
action, and can be as short as 1 day.
The local weakening effect is dose related and with a peak effect at 1–2 weeks
after injection, and the symptom-free duration lasts for 2–3 months in 90% of
patients (Dutton and Buckley 1988 ) . More than 5% of treated patients experience
relief for longer than 6 months, whereas some patients require injections as often as
monthly. Restoration of muscle activity is usually complete by 3–4 months after the
injection, and results from sprouting of the axon and the formation of additional
motor endplates de novo (Harrison 2003 ) . Histopathologically, the nerve terminals
show a mild degree of demyelinating changes after toxin. Subsequent regeneration
is seen at the neuromuscular junctions in the form of “onion bulb” formations and
nerve sprouting (Osako and Keltner 1991 ) . Patients should be aware that the aim of
treatment is to control rather than cure their symptoms, and the injection must be
repeated inde fi nitely because of its transient effect.
BoNT/A preparations should be rehydrated with preservative-free physiologically
normal saline, which should be introduced slowly into the wall of the vacuumsealed
vial to prevent frothing. Most physicians reconstitute Botox ® (100 units/vial)
in 2 mL of non-preserved saline so as that 0.1 mL solution contains 5 units of
Botox ® . The manufacturers recommend discarding the BoNT solutions after 4–24 h
of reconstitution, but many studies have shown clinical activity that persists for
several weeks after reconstitution.