Botulinum toxin In ortho

1. BOTULINUM TOXIN IN
ORTHOPAEDICS

2. INTRODUCTION
• Emile Pierre van Ermengem, Professor of Bacteriology at the
University of Ghent, first discovered the bacterium Clostridium
botulinum in the late 19th century, naming it after the food
poisoning sustained after ingestion of blood sausage described
earlier that century by a German physician, Justinus Kerner (the
Latin for sausage is botulus).
• Botulinum toxin (BTX) was used successfully as a research tool in
the study of the physiology of the spinal cord in the 1970s, and
subsequently BTX-A injections were first used therapeutically as a
treatment for strabismus in the early 1980s.
• The first published report of the orthopaedic use of BTX-A to treat
spasticity in children with cerebral palsy was published in 1993.
• Clostridium botulinum produces a complex mixture of proteins
containing botulinum neurotoxin and several non-toxic proteins

3. Botulinum toxin and its mechanism of
action
• There are seven different serotypes of the
neurotoxin, named A to G.
• all inhibit release of acetylcholine from nerve
terminals, they vary greatly in their intracellular
protein targets, potency and duration of effect.
• BTX-A is the serotype which has been studied
most widely in terms of therapeutic application
• BTX-B and BTX-F have also been used in clinical
practice, but are less potent than BTX-A and have
a shorter duration of action.

4. mechanism of action

5. • The specific protein complex involved, a soluble (N-ethylmaleimide-
sensitive fusion (NSF)) attachment protein receptor (SNARE) complex,
mediates the fusion of neurotransmitter-containing vesicles with the
synaptic membrane.
• BTX-A destabilises the SNARE complex by cleaving SNAP-25
• By preventing release of acetylcholine at the neuromuscular junction, BTX
reduces muscular activity in a dose-dependent manner.
• Within four weeks, restoration of the turnover of the SNARE protein
complex allows exocytosis of acetylcholine to resume
• To maximise the clinical effectiveness of BTX-A, several conditions must be
met. The toxin must be injected inside the fascial compartment of the
muscle, in a dose sufficient to neutralise neuromuscular junction activity
and in an appropriate volume so that diffusion to these junctions in the
end-plate zone occurs while unwanted spread is minimised.

6. Techniques for administration
• BTX-A is available as two commercial preparations, Botox
(100 International Units (IU) per vial; Allergan Inc, Irvine,
California) and Dysport (500 IU per vial; Ipsen Ltd, Slough,
United Kingdom).
• The most effective dose per muscle is unknown, although
recommendations have been given.14 It is likely that the
dose required for effective muscle weakening varies with
the density of neuromuscular junctions in any given
muscles and perhaps with the pathology being treated as
well as its chronicity.
• There is a total-body dose which must not be exceeded if
toxicity is to be avoided. The recommendations for a safe
total-body dose are 12 units/kg for Botox and 30 units/kg
for Dysport

7. • Localisation of the individual target muscle is often
done by palpation and based on clinical experience and
anatomical knowledge.(IN THE COSMETIC INDUSTRY)
• Chin et al have recommended the use of electrical
stimulation or other guided techniques for the accurate
placement of the needle in all muscles.
• Since the toxin exerts its effect at the neuromuscular
junctions and as, in many muscles, these lie in well-
defined zones, there is a view which supports targeting
the injection at the end-plate zone.

8. • Motor points, defined as the area in a muscle
where a minimal-intensity, short-duration
electrical stimulus causes contraction.
• the motor point corresponds to the area in the
muscle where small motor nerves terminate, and
effectively correlates with a point distal to the
entrance of the nerve into the muscle. For many
muscles, localisation of the motor point is
probably as logical, appropriate and easier than
that of the end-plate zone

9. Indications for use
• the use of BTX has gained popularity as a
treatment for spastic or dystonic muscle, most
commonly due to damage to the central
nervous system.
• Its most frequent use is in children with
cerebral palsy, but many other potential uses
have been identified

10. EXAMPLES
1. Alter motor function by improving the balance between agonist and
antagonist forces(Improve equinus gait in cerebral palsy Improve arm
function following a cerebrovascular accident Bladder control in spinal
injury)
2. Prevention of deformity(Acetabular dysplasia in cerebral palsy Glenoid
dysplasia in obstetric brachial plexus palsy)
3. Decrease ‘spasticity’-related pain.(Cerebral palsy)
4. Improve quality of life(Prevention of involuntary movements )
5. Pre-surgical diagnostic tool(Predicting the effect of release of tendo
Achillis Improvement of hand function in cerebral palsy).
6. Protection of soft-tissue repair(Flexor tendon repairs in children).
7. In patients with progressive subluxation of the hip, symptoms of pain
and stiffness can be improved by the injection of the involved adductors
and iliopsoas, when combined with bracing of the hip in abduction.
8. The concomitant use of a plaster cast with BTX injections is quite
common

11. Other conditions of the central
nervous system
• Multiple sclerosis.
• Stroke(improvements in the pain associated with
spasticity, the range of movement in the joints and
function of the upper limb have been noted after BTX
injections.)
• Head injury.(once an equinus posture had developed,
BTX injections improved gait and the range of
movement.)
• Spinal injury(BTX injections are used most frequently to
aid the control of bladder function. Injections have also
been used for relief from pain and the avoidance of
joint contracture and muscle shortening)

12. Other orthopaedic conditions
• Congenital talipes equinovarus
• Congenital muscular torticollis.
• Pain syndrome(The study by Barwood et al
which found a significant reduction in post-
operative pain in children with cerebral palsy
secondary to a reduction in muscle spasm)
• Tendon repair.

13. Contraindications
• Resistance or antibodies to BTX-A
• Fixed deformity or contracture
• Failure of previous response
• Concurrent use of aminoglycosides.

14. Thank you.