1. Sharon English Urologist Christchurch
Taking the Wrinkles out of the Bladder The Use of Botulinum Toxin in the Bladder
Sharon English
Urologist
Christchurch

2. After I started botoxing I just could not stop

3. Medical Uses of Botulinum Toxin
blepharospasm pelvic pain
strabismus
achalasia focal dystonias
muscle spasms
spasticity wrinkles
hyperhidrosis bladder overactivity
painful bladder migraine
1949 recognised that Botulinum toxin blocked nerve synapses
first medical use in stabismus and blepharospasm

4. Clostridium botulinum spore prior to germination
The lethal dose of botulinum toxin for humans is not known but can be estimated from primate studies. By extrapolation, the lethal amounts of crystalline type A toxin for a 70-kg human would be approximately µg intravenously or intramuscularly, µg inhalationally, and 70 µg orally.10, Therapeutic botulinum toxin represents an impractical bioterrorist weapon because a vial of the type A preparation currently licensed in the United States contains only about 0.3% of the estimated human lethal inhalational dose and 0.005% of the estimated lethal oral dose.
All forms of botulism result from absorption of botulinum toxin into the circulation from either a mucosal surface (gut, lung) or a wound. Botulinum toxin does not penetrate intact skin

5. Botulinum Toxin A (Botox®)
7 distinct types
Botulinum toxin A,B,C,D,E,F,G
Type A and B used in medicine

6. Mechanism of Action of Botulinum Toxin
Figure 1. Mechanism of Action of Botulinum Toxin
A, Release of acetylcholine at the neuromuscular junction is mediated by the assembly of a synaptic fusion complex that allows the membrane of the synaptic vesicle containing acetylcholine to fuse with the neuronal cell membrane. The synaptic fusion complex is a set of SNARE proteins, which include synaptobrevin, SNAP-25, and syntaxin. After membrane fusion, acetylcholine is released into the synaptic cleft and then bound by receptors on the muscle cell. B, Botulinum toxin binds to the neuronal cell membrane at the nerve terminus and enters the neuron by endocytosis. The light chain of botulinum toxin cleaves specific sites on the SNARE proteins, preventing complete assembly of the synaptic fusion complex and thereby blocking acetylcholine release. Botulinum toxins types B, D, F, and G cleave synaptobrevin; types A, C, and E cleave SNAP-25; and type C cleaves syntaxin. Without acetylcholine release, the muscle is unable to contract. SNARE indicates soluble NSF-attachment protein receptor; NSF, N-ethylmaleimide-sensitive fusion protein; and SNAP-25, synaptosomal-associated protein of 25 kd.

7. Mechanism of Action of Botulinum Toxin
blocks neuromuscular conduction
binds to receptor sites on motor nerve terminals
inhibits release of acetylcholine (ACh)
Inhibition involves cleavage of SNAP-25,
a protein necessary for the release of ACh from vesicles within nerve endings.
Results in a partial chemical denervation causing a localised paralysis

8. Regrowth of Axons

9. Uses of Botulinum Toxin in Urology and Gynaecology
neuropathic bladder conditions
detrusor overactivity
detrusor sphincter dysenergia
bladder overactivity
painful bladder syndrome
pelvic pain
outflow obstruction symptoms
urinary retention

10. Injecting Botulinum into the Bladder
100 units diluted with 10mls of normal saline
given as 1 ml injections
dose of units
spare the trigone

11. Injecting Botulinum Toxin
Rigid cystoscope
using GA
day patient
higher doses
more precise
Flexible cystoscope
using LA
outpatient clinic
well tolerated

12. Injecting Botulinum toxin

13. Flexible Cystoscopy

14. Injection of Botulinum Toxin in the Bladder

15. Side Effects Very rare Contraindications no severe effects reported
minor effects
dysphagia, diplopia, blurred vision
periheral muscle weakness
Contraindications
pre-existing neuromuscular conditions

16. Bladder Overactivity Collection of Symptoms
urgency
urge incontinence
frequency
nocturia
Very common problem especially in the elderly

17. Treating Bladder Overactivity
Treatment
oxybutynin
imipramine
very expensive anticholinergics
major surgery
Now can offer Botulinum toxin if medications do not work

18. Choosing the Botox Patient
Symptoms of urgency, urge incontinence
No UTIs
Failed/intolerant oxybutynin
No voiding dysfunction
Urodynamics

19. Urodynamics showing Detrusor Overactivity

20. Treating Bladder Overactivity with Botulinum Toxin
Effects take 1-3 weeks
Check residual if symptoms worsen
Retention improves after 6-8 weeks
UTIs
Effects last 6-16 months
Can repeat treatment

21. Literature Results 100 units 200 units Urge incontinence resolved 86%
Nocturia 4 – 1.5
Frequency 14 – 7
Retention 4%
200 units
Urge incontinence resolved 50%
Nocturia
Frequency 15 – 8
Retention 37%

22. Repeat Treatments Effect on smooth muscle Repeat treatments results in
fades after 6-12 months
axonal regeneration
Repeat treatments results in
same response
antibodies to Type A very uncommon

23. Neurogenic Detrusor Overactivity
Occurs in
spinal cord injury
multiple sclerosis
Parkinson’s
post-stroke

24. Neurogenic Detrusor Overactivity

25. Neurogenic Detrusor Overactivity
10 unit injections
Use a higher dose: 300 units
Patients already self-catheterising

26. Painful Bladder Syndrome
Two studies
one effective
one ineffective
Tried two patients with mixed effect
Raises questions as to how Botulinum toxin works