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Overactive Bladder
Table 1: Important Definitions from the Standardisation of
Botulinum Injections
Terminology by the International Continence Society
1
Botulinum neurotoxin-A (BoNT-A) prevents synaptic release of
neurotransmitters, notably from cholinergic terminals but perhaps
Urgency The complaint of a sudden compelling desire to pass
additionally affecting other transmitters. This has the effect of
urine that is difficult to defer
Increased daytime frequency The complaint by the patient who considers that he/
counteracting nerve-evoked detrusor contraction. However, it may also
she voids too often by day
have effects on the afferent limb of the micturition reflex, consequently
Nocturia The complaint that the individual has to wake one or reducing the level of sensory information,
27
thus raising the total
more times at night to void
intravesical volume at which bladder contractions arise and counteracting
Overactive bladder syndrome Urgency, with or without urge incontinence, usually
the increased filling sensations that characterise OAB. Thus, from a
with frequency and nocturia
background of successful management of DO in neuropathic bladder
Detrusor overactivity A urodynamic observation characterised by
dysfunction,
28
a substantial amount of evidence has been published to
involuntary detrusor contractions during the filling
phase, which may be spontaneous or provoked
support the clinical efficacy of intramural injections of BoNT-A in
idiopathic DO.
Antimuscarinic drugs have to be given in sufficient doses and duration, and
patients need to be informed of what to expect from the drugs. Where the One particular concern is the possibility of increasing post-void residual
first-line drug is ineffective or poorly tolerated, alteration of the dose or volume, which is seen in 43% of women with idiopathic DO receiving
drug should be considered, since responses are often idiosyncratic with 200 units of one BoNT-A formulation;
29
a lower dose may reduce the risk
regard to both efficacy and adverse effects. The first-line choice of drug of this problem.
30
Nonetheless, this method is currently unlicensed for
varies, hampered by the relative lack of trials undertaking direct comparison both neurogenic and idiopathic DO and OAB. There is more than one
between agents.
15
The area is still evolving, with the recent introduction of commercially available compound marketed and they are not dose-
another oral antimuscarinic drug, fesoterodine,
16
and research into gel- equivalent. For each type of BoNT-A, substantial work is still needed to
based topical preparations of oxybutynin.
17
identify optimal dose, sites of injection and maintenance regimes.
31
Furthermore, predictors of response are needed regarding both efficacy
Specialised Treatment of Detrusor Overactivity and urinary retention, and to demonstrate efficacy and safety
The emphasis on urinary urgency in OAB indicates that the main feature after long-term use. The area is evolving rapidly for patients who are
is the sudden compelling desire to pass urine and drives the justification bothered by symptoms and are willing to accept the risk of needing to
for use the of antimuscarinic drugs with only minimal investigation. In self-catheterise, but currently BoNT-A is used off-licence for refractory
refractory OAB, the objective demonstration of urodynamic parameters OAB in many centres.
is recommended in the EAU Guidelines on Urinary Incontinence. For
both detrusor overactivity (DO) and people with increased bladder Basic Science
sensation – which replaces sensory urgency in the ICS nomenclature – The ability of urodynamic studies to objectively demonstrate overactive
the recommended options are neurostimulation, sacral blockade, detrusor contractions and the established pharmacological and
botulinum toxin detrusor injections, bladder augmentation/substitution physiological approaches to investigate nerve and muscle function means
or urinary diversion. there is extensive literature on the scientific basis of DO, underpinned by
two main hypotheses. The neurogenic hypothesis states that damage to
Neurostimulation central inhibitory pathways or sensitisation of peripheral afferent
Sacral neuromodulation has shown sustained improvement in symptoms terminals in the bladder can unmask primitive voiding reflexes that trigger
in a proportion of patients with OAB or urgency incontinence.
18
There are bladder overactivity.
32
The myogenic hypothesis states that alterations in
health-economic implications, with a high initial cost and the need for the functional properties of detrusor myocytes are a common feature of
careful follow-up. Tibial nerve stimulation is effective in a proportion of all forms of DO,
33
comprising muscle cell supersensitivity and increased
patients with refractory OAB,
19
but ongoing maintenance treatment is intercellular communication. Since the myogenic and neurogenic
needed in the majority.
20
Alternative strategies for nerve stimulation are hypotheses were put forward, there have been ongoing developments in
in development,
21
including stimulation of the pudendal nerve.
22
understanding the cellular physiology of the bladder and the organisation
of the CNS.
Augmentation Cystoplasty
This method has long been the main surgical procedure in severe Smooth Muscle
refractory DO.
23
Detrusor myectomy, also termed autoaugmentation, The detrusor myocyte manifests several functional changes in OAB/DO,
has been reported as having sustained benefits,
24
but is not including changes in the surface ion channels.
34,35
The nature of the
widely undertaken. second messenger pathways involved in mediating myocyte contraction
is also becoming more clearly understood: in addition to the importance
Urinary Diversion of the inositol triphosphate pathway,
36
the roles of Rho kinase, cyclic
This procedure is undertaken in severe cases following careful adenosine monophosphate (cAMP)
37
and calcium sensitisation
38
have
consideration. The evidence as to outcome in these patients is limited.
25
become apparent. Potentially, it may be possible to influence bladder
Other previously used procedures aimed at reducing sensory information contractility at this level, for example by modulating the intracellular
reaching the central nervous system (CNS), notably bladder distension phosphodiesterases (PDEs),
39
particularly PDE1 and PDE4.
40
Furthermore,
and other denervation techniques. However, while initial results were alterations in intercellular connectivity are seen in animal models,
41
which
sometimes good, long-term outcomes were unsatisfactory.
26
These could aid insight into the abnormal propagation of spontaneous activity,
approaches are not recommended by expert bodies. which is a feature of DO.
42
56 EUROPEAN UROLOGICAL REVIEW
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