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Uro-Neurology
Jalesh N Panicker,1 Clare J Fowler2
1
Locum Consultant Neurologist Neurogenic lower urinary tract dysfunction—the external and internal urethral sphincters,
in Uro-Neurology, Department so-called neurogenic bladder—can result from along with parasympathetic mediated detru-
of Uro-Neurology, The National many neurological conditions. The importance sor contraction.
Hospital for Neurology and
Neurosurgery, UCL Institute of of this problem to patient health and quality of ▶ Intact neural pathways between the bladder
Neurology, London, UK life is now better recognised, particularly as these and the pontine micturition centre are essen-
2
Professor of Uro-Neurology, days many of the symptoms can be treated.
Department of Uro-Neurology,
tial for the coordinated activity between the
The National Hospital for detrusor and urethral sphincters.
Neurology and Neurosurgery, ▶ The prefrontal cortex is responsible for com-
UCL Institute of Neurology, THE LOWER URINARY TRACT AND ITS
plex cognitive and socially appropriate behav-
London, UK NEUROLOGICAL CONTROL
iours, including voiding.
Optimal patient management requires an under-
Correspondence to standing of the physiology of the lower urinary
Dr J N Panicker, Department
of Uro-Neurology, The National tract, and its derangement in neurological dis- NEUROGENIC BLADDER DYSFUNCTION
Hospital for Neurology and ease. The lower urinary tract consists of the blad- Storage phase dysfunction most commonly
Neurosurgery, UCL Institute der and urethra and has just two roles: storage of results from lesions of the spinal or suprapontine
of Neurology, London WC1N urine and voiding at appropriate times. To regu-
3BG, UK; pathways controlling micturition. This results in
j.panicker@ion.ucl.ac.uk late this, a complex neural control system acts involuntary spontaneous or induced contractions
like a switching circuit to maintain a reciprocal of the detrusor muscle (detrusor overactivity)
relationship between the reservoir (storage) func- which can be identified during the fi lling phase in
tion of the bladder and the continence (voiding) urodynamic studies (figure 2).
function of the urethra (figure 1). The pontine Voiding phase dysfunction usually results from
micturition centre is responsible for switching lesions of the spinal or infrasacral pathways.
between the ‘storage’ phase and ‘voiding’ phase. In myelopathy, this is due to simultaneous con-
It in turn receives input from other centres, par- traction of the external urethral sphincter and
ticularly the periaqueductal grey of the midbrain, detrusor muscle—detrusor–sphincter dyssyner-
hypothalamus and cortical areas such as the pre- gia—which can result in both incomplete bladder
frontal cortex. emptying and abnormally high pressures in the
bladder. Impaired detrusor contractions due to
Storage phase reduced parasympathetic drive from the descend-
▶ In health, the bladder is in the storage phase for ing bulbospinal pathways may also contribute to
99.8% of the time, achieved by inhibition of incomplete bladder emptying. In lesions affect-
parasympathetic activity and so relaxation of ing the infrasacral pathway, such as of the cauda
the detrusor muscle of the bladder wall. This equina (or occasionally a peripheral neuropathy),
results in ‘bladder compliance’ so that intra- voiding dysfunction results from poorly sustained
vesical pressure remains below 10 cm H 2O. detrusor contractions and possibly non-relaxing
sphincters.
▶ Simultaneously, sympathetic and pudendal
nerve mediated tonic contraction of the ure-
thral sphincters ensures continence. COMPLICATIONS ARISING FROM THE
▶ Functional imaging suggests that the pon- NEUROGENIC BLADDER
tine micturition centre is tonically inhib- ▶ Detrusor overactivity and reduced bladder
ited during bladder filling by signals arising wall compliance result in raised intravesical
from the periaqueductal grey. Other areas pressure which can in turn lead to structural
that show ‘activation’ during bladder fill- changes in the bladder wall such as trabecula-
ing include the anterior cingulate gyrus and tions and diverticuli.
right insula. ▶ The upper urinary tract (kidney and ureter)
can also show changes such as vesicoureteric
Voiding phase reflux and hydronephrosis, predisposing to
▶ When it is consciously deemed appropriate renal impairment and even end stage renal
to void, the periaqueductal grey no longer disease.
exerts tonic inhibition on the pontine mic- ▶ For reasons that are unclear, upper urinary
turition centre. This results in relaxation tract damage and renal failure are surprisingly
of the pelvic floor muscles as well as the unusual in multiple sclerosis (MS).
Figure 1 Innervation of the lower urinary tract. (A) Sympathetic fibres (blue) originate in the T11–L2 segments of the spinal cord and run through
the inferior mesenteric ganglia (inferior mesenteric plexus, IMP) and the hypogastric nerve (HGN) or through the paravertebral chain to join the pelvic
nerves at the base of the bladder and the urethra. Parasympathetic preganglionic fibres (green) arise from the S2–S4 spinal segments and travel in
sacral roots and pelvic nerves (PEL) to ganglia in the pelvic plexus (PP) and in the bladder wall; this is where the postganglionic nerves that supply
parasympathetic innervation to the bladder arise. Somatic motor nerves (yellow) that supply the striated muscles of the external urethral sphincter
arise from S2–S4 motor neurons and pass through the pudendal nerves. L1, first lumbar root; S1, first sacral root; SHP, superior hypogastric plexus; SN,
sciatic nerve; T9, ninth thoracic root. (B) Efferent pathways and neurotransmitter mechanisms that regulate the lower urinary tract. Parasympathetic
postganglionic axons in the pelvic nerve release acetylcholine (ACh) which produces bladder contraction by stimulating M3 muscarinic receptors in the
bladder wall smooth muscle. Sympathetic postganglionic neurons release noradrenaline (NA) which activates β3 adrenergic receptors to relax bladder
wall smooth muscle and activate α1 adrenergic receptors to contract urethral smooth muscle. Somatic axons in the pudendal nerve also release ACh
which produces contraction of the external sphincter striated muscle by activating nicotinic cholinergic receptors. Reproduced with permission from
Fowler et al (Nat Rev Neurosci 2008;9:453–66).
▶ On the other hand, patients with spinal cord ▶ Patients with storage dysfunction complain of
injury are prone to upper tract damage and frequency of micturition, nocturia, urgency
renal disease, and have five times the age stan- and urgency incontinence.
dardised risk for renal failure compared with ▶ Patients with voiding dysfunction complain
the general adult population. of hesitancy, straining for micturition, slow
▶ Similarly, the risk is higher in adults with spina and interrupted stream or may be in urinary
bifida, who have an eight times risk for devel- retention. Unfortunately, the history of void-
oping renal failure, and this may be a leading ing function is often unreliable as more than
cause of death. 50% of patients may be unaware of incomplete
▶ Risk of renal failure is highest in patients who bladder emptying. The history should there-
have raised intravesical pressure due to detru- fore be supplemented by a bladder scans (see
sor overactivity, low bladder compliance and a below).
competent bladder neck. ▶ The bladder diary records the time and vol-
▶ Patients are prone to various genitourinary ume of each voiding, urinary output and epi-
tract infections such as cystitis, pyelonephri- sodes of incontinence and urgency, and is an
tis and epididymo-orchitis and also to bladder extension of the history (figure 3).
stones.
Screening for urinary tract infections
Combined rapid tests of urine, using reagent strips
DIAGNOSTIC EVALUATION for urinalysis (‘dipstick’ test), is advisable for
History patients presenting with new bladder symptoms
As ever, history taking is the cornerstone of evalu- or at follow-up if there are unexplained changes in
ation and should assess both the storage and void- bladder symptoms. The negative predictive value
ing phases of micturition. for excluding urinary tract infection is 98% but
Figure 2 Filling cystometry demonstrating detrusor overactivity. Red trace (Pabd), intra-abdominal pressure recorded by the rectal catheter; dark
blue trace (Pves), intravesical pressure recorded by the bladder catheter; pink trace (Pdet), subtracted detrusor pressure (Pves−Pabd). Green traces
represent volume infused during the test (Vinf) and volume voided (Vura) while the orange trace represents urinary flow (Qura). Black arrows indicate
detrusor overactivity and black arrowhead indicates incontinence.
cal examination, it is often important to estimate are more invasive tests that measure pressure–
postvoid residual urine by ultrasonography, most volume relationships during bladder fi lling
commonly using a portable bladder scanner, or by and voiding (figure 2).
‘in–out’ catheterisation. ▶ Urodynamic evaluation also helps to identify
Ultrasonography is helpful to exclude compli- concomitant local disorders that may contribute
cations such as bladder stones and should be per- to lower urinary tract dysfunction such as bladder
formed periodically to assess the integrity of the outlet obstruction due to prostate enlargement
upper urinary tract in patients known to be at in men and stress incontinence in women, and
risk of damage. their relative contribution to bladder symptoms.
contribute to bladder dysfunction. A single mea- ▶ Caffeine reduction may reduce urgency and
surement is not representative and, when pos- frequency in people who drink plenty of cof-
sible, several should be made over 1–2 weeks. fee and tea.
Complete bladder emptying is important for ▶ Bladder retraining, whereby patients void by
avoiding recurrent urinary tract infections, the clock and voluntarily ‘hold on’ for increas-
maintaining upper urinary tract function and ingly longer periods, aims to restore the nor-
optimising the management of storage symp- mal pattern of micturition.
toms. As there are no effective medications for ▶ Pelvic floor exercises and neuromuscular stim-
improving voiding, catheterisation is usually the ulation may have a role, if voiding dysfunc-
best option. tion has been excluded, for ameliorating mild
Clean intermittent self-catheterisation is preferred symptoms.
as it avoids the long term complications asso-
ciated with a permanent indwelling catheter. Antimuscarinic medications competitively inhibit
However, the patient’s cognitive state, moti- acetylcholine at muscarinic receptors and improve
vation, manual dexterity and visual acuity are urgency, frequency and incontinence; their effect
important factors to consider. Frequency of cath- is by relaxing the detrusor muscle. Since the intro-
eterisation depends on the postvoid residual vol- duction of oxybutynin, several newer agents have
ume, detrusor pressure and fluid intake. been marketed (table 2) but the only significant
Reflex voiding using trigger techniques, and difference between them is their adverse effect
Credé’s manoeuvre (non-forceful, smooth even profi le.
pressure from the umbilicus towards the pubis), Adverse effects resulting from the non-specific
are usually not recommended as they may result anticholinergic action include dry mouth, blurred
in high detrusor pressures and incomplete bladder vision for near objects, tachycardia and consti-
emptying during voiding. pation. These drugs can also block central mus-
Suprapubic vibration using a mechanical ‘buzzer’ carinic M1 receptors and cause impairment in
has been demonstrated to be effective in MS cognition and consciousness in susceptible indi-
patients with incomplete bladder emptying and viduals; this might be mitigated by medications
detrusor overactivity, but its effect is limited. with low selectivity for the M1 receptor such as
α-Blockers relax the internal urethral sphincter darifenacin or restricted permeability across the
in men and there is evidence that they improve blood–brain barrier such as trospium.
bladder emptying and reduce postvoid residual Postvoid residual urine may increase following
volumes. However, this is not consistently seen in treatment and should be monitored by repeat blad-
clinical practice unless there is concomitant blad- der scans, especially if initial beneficial effects are
der outlet obstruction. short lasting. In many patients, there may also be
Botulinum toxin injections into the external ure- underlying voiding dysfunction and often it is the
thral sphincter may improve bladder emptying judicious combination of antimuscarinic medica-
in patients with spinal cord injury and significant tion with clean intermittent self-catheterisation
voiding dysfunction. which provides the most effective management
for neurogenic bladder dysfunction (figure 5).
Storage dysfunction Desmopressin, a synthetic analogue of arginine
Non-pharmacological measures are generally effec- vasopressin, temporarily decreases urine produc-
tive in the early stages when symptoms are mild. tion and volume determined detrusor overactivity
by promoting water reabsorption at the distal and
▶ Fluid intake of around 1–2 l a day, although collecting tubules of the kidney. It is useful for the
this should be individualised and it is often treatment of frequency or nocturia in conditions
helpful to assess fluid balance by means of a such as MS and spina bifida, providing symptom
bladder diary. free periods of up to 6 h. It is also helpful in man-
aging nocturnal polyuria which may be seen in
Parkinson’s disease and dysautonomia. However,
it should be prescribed with caution in patients
Table 2 Antimuscarinic medications available in the UK (presented alphabetically) over the age of 65 years or with dependant leg
Generic name Trade name Daily dose (mg) Frequency oedema, and should not be used more than once in
24 h for fear of hyponatraemia and heart failure.
Darifenacin Emselex 7.5–15 od
Botulinum toxin type A injected into the detrusor
Fesoterodine Toviaz 4–8 od
muscle under cystoscopic guidance appears to be
Oxybutynin immediate release Ditropan, cystrin 2.5–20 bd–qds
Oxybutynin ER Lyrinel XL 5–20 od
a highly promising, although as yet unlicensed,
Oxybutynin transdermal Kentera 36 mg (3.9 mg/24 h) One patch twice weekly
treatment for intractable detrusor overactivity.
Propantheline Pro-banthine 15–120 tds (1 h before food) Although patients often have to perform clean
Propiverine Detrunorm 15–60 od–qds intermittent self-catheterisation afterwards,
Solifenacin Vesicare 5–10 od the effect lasts 9–13 months and it significantly
Tolterodine immediate release Detrusitol 2–4 bd improves storage symptoms and quality of life.
Tolterodine extended release Detrusitol XL 4 od Patients have fewer urinary tract infections and
Trospium Regurin 20–40 bd (before food) reduced urethral leakage when using an indwell-
bd, twice daily; od, once daily; qds, four times daily; tds, three times daily. ing catheter (catheter bypassing).
URINE INFECTION
▶ Urine should not be routinely tested unless
there are symptoms suggesting infection;
asymptomatic bacteriuria alone in a patient
performing clean intermittent self-catheteri-
sation is not an indication for antibiotics.
▶ Antibiotics should be limited to symptomatic
urinary tract infections.
▶ Unrestricted use of prophylactic antibiotics
can lead to drug resistance; however, in indi-
Figure 5 Algorithm for the management of neurogenic bladder dysfunction. viduals with proven recurrent urinary tract
Reproduced with permission from the BMJ Publishing Group (J Neurol Neurosurg infections in whom no urological structural
Psychiatry 2009;80:470–7). CISC, clean intermittent self-catheterisation; PVR, postvoid abnormality has been identified and whose
residual volume; UTI, urinary tract infection. intermittent catheterisation technique cannot
Figure 6 Stepwise approach to neurogenic bladder dysfunction management with progressing disability.