Botulinum toxin for neuropathic bladder

Amir Hooshang Vahedi MD - Physiatrist

Neuroanatomy and Neurophysiology of Voiding

Central Pathways Corticopontine Mesencephalic Nuclei–

Frontal Lobe Pontine Mesencephalic Pelvic and Pudendal Nuclei–Sacral

Micturition Motor Cortex to Pudendal NucleusPeripheral Pathways Parasympathetic Efferents–S2–S4 Sympathetic Efferents–T11–L2 Somatic Efferents–S2–S4 Afferent Fiber

Urethral Sphincter

Internal Sphincter: Innervated by T11–T12 sympathetic

nerve Contracts sphincter for storage Smooth muscleExternal Sphincter: Innervated by S2–S4 pudendal nerve Prevents leakage or emptying Skeletal muscle, voluntary control

autonomic receptors Cholinergic Muscarinic–M2:Located in the bladder wall, trigone,

bladder neck, urethra Beta 2 Adrenergic:Concentrated in the body of the bladder,

neck Alpha adrenergic:Located on the base of the bladder (neck

and proximal urethra)(Note: Bladder wall does not have

baroreceptors alpha)

Bladder and proximal urethra

distribution of autonomic receptors

Note:Alpha Adrenergic receptors

respond to the appearance of norepinephrine with contraction

Beta adrenergic receptors respond to the appearance of norepinephrine with relaxation

StorageSympatheticT11–L2 sympathetic efferents Travel through the hypogastric nerve Causes the sphincter to contract and body to

relax Urine is storedAlpha1 Receptors Adrenergic NE causes contraction of neck of bladder and

prevents leakage Closes internal urethral sphincter and detrusor

outlet, promoting storageB2 Receptors Adrenergic Located in body of bladder Activation causes relaxation of body of bladder

to allow expansion Inhibitory when activated

Storage reflexes.

During the storage of urine, distention of the bladder produces low-level bladder afferent firing. Afferent firing in turn stimulates the sympathetic outflow to the bladder outlet (base and urethra) and pudendal outflow to the external urethral sphincter. These responses occur by spinal reflex pathways and represent “guarding reflexes,” which promote continence. Sympathetic firing also inhibits detrusor muscle and transmission in bladder ganglia.

EmptyingParasympatheticMuscarinic (M2) cholinergic receptors are

located in The bladder wall Trigone Bladder Neck UrethraStimulation of pelvic nerve

(parasympathetic) Allows contraction of bladderB2 Receptors Adrenergic Relaxation of the bladder neck on the

initiation of voiding

Voiding reflexes.

At the initiation of micturition, intense vesical afferent activity activates the brainstem micturition center, which inhibits the spinal guarding reflexes (sympathetic and pudendal outflow to the urethra). The pontine micturition center also stimulates the parasympathetic outflow to the bladder and internal sphincter smooth muscle. Maintenance of the voiding reflex is through ascending afferent input from the spinal cord, which may pass through the periaqueductal gray matter (PAG) before reaching the pontine micturition center.

LMN Bladder:Big Hypotonic Bladder (flaccid,

areflexic bladder),Tight Competent Sphincter

Results in:Failure to Empty

UMN Bladder:Small Hyperreflexic, Overactive,Little

BladderResults in:Failure to Store

(Incontinence)

Therapy with Botulinum toxinincreases maximal cystometric

bladder capacity reduces maximum detrusor pressurereduces incontinence episodes

Functional bladder capacity = voided volume + residual urine volume

Detressor pressure=bladder pressure-rectaum pressure

Botulinum toxin injection of the detrusor muscle has proved a valuable tool in refractory conditions with hyperactive bladders.

The botulinum toxin is diluted in normal saline and injected through a cystoscope.

Most patients will have a therapeutic benefit that lasts for more than six months.

Some patients with problems with pain from a catheter or by-passing owing to a hyper-reflexic bladder can benefit from intravesical botulinum toxin.

The role of botulinum toxin in the management of this problem is not certain.

A recent trial had to be stopped prematurely as patients with multiple sclerosis and detrusor–sphincter dyssynergia receiving intravesical botulinum toxin showed no improvement in relation to placebo-injected controls.

Several studies have shown the effectiveness of intraperineal urethral injection of botulinum toxin in patients with spinal cord injuries.