Botulinum toxin for neuropathic bladder Case Studies in Neurological Rehabilitation Alireza Ashraf, M.D. Associate Professor of Physical Medicine & Rehabilitation Shiraz Medical school
A 36-year-old woman with a 12 year history of multiple sclerosis;used tolterodine, intermittent catheterisation and intravesicaloxybutininto manage her neuropathic bladder but was still having several problems with urgency, frequency and occasional incontinence.Thepatient is not keen on either a urethral or a suprapubic catheter as she is sexually active.
Neuroanatomy and Neurophysiology of Voiding Central Pathways • CorticopontineMesencephalic Nuclei–Frontal Lobe • Pontine Mesencephalic • Pelvic and Pudendal Nuclei–Sacral Micturition • Motor Cortex to Pudendal Nucleus Peripheral 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 muscle External 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)
Note: • Alpha Adrenergic receptors respond to the appearance of norepinephrinewith contraction • Beta adrenergic receptors respond to the appearance of norepinephrine with relaxation
Storage Sympathetic T11–L2 sympathetic efferents • Travel through the hypogastric nerve • Causes the sphincter to contract and body to relax • Urine is stored Alpha1 Receptors Adrenergic • NE causes contraction of neck of bladder and prevents leakage • Closes internal urethral sphincter and detrusor outlet, promoting storage B2 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.
Emptying Parasympathetic Muscarinic (M2) cholinergic receptors are located in • The bladder wall • Trigone • Bladder Neck • Urethra Stimulation of pelvic nerve (parasympathetic) • Allows contraction of bladder B2 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 pontinemicturition 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 pontinemicturition center.
LMN Bladder: • Big Hypotonic Bladder (flaccid, areflexic bladder),Tight Competent Sphincter • Results in:Failure to Empty UMN Bladder: • Small Hyperreflexic, Overactive,Little Bladder • Results in:Failure to Store (Incontinence)
Therapy with Botulinum toxin • increases maximal cystometric bladder capacity • reduces maximum detrusor pressure • reduces 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 intravesicalbotulinum 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 intravesicalbotulinum 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.