Buddhist Tzu Chi General Hospital The Spastic Sphincter Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital

Function of urethral sphincter Provide adequate urethral resistance at filling phase to prevent incontinence Active relaxation during voiding phase for micturition Inhibition of detrusor nucleus to postpone voiding before threshold Release of inhibitory effect on detrusor nucleus at initiation of voiding (on-off switch)

Anatomy of male urethral sphincter

Anatomy of Female Urethral sphincter

Toilet training – A learning process influences voiding Traditional voiding control by age 3 CNS plasticity and adaptation to sensory input of micturition process Retentive behavior of children Parent pushing of toilet training Behavioral stress to muscles and change in functional integrity of tissue

The overactive sphincter Incorrect conditioning of voiding reflexes during CNS maturing Symptoms ranging from incontinence to retention Chronic LUT dysfunction is maintained by permanently up-regulated sacral reflex arcs Dysfunctional voiding develops

The Pelvic Floor Deep layer – Levator ani provide relaxation during micturition and defecation (S3,4), contraction to lift pelvic organ upward and compression Transverse perinealis, ischeocavernous, bulbocavernous, urethral sphincter, anal sphincter muscles (S2) provide squeezing effect on pelvic organs

Anatomy of Pelvic Floor

Innervation of Pelvic Floor Perineal skin sensation from S2 nerve Skin sensation can be impaired unilaterally or bilaterally in S2 nerves Loss of skin sensation often reflects a loss of urethral sphincter integrity Deficits in S3,4 nerves are not associated with significant incontinence Hypersensitivity of bladder is often mirrored hypersensitivity of the levator (S3,4)

Neuroregulation of sacral nerves in micturition reflex Loss of pudendal afferent input can dampen the detrusor reflex Enhanced afferent input to micturition center can augment detrusor reflex Supraspinal inhibition or increased inhibitory input to micturition center can suppress detrusor reflex Chronic anxiety or via behavioral pathway can cause loss of volitional or ability to relax the sphincter with void efforts

Pathophysiology of pelvic floor dysfunction Changes in peptide release from nerve endings secondary to stress (supraspinal) Enhanced release of inflammatory or neural-sensitizing peptides into tissue (local inflammation) Inadequate pelvic floor control due to learned behavior (dysfunctional voiding)

Detrusor instability and Holding urine during involuntary DI

CNS Control of Pelvic floor Medial part of dorsal pontine tegmentum (M-region) – sphincter relaxation and detrusor contraction Lateral part of pontine tegmentum – sphincter contraction and detrusor inhibition Onuf’s nucleus – spinal control center of pelvic floor – linkage to paraventricular nucleus

Micturition and Continence center in CNS

Central peptide pools linked to CNS centers regulating LUT function Paraventricular peptide pool Vasopressin, oxytocin, substance P Somatostatin, dopamine, neurotensin Glucagon, renin Corticotropin-releasing factor Met- and leu-enkephalin Nucleus Onuf peptides (for sphincter control) Somatostatin, neuropeptide Y, serotonin Substance P (from paraventricular nucleus, dorsal and ventral roots) Met-and leu-enkephalin

Neurobiological background of pelvic floor dysfunction

Clinical assessment of a hypertonic pelvic floor LUT Symptoms – frequency, urgency, suprapubic, perineal, deep pelvic pain, lower backpain, slow stream, intermittency, recurrent UTI, retention Constipation or difficult defecation Sexual dysfunction Insomnia and other somatic complaints

Important past history Current symptoms? Since when? development over the last time? change in last time? Pain? Where?, character?, intensity (using visual analog scale 0-10), Change over time? Micturition? Any problems?, double voiding?, infections?m burning?, inability to void? Defecation? Frequency, consistency Sexual life? Dysfunction?, emotional problems?, female: vaginism? Childhood prolonged bedwetting?, excessive exercises to achieve early urinary continence?, punishment for bedwetting?, retentive voiding habits (I.e.,low micturition frequency?), sexual abuse (female)? Adolescence Female:painful menses?,frequent urinary tract infections? Male:urinary tract infections Adulthood Female: childbirths?, vaginal delivery?, pelvic surgery?, infections?, voiding habits over time,profession, personal satisfaction Male:voiding habits, profession,social life

Hypertonic pelvic floor = hypertonic urethral sphincter? Urethral sphincter and external anal sphincter are mainly innervated by S2 Levator ani are innervated by S3,4 Reflex coordination to bladder sensory input is synchronized in most of cases Isolated denervation or impairment in conduction may occur

Hypertonic urethral sphincter Straining to initiate voiding

Hypertonic urethral sphincter Straining to open urethra

Hypertonic urethra = hyperactive urethra? Hypertonic urethra indicates increased and sustained urethral pressure (tonic) during resting state Hyperactive urethra indicates increased activity of urethral sphincter during voiding state A spastic urethral sphincter causes difficulty in initiation of voiding

Hyperactive urethral sphincter during initiation & voiding

SCI with type 1 DESD and low detrusor contractility

States of dysfunctional voiding due to spastic sphincter 1. Fill phase (normally very stable pressure 60-80 cmH2O) Pathology High sphincter pressure (>80) Hypersensitivity Clonic or hyperreflexic dynamic Spasms (pain)versus spontaneous relaxations (leakage episodes) 2.Transition phase (normally smooth) Nonrelaxation Hesitant/delayed relaxation Precipitous relaxation Aborted relaxation Rising sphincter pressures 3.Void phase (normally coordinated) Partial relaxations Intermittency of sphincter relaxation 4.Recovery stage (normally smooth) Intermittency (dribbling)

Clinical assessment of pelvic floor muscle function Uterine prolapse or cystocele Sensation of perineal skin Anal tone measurement Volitional contraction of pelvic floor Search for inflammatory sources (hemorrhoid, prostatitis, vaginitis) Focal neurological findings (Bulbocavernous reflex, deep tendon reflex)

Digital rectal examination of Pelvic floor muscles Deep and superficial sphincter muscle tone, weak, high, or normal? Hypersensitivity or tenderness of the levator or urethral sphincter Motor identity of sphincter muscles or levator ani muscles Voluntary repetitive contractions of sphincter and levator muscles

Tentative diagnosis of pelvic floor hypertonicity Spastic urethral sphincter – a chronic hypertonic urethral sphincter causing functional bladder outlet obstruction Poor relaxation of pelvic floor muscles – inadequate relaxation during voiding causing hesitancy, low intermittent flow Non-relaxing pelvic floor or urethral sphincter –-- no relaxation during voiding efforts by abdominal straining or Valsalva maneuver

Diagnosis based on initial investigations LUT symptoms Negative urinalysis or urine culture High pelvic floor muscle tone Low maximal flow rate and obstructive intermittent flow pattern No evidence of BPH or other pathology Voiding diary verified LUTS

VUDS Analysis in 112 Non-obstructive Men with LUTS Normal bladder & urethra 25 (22.3%) Hypersensitive bladder 17 (15.2%) Detrusor instability 6 (4.5%) Detrusor failure 3 (2.7%) Poor relaxed external sphincter 61(54.5%)

Urodynamics Uroflowmetry & EMG Cystometrogram & EMG Pressure flow study Videourodynamic study Urethral pressure profilometry Pudendal nerve latency time Evoke potential study

Intermittent Flow

Relaxation of urethral sphincter at initiation of voiding

Poor relaxation of urethral sphincter during voiding

Intermittency due to poor relaxation of ES

Pseudodyssynergia in CVA causing high voiding pressure

Inhibition of detrusor contraction by urethral sphincter during voiding

Stop test – volitional sphincter contraction and inhibition of voiding

Guarding reflex – during uninhibited detrusor contractions

Coordinated sphincter activity during filling phase in Enterocystoplasty

Increased sphincter activity causing isolated obstruction in detrusor areflexia

DHIC and increased sphincter activity during filling

Detrusor overactivity and overactive sphincter & pelvic floor

Type I DESD in C5,6 SCI

Type II DESD in Thoracic SCI

Urethral sphincter v Pelvic floor muscles – analogue?

Discoordinated urethral sphincter in dysfunctional voiding

Chronic pelvic floor spasticity – A cause of pelvic pain? Increased muscle tone of pelvic floor muscles Spasticity of urethral sphincter Spasticity of external anal sphincter Hypertonicity of pyriformis muscles Fascitis of pubococcygeus or coccygeus muscles Physiotherapy and medication for pelvic floor spasticity can relieve pelvic pain Should search for tendered points or infection

Chronic prostatitis syndrome Symptoms of frequency, urethral irritation, hesitancy, intermittency, residual urine sensation, perineal pain and lower back pain Spastic urethral sphincter might be a cause of chronic prostatitis or reflux abacterial prostatitis Treated as spastic sphincter may work

Spastic urethral syndrome and constipation Chronic constipation causes hypertonic anal sphincter and hence, pelvic floor muscles Poor relaxation of pelvic floor muscles results in inhibition of detrusor contractions during voiding Concomitant treatment of constipation can relieve voiding symptoms

Treatment of spastic urethral sphincter Behavioral therapy: hydration, laxatives, time voiding, changing voiding posture Physiotherapy: pelvic floor muscle exercises Electric stimulation : interferential current stimulation Biofeedback: visual or Uroflowmetry & EMG Medication: baclofen, alpha-adrenergic blockers, estrogen, combination therapy Urethral injection of botulinum A toxin

Therapeutic results of baclofen and terazosin in treatment of spastic urethral sphincter IPSS Qmax Residual urine Baseline Trated Treated Baclofen (n=73) 15.2±6.7 10.4±5.7 14.3±9.7 16.7±8.1 65.7±33.9 37.5±21.7 % of change 31.6±21.5 16.87±12.7 42.9±34.1 Baclofen plus 12.7±7.9 61.±4.5 14.8±11.0 22.677.5 58.1±21.8 31.01±31.2 Terazosin (n=64) 51.7±27.4 52.7±31.1 46.5±29.3 Statistics* P<0.05 NS

Biofeedback pelvic floor muscle relaxation

Strengthened PFM after 3 M training

Botulinum A toxin

Identification of External Sphincter in Man

Preliminary Result in Reduction of MUCP

Results of Botulinum A Toxin in Patients with Voiding Dysfunction Good Improved Failed Detrusor underactivity (n=27) 13 (48.2%) 8 (29.6%) 6 (22.2%) DESD (n=18) 3 (16.7%) 10 (55.6%) 5 (27.8%) Dysfunctional voiding (n=18) (33.3%) 2 (11%) Poor relaxation of urethral sphincter (n=12) (25%) 7 (58.3%) (16.6%) TOTAL (n=75) 25 35 (43.7%) 15 (20%) DESD=Detrsor external sphincter dyssynergia

Influence of Detrusor contractility and Urethral sphincter activity on Botox Effects Good Improved Failed High pressure contractility (n=26) 8 (30.7%) 15 (57.6%) 3 (11.5%) Low pressure contractility (n=49) 17 (34.6%) 20 (40.8%) 12 (24.4%) No-relaxing sphincter (n=27) 13 (48.2%) (29.6%) 6 (22.2%) Hyperactive or poorly relaxed urethral sphincter (n=48) (25%) 27 (56.2%) 9 (18.7%) TOTAL (n=75) 25 (33.3%) 35 (43.7%) (20%)