Urgency Frequency Syndrome

1. Urgency Frequency Syndrome Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien

2. Lower Urinary Tract Symptoms • Storage symptoms -- Frequency, urgency, urge incontinence, nocturia, suprapubic pain • Empty symptoms -- Hesitancy, intermittency, dysuria, poor stream, terminal dribble, residual sensation, micturition pain

3. The Urge Syndrome Sensory urgency – hypersensitivity of bladder or urethra or both, which causes -- a constant desire to void which is unrelieved by voiding -- a desire to void at a low bladder volume Motor urgency – occurrence of involuntary detrusor contractions which make patients urge to void and/or urine leakage

4. Frequency & Polyuria (Pollakisuria) • A number of patients may have large daily urine output >2800ml/day • Polydipsia, high water intake • Frequency with voided volume >350ml is physiologically normal • Should check metabolic status (DM, azotemia, hyperlipidemia, etc.) or diuretics

5. Sensory Urgency & Frequency • Reduced capacity of first desire (<150mL) or urgency (<350mL) subjectively • Absence of detrusor instability • Absence of urinary tract infection • The incidence of sensory urgency has been estimated 6%, compared with an incidence of 31% for detrusor instability

6. Known Causes of Sensory urgency freqency • Urinary tract infection • Lower ureteral stone or bladder stone • Bladder tumor • Irradiation cystitis • Interstitial cystitis • Chonic cystitis and reduced capacity • Foreign body or bladder injury

7. Etiology of Idiopathic Urgency Frequency • Psychological factors • Urothelial leak syndrome • Reduced bladder compliance • Diuresis • Learned habit • Detrusor instability • Occult neuropathy

8. Sensory UrgencyA Psychosomatic Complaint ? • Bladder retraining is effective in treating sensory urgency • Relaxation training, biofeedback, hypnosis, acupuncture have a 85% initial response, but relapse rate is 50% • Cognitive factor to maintain high stress and arousal levels, increase vigilance concerning bladder sensation and fullness

9. Psychological Social & Psychiatrical Factors • High level of distress • High level of anxiety • Symptoms may worsen in relation to work or stress • Belief of relationship with disease – uremia, infection, cancer • Overestimate the significance of symptoms

10. Sensory Urgency Frequency • A disease of exclusion • Acute symptoms and chronic symptoms? • Related to empty symptoms or not? • Related to painful syndrome (painful bladder, painful perineum, urethral pain)? • Intermittent? Persistent? Waxing & waning? • Related to urge or stress incontinence?

11. Diagnostic Work-up • Urinalysis • Uroflowmetry & residual urine amount • Voiding diary – 3 days • KUB or Cystoscopy • Ultrasound of bladder and urethra • Cystometry & sphincter EMG • Pressure flow study or videourodynamics

12. Pathophysiology of LUTS in 256 Taiwanese Women • Normal bladder and urethra 46 • Hypersensitive bladder 102 • Detrusor instability 44 • Low detrusor contractility 77 • Poor relaxation of urethral sphincter 76 • Genuine stress urinary incontinence 49 • Bladder outlet obstruction 21

13. Urethral sensitivityAn etiology of urgency frequency? • Increased urethral sensitivity was found in reduced bladder capacity and in women with normal CMG who complain of frequency urgency & dysuria • A higher incidence of bladder neck incompetence in patients with urgency frequency than the controls • Pelvic floor exercises and bladder neck suspension improves urgency frequency symptoms

14. Bladder Neck Incompetence in Urgency Frequency Syndromes

15. Ultrasound of Bladder neck incompetence in urgency frequency

16. Bladder Neck Decsent & Incompetence before Pelvic Floor exercises

17. Improved Bladder neck Incompetence after Pelvic Floor exercises

18. Detrusor Instability as an etiology of urgency frequency • Minute detrusor contraction occur in the normal bladder – C-fiber dominates? • Increased perception of bladder fullness during diuresis • No significant difference in perception of bladder fullness between sensory urgency and detrusor instability • Similar clinical efficacy of oxybutynin in treating sensory urgency (62.5%) and DI (60.4%)

19. Increased amplitude of detrusor contractions in bladder filling

20. Sensory nerves of bladder • Dual sensory innervation of mammalian bladder • Myelinated A-delta fibers – mediate stretch and micturition reflex • Unmyelinated C-fibers (capsaicin sensitive sensory fibers) – mediate pain, temperature, noxious stimuli • Sensory axons are present in lamina propria

21. Sensory Innervation of Bladder

22. Capsaicin sensitive sensory fiber • Sensory function – regulating micturition threshold (especially after spinal cord transection), mediating pain, activating cardiovascular responses • Efferent function – activating local motor responses, regulating nerve excitability, local control of vascular blood flow and permeability (neurogenic inflammation ?)

23. Treatment of sensory urgency by intravesical capsaicin • Capsaicin in 10 micro-M can effectively treat hypersensitive disorders • Transient desensitization of capsaicin-sensitive afferents without interfering motor function • Little effect was found in classical Interstitial cystitis • Resiniferatoxin may have similar effects

24. Role of Potassium in pathogenesis of Urgency Frequency Syndrome • Chronic diffusion of urinary potassium into bladder interstitium may induce sensory symptoms, damage tissue, and possibly cause interstitial cystitis • Intravesical potassium test (40ml, 0.4M) is a reliable method for detecting abnormal urothelium permeability

25. Potassium test in Urgency Frequency Syndrome

26. Nerve Growth Factor • Increased nerve growth factor levels in the bladder biopsies from sensory urgency, chronic cystitis, and interstitial cystitis than in controls • Immunostaining showed increased NGF expression in the urothelium, most marked in idiopathic sensory urgency • Anti-NGF treatment may be rational

27. NGF immunostaining in Idiopathic Sensory Urgency

28. Urgency frequency associated with Bladder or perineal pain • Suprapubic pain or perineal pain at bladder fullness • The pain may/not disappear after voiding • A tight sphincter EMG at bladder capacity • Reduced bladder compliance • Urethral obstruction due to stricture or spastic urethral sphincter as etiologies

29. Reduced bladder capacity and Frequency urgency bladder pain

30. Frequency urgency & pain Spastic pelvic floor & sphincter

31. Differential diagnosis of Urgency Frequency Syndrome • History – Bladder injury, foreign body • Urinalysis – UTI • Uroflowmetry – BOO • Cystoscopy – bladder tumor, bladder stone, irradiation cystitis, chronic cystitis • Ultrasound – bladder neck and/or urethral incompetence • Cystometry – low compliance, DI, DESD

32. Pressure flow study for Urgency frequency syndrome • Cystometry can only detect capacity, detrusor instability, compliance, and bladder sensation during filling phase • Pressure flow study can diagnose bladder outlet obstruction, low detrusor contractility, poor relaxation of urethral sphincter, and DESD accurately

33. Urodynamic study in Urgency frequency syndrome- Detrusor overactivity

34. Urodynamic study in Urgency frequency syndrome- Detrusor underactivity

35. Urodynamic study in Urgency frequency syndrome- Bladder outlet obstruction

36. Urodynamic study in Urgency frequency syndrome- Low compliant bladder

37. Urodynamic study in Urgency frequency syndrome- Pseudodyssynergia

38. Urodynamic study in Urgency frequency syndrome- Idiopathic Sensory Urgency

39. LUTS Analysis of Voiding dysfunction

40. Treatment of Frequency urgency syndrome & Normal UDS • Reassurance • Bladder biofeedback • Restrict fluid intake • Avoid diuretics and certain acid foods • Sedatives or mild tranquilizers

41. Foods to be Avoided

43. Bladder biofeedback for Urgency frequency syndrome • Urodynamic proven sensory urgency • Bladder biofeedback – increased each voiding interval by holding urine for 5 min more • Increase fluid intake gradually • Improved functional capacity (296 v 96ml) and decreased daytime frequency (5.7 v 15.8) and nocturia (0.3 v 2.3) after treatment

44. Intravesical Heparin therapy • Patients with urgency frequency and a positive potassium test • Intravesical Heparin 25000u/10ml saline and holding for 2 hours • 2x or 3x per week for 12 weeks • 67% patients have improvement in symptoms and increase in bladder capacity

45. The changes of urodynamic parameters before and after heparin treatment

46. Urodynamic finding before and after Heparin Therapy

47. Intravesical Capsaicin Therapy • Patients who are refractory to conventional treatment • Capsaicin 10 -5 M in 30ml N/S instilled to bladder for 30 minutes • Resiniferatoxin 10-8 M in 30ml N/S • A burning sensation or urge at instillation • Relief of pain and urge in the later days

48. Cystometric Results after Capsaicin Instillation *P<0.05

49. A Cocktail Preparation for Idiopathic Urgency Frequency ? • Mixture of Xylocaine, Resiniferatoxin, Heparin, Oxybutynin with certain vehicle • To provide local anesthesia, C-fiber desensitization, repair of defected glycosaminoglycan layer, anticholinergic effect together in one instillation • Clinical trial is undergoing

50. Anticholinergics Treatment • Oxybutynin – the most effective and safe drug currently available • Detrusitol – M3 antagonist, less salivary and GI side effects than ditropan • Flavoxate – mild effect in detrusor • Imipramine – central and anticholinergics