1. Physiology of Lower Urinary Tract Function (including Neurogenic Bladder) Eric S. Rovner, M.D. Professor of Urology Medical University of South Carolina

2. Outline l Physiology of Micturition  Micturition cycle  Neurologic factors  Pharmacology l Neurogenic Bladder  Lesions above pons  Lesions below pons above sacral SC  Lesions of sacral SC and peripheral NS

3. Ideal Plumbing Requirements for a Terrestrial l Store a reasonable amount of urine at a pressure < kidney filtration pressure (25 to 40 cm H 2 O) l Rapid on-demand emptying

4. l The micturition cycle:  Filling/Storage  Emptying Micturition Cycle: Simplified* *Wein

5. Bladder Filling and Urine Storage Requirements: l Reservoir:  Accommodation of increasing volumes of urine u At a low intravesical pressure (compliance) u With appropriate sensation  Absence of involuntary bladder contractions u Overactivity l Outlet:  A bladder outlet that is closed at rest and remains so during increases in intra-abdominal pressure

6. Urine Emptying Requirements: l Reservoir:  Coordinated bladder contraction of adequate magnitude (or other increase in pressure) l Outlet:  Absence of anatomic obstruction  Concomitant lowering of resistance at the level of: u Smooth muscle of bladder neck and proximal urethra u Striated muscle that surrounds urethra

7. Voiding Dysfunction* l Pathophysiology simplified  All voiding dysfxn is sub-classified as abnormality of: u Filling/storage: Bladder Urethra Both u Emptying: Bladder Urethra Both Key factors: Bladder Smooth sphincter Striated sphincter Sensation *Wein

8. Voiding dysfunction l Because of urethra  Too weak: u SUI (sphincteric)  Too strong u BOO/retention/DESD l Because of the bladder  Too weak u Detrusor underactivity (retention)  Too strong u Detrusor overactivity ( OAB/UUI) l Because of both (MIXED)

9. “I am not certain why humans or animals are continent of urine and feces and I am not convinced that anyone really knows.” J. Berry, 1961 (Berry Prosthesis)

10. Physiology of Urinary Continence Continence = urethral closure forces > bladder expulsive forces Bladder Urethra > 1.Sphincters 2.Connective tissue 3.Urethral mucosa 1.Intravesical (IBC’s, compliance) 2.Extravesical (abdominal, etc.) = Continence

11. Micturition reflex at sacral SC: Coordination/influenced by higher centers

12. What defines neurogenic voiding dysfunction? l Abnormality in storage or voiding function of the bladder as a result of a neurologic disturbance l Must be confirmed by objective evidence of a nervous system disorder

13. Patterns of Neurogenic dysfunction l Often predicted by level of injury/disease l However, limited by  Complete/Incomplete  Description of sx’s is often poor (sensory loss) “….the bladder is an unreliable witness”  Other co-morbidities (diabetes, CHF, etc.)  Other pelvic disease (POP, SUI, BPH, etc.)

14. Incidence of Bladder Dysfunction l Spinal cord injury (8k new/yr) 70%–80% l Multiple sclerosis (400k) 50%–80% l Lumbo-sacral DDD27%-92%  (60-90% overall prevalence with 5% sciatica) l Radical pelvic surgery16%-20% l Parkinson’s disease15%–35% l Diabetes (17,000,000) 10%–30% l CVA (540k new/yr) 10%–15%

15. Central Nervous System Cortex, Basal Ganglia, Cerebellum -Frontal lobes and cingulate gyrus -Voluntary initiation of voiding -Inhibition of reflex voiding activity - Supra-pontine structures are generally inhibitory on the LUT -Injuries (CVA, etc.) release this inhibition -detrusor overactivity, and clinical sxs of urgency, frequency, incontinence

16. Central Nervous System: Pons Coordination of sphincter and bladder - Afferent input (ascending and descending) -bladder wall and supra-pontine centers - Efferent outflow (descending) -sacral spine - somatic - parasympathetic centers for voiding -T-L spine -sympathetic nerves for accomodation Injuries separating Pons from LUT(SCI, MS) : reflex voiding patterns and uncoordinated voiding

17. Supra-sacral spinal injury/disease l Functional Abnormality  Depends on u chronology, type of lesion u completeness  Neurogenic Detrusor Overactivity  Striated sphincter dysynergia u If above T6 (Sympathetic Outflow Tract) Smooth sphincter dysynergia Autonomic dysreflexia

18. Infrasacral Injury/Disease l Clinical Presentation  Urge/frequency or urinary retention  +/- straining to void  Usually continent l Most common urodynamic abnormality  Detrusor areflexia  Normal innervation of the striated sphincter  Normal smooth sphincter function  Irritative lesions- detrusor overactivity

19. Goals of NGB Evaluation l Accurate diagnosis  characterization of voiding dysfunction (NGB) u Reassess as needed  recognition of concomitant non-neurogenic VD u BPH, SUI, etc. l Assess prognosis  Urological u Neurological l Direct management

20. Neurourologic Evaluation l History l Physical examination  neurologic examination l PVR l Creatinine l U/A, C&S l +/- Upper tract study l +/- Urodynamic study l +/- Cystoscopy

21. Urodynamics: Utility in prognosis and treatment in NGB  LUTS and PE do not correlate well with of type, extent or level of injury/disease…..or UDS findings  LUTS and PE do not correlate well with prognosis or “danger” to upper tracts (but UDS does!!!!)  In SCI/MS, level of injury not always predictive of UDS* u Correlation of neuro imaging and UDS not exact l Therefore management often dictated by UDS *Weld and Dmochowski, 2000

23. Detrusor overactivity with UI Valsalva induced DO with UI MS with sx’s of SUI with urge +/- UUI SUI

24. Q Vol pVes pAbd pdet EMG 47 y.o. with Sx’s of SUI after Rad Hyst. PVR=175cc

25. Treatment Issues in NGB l Assessing Safety 1st  Upper tracts  Risk factors: compliance, UTI’s, VUR, etc  Other l Relieving Symptoms 2nd  Incontinence  Frequency, urgency  Other

26. Goals of Management l Upper Tract Preservation (or improvement) l Absence or control of infection l Continence l Reduce or eliminate impact on QOL l Make an acceptable solution for the patient  Physically  Economically  Socially  Culturally

27. How to achieve goals l Adequate urine storage at low pressure l Adequate emptying in absence of obstruction l Adequate urethral closure forces (competence) l Selecting least invasive/expensive Rx option. l Individual management.

28. Rx of NGB Bladder Urethra All Rx either Δ urethral or Δ bladder pressure or both

29. Lesions above the pons CVA, brain tumor, etc. Usually: Clinical presentation: 1. frequency/urgency 2. incontinence 3. usually normal upper tracts Urodynamics: 1. detrusor overactivity 2. synergic sphincters 3. normal sensation 4. normal emptying

30. Treatment: Lesions above pons l Strategy: Reduce detrusor overactivity  Sphincters are OK usually l Management:  Behavioral modification  Antimuscarinics  Sacral neuromodulation  Botulinum toxin A  Augmentation cystoplasty

31. Lesions between pons and sacral spinal cord MS, SCI, transverse myelitis, etc. Clinical presentation: 1. frequency/urgency (if sensation) - overactivity vs. retention 2. incontinence (+/- awareness) 3. beware upper tracts Urodynamics: 1. detrusor overactivity - sometimes underactivity 2. dyssynergic sphincters 3. +/- sensation 4. abnormal emptying

32. Lesions between pons and sacral spinal cord MS, SCI, transverse myelitis, etc. l Strategy:  1. reduce detrusor overactivity (if present)  2. improve emptying (when problematic)  3. reduce storage pressure  4. protect upper tracts l Management:  1. Rx detrusor overactivity (drugs, Botox, etc.)  2. +/- CIC  3. +/- urinary diversion

33. Autonomic Hyperreflexia (Dysreflexia)

34. l THIS IS AN EMERGENCY l Lesions above T6-T8  Occurs after resolution of spinal shock u Often years later  Must have viable distal SC l Assoc. with DSD

35. Autonomic Hyperreflexia (Dysreflexia) Precipitating factors:  Any distention of rectum or LUT  LUT instrumentation (UDS)  Urinary catheter issue u Tube change u Obstructed catheter clot retention, etc.  Long bone fracture  Decubiti  GI pathology  Sexual activity  Other

36. AH: Treatment l Find and reverse precipitating stimulus l Acute:  Parenteral ganglionic blockers  α blockers  Others l Prophylaxis:  Do procedures under spinal or general with careful monitoring ??????  Nifedipine 10–20 mg orally 30 minutes prior; SL during  Chronic α blockade (i.e. terazosin)

37. Lesions distal to the spinal cord Disc disease, radical pelvic surgery, diabetes etc. Usually: Presentation: 1. frequency, urgency +/- incontinence 2. +/- urinary retention, straining 3. upper tracts at risk Urodynamics: 1. detrusor overactivity or underactivity 2. impaired compliance, +/- contractility 3. normal sensation 4. no dyssynergia

38. Lesions distal to the spinal cord Disc disease, radical pelvic surgery, etc. Strategy: 1. improve emptying (when problematic) 2. reduce storage pressure 3. protect upper tracts Management: 1. Rx poor emptying +/- CIC 2. improve compliance

39. Infrapontine lesions: Chronic Risk Factor l High intravesical storage pressure