Recent Advances in Management of the Neurogenic Voiding Dysfunction

1
Recent Advances in Management of the Neurogenic
Voiding Dysfunction

• Hann-Chorng Kuo
• Department of Urology
• Buddhist Tzu Chi General Hospital

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Neurogenic Voiding Dysfunction (1997-2002)
?. Intracranial Lesion (n141) CVA 113
?. Intracranial Lesion (n141) Parkinsons disease 18
?. Intracranial Lesion (n141) Dementia 3
?. Intracranial Lesion (n141) ICH 7
?. Spinal Cord Lesion (n195) Cervical 78
?. Spinal Cord Lesion (n195) Thoracic 69
?. Spinal Cord Lesion (n195) Lumbar 25
?. Spinal Cord Lesion (n195) Sacral 23
?. Cauda equina lesion 17
?. Peripheral neuropathy (n57) Cervical Ca 43
?. Peripheral neuropathy (n57) Rectal Ca 7
?. Peripheral neuropathy (n57) Others 10
?. DM 109
Total 519
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Neurogenic voiding dysfunction

• Failure to store Detrusor hyperreflexia
• Urethral incompetence
• Failure to empty Detrusor areflexia
• Bladder neck dysfunction, BPO, External
  sphincter dyssynergia
• Combined failure to store and empty
• DESD, DHIC

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Symptomatology of Neurogenic Voiding
dysfunction
Urine retention Incontinence Frequeny urgency Dysuria UTI
Intracranial lesion (n141) 43 (30.5) 69 (48.9) 41 (29.1) 79 (56) 58 (41.1)
SCI (n195) 44 (22.6) 80 (41) 16 (8.2) 79 (39) 103 (52.8)
Cauda equina lesion (n17) 4 (23.5) 10 (58.8) 4 (23.5) 9 (52.9) 4 (23.5)
Peripheral neuropathy (n57) 7 (12.3) 31 (54.4) 17 (29.8) 36 (63.2) 19 (33.3)
DM (n109) 36 (33) 45 (41.3) 35 (32.1) 56 (51.4) 63 (57.8)
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Urodynamic findings in Neurogenic
Voiding dysfunction
Detrusor areflexia Detrusor hypereflexia DHIC
?.Intracranial Lesion (n141) 13 (9.2) 128 (90.8) 51 (36.2)
?.SCI (n195)
Cervical (78) 6 (7.7) 72 (92.3) 13 (16.7)
Thoracic (69) 28 (40.6) 41 (59.4) 10 (14.5)
Lumbar (25) 13 (52) 12 (484) 3 (12.0)
Sacral (23) 13 (56.5) 10 (43.5) 5 (21.7)
?.Cauda equina lesion (n17) 13 (76.5) 4 (23.5) 4 (23.5)
?.Peripheral neuropathy (n57) 49 (86) 8 (14) 8 (14)
?.DM (n109) 20 (18.3) 89 (81.7) 48 (44)
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Urinary Tract Abnormalities in
Neurogenic Voiding Dysfunction
Trabeculated Bladder VUR Hydronephrosis BOO
?.Intracranial Lesion (n141) 31 (22) 1 (7.1) 4 (2.8) 61 (43.3)
?.SCI (n195)
Cervical (78) 27 (34.6) 3 (0.7) 9 (11.5) 57 (73.1)
Thoracic (69) 19 (27.5) 3 (3.8) 14 (20.3) 38 (55.1)
Lumbar (25) 3 (12) 1 (4.3) 5 (20) 15 (60)
Sacral (23) 7 (30.4) 1 (4) 2 (8.7) 11 (47.8)
?.Cauda equina lesion (n17) 3 (17.6) 0 (0) 0 (0) 3 (17.6)
?.Peripheral neuropathy (n57) 10 (17.5) 3 (5.3) 6 (10.5) 19 (33.3)
?.DM (n109) 20 (18.3) 1 (0.9) 8 (7.3) 32 (29.4)
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Pseudodyssynergia in Stroke
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DESD in Multiple Sclerosis
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Detrusor external sphincter dyssynergia in
cervical SCI
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Bladder neck dysfunction and DESD in Spinal cord
lesion
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Medication for Detrusor hyperreflexia

• Oxybutynin anticholinergics
• Imipramine
• Intravesical capsaicin resiniferatoxin
• Intra- detrusor botulinum toxin
• Multiple medication increases adverse effect
  especially in elderly with inadequate detrusor
  contractility (DHIC)

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Medication for Bladder outlet obstruction

• Bladder neck alpha-adrenergic blocker
• Smooth muscle Nitric oxide donors
  (nitroglycerine, isosorbid mononitrate),
  anticholinergics
• Striated muscle baclofen, diazepam, dantrolene,
  calcium channel blocker, NO donors, botulinum A
  toxin
• Enlarged Prostate finasteride (Proscar)

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Priority of Management of Neurogenic voiding
dysfunction

• Preservation of renal function
• Freedom of urinary tract infection
• Efficient bladder empty
• Freedom of indwelling catheter
• Achievement of urinary continence
• Patients will of management
• Avoid medication after management

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Reduced frequent detrusor contractions after
Oxybutynin
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Tolterodine vs Oxybutynin

• A secondary amine with competitive muscarinic
  receptor blocking property
• As potent as oxybutynin in inhibiting detrusor
  contractions
• 8 times less potent in inhibiting salivation than
  oxybutynin
• 2mg bid tolterodine in comparison to 5mg tid of
  oxybutynin
• Titration doses from 1-2 mg bid to 4mg bid

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Side effects of Anticholinergic

• Post-synaptic receptors M1 and M2 are widespread
  in CNS, anticholinergics may have cognitive
  dysfunction, especially in elderly
• Dry mouth, constipation, blurred vision
• Darifenacin has 11-fold higher affinity to M3
  than M2 receptors and a 5-fold lower affinity for
  M receptors in parotid gland

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Pharmacology of Detrusor Overactivity
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Extended-release system for oxybutynin
tolterodine
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Electrostimulation and electromodulation for NVD

• Detrusor contractility reduces during
  electrostimulation of pelvic floor
• Detrusor overactivity
• Sacral neuromodulation,
• Surface sacral electromagnetic current
  stimulation
• Detrusor underactivity Sacral nerve or
• Intravesical neurostimulation

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Implantation of Sacral Stimulator
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Correct placement of electrode on Sacral nerves
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Surgical Treatment for Neurogenic Voiding
Dysfunction

• Detrusor hyperreflexia
• Augmentation cystoplasty
• Bladder autoaugmentation
• Sacral posterior root rhizotomy
• Detrusor areflexia
• TUI-bladder neck, TUR-prostate
• External sphincterotomy
• Urethral stent

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Surgical technique of augmentation cystoplasty
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Abdominal straining to void after
Enterocystoplasty
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Bladder Autoaugmentation
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Seromuscular enterocystoplasty
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Technique of Sphincterotomy

• 12 oclock position
• Incision from BN to bulbous
• Cutting deep to fat vessel
• Bleeding can be controlled
• Avoid diffused coagulation
• On Foley catheter for 2 days

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Urethral Stent Implantation
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Surgical procedures for Neurogenic urethral
incontinence

• Pubovaginal sling procedure for women
• Periurethral collagen or Teflon injection for
  urethral sphincteric deficiency
• Combined urethral augmentation (by collagen or
  Teflon) with bladder augmentation
• Artificial sphincter implantation
• Closure of bladder outlet and continent
  cystostomy using appendix or ileum

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Pubovaginal sling procedure for Urethral
incontinence
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Periurethral Teflon injection in SCI with
urethral relaxation
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Intravesical Therapy for Detrusor overactivity

• Blocking efferent cholinergic fibers
  intravesical oxybutynin, atropine
• Blocking neuromuscular junction intravesical
  botulinum A toxin injection
• Blocking afferent fibers that mediate detrusor
  reflex intravesical lidocaine
• Blocking C-fiber mediated detrusor contractions
  intravesical capsaicin, resiniferatoxin

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Treatment of DH Reduced Detrusor Contractility
after Capsaicin therapy
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Therapeutic Effects of Resiniferatoxin on
Detrusor Overactivity

• 10 -5 to 10 -7 M RTX is effective for DH of SCI
  and DH of CNS origin
• 10 -8 M RTX can significantly improve voiding
  pattern and pain score in hypersensitive
  disorders and bladder pain
• RTX is safe for application in humans
• Less initial irritative response in RTX treatment
  than capsaicin

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Initial Response of RTX therapy
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Urodynamic Result after RTX Therapy in a SCI
patient
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Urodynamic Changes after RTX in Chronic SCI with
DESD
Baseline Post-RTX Stastistics
Cystometric capacity(ml) 102.131 236.688.6 Plt0.001
Bladder compliance (ml/cmH2O) 23.712.1 25.915.3 Pgt0.05
Voiding pressure (Pdet, cmH2O) 55.923.2 47.528.1 Pgt0.05
Presence of DESD (n20) 100 100
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Intravesical RTX in treatment of Neurogenic
Detrusor Overactivity

• C-fiber mediated detrusor reflex does not
  predominate neurogenic detrusor overactivity in
  lesion above pons
• Resiniferatoxin in 10-6-7 M can activate
  initial excitatory responses
• Therapeutic results are not as satisfactory as
  that in SCI patients
• An alternative for patients who cannot tolerate
  or refractory to anticholinergic agents

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Urodynamic results after RTX therapy in
Neurogenic detrusor overactivity
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Therapeutic Results of RTX in Neurogenic v
Non-neurogenic Voiding Dysfunction

• 22/41 patients (53.6) with detrusor overactivity
  improved after RTX 10-7M instillation (initial
  concentration)
• 6/10 (60) Neurogenic DH, 4/13 (31) Idiopathic
  DI, 12/18 (67) BOO related DI improved
• 6/7 (86) type I, 1/3 (33) type II,
• 7/16 (44) type III, 8/15 (53) type IV

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Urodynamic Changes after RTX in Detrusor
Overactivity
Baseline Post-RTX Statistics
Cystometric capacity(ml) (n41) 216106 302133 P0.000
Qmax (ml/sec) 12.77.6 21.828.9 P0.224
Voiding pressure (Pdet, cmH2O) 33.611.7 34.119.5 P0.923
Residual urine (ml) 41.152.7 49.498.9 P0.725
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Botulinum A toxin Injection

• Inhibition of acetylcholine (Ach) release from
  presynaptic cholinergic fiber
• Induce paralysis of muscle fibers
• Intravesical injection can inhibit detrusor
  overactivity
• Urethral injection can reduce urethral resistance
  and sphincter spasticity
• Duration of effect about 3-6 months

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Transurethral injection of Botulinum A toxin in
male urethral sphincter




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Injection of 3,6, 9, and 12 oclock Position of
Urethral Sphincter
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Reduced voiding pressure after botulinum A toxin
injection
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Reduced MUCP after Botulinum A toxin injection
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Table 1.The Urodynamic Parameters at Baseline and
after Botulinum Toxin in Effective Patients
Baseline Post-Botox Statistics
Capacity (n53) 331.4148.8 333.2155.4 0.922
Qmax (n53) 6.7 6.7 9.4 5.7 0.003
Voiding pressure (n53) 62.0 43.1 45.937.8 0.000
MUCP (n21) 97.131.7 51.123.2 0.027
FPL (n21 3.350.59 3.300.33 0.773
PVR (n53) 225.4174.4 110.1137.6 0.000
MUCPmaximal urethral closure pressure,
FPLfunctional profile length, PVR postvoid
residual volume Comparison between baseline and
4weeks after treatment
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Therapeutic Results after Botox Urethral
Injection for Voiding Dysfunction
Good Improved Failed
Detrusor underactivity (n27) 13 (48.2) 8 (29.6) 6 (22.2)
DESD (n18) 3 (16.7) 10 (55.6) 5 (27.8)
Dysfunctional voiding (n18) 6 (33.3) 10 (55.6) 2 (11)
Poor relaxation of urethral sphincter (n12) 3 (25) 7 (58.3) 2 (16.6)
TOTAL (n75) 25 (33.3) 35 (43.7) 15 (20)
DESDDetrusor external sphincter dyssynergia
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Botulinum Toxin Detrusor Injection for Detrusor
Hyperreflexia
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Btulinum A Toxin Detrusor Injection for DH
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Initial Results of BotulinumToxin Detrusor
Injection for Incontinence
No Sex / Age Disease DESE Capacity Dysuria Incontinence
1 M / 35 DESD 250 U Improved -
2 F / 10 DI 100 U No Change -
3 F / 45 DI 200 U Improved - -
4 M / 48 DHIC 200 U Improved -
5 F / 56 DH 200 U Improved - -
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Recovery of Detrusor function after Stroke
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Considerations in management of neurogenic
urethral incontinence

• Bladder compliance must be improved concomitantly
  in treatment of incontinence
• CISC may be necessary in patients with detrusor
  areflexia
• Balance the quality of life after surgical
  management of urethral incontinence and surgical
  complications
• Avoid surgery with unpredictable good surgical
  outcome