Buddhist Tzu Chi General Hospital Hualien Spinal cord injury Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital Hualien

Leading causes & Location of Spinal cord injury Motor vehicle accidents (47%) Falls (21%) Sports (14%) Act of violence (14%) Location of SCI: cervical (53%), thoracic (35%), lumbar and sacral (10%)

Urinary tract symptoms in Acute spinal cord injury Spinal shock stage: detrusor areflexia, complete anesthesia of fullness or voiding Recovery of micturition reflex gradually about 1-3 months after recovery of somatic reflexes Prolonged recovery of voiding reflex may be due to overdistension of the bladder after injury or complication

Micturition Control Micturition reflex center – sacral cords S 2-4 Sympathetic nucleus – T10-L1 Micturition control center – pons Sensory motor center – frontal lobe Limbic system Cerebellum, Basal ganglia

Pathophysiology of lower urinary tract dysfunction after SCI Suprasacral cord lesion – interruption of coordination of detrusor contraction and sphincter relaxation Lesion above T6 SCI – sympathetic hyperactivity during activation of visceral input, bladder distension, rectal distention, cold and noxious stimulation, surgery and infection

Chronic spinal cord injury and urinary tract dysfunction Autonomic dysreflexia – SCI above T5,6 (sympathetic nucleus) Detrusor external sphincter dyssynergia (DESD) – lesion above S2-4 Detrusor hyperreflexia – complete or incomplete SCI above sacral cords Detrosor areflexia – sacral cord SCI or cauda equina lesions

Urodynamic findings in SCI Cervical (n=68) Thoracic (n=53) Sacral or infrasacral (n=40) Detrusor hyperreflexia 47(69%) 29 (55%) 2 (5%) Detrusor areflexia 21(31%) 24 (45%) 38 (95%) DESD Presence 41(60%) 20 (38%) - Absence 27(40%) 33 (62%) 40 (100%) AD 22(32%) 1 (2%) 46(68%) 52 (98%) DESS=Detrusor external sphincteric dyssynergia; AD=autonomic dysreflexia.

Major concern in managing SCI Preservation of renal function Free of symptomatic urinary tract infection Efficient bladder emptying Freedom of catheter Continence

High risk SCI Patients Complete neurological lesion Cervical SCI with quadriplegia Prolonged indwelling catheter High detrusor leak-point pressure Presence of DESD and AD Large residual urine Presence of vesicoureteral reflux

Detrusor leak-point pressure The intravesical pressure (detrusor pressure) at the end of filling or urinary incontinence A detrusor LPP of over 40cm water will endanger the upper tract in meningomyelocele Reduction of detrusor LPP can improve renal function, reduce the risk of UTI, decrease the degree of hydronephrosis, improve vesicoureteral reflux and restore continence

Hydronephrosis in SCI Hydronephrosis is a sign of upper tract deterioration after SCI In 251 SCI patients, 24 (9.6%) had hydronephrosis, including: Cervical SCI 7 (5.9% of 118), 7+ 4 (3-15) years Thorac& lumb 8 (8.6% of 93), 9.9+ 6.5 (3-22) Sacral 9 (22.5 of 40), 17+ 6.1 (8-26)

Autonomic dysreflexia Spinal cord lesion above T6 Hypertension and increased sympathetic outflow, flushing, sweating above dermatome during increased visceral input (bladder over-distension,urination, rectal distension, surgery, UTI) Risk of heart failure and stroke Bladder neck contraction during voiding

Cervical SCI autonomic dysreflexia and BN dysfunction

Detrusor external sphincter dyssynergia (DESD) Spinal cord lesion above micturition reflex center Lack of coordination in the micturition center External sphincter contrction during detrusor contractions Dysuria, difficult to initiate voiding, high voiding pressure, large residual urine Result in frequent UTI and upper tract damage

Grades of DESD Grade 0- 3 according to the sphincteric activity Grade 0 – normal or synergia Grade 1 – DH &high Pves, hyerreflexic sphincter at initiation, voiding with mild residual urine Grade 2 – DH or hyporeflexic detrusor, intermittent hyperreflexic sphincter, large residual urine Grade 3 – DH, closed hyperreflexic sphincter, no spontaneous voiding

Grade 1 DESD

Grade 2 DESD- High voiding pressure and increased EMG

Gr 2 DESD with low voiding pressure and no flow

Grade 3 DESD

Recovery from spinal shock in Cervical SCI

Late Urological Complications in Spinal cord injury Urinary tract infection induced sepsis Hydronephrosis and uremia Stone formation (renal& bladder stone) Contracted bladder & VU reflux Incontinence and associated complications Bladder tumor formation (chronic indwelling catheter)

Hydronephrosis in chronic SCI

Bladder stones in chronic SCI

Vesicoureteral reflux in chronic SCI

Analysis of LUTS in 704 SCI 頸髓脊髓損傷 胸髓脊髓損傷 腰髓脊髓損傷 薦髓及以下脊髓損傷 完全 不完全 尿瀦留 14 5 12 3 2 尿失禁（無感覺） 50 18 92 31 13 尿失禁（有感覺） 27 32 24 1 滿溢性尿失禁 8 17 16 11 20 排尿困難 21 4 10 頻尿急尿 9 正常排尿 7 總　　計 122 149 165 72 61 104 26

Analysis of UTI in 704 chronic SCI 頸髓脊髓損傷 胸髓脊髓損傷 腰髓脊髓損傷 薦髓及以下脊髓損傷 總計 完全 不完全 從來沒有UTI 31 56 32 21 19 41 4 5 209 (29.7%) <1 / year UTI 45 46 66 17 22 3 218 (31%) ≧ 1 / year UTI 38 15 57 12 14 1 155 (22%) 不知道 8 10 18 11 24 122 (17.3%)

Late complications in 704 SCI 頸髓脊髓損傷 胸髓脊髓損傷 腰髓脊髓損傷 薦髓及以下脊髓損傷 總計 完全 不完全 完全沒有 44 60 43 16 18 3 231 (32.8%) 反覆尿路感染 51 37 78 24 27 22 4 243 (34.5%) 尿路結石 11 10 38 15 5 1 90 (12.8%) 腎臟水腫 6 21 2 8 62 (8.8%) 輸尿管逆流 14 7 19 55 (7.8%) 腎衰竭 25 (3.6%)

Management of voiding in 704 SCI in Taiwan 頸髓脊髓損傷 胸髓脊髓損傷 腰髓脊髓損傷 薦髓及以下脊髓損傷 完全 不完全 尿道留置導尿 23 10 14 7 4 2 - 膀胱造廔 13 5 16 1 腹壓排尿 17 39 19 28 11 敲擊腹部 29 24 12 自行反射 27 55 21 3 間歇導尿 6 正常感覺 57 40 其　他 總　計 122 149 165 72 61 104 26

The relationship of UTI frequency and SCI level and voiding management UTI Fequency 0/year 1/year 2/year 3/year sepsis Level of SCI Cervical SCI 41(34.7%) 20 (16.9%) 15 (12.7%) 42 (35.6%) 7 Thoracic or lumbar SCI 17 (18.3%) 21 (22..6%) 38 (40.9%) 4 Sacral or infrasacral SCI 2 (5%) 9 (22.5%) 7 (17.5%) 22 (55%) Complete lesion 15 30 28 51 9 Incomplete lesion 45 20 11 2 Initial management Urethral Foley catheter 12 10 16 6 Suprapubic cystostomy 3 14 1 Crede maneuver 13 65 Abdominal tapping,reflex 5 - CISC Normal CISC=Clean intermittent self-catheterization.

Considerations in management of LUTD in chronic SCI Correct complications Treat hydronephrosis, treat UTI, treat vesicoureteral reflux Improve quality of life Treat incontinence, convenience of bladder emptying, free of catheter,free of medication Individual treatment strategy for each SCI patient

Medical Treatment for LUTD in chronic SCI To reduce detrusor hyperreflexia – anticholinergics (oxybutynin,imipramine) To reduce bladder neck hyperreflexia – alpha-blocker (tamsulosin, terazosin, prazosin) To reduce striated sphincter spasticity – skeletal muscle relaxant (baclofen, diazepam) To increase detrusor muscle tone – cholinergic agent (urecholine)

Combination of medication for LUTS in Chronic SCI To treat incontinence – anticholinergics and adrenergic agnist (methylephedrine) – CISC is needed, residual urine, UTI should be monitored To facilitate voiding – cholinergic agent and alpha-blocker and skeletal muscle relaxant – incontinence exacerbates, upper tract deterioration if detrusor LPP is high

Side effects of Medical Treatment in chronic SCI Constipation -- anticholinergics Hypotension –alpha-blocker Nasal congestion –adrenergic agonist General weakness – skeletal muscle relaxant Side effects increase as combination of medication Cost benefit should be considered

Intravesical therapy for SCI Detrusor hyperreflexia – oxybutynin, capsaicin, resiniferatoxin, botulinum injection Reversible response Periodic instillation or injection

Capsaicin and resiniferatoxin Intravesical agents for overactive bladder have been mostly been used in neurogenic bladder disorders Capsaicin and resiniferatoxin have been successfully used intravesically to reduce urinary incontinence in neurogenic detrusor hyperreflexia Resiniferatoxin has less acute side effect and similar efficacy as capsaicin Resiniferatoxin is effective in treating detrusor hyperreflexia refractory to capsaicin treatment

Therapeutic effects of resiniferatoxin 10 -5 to 10 -7 M RTX is effective for DH of SCI 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 Is RTX effective for DESD through inhibition of DH in SCI patients？

Successful Therapeutic Effects Patient became dry Increase in 50% of maximal cystometric capacity Subjective improvement rate by >50% in incontinence or dysuria Significant change in quality of life in urination subjectively

Side Effects of RTX Treatment Autonomic responses Elevated blood pressure Headache Bradycardia General malaise RTX was drained out and bladder irrigation was performed if systolic BP >200mmHg

Results of resiniferatoxin therapy 20 patients (7 women and 13 men) Mean age 42.2 ±13.2 (24 – 66) years 10 cervical, 10 thoracic SC lesion 18 traumatic SCI, 2 multiple sclerosis All had DESD, 9 had autonomic dysreflexia 18 incontinence, 13 dysuria, 8 recurrent UTI

Responses of RTX instillation Initial excitatory response at 1-5 min Four types of initial responses Type 1: A sustained high pressure followed by complete detrusor non-contraction Type 2: A high pressure contraction followed by progressively lower amplitude contractions Type 3: Intermittent high pressure contractions Type 4: Intermittent low pressure contractions

Initial CMG Tracing after RTX

Therapeutic Results of RTX 4/20 became dry during the daytime but incontinent at night time 8/20 had increased in frequency interval and voided volume 8/20 had no significant improvement 8/13 with dysuria had improvement in spontaneous voiding (5) or on Crede maneuver (3)

Urodynamic Changes after RTX Baseline Post-RTX Stastistics Cystometric capacity(ml) 102.1±31.5 236.6±88.6 P<0.001 Bladder compliance (ml/cmH2O) 23.7±12.1 25.9±15.3 P>0.05 Voiding pressure (Pdet, cmH2O) 55.9±23.2 47.5±28.1 Presence of DESD 100%

Side Effects and QOL after RTX Dizziness and headache with high BP and bradycardia (4/20) Initial gross hematuria (5/20) Bladder irritation and frequency in all patients 7/20 responded that quality o life improved after RTX 13/20 did not notice any significant change in QOL although objective data showed improved

Correlation of RTX Responses with Therapeutic Results A good response was noted in 12 patients Type 1: 5 (100%) Type 2: 4 (80%) Type 3: 2 (40%) Type 4: 1 (25%) Duration of RTX responses: 1 (6m), 6 (3m), 3 (2m), 2 (1m), repeat instillation in 7/12

Urodynamic tracings before, during and after resiniferatoxin

Botulinum toxin injection Botlinum toxin has been used to inject striated urethral sphincter for grade 3 DESD Refractory detrusor hyperreflexia can be eradicated by intra-detrusor injection of botox Reversible effect and possibilty of antibody formation after repeated injection Cost-benefit should be weighed

Reduction of Voiding pressure after Botulinum toxin in DA

Rhythmic detrusor contractions in SCI with DESD after Botox

Botulinum A Toxin Detrusor Injection for Detrusor Hyperreflexia 5 IU/Kg Botox (Botulinum A toxin) was injected to 30 sites into detrusor muscle Decreased detrusor pressure and increased cystometric capacity after Botox Increased residual urine and CISC is needed Abdominal tapping to void Indicated in refractory detrusor hyperreflexia

Botulinum A toxin 250 U Detrusor Injection for Detrusor Hyperreflexia

Cauda equina lesion and Detrusor areflexia

Grade 1 DESD in a SCI Women

Grade 1 DESD in Cervical SCI

Failure of Pharmacological Mx Presence of vesicoureteral reflux Severe bladder fibrosis and trabeculation Presence of severe bladder outlet obstruction Severe outlet incompetence Azotemia or renal failure No improvement in quality of life

Surgical treatment for complications of chronic SCI External sphincterotomy and urethral stent Augmentation cystoplasty Bladder autoaugmentation Continent urinary reservoir formation (Kock pouch) Pubovaginal sling procedure Continent cystostomy Ureteral reimplantation

External Sphincterotomy Indicated in quadriplegic patients with DESD Potentially not result in total incontinence Urinary tract infection can be eliminated Free of catheterization Re-do is possible in 25% patients with inadequate sphincter relaxation or scarring 25- 30 % may have persistent hydronephrosis

Technique of Sphincterotomy 12 o’clock position Incision from BN to bulbous Cutting deep to fat & vessel Bleeding can be controlled Avoid diffused coagulation On Foley catheter for 2 days

Intravesical pressure after external sphincterotomy

Reduction in MUCP after External sphincterotomy

Urethral Stent Indwelling a distensible urethral stent for scarred membranous or severe DESD refractory to sphincterotomy Complication should be weighed: stone formation, stent erosion, persistent UTI, total incontinence Only 2/11 longer follow-up patients needed to be removed

Implantation of a urethral stent

Augmentation cystoplasty A bladder capacity of less than 250ml Overflow incontinence and large residual urine Presence of hydronephrosis Azotemia and frequent pyelonephritis Patient is able to catheterize by himself Side effect or refractory to pharmacological therapy

Technique of augmentation cystoplasty

Surgical results after augmentation cystoplasty

Bladder autoaugmentation Partial myomectomy of bladder wall Increase bladder compliance and capacity by distensible bladder mucosa Less surgical morbidity and complication Secondary fibrosis and reduced capacity after long-term follow-up Serve as first line surgical procedure for SCI

Bladder autoaugmenttion

Ureteral reimplantation Not suitable in trabeculated bladder High failure rate after ureteral reimplantation or collagen injection Contraindicated in SCI patients with DESD & AD Combined augmentation and anti-reflux procedure is a better way

Anti-reflux afferent nipple valve

Continent Reservoir (Kock pouch) Creation of a continent reservoir by a 40-cm segment of ileum Detubularization and double folded ileum can have a volume of 600ml Anti-reflux and anti-incontinence nipple valves Self-catheterization is needed Suitable for female SCI with good hand function

Sonography of Kock pouch

Degeneration of intestinal wall in Urinary reservoir

Transurethral injection Transurethral injection of botulinum toxin may reduce sphincteric tone and facilitate voiding in SCI with DESD or detrusor areflexia Transurethral injection of collagen or Teflon paste may bulk sphincter and increase urethral tone, eliminate incontinence in lower level SCI Other new devices implant into bladder neck or sphincteric urethra to combat incontinence

Artificial Urethral Sphincter

Artificial Urethral Sphincter 95% in the NVD patients (half of 250) receiving AUS implantation became continent, 78% at the first AUS attempt Revision rate in neurogenic voiding dysfunction is 33% Annual incidence of erosion was 5% Overall success rate was 77%,revision rate 59% in 107 children