Spinal cord injury

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

2. 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%)

3. 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

4. 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

5. 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

6. 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

7. Urodynamic findings in SCI

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

9. 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

10. 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

11. 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)

12. 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

13. Cervical SCI autonomic dysreflexia and BN dysfunction

14. 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

15. 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

16. Grade 1 DESD

17. Grade 2 DESD- High voiding pressure and increased EMG

18. Gr 2 DESD with low voiding pressure and no flow

19. Grade 3 DESD

20. Recovery from spinal shock in Cervical SCI

21. 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)

22. Hydronephrosis in chronic SCI

23. Bladder stones in chronic SCI

24. Vesicoureteral reflux in chronic SCI

25. Analysis of LUTS in 704 SCI

26. Analysis of UTI in 704 chronic SCI

27. Late complications in 704 SCI

28. Management of voiding in 704 SCI in Taiwan

29. The relationship of UTI frequency and SCI level and voiding management

30. 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

31. 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)

32. 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

33. 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

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

35. 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

36. 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？

37. 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

38. 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

39. 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

40. 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

41. Initial CMG Tracing after RTX

42. 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)

43. Urodynamic Changes after RTX

44. 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

45. 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

46. Urodynamic tracings before, during and after resiniferatoxin

47. 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

48. Reduction of Voiding pressure after Botulinum toxin in DA

49. Rhythmic detrusor contractions in SCI with DESD after Botox

50. 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