1. Determining the Effectiveness of an Intradural Lumbo-Sacral Nerve Rerouting Procedure Neurosurgery: Gerald Tuite, Luis Rodriguez, Carolyn Carey, Bruce Storrs Urology: Yves Homsy, Ethan Polsky, Mike Reisman, Mark Kolligan Physical Therapy: Maggie Reilly, Kathleen Thompson Neurology: Parrish Winesett Research Nurse Coordinator: Lisa Tetreault Pathology: Ignacio Gonzalez All Children’s Hospital and Johns Hopkins Medicine St. Petersburg, FL

4. Two Efficacy Studies for Patients with Neurogenic Bladder Patients who do not have spina bifida o Spinal cord injury (exclude conus/cauda equina) o Prospective o Longitudinal Patients with spina bifida Only patients who require detethering Randomized at the time of surgery Double blinded

5. Clinical Trial Initiation, March 2009 Left L5 ventral root to Sacral root anastomosis

6. One Spinal Cord Injury Patient Primary End Points – Voiding – Scratch Test described by Xiao et al – Continence Secondary end points – Motor and sensory function – Bowel function – Urodynamic changes – Sexual function – Quality of life – Ability to perform ADL – Frequency and severity of surgical complications

7. Assessment at 3,6,12,18 and 24 months Six Months – initial optimism Some improvement in bladder and bowel function Possible initiation of voiding? Urologists saw bladder contractions on urodynamic testing in the proper dermatomal distribution to suggest bladder reflex Two Years No clinical improvement No initiation of voiding with scratching No contractions by urodynamic testing

8. Surgical re-exploration of spinal cord injured patient Bladder volumes too small Transplant candidate if bladder volumes larger Selective Sacral Rhizotomy vs. Bladder Augmentation Prior experience with selective rhizotomy: Schneidau T, Franco I, Zebold K, Kaplan W: Selective sacral rhizotomy for the management of neurogenic bladders in spina bifida patients: long-term follow-up, J Urology 154, 766-768, 1995

10. In anatomic continuity, sensory L5 root intact No contraction of bladder with stimulation (bladder electrode in place) Nerve action potentials could not be measured across the anastomosis

13. NEUROFILAMENTS

14. S100 protein

16. Single Patient with L5-Sacral Anastomosis 1.Some initial improvement at six months 2.No clinical improvement at two years 3.Anastomosis intact on gross inspection 4.No electrophysiological activity 5.Nerves did not grow past anastomosis

17. Twenty Children with Spina Bifida Undergoing Spinal Cord Detethering Surgery Spina bifida patients who require detethering – Not just a radiographic diagnosis – Clinically confirmed by multidisciplinary team Neurogenic bladder – Urodynamically confirmed – Stable or worsening condition – Urologist confirmed Lower thoracic or lumbar neurologic level

18. Exclusion Criteria Surgical: anesthesia problems, fusion Current shunt malfunction Comprehension of study and willing to participate in follow-up Bladder cancer, radiation, augmentation Anatomic bladder outlet obstruction If they can control their own urination

19. Randomized and Double Blinded ½ Detethering (D) ½ Detethering + Xiao Procedure (D + X) (D + X) – D = X

20. Why have a control group? In spina bifida patients, spinal cord detethering is required to perform the Xiao procedure Detethering alone can impact bladder function Placebo effect Safety: patients who require a spinal cord detethering anyway Why double blinded? Patients, doctors, nurses, families ALL WANT THIS TO WORK!!!

21. Objectives Primary End Points – Voiding – Scratch Test described by Xiao et al – Continence Secondary end points – Motor and sensory function – Bowel function – Urodynamic changes – Sexual function – Quality of life – Ability to perform ADL – Frequency and severity of surgical complications

22. Multidisciplinary Assessment (No assessment by surgeons who performed the operation) Preop and 3, 6, 12, 24, 36 months after surgery Same Questionnaires as Before Surgery – PEDI – Bowel, Bladder, Sexual function Urodynamics (with Scratch test) PT: motor and sensory function Scratch Test The family and all evaluators are blinded to randomization in the study involving patients with spina bifida End of study: patient/family notified, crossover possible

23. Current Status of ACH Trials Both IRB Approved Randomized Spina Bifida Trial – Enrollment stopped: 20 patients total – Procedure can be safely performed as an adjunct to spinal cord detethering procedure – Two more years of follow-up Spinal Cord Injury Study – No further enrollment – Awaiting outcome of spina bifida study

25. Roots Can Be Difficult to Characterize

26. Anastomosis Not Difficult Yet

27. Multidisciplinary Project

28. Why Expose Asymptomatic Patients to Spinal Cord Dissection Unnecessarily?