MP07-01: Restoration of bladder, urethral and anal sphincter function after surgical reinnervation in lower motor neuron lesioned canines.

Ekta Tiwari*, Lucas Hobson, Danielle Porreca, Alan Braverman, Nagat Frara, Geneva Cruz, Dania Giaddui, Philadelphia, PA, Justin Brown, Boston, MA, Michael Mazzei, Michel Pontari, Ida Wagner, Mary Barbe, Michael Ruggieri, Philadelphia, PA

Introduction: :  A prior interim study suggested that new neuronal pathways created by somatic nerve transfer can restore bladder sensation and motor function in long term decentralized canines. This study continues to explore the effectiveness of reinnervation in nerve transferred canines by examining micturition and defecation behaviors, functional electrical stimulation of transferred nerves, retrograde labeling from bladder.

Methods: Twelve female canines underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7 and hypogastric nerves. Four were euthanized at 11-21 months post decentralization. Eight underwent nerve transfer at 9-13 months post decentralization, then euthanasia 8-12 months later. Controls included 5 sham and 3 unoperated animals. Squat and void postures were tracked pre and post decentralization, post reinnervation, and during awake cystometry. Retrograde dye was injected into the bladder three weeks prior to euthanasia. At euthanasia, transferred nerves were electrically stimulated to evaluate motor function. Spinal cord segments and associated DRG (L2-S3) were collected and assessed for dye labelled neurons.

Results: Eight of twelve canines showed no or few squat and void postures during the decentralization period. In four, postures were observed with high frequency (>10) during the initial months and decreased when bacteriuria was cleared with antibiotics. Seven nerve transfer canines began showing postures by 6 months post reinnervation. One showed voluntarily voiding twice following awake cystometry. Four showed elevated detrusor pressure after stimulation of obturator-to-pelvic transferred nerves. Four showed elevated urethral and all showed elevated anal sphincter pressure after stimulation of sciatic-to-pudendal transferred nerves. Detrusor pressure was higher in reinnervated animals after stimulation of L2-L6 roots, compared to L7-S3. Sensory and motor reinnervation was confirmed by increased dye labeled cells in L2-L6 DRG and ventral horn region of cord (source of obturator nerve in canines), compared to controls.

Conclusions: Novel nerve transfer techniques can be applied to human patients in future to restore bladder, urethral and anal sphincter function.

Source of Funding: NIH 1R01NS070267