Neural reconstruction methods of restoring bladder function

Abstract

During the past century, diverse studies have focused on the development of surgical strategies to restore function of a decentralized bladder after spinal cord or spinal root injury via repair of the original roots or by transferring new axonal sources. The techniques included end-to-end sacral root repairs, transfer of roots from other spinal segments to sacral roots, transfer of intercostal nerves to sacral roots, transfer of various somatic nerves to the pelvic or pudendal nerve, direct reinnervation of the detrusor muscle, or creation of an artificial reflex pathway between the skin and the bladder via the central nervous system. All of these surgical techniques have demonstrated specific strengths and limitations. The findings made to date already indicate appropriate patient populations for each procedure, but a comprehensive assessment of the effectiveness of each technique to restore urinary function after bladder decentralization is required to guide future research and potential clinical application.

Figure 1

Spinal cord neuroanatomy and bladder innervation in humans and other mammals. After exiting the spinal cord, dorsal and ventral roots (which consist of small rootlets that unite to form the large root) join into a mixed spinal nerve that divides into a dorsal ramus, a ventral ramus, the sympathetic chain, and splanchnic nerves. The bladder is innervated via sympathetic axons that project from T10 to L2 (only T12 contributions are illustrated) through either splanchnic nerves to the inferior mesenteric ganglion on the aorta or descend within the sympathetic chain to upper sacral ganglia, where they synapse on neurons that project to the bladder. Parasympathetic bladder innervation from pelvic splanchnic nerves consists of preganglionic axon projections from S2 to S4 (only S2 contributions are illustrated) in most mammalian species to ganglia located near the bladder wall. Sensory feedback travels to the spinal cord from visceral and somatic structures by ‘hitchhiking’ on autonomic and somatic motor nerves. Abbreviations: CG, coccygeal segment; DRG, dorsal root ganglion; EUS, external urethral sphincter; IMG, inferior or caudal mesenteric ganglion; IVF, intervertebral foramen; L, lumbar; S, sacral; T, thoracic.

Figure 2

Homotopic root repair.^{, , ,} a | Intradural repair of ventral roots S1 and S2 in a cat model using a tubulation technique (exemplified for S1). The cylinder consists of mesh sheets and filter material, rolled into a tube around nerves and secured by ligatures or silver clips. b | Extradural bilateral repair of S1 and S2 ventral and dorsal roots in a canine model using end-on-end realignment and suturing (exemplified for ventral S1 and S2). One site is surrounded by a silicone sheath to enable delivery of BDNF. Bilaterally, a nerve cuff electrode is placed immediately proximal to the repair site to assess neurally evoked bladder emptying via FES. Abbreviations: BDNF, brain-derived neurotrophic factor; CG, coccygeal segment; FES, functional electrical simulation; IVF, intervertebral foramen; L, lumbar; S, sacral.

Figure 3

Heterotopic root repair.^{, ,} a | Unilateral transfer of the L7 dorsal and ventral roots to ipsilateral S2 and S3 dorsal and ventral roots in a dog. b | Unilateral intradural transfer of T12 or L1 dorsal roots to combined dorsal and ventral roots at S2 to S4 in a patient with a SCI extending from T12 thru L4. c | Bladder decentralization by severing S1 and S2 ventral and dorsal roots intradurally and bilaterally in a dog, followed by extradural end-on-end repair, using proximal ends of transected CG1 and CG2 ventral roots, and placement of a NCE around the root bundles. Abbreviations: CG, coccygeal; DRG, dorsal root ganglion; ; L, lumbar; NCE, nerve cuff electrode; S, sacral; SCI, spinal cord lesion; T, thoracic.

Figure 4

Extradural-to-intradural transfer of spinal nerves to sacral roots.^{, ,} . a | After extradural transection of the L1 nerve in its IVF, the nerve is moved back into the dural sac and sutured to the proximal ends of S3 and S4 dorsal and ventral roots. b | T12 nerves are extradurally transected, moved intradurally and anastomosed end-to-end to S2 and S3 ventral and dorsal roots, using a silicone elastomer filter formed into a tube and secured with silver clips. c | Extradurally neurolysed T11 and T12 nerves are reintroduced into the vertebral canal at the upper sacral level and aligned to S2 and S3 ventral roots, using a polymeric film secured with biological glue. Abbreviations: CG, coccygeal; IVF, intervertebral foramen; L, lumbar; S, sacral; T, thoracic.

Figure 5

Intradural-to-extradural transfer of lumbar or sacral roots to sacral spinal nerves.^{, ,} . a | Transfer of L7 or S1 dorsal sensory roots to S1 or S2 spinal nerves, respectively, in a cat model, using a tubulation method. Ventral motor roots and sacral efferent fibres other than indicated S1 and S2 roots are left intact. b | Transfer of L7 dorsal and ventral roots to the S1 spinal nerve, after extradural unilateral transection of L7 to S3 roots, in a cat model, using a bridging S2 root graft in some animals. Abbreviations: CG, coccygeal; L, lumbar; S, sacral.

Figure 6

Transfer of peripheral nerves to pelvic nerves.^, ,^–. a | Transfer of the hypogastric or obturator nerves to the pelvic splanchnic nerves (transected between the spinal cord and the pelvic plexus), or repair of the transected pelvic nerve ends. b | Transfer of the genitofemoral nerve to the anterior vesical branch of the pelvic nerve after bilateral transection of the dorsal and ventral sacral roots to the bladder. Abbreviations: CMG, caudal mesenteric ganglion; L, lumbar; NCE, nerve cuff electrode; S, sacral.

Figure 7

Direct detrusor muscle reinnervation by somatic nerve transfer. In a canine model, the bladder is decentralized by bilateral pelvic nerve neurectomy (1) or intradural sacral rhizotomy of S2 and S3 roots (2). 10 days later, either the obturator nerve (3) or femoral nerve (4) is sectioned and their distal ends implanted directly into the detrusor muscle close to the ureterovesical junction, using an arterial sleeve. Abbreviations: L, lumbar; S, sacral.

Figure 8

Artificial skin–CNS–bladder reflex pathway methods.^–. After hemilaminectomy from L4–S3, the dorsal and ventral roots from L5–S3 are exposed, the ventral roots of L5 and S2 separated from their respective dorsal roots and sectioned. Then, the proximal end of the L5 ventral root is sutured to the distal end of the S2 ventral root in human subjects. Variations included transfer of the L4 to L6 ventral roots, L5 ventral root to S3 ventral roots, L7 to S1 ventral roots, or S1 to S1 and/or S2 ventral roots. Abbreviations: CG, coccygeal; CNS, central nervous system; L, lumbar; S, sacral. Not sure why some changes were made - are you, the editor intending to focus on human only? I added human and animal subject variations (Barbe)