Login to Access Video or Poster Abstract: MP85-04
Sources of Funding: LAH (California Institute for Regenerative Medicine RT3-07616; Department of Defense SC090273; Adelson Medical Research Foundation; NIH P51 OD011107); HHC (NIH DK106181)

Introduction

A conus medullaris syndrome results from an Injury to the conus medullaris and cauda equine portions of the spinal cord. The clinical presentation is characterized by a lower motor neuron weakness affecting both skeletal muscles and pelvic organs with signs of paralysis, sensory disturbance and impairments of bladder, bowel, and sexual functions. The goal of the present study was to translate the unilateral lumbosacral ventral root avulsion (VRA) injury model from the rat to rhesus macaques, and to determine early and late effects of pelvic target denervation on lower urinary tract and external anal sphincter (EAS) function.

Methods

A total of 6 female rhesus macaques were included. A unilateral L6-S3 VRA injury was performed and resulted in a lesion of all preganglionic parasympathetic fibers of the ipsilateral pelvic nerve and all somatic motor fibers of the ipsilateral pudendal nerve. Urodynamic studies and EAS electromyography (EMG) were performed under ketamine anesthesia in control subjects (n=6), and at 1 month and 6 months after the unilateral VRA injury (n=4).

Results

The bladder infusion rate was between 85 and 120 mL/min to partially fill the bladder and induce reflex voiding. Poor voiding efficiency and compliance, and a slower urine flow rate were found in VRA subjects. The EAS guarding reflex was tested using a rectal probe. The maximum amplitude and area under the curve of EAS EMG were significantly decreased at 1 month after injury, but recovered at 6 months. Power spectrum (Fig. 1) showed that the peak frequency increased at 1 month after injury, but it was reduced to normal state at 6 month. The mean frequency was decreased at 1 and 6 months after injury.

Conclusions

This model eliminated the parasympathetic fibers of pelvic nerve and the somatic motor fibers of pudendal nerve, which resulted in detrusor underactivity and poor EAS contractility. Power spectrum analysis indicated that fewer motor units fired during EAS contraction after injury. This model in rhesus macaques mimics the clinical phenotype of conus medullaris syndrome using a lumbosacral VRA injury approach in long-term studies. It may provide a useful model to test the utility of emerging treatments after denervation of pelvic targets.

Funding

LAH (California Institute for Regenerative Medicine RT3-07616; Department of Defense SC090273; Adelson Medical Research Foundation; NIH P51 OD011107); HHC (NIH DK106181)