TITLE: Pudendal Nerve Mapping in Humans
AUTHORS: Amador C Lagunas, Po-Ju Chen, Priyanka Gupta, Tim Bruns

[DESCRIPTION]
The goal of this study is to map the pudendal nerve with imaging and electrophysiology by gathering additional data from patients receiving an implanted neurostimulator as part of their normal clinical care, and to examine the response of the bladder and urethra to different pudendal nerve stimulation frequencies in humans. There are 5 main parts to this study. Participants complete pre and post study questionnaires to asses their pelvic health and functional change. Volumetric imaging with MRI and CT scans are done to create patient specific maps of each participant's pelvic anatomy. Additional details on the parameters used for the MRI and CT scans can be found here:dx.doi.org/10.17504/protocols.io.yxmvm978bl3p/v1. During device implantation experimental trials are performed in the OR to asses the impact of different simulation parameters on the pelvic floor. After device implantation experimental trials are performed during a cystometrogram to asses how bladder state and stimulation parameters affect pelvic floor and lower urinary tract function.

[STEPS]
SECTION: Stage 1 Intraoperative Testing
6. After multicontact lead has been placed next to the pudendal nerve as described in Peters 2013, connect the external pulse generator to electrode 0 and a surface patch electrode placed on the ankle.
8. Change pulse width to 210 microseconds.
7. Change stimulation frequency of the external pulse generator to 3 Hz.
9. Increase stimulation amplitude until external anal sphincter contraction is detected by intraoperative nueromonitoring team on EMG readout then turn off stimulation.
10. Change pulse width to 60 microseconds.

9.2. Double previous stimulation amplitude and apply stimulation for 10 seconds. 
11. Repeat step 9 and all substeps.

12. Change pulse width to 450 microseconds.
13. Repeat step 9 and all substeps.

14. Connect to electrode 1.
15. Repeat steps 8-13.

16. Connect to electrode 2.
17. Repeat steps 8-13.

18. Connect to electrode 3.
19. Repeat steps 8-13.

20. Connect implanted lead to temporary pulse generator.
21. Set the electrode with the lowest external anal sphincter activation threshold as the cathode and set the electrode with the second lowest external anal sphincter activation threshold as the anode.
22. Repeat steps 8 and 9.

23. Set the electrode with the second lowest external anal sphincter activation threshold as the cathode and set the electrode with the lowest external anal sphincter activation threshold as the anode.
SECTION: Stage 1 Intraoperative Testing
4. Add lubricating jelly to the tip of the Manoscan catheter and place catheter into the urethra until resistance is met and catheter cannot go any deeper.
SECTION: Stage 1 Intraoperative Testing
5. Place electromyography (EMG) needles across the anal sphincter at the 3 and 9 o'clock position until the needle is no longer visible [7].
 
 Connect the needle electrodes to Cadwell Cascade Elite intraoperative neuromonitoring system and begin recording with a sampling rate of 333 Hz.
SECTION: Cystometrogram Experimental Trials
31. Place urodynamics TDOT air charged catheter into the urethra and rectum. Place EMG patch electrode across the anus at the 3 and 9 o'clock position. Connect sensors to Laborie urodynamics system and begin recording. 
SECTION: Cystometrogram Experimental Trials
32. Using the pudendal neurostimulator control software set the case as the anode and electrode 0 as the cathode. Determine the sensory threshold and maximum tolerable threshold at 14 Hz and 210 microsecond pulse width.
SECTION: Cystometrogram Experimental Trials
33. Fill the bladder until participant feels a strong urge to void.
SECTION: Cystometrogram Experimental Trials
47. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
48. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds. Then turn off stimulation.
SECTION: Cystometrogram Experimental Trials
49. Change stimulation frequency to 30 Hz.
SECTION: Cystometrogram Experimental Trials
50. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
51. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
52. Set stimulation frequency to 3 Hz, set electrode with lowest sensory threshold as the anode, and set the electrode with the second lowest sensory threshold as the cathode.
SECTION: Cystometrogram Experimental Trials
53. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
54. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
55. Change stimulation frequency to 30 Hz.
SECTION: Cystometrogram Experimental Trials
56. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
57. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
58. Change electrode combination to match what the participant uses for at home therapy. 
 


SECTION: Cystometrogram Experimental Trials
59. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
60. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds.
SECTION: Pre-study surveys
1. Have participants complete American Urological Association Symptom Index (AUASI) [1]
 
, Michigan Incontinence Symptom Index (MICI)[2]
 
,  Female Sexual Function Index short form (FSFI-6) for women [3]
 
 or the International Index of Erectile Function (IEEF-5) men[4]
 
, Colorectal-Anal Distress Inventory 8, and Female GenitoUrinary Pain Index (FGUPI) for women[5]
 
 or Male GenitoUrinary Pain Index (MGUPI) for men [6].
 



SECTION: CT Imaging
63. Complete CT imaging of the pelvis after implantation of the device lead to that the lead location can be co-localized into a participants specific model of their pelvic anatomy.
SECTION: Post Study Survey
64. Have participants complete the same surveys that were issued in step 1.
SECTION: Stage 1 Intraoperative Testing
3. Turn on Manoscan recording software and calibrate Manoscan high-resolution esophageal small diameter catheter per Manoscan manual guidelines. 
SECTION: Cystometrogram Experimental Trials
30. Set up as described in steps 3 and 4.
SECTION: Cystometrogram Experimental Trials
62. End of session. Save data from Manoscan and shut down software. Remove remaining catheters from the participant. Collect pressure and EMG data from the urodynamics system.
SECTION: Stage 1 Intraoperative Testing
4.1. Record the first visible sensor outside the body using the numbered label on the catheter.
SECTION: Stage 1 Intraoperative Testing
4.2. Tape the catheter to the patients body so that it remains in place and does not change position or slide out.
SECTION: Stage 1 Intraoperative Testing
3.1. Begin data recording session and change display so only channels in the bladder, bladder neck, and urethra are visible.
9.1. Apply stimulation for 10 seconds then turn off stimulation.
24. Repeat steps 8 and 9.
25. Set the electrode with the third lowest external anal sphincter activation threshold as the cathode and set the electrode with the lowest external anal sphincter activation threshold as the anode.
26. Repeat steps 8 and 9.
27. Set the electrode with the fourth lowest external anal sphincter activation threshold as the cathode and set the electrode with the lowest external anal sphincter activation threshold as the anode.
28. Repeat steps 8 and 9.
29. End of session. Save Manoscan recording data and close software. Remove catheter from participant. Collect anal sphincter EMG data from recording system for later analysis.
SECTION: Cystometrogram Experimental Trials
32.1. Determine the sensory threshold and maximum tolerable threshold for each of the remaining electrode with the case as the anode.
SECTION: MR Imaging
2. Complete MR imaging of the pelvis. Imaging protocols enable pudendal nerve visualization and are described in dx.doi.org/10.17504/protocols.io.yxmvm978bl3p/v1.
9.3. Repeat step 9.2 until stimulation amplitude would be above 5 mA.
SECTION: Cystometrogram Experimental Trials
46. Set stimulation frequency to 3 Hz, set electrode with lowest sensory threshold as the cathode, and set the electrode with second lowest threshold as the anode.
SECTION: Cystometrogram Experimental Trials
34. Set stimulation frequency to 3 Hz, set electrode with lowest sensory threshold as the cathode, and set the case as the anode.
SECTION: Cystometrogram Experimental Trials
35. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
36. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds. Then turn off stimulation.
SECTION: Cystometrogram Experimental Trials
37. Change stimulation frequency to 30 Hz.
SECTION: Cystometrogram Experimental Trials
38. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
39. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds. Then turn off stimulation.
SECTION: Cystometrogram Experimental Trials
40. Set stimulation frequency to 3 Hz, set electrode with second lowest sensory threshold as the cathode, and set the case as the anode.
SECTION: Cystometrogram Experimental Trials
41. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
42. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds. Then turn off stimulation.
SECTION: Cystometrogram Experimental Trials
43. Change stimulation frequency to 30 Hz.
SECTION: Cystometrogram Experimental Trials
44. Increase stimulation amplitude until participant first senses stimulation. Remain at this amplitude for at least ten seconds.
SECTION: Cystometrogram Experimental Trials
45. Increase stimulation amplitude to participants maximum tolerable threshold. Remain at this amplitude for at least ten seconds. Then turn off stimulation.
SECTION: Cystometrogram Experimental Trials
61. Apply stimulation using at-home stimulation settings and with the at-home stimulation amplitude. Have the participant attempt to void with both catheters in the urethra.