Alan Wein: Hi, I'm Alan Wein from UroToday, and I have the pleasure today of interviewing John Heesakkers, who's one of the true luminaries in functional urology in the world. John and I were at a meeting in China not too long ago where he gave a great talk about the history of neuromodulation, and also about the current varieties of neuromodulation.

And I thought that would be a great way to start today's discussion, so I'm going to turn it over to John for that discussion. And I had asked him to try and answer a number of questions about neuromodulation during the talk, and then we'll have a short discussion afterwards to amplify some of those points. So, John, your turn.

John Heesakkers: Thanks very much, Alan. Yeah, that was quite a remarkable meeting in China with many enthusiastic people, I must say. Because we all have the idea that neuromodulation is a US and European invention and it developed there, which is definitely true, but it's picked up in other countries as well and that makes it also quite international at the moment. And I think that also many people can benefit from it because it can be done in a very complicated way, but also in a very easy way. And then it is accessible for many people, I think, and many patients. So if you allow me, I will share my screen and show you some slides and talk you through it. And if you want to intervene, please do, Alan. I think we more or less celebrated the 40th year of neuromodulation this year. And it started as a research tool, of course, many years before also in urology fields. But the real applications came a bit afterwards, and that was about 40 years ago.

And this is more or less the idea. If you look at this innervation scheme of the lower urinary tract, you see that areas that are involved like the hypogastric nerve, pelvic nerve, pudendal, tibial. We have, of course, the end organs, we have the bladder, we have the sphincter or sphincteric complex, whatever you want to call it. And the idea is finally that if you don't have a proper behavior of the lower urinary tract, it means that something is wrong and that quite often is a steering thing. It's different than if you have a urinary tract infection because then the reason is clear that you go to the toilet quite often that you have pain, et cetera. But if that's not the case, then something can be wrong with the steering mechanism. And that quite often is seen in neurogenic patients or patients with a neurogenic disease.

But you can also see that in non-neurogenic patients. And while the simple idea is that if there is something pathological signaling to the innervation areas of the lower urinary tract, something is wrong. And if you want to correct that you should, one way or the other, put electrical current on this innervation scheme, on the nerves, on the centers, et cetera. And this is put very simple because what we have at the moment, and that's quite intriguing, is that we have one treatment that treats complete opposite diseases or disorders. So we have overactive bladder complaints, meaning you go to the toilet very often, you have urgency, there is frequency, there is incontinence. And for that we have neuromodulation. But we also have neuromodulation in those patients that have, as it is called, non-obstructive retention. And then you do exactly the same thing. You have the same stimulator at the same location with the same parameters, and you treat the complete opposite disorder with exactly the same.

So we have a pathological signal and we have a therapeutic signal, and we don't really know yet how this is functioning. Well, the best known therapeutic signal is if you stimulate the sacral roots, that's called sacral nerve stimulation or sacral nerve modulation. But you can also stimulate the tibial nerve and you can even stimulate the pudendal nerve, perhaps that's even more powerful if we finally know how to do it. We are not there yet, but it's coming close. And then if you go to the history. Since 1985, there's something like sacral neuromodulation called that way, and then it became known also in clinical practice. In 1997, there was the FDA registration for overactive bladder complaints and urgency and frequency. In 1999 for the opposite, nonobstructive retention. And that was the sacral nerve modulation part. At the same time, developments were tried at other nerves like the tibial nerve. And finally in 1999, Marshall Stoller, who's a urologist specialized in stone treatment as I understand, but he did some interesting experience with animals at that time and he found out that if you stimulate the tibial nerve, you can also have some effects on bladder behavior. So at first it was called SANS, Stoller's Afferent Nerve Stimulation, and then it became known worldwide as PTNS, percutaneous or posterior tibial nerve stimulation. That was done with needles, it was done with surface electrodes. You can do it also transcutaneously. And finally, there were some attempts to have also an implant at the tibial nerve in order to have more or less the same situation as sacral nerve stimulation on a different location. So different trials. In Nijmegen, where I was at that time in 2003 for the first time, and that stimulator was called the Urgent-SQ. And finally it was picked up by other developers and companies.

And finally there was an approval from the FDA for eCoin for urgency urinary incontinence in 2022. And in '23, that was followed by the Revi system, the system from BlueWind. It also got FDA approval for urgency urinary incontinence. And that's more or less the situation where we're in now. 

Alan Wein: John, thank you so much. And thank you to the audience for listening.

John Heesakkers: You're welcome. Thank you.