Hi, and welcome to the Oggs Urogynecology webinar series. I'm Dr. Padma Khandadai, and I'm a member of the Oggs Education Committee and the moderator for today's webinar. Today's webinar is titled Neurophysiology of the Micturation Cycle and Neurogenic Bladder, and we are very lucky to have our speaker today, Dr. Kristi Borowski. Dr. Borowski did her undergraduate degree at Rensselaer Polytechnic Institute and followed in medical school in Albany, New York, at Albany Medical Center. She went to Duke Medical Center for her residency in urologic surgery and stayed on for an additional year for fellowship in incontinence reconstruction and neurodynamics. She has been at the University of North Carolina since 2010. Her areas of focus are neurogenic bladder, urinary incontinence, and lower urinary tract infection. As a reminder, this presentation will run around 45 minutes. The last 15 minutes of the webinar will be dedicated to the Q&A. Before we begin, I'd just like to review a few housekeeping items. Oggs designates this live activity for a maximum of one AMA PRA Category 1 credit. To claim your CME credit, you must log into the Oggs eLearning portal and complete the evaluation form following the completion of the webinar. This webinar is being recorded and live streamed. A recording of the webinar will be made available in the Oggs eLearning portal. Please use the Q&A feature of the Zoom webinar to ask any of the speakers questions. We'll answer them at the end of the presentation. Please use the chat feature if you have any technical issues, and Oggs staff will be monitoring the chat to assist. Dr. Barofsky, we're so excited for this talk, and you may begin. Thank you so much for inviting me. This is really an honor and a privilege to be able to talk to you. I saw Amy Kawasaki pop on. Hi, Amy. Amy and I were fellows together at Duke, so it's always good to see her name in here. The goal of today is just to review the neurologic controls and the neurophysiology of micturition. My hope is that if we understand the normal, we can then go ahead and understand the abnormal and be able to predict what we may see with certain levels of injury and also with certain disease-specific states. And then what we'll finish with is going over some of the guidelines. We'll go over the evaluation of patients with neurogenic lower unit tract dysfunction. As part of this, I don't have any focus on treatment options, but it is something that I'm definitely happy to talk about afterwards during the Q&A session. All right, so I have no disclosures. So again, the goal of this is understanding the neurocontrol of micturition. We're going to review the patterns of lower unit tract symptoms associated with specific neurologic diseases. And then we're going to review the updated guidelines from the American Urologic Association for the evaluation of patients with neurogenic lower unit tract dysfunction. And so if we think about the lower urinary tract and what the function of this is, the function is to hold urine and to fill it to normal capacity, to do so at low pressures, to hold urine until it's a socially acceptable time to void, and then to void with relative efficiency at low pressures. And we don't think about this, right? This is normally just something that is unconsciously happening, but it takes an extraordinary amount of communication from different levels of the brain, brainstem, spinal cord, and then out to the end organ in order to make this happen efficiently and effectively. And so let's go over what some of those components are. And again, if we think about this, it takes an extraordinary amount of communication, like we just talked about before, between not only the efferents, so our autonomic and somatic efferent pathways, but also communication and coordination of our afferent signals going from the bladder up to the brain and then back out again to the bladder. And so let's first function on our efferent pathways. So again, the pathways are going to be going out to bladder and to outlet. So we're going to focus on three main sets of peripheral nerves. We're going to go over the autonomic nerve groups, which are going to be our parasympathetic and our sympathetic. And then we're going to talk about the somatic, which will be our pudendal. So let's start out with our parasympathetic. So with parasympathetic, these are going to originate at the sacral core from S2 to S4. These are going to then go out as postganglionic nerves, and they're going to excite the bladder muscle. And so when we think about this simply, I usually, when I'm trying to teach residents and fellows and our students, I'm a big believer in mnemonics. And so parasympathetic is going to push P out. It's going to make that bladder muscle or the intrusive muscle contract, and it's going to do so via two main pathways. The main one of which is this cholinergic pathway via a muscarinic receptor activation. If you recall, there's five different muscarinic receptors. M2 and M3 are the receptors that predominate in bladder, and M3 is the one that we think is really mostly, mostly mediates bladder contraction in humans. There is, though, some noncholinergic pathways that tend to be more via ATP, via the P2X receptor, of which P2X1 is the major subtype. Again, this is not the kind of main pathway for activating bladder contraction, but it is a pathway that's being looked at, you know, kind of for down the road, potentially for options for urinary retention. So again, simply put, parasympathetic pushes P out. Parasympathetic, though, is also going to have some impact on the urethral sphincter. So on that external sphincter, it is going to promote relaxation, and it does so via a nitric oxide pathway, which would make sense that it would do that, because if we're going to have the bladder squeezing, it makes sense that we would also have something that would make that outlet or that urethra relax. If we then switch to the sympathetic nervous system, the sympathetic is going to start from the T11 to L2. Remember, when we're talking about these levels, we're talking about nerve level, not bony level. And so it's going to go from T11 to L2 via a very circuitous pathway out to the bladder. It's going to go from sympathetic chain to prevertebral ganglia, then to the superior hypergastric and pelvic plexus, out to different levels of bladder. And it's going to mainly go to the body of the bladder and to bladder neck, and in my male patients, also into prostatic urethra. And so postganglionic nerves for the sympathetic system are going to release norepinephrine with the goal being to allow the bladder to store. And if we think about what something needs in order to store, we want to be able to relax the body of the bladder, preventing that squeeze, and we want to tighten the outlet of the bladder. And that's what the sympathetic system is going to do via mainly two separate pathway receptors. It's going to tighten the outlet via these alpha-1, of which alpha-1A is the predominant, and then it's also going to relax the body of the bladder via the beta-3s. The last peripheral nerve is then going to be the somatic, and this is going to be via our prudendal. Very similar to parasympathetic, it's originating at S2 to S4, it's originating in onus nucleus, and it's going to travel to the external sphincter and provide excitatory or activation input to that external sphincter. So again, I love my mnemonics, somatic squeezes the sphincter shut, so it's going to help to keep that external sphincter shut. Now not only do we have this routing to the external sphincter via onus nucleus, but there's also kind of a separate pathway, same nerve groups, but originating from the medially placed motor nucleus that also will go to innervate pelvic floor. So when we think about somatic and prudendal, we're going to both external sphincter, but also then pelvic floor. There has to though be signals that are getting from the bladder back up, back up rostrally, because there has to be some sensation of fullness that is going to allow us to say when we need to go to the bathroom. And so there's going to be different levels of afferent signals coming from the various levels of bladder, meaning from the body of the bladder, from the outlet and from urethra that are going to route back up rostrally into the lumbosacral spinal cord. There's two main fiber groups that we see with our afferent signals. And the patient without neurologic insult, these tend to be our small myelinated A-delta fibers. And these are going to be the ones that are, we think about them as tension receptors. And so this is going to be what is responding to that passive dilation or active contraction. So kind of sensing that tension of the bladder wall. And these are what we think that once this reaches a sensory threshold, it's going to go ahead and activate or trigger that normal micturition reflex. Now that's different than our unmyelinated C-fibers. And we think about these as kind of the unhappy afferent nerves. And so these are typically silent. We typically don't see them playing a big role in kind of our normal micturition reflex, but they can play a role in response to some noxious stimuli, like cold, like chemical. And these are the ones that we see tend to waken up more after injury, especially after spinal cord injury, that tend to then start to take over and create some of that reflexive voiding pathways that can create some problems down the road for those patients. But there has to be control mechanisms. All of this can't be happening at the same time, or else we would never be able to avoid effectively, efficiently, incontinently. So there's multiple different levels of control that need to all communicate in order to make happen. Simply speaking, we've got three different levels. And we're going to go over these three, these three, pardon me, control centers, kind of from more of a higher level view, and then we'll get a little bit more into the details of each of them. But if we think about these, the first one we're going to talk about is the cerebral or the cortical micturition center. And again, when I'm talking to residents about this, we'll try to kind of simplify it down and say, the brain's main job is to tell the bladder, you don't have to go. So the brain's main job is kind of processing and assessing those apparent signals for the degree of bladder fullness and saying, no, it's not time, relax, you don't need to go yet. So this is telling the bladder when it's going or controlling when it's going. And so I love sports analogies. So I'll usually say this is like the head coach. It's kind of telling everybody and controlling when things are about to start, about to happen. We think this is done via multiple different pathways. So there's multiple different levels of apparent innervation from different areas of the brain that are getting in to allow for this kind of sensation of fullness. And a lot of this is centered around something called the periaqueductal gray, or let's just call it the PAG. And so the PAG is what's going to be responsible for processing a lot of these signals from different areas and then saying when it's full enough. And then when it's full enough, activating that reflex, which really means it's then activating the pontine micturition center, which we'll talk about in a second, to say it's time to go. And so of the three circuits that we think there are that help to kind of coordinate and communicate with the periaqueductal gray, the prefrontal cortex in the insula is the one that we think is most responsible for kind of that normal tonic suppression of void and normal sensation of fullness. But there are other areas and other circuits that we can tend to see heightened more in some patients with significant urgency, frequency, and overactive bladder. And those tend to be the dorsal anterolateral cortex and the supplemental motor cortex, as well as subcortical, and that's more of the unconscious. But again, I think to simply put this, it's really all of these different areas that are eventually communicating with the periaqueductal gray or the PAG, which is interpreting that all of these levels of fullness and then saying whether or not it's time to go. And when it is, they are then activating that pontine micturition center. And so the pontine micturition center, I'll liken it as this is the offensive coordinators. This is now receiving the signal from the head coach saying it's time to go, and then it is now telling people how to make it happen. So it is kind of designing the plays in order to make the patient void efficiently. And so this is responsible for coordinating the activities of the sphincters and bladder so the patient can void effectively and efficiently. And so this is all again centered around the periaqueductal gray. The periaqueductal gray is assessing those sensations, those afferent signals, and then activating the pontine micturition center once that sensory threshold has been reached. And so the pontine micturition center is then going to impact our descending pathways, right? And it needs to relax the outlet first. So we need to have activation of that parasympathetic on the urethral sphincter, releases nitric oxide, relaxes there. We need to have cessation or removal of the adrenergic from the sympathetic and also removal of the somatic input to the external sphincter. So now we have that turning off of that storage, relaxation of that external sphincter, and then finally activation of that cholinergic pathway via the parasympathetic system to get the bladder muscle to squeeze, right? So again, relaxing the outlet, then a couple seconds later squeezing the bladder in order to allow the patient to void efficiently. And then the last one is the sacral micturition center. And this is the workhorse. So this is our players. This is the center that actually gets stuff done. And this is also called kind of that reflexive voiding center. And so from here, this is at the sacral cord. Remember that the sacral cord is at bony level about T11, L2-ish. And this is where we are going to have our afferents routing up and we are going to have our parasympathetic and our prudendal efferents routing out. And so as long as that arc is intact, meaning as long as we can get afferent signals from the bladder to the sacral micturition center, and as long as we can have our efferents from parasympathetic and prudendal routing out to the bladder, we can get this reflexive void. And normally the reflexive voiding center or this micturition center is being told what parts of it to activate and not activate from the pontine micturition center. But in the absence of that, so specifically in patients with spinal cord injury, we can see this awakening of this reflexive voiding center that can create some long-term dysfunction, which we'll talk about in just a little bit. Okay, so we're going to switch from focusing on what are the specific nerve roots, parasympathetic, sympathetic, prudendal efferents, what are our control centers, cerebral, pontine, sacral micturition center, to now if you understand those, you understand the mechanisms of the three nerve groups, you understand the mechanisms of the three control centers, we then should be able to predict what we may see with different patterns of neurologic injury. And so let's first talk about lesions above pontine micturition center. So these are going to be any lesion that can impact all of those different circuits that are assessing our afferent innervation from bladder and sending that information to periaqueductal grates. Anything that can interfere with those circuits or make those circuits fire early, what are we going to see? We're going to see then change or alteration in that tonic, an inhibitory signal, and we're going to then activate that pontine micturition center early. So anything that can impact with the brain's ability to sense those afferent signals or anything that can trigger those afferent signals to fire sooner is going to cause an overactive bladder. So it's going to trigger that pontine micturition center early, but then the pontine micturition center is going to tell everybody what to do. So we're going to have an overactive bladder, but it is going to be a synergic overactive bladder, meaning we're going to see sphincters relax, bladder squeeze, and then the patient will void. Okay, so we're going to see again overactive bladder that is synergic. Now that's going to be different from a super, super sacral spinal cord injury. So now we're talking about patients with spinal cord injury. We're talking about transverse myelitis, multiple sclerosis with cord lesions, spina bifida. So in this we are now having potential loss of all or some of that cortical micturition center as well as that pontine micturition center, but that sacral arc of that sacral micturition center from the bladder to sacral micturition center and back out, that arc is still intact. All right, so what happens there? We're seeing the bladder fill. It's triggering. The sacral micturition center knows that it has been triggered, but it's not getting told what to do by the pontine micturition center or the cerebral. So it's going to activate. It's going to activate whatever it can because it knows that something was processed and it's just waiting for a signal, and in the absence of a signal, it's going to turn itself on. And when it turns itself on, it turns everything it cannot, which is parasympathetic bladder squeezing, which is pudendal external sphincter squeezing. So we're going to get to trucer sphincter dyssynergia. And so that is what we call that reflexive void is that overactivity with dyssynergia. This is the one that we worry could potentially impact or harm upper tracts. If there are lesions above T6, we may also see internal sphincter or bladder neck dysinertia. Now that's going to be more of an issue sometimes in my male patients where we really have separation there comparatively to my to my female patients. This is also going to be different than those patients with a sub-sacral spinal cord injury, right, because now we have loss of all three centers, and in this we're going to separate out those that are still within spinal cord to those that are now moving further distal to the bladder. So if we think about sub-sacral spinal cord, now we're talking about kind of our classic cauda equinae bladder, and with this what we have is now we have loss of everything that is going up and out except sympathetic. Our sympathetic member has already branched off at, you know, T11 to L2, so that is already out and gone, but we have lost everything in that cauda. So we have our afferents coming up, we have our parasympathetic and our pudendal going out, and so that classic cauda bladder, if we lose our afferents, we're going to lose that sensation. If we lose our parasympathetic, we're going to have impact on the contractility of the detrusor, and if we lose our pudendal, we're going to have denervation of that external sphincter and pelvic floor, and when that happens, they become fixed. So you end up getting, you know, kind of an increased tone, which can put the patient in retention, but not the ability to recruit. So you may get that cough, laugh, stress incontinence. So kind of the classic cauda equinae bladder is a patient that has, you know, decreased or absent sensation, decreased or absent detrusor contractility with stress incontinence from impaired external sphincter. Now that's a little bit different comparatively to some of the surgical sub-sacral lesions that we see. Most commonly where I see this is with some of the GI surgeries, specifically the abdominal peroneal resections, where we are now getting a lot of dissection in and around the bladder, where we may now impact parasympathetic, sympathetic and pudendal as they're kind of routing and getting out closer to the bladder. And if we lose parasympathetic, sympathetic, pudendal, we are going to get very same similar picture to what we had with cauda, but if you lose that sympathetic, we now may also introduce a little bit of stiffness to the bladder, perhaps a little bit of loss of compliance there. So that's going to be really that main difference between cauda versus versus something like an abdominal peroneal resection with closer to the bladder and loss of that sympathetic system. Okay, so if you understand the nerve groups, control centers and then some of those patterns that we saw, we can now predict what you may see also with certain specific disease states. And we're certainly not going to go through every neurologic insult there is because that would take forever, but I just want to highlight some of the common ones that we'll see and also some of them that have some very specific findings associated with them. Right, so stroke. A lot of patients that have had a history of stroke and I think that we don't recognize or specifically maybe primary care neurology may not recognize how much we may see bladder symptoms following a stroke. Okay, why and what is stroke impact, right? Simply put, stroke is going to input, it has the potential to impact all of those three circuits that could better than feeding into the periaqueductal gray. So it's going to impact that inhibitory signal. So we're going to see overactive bladder. In fact, 40% of patients with stroke are going to go on to develop these irritative lower urinary tract symptoms with urgency frequency with potential urgent confidence. And risk factors for this tend to be larger stroke, hemorrhagic stroke, stroke involving the parietal lobe, pardon, and patients who develop depression post-stroke. So I think again it's a question that we want to be asking patients because they are going to have a high likelihood of developing this post-injury. If we then switch to Parkinson's disease. So Parkinson's disease, again, if we think about what happens is you lose some of these dopaminergic cells within the substantial nigra and in the basal ganglia. And so it is thought that the basal ganglia works as part of those circuits to inhibit the micturition reflex via these dopaminergic receptors. And as part of the disease process with Parkinson's, right, what happens? We lose, we have cell loss of the dopaminergic cells. And so if you lose those cells, you're going to have loss of that D1-mediated inhibition with a result in overactivity. And in large percentage of patients, 20 to 65 percent of patients with Parkinson's are going to develop urgency, frequency, and nocturia. Now what I think is an important distinction of is we really need to have some of that cell loss before we're starting to see some of the onset of these urinary symptoms. So it's very common with Parkinson's disease that urinary symptoms are going to happen years after the onset of neurologic symptoms. You know, that is different than with multisystem atrophy. And multisystem atrophy is something that I'm seeing a little bit more commonly, and I think that may be because there's maybe better recognition of the diagnosis of this amongst the neurologist. And so multisystem atrophy, also called Scheidrager, is something that can start very similar to Parkinson's. So these patients are going to present with Parkinsonian-like symptoms, but they often won't respond as well as some of the dopaminergic treatments. And then you will also have different progression comparatively to patients with Parkinson's. And so with multisystem atrophy, what we have is progressive loss of this autonomic nervous system of autonomic function. And for reasons why they don't know, they also have selective loss of cells at onus nucleus. Remember that onus nucleus is what is going to prepudendal and is going to external sphincter. So a large percentage of patients, 80 to 90 percent of patients with multisystem atrophy, are going to develop urinary symptoms. Most commonly what we'll see first is urgency-frequency, and as we start to see that progressive loss of autonomic system, which we'll go over in the next slide, you're going to see a different progression of urinary symptoms comparatively to patients with Parkinson's. But I also think a very important distinction is that it's the onset of symptoms. So a lot of these patients are going to have the onset of urinary symptoms either at the time of or predating the onset of their neurologic symptoms. So if I'm seeing someone with this history, you're going to ask, you know, when did these urine symptoms start to help in helping to maybe potentially differentiate between Parkinson's and MSA. And so what we see with MSA is going to be a progression. So initially, kind of I'll tell residents, as you're tickling the parasympathetic system, you're going to start seeing initially that urgency- frequency. And then you can start to transition as you get loss of that parasympathetic, you can transition into urgency-frequency with incomplete emptying. Then you can see that incomplete emptying get worse as you get progressive loss of parasympathetic. You also, with loss of sympathetic, a lot of these patients also have underlying hypotension. And then again, remember you lose selectively those onus nucleus, so you get loss of pudendal, which means you get loss of function of that external sphincter, which can give you stress incontinence. And so kind of that is the progression that we will sometimes see with these patients with MSA. And why I think it's important to understand the distinction here is really because we're talking about continence. So for my male patients, you know, I would not want to do any kind of procedure that would impact bladder neck because they're going to be incontinent afterwards because that external sphincter is not going to be functional. From our standpoint with our female presenting patients, we need to be very very cautious at anything that we would do to augment their outlet, like sling or otherwise, because they're going to get progressive loss of that parasympathetic and detrusor kick. And so they're going to be at a much much higher risk for having retention afterwards. And because of the neurologic function and the loss of function, intermittent catheterization, especially performed by themselves, is going to be very very difficult. So just something that we need to think about a little bit more closely with this specific disease set comparatively to our patients with Parkinson's. All right, if we then switch to MS, obviously this is something that we all see quite frequently because a large amount of patients with MS, that's 65% on review from the North American Research Committee on Multiple Sclerosis under registry, 65% had moderate to severe lower urinary tract symptoms. We tend to see this more with longer disease progression, with progressive disease, but again you can see it with all comers. The most common symptoms that we will see, nocturia, urgency, frequency, but you can also certainly see hesitancy and retention as we start to get cord lesions where we can start to pick up some detrusor sphincter dysinertia or even perhaps some detrusor hypocontractility. And the pathophysiology of what we may see with multiple sclerosis is really going to be dependent on where these lesions are. And so the majority of patients with MS are going to have intracranial lesions. With intracranial lesions, much like with stroke, with Parkinson's, we're going to get loss of that, of all of the circuits feeding into the periaqueductal fray, which means we're going to get loss of that inhibition. We'll see overactivity. So patients really with just kind of pure intracranial lesions, overactivity that tends to be synergic is what we will see really most commonly. But when we're seeing somebody with MS, I'm always encouraging our residents, fellows, and students to look at their MRIs to see where we also have lesions, because a lot of these patients are going to have cervical and thoracic lesions. And once we start introducing lesions in that sub subpontine super sacral area, we now start to introduce the potential risk for detrusor sphincter dysinertia. It's not as common that we see patients with MS with sacral lesions, but you know we certainly can. And with that we then can start to see more caudal-like symptoms as well. Now thankfully, even though a lot of these patients may have, you know, significant underlying voiding symptoms, including incomplete emptying from detrusor sphincter dysinertia, patients with MS are much less likely to progress to upper tract deterioration, comparatively to patients with spinal cord injury or spina bifida, and some of the same underlying bladder pathology. And I don't understand that the reason behind, but they tend not to progress to the extent that our patients with spinal cord injuries will. And so with that, let's switch over to spinal cord injury. Pardon. The vast majority of patients with spinal cord injury are going to have underlying bladder dysfunction. And I think one of the biggest hindrances in taking care of patients with spinal cord injury is that that word is thrown around a lot. And so you're going to have an incredible variation in the levels of injury, completeness of injury. If anybody's familiar with the Asia scale, you know, whether it be complete, incomplete, you're going to have a lot of different presentations within kind of that same, you know, quote, diagnosis. And so we're going to see also a progression, especially with complete injuries. The first thing that we will happen is see spinal shock. And the kind of hallmark of that is the bladder is going to do and signal absolutely nothing. So their patient's going to be in retention. They will usually have no sensation. These are going to be folks that may be catheterized for a liter, a liter and a half with no sensation. And so again, retention is really the rule. And this can last for six to 12 weeks until we start to see awakening of some of the other reflexes. And so we'll start to see return of this bladder reflex that corresponds with recovery of some of the other lower extremity, deep tendon reflexes. And then after resolution is where we start to see this awakening of this kind of autonomic pathway or this reflex avoiding pathway. And that's where we can start to see some of the dysfunction arise, because if it's not being told correctly what to do, that's when we're going to get that reflex avoiding, which again can be that tracheosterone sphincter dysinertia. This is where we also think that kind of modification of afferent activity from those A-delta fibers kind of changing over to those C fibers is going to happen once we start to kind of develop this reflex avoiding pathway after injury. And the dysfunction though is really going to be very dependent on level and the completeness of injury. And there have been studies that have looked at urodynamic findings that show you can't really predict what you're going to find based on solely off of the, okay, if I have this level, I'll have this, this level, this, this level, this. It really is very, very hit or miss depending, I think, on the location and the completeness. And so if we look back in the past, we used to do a terrible job at managing patients with spinal cord injury. And if we look back into the 1950s, 1960s, 30 to 40 to even sometimes studies that showed as high as 50% of patients were developing significant upper tract deterioration with subsequent morbidity and mortality from that. If we then look towards the 80s and 90s, you know, we got a lot better. However, even though patients are not dying or, you know, as frequently from underlying urologic dysfunction, it still causes quite a significant amount of morbidity for patients with urinary tract infections, especially lower urinary tract infections. But again, seeing things move all the way up. So it is still a significant cause of morbidity for the patient, but also cost to the healthcare system. Okay. We're going to take a step back here for a moment and now focus on, sorry, how do we evaluate these patients? So you now have a patient that's coming to your office. They are coming in with this diagnosis of neurogenic bladder or that you think they may because of one of their underlying conditions. And so what do we do? And so, you know, this has undergone a lot of change, which I, and I think change for the better of really allowing us to, to kind of use common sense and to allow us to risk stratify these patients. So we don't have to, nor should we be doing the full kit and caboodle evaluation on every single patient that carries that diagnosis of neurogenic bladder, understanding that there are some of these conditions that are going to put the patient on a much higher risk comparatively than, than others. And so this has really allowed us to tailor that initial evaluation more, saving patients from invasive testing and also saving the healthcare system a lot of waste. So we're going to mainly be reviewing our guidelines. And so these came out from, from my governing body, the American Neurologic Association. This was released in, in, in 2021. They also have a correlate treatment that, that is, I think, excellent, great review if you ever have time to go, to go and look at it. So the next several slides are all going to be, again, based off of, of this article. And so for the first, you know, kind of the first one, we are not going to go through every, every data point here, but I think just kind of highlighting some of the very important statements. And so first there, we want to go ahead and risk stratify these patients that we're seeing. We want to risk stratify them into low risk category or the I'm not sure category. And so the low risk category are those in whom we don't have any suspicion or dyssynergic voiding. So these are going to be those suprapontine lesions. So stroke, Parkinson's, TBI, they don't have anything that would make us get concerned, meaning they're voiding, they have low residuals, they're not having recurrent infections. If they have had any renal functions, it's normal. If they've had any, any imaging, any upper tract imaging, it's normal. And they're avoiding symptoms are stable. So if we have those patients, they're falling into the low risk category. And we really think that we can just manage them, you know, really without any invasive testing and just go based off of our history, physical and post-mortem residual findings. With that being said, if we have patients that we don't know the risk, so they may be at risk for something that may compromise their upper tract. So these are going to be our suprasacral lesion. So our spinal cord injuries are, are, are, are patients that have hydroreneuronephrosis on imaging, they have elevated post-mortem residuals, they have recurrent infections, or they're having progressive change and worsening of their lower urinary tract symptoms. For those patients we don't know, they may have something that's going to be at a higher risk finding. And so we're going to want to go ahead and do a little bit more testing in those, in those specific individuals. So all of these patients, regardless of their risk profile, should undergo a history, physical exam, and urinalysis. They should all, on patients who are voiding, have a post-void residual be checked. Because if it's elevated, we want to then change their risk profile now from low risk to that unknown risk. And for patients with low risk, so there's nothing that they're giving us, and, and what I'll call it is there's no red flags, that we don't want to do a lot of work up. Because the chances of us finding something actionable are very low, comparatively to the, both the financial harm and potential kind of incidental finding harm. So we're not going to want to do routine upper tract imaging. We don't need to do routine renal function, nor should we need to do urodynamics in those patients with no concerning or no red flag findings. If we have patients with unknown risk, so they have some potential things that could put them in harm's way. We want to go ahead and obtain that baseline upper tract imaging, the renal function, and the multi-channel urodynamics. Now, you'll notice these recommendations don't necessarily say video urodynamics. So those that was from the European guidelines historically that they recommended video urodynamics, and here it's really just multi-channel urodynamics allowing for that difference. If we think then about how they want us to assess renal function, historically that was just creatinine. The problem that we're recognizing is that that causes some overestimation of renal function in those patients with muscular loss, especially those with spinal cord injury, and also perhaps those with spina bifida who have just baseline less muscle comparatively to societal norms. So there's more of a push to using a cystatin C, which is a non-muscle-based marker of renal function for that patient population. We also do not recommend routine cystoscopy. Unfortunately, this is still being done in a lot of patients that come in with urinary symptoms, but it really does not add much to that index low-risk patient. Really, we just think it's increasing the risk of them having a complication such as a lower urinary tract infection from the cystoscopy. If we have these unknown risk patients and we think we're going to go ahead with further testing, multi-channel urodynamics or cystoscopy only if indicated, we want to make sure that we have screened them for the potential risk of developing autonomic dysreflexia. So this is something that we need to be worried about in spinal cord injured patients with lesions above T6. We have to make sure that we are monitoring them for that, and then knowing how to react should we see that. So for our patients with spinal cord injury, we have them hooked up to a blood pressure machine that we cycle every five minutes, or with any change in tracer function on urodynamic or with any reported symptom change. If we do see evidence for dysreflexia, and we're going to go over that more a little bit in the next slide, then you stop the study immediately, you empty the bladder, and then you monitor for that blood pressure to come down. Now, we also keep nitro paste in our pyxis, because if for some reason we are unable to or we are not seeing that pressure come down, we'll go ahead and apply an inch of nitro paste above the level of the injury until we can see that pressure start to come down. So autonomic dysreflexia, and if you manage spinal cord injured patients, you have to be aware and your staff has to be aware, especially if your studies are being performed by nursing staff, they have to be aware of what autonomic dysreflexia is. So this is going to be a sudden increase in blood pressure that we can see in patients with injuries above T6. Now, the norm is above T6. There are some reports that you can see it in low-level injuries, but that's again the most common place we see it is with T6 and higher. So this is going to be a sudden increase in pressure, anywhere from 20-40 millimeters of mercury above their baseline with reflexive bradycardia. The patient will say that they may feel pressure, a headache, sweating, flushing, goosebumps, and they just don't feel well. Then again, this can be pretty marked if you haven't seen it, especially some of our patients with higher-level cervical injuries. They may have baseline blood pressures in the 60s and 70s systolic, and then with dysreflexia, they are up in the 180s to 200. So imagine if your blood pressure all of a sudden was 380, everybody would be panicking. So we need to have that same degree of urgency for these patients. From our standpoint, we are most likely seeing this happen as a part of bladder distention, but we can also see it for really any noxious stimuli. So constipation also being another very, very common one that we see. But this is something that we have to be comfortable and able to recognize and manage at the time. So when we're doing these studies in patients with known dysreflexia, we'll always have a catheter ready to go to be able to get them empty quickly. All right. If we keep going on, then if we now look on how are we monitoring these patients, again, we want to risk stratify that monitoring. So if this is a low-risk patient, we don't want to do a lot of invasive studies just because we can unless we're seeing change in symptoms. Now, that's different from if we start seeing patients with increasing risk factors. So if we start now having moderate risk, we want to look at them a little bit more closely. So then we may want to monitor renal function. We want to look at their upper tracts every year or two, and then consider multi-channel study, urodynamic study, if we're seeing change in urinary symptoms. So that's going to be, we're going to follow those with higher risk disease. So those are going to be folks who have poor compliance, elevated tracheal pressures, bad DSD reflux, and we're going to go over these in just a moment. We're going to want to follow those patients a lot more closely with annual upper tract, annual renal function, and then considering multi-channel urodynamics, if we have any clinical reason to do so. So with that, it's going to be any change in symptoms, renal function, or how things look on upper tract imaging. Let's go ahead just in interest of time and move on. So we're just going to very, very quickly go over some of those things that would create if we looked at here those high-risk profiles. So what are the findings that we're seeing on urodynamics that would make us say this person is at high risk for developing potential upper tract deterioration, and that they're going to warrant closer follow-up? So again, we're trying to decide where they fall right on this risk spectrum. One of the findings that will place patients at the highest degree of risk is going to be a change in compliance. Remember, compliance is change in volume over change in pressure. We should be able to put a lot of urine into somebody's bladder without an increase in pressure, and so we really shouldn't see that tonic tone of that bladder wall increase. So we should be able to put at least 20 milliliters of fluid in for every centimeter of water increase that we see in the tone of the bladder. There are a lot of things that we can see that can alter that compliance or make the patient have a poorly compliant bladder. Certainly, a lot of these neurologic conditions that we've been talking about, radiation, pelvic therapy, chronic infections, prolonged catheterization, really anything that can impact the tone of that wall. There's something called the detrusor leak point pressure. So when I'm reporting on compliance, I'm reporting what we call a calculated compliance or that change in pressure over change in volume, but then we're also reporting detrusor leak point pressure. So this is, we think about the tone of the wall. So this is the detrusor pressure at which we see leak in the absence of a detrusor contraction. So this is not saying the bladder muscle is squeezing here, we see a leak. It's what is the stiffness of the bladder wall or the tone that is eventually overcoming the outlet. We don't want that number to be high because simply put, our kidneys are up here squirting urine down on a pressure gradient, and it needs to be higher up here than it is in the bladder. So a higher number has a potentially increased risk for developing upper tract deterioration. A hallmark study from Ed McGuire out of Michigan said if that number is more than 40, that that is associated with an increased risk for upper tract deterioration. Meaning if the tone of the bladder gets above 40 and we don't see a compensatory leak, that's going to increase their risk for developing upper tract injury. And so we do think that this is clinically significant. A lot of the Ed McGuire studies came from patients with spina bifida. But we also see that this is kind of correlating and carrying out to patients with spinal cord injury, etc. So we really want to make sure that we are maintaining a good compliance. And in those patients with poor compliance, we need to follow them a lot more closely. Because this is what we don't want to see, which is vascular ureteral reflux that's arising from that tone of the bladder just overcoming that anti-reflux mechanism. Detrusor sphincter dysenergia is also another risk factor that we're seeing. And that's, again, coming from that reflexive pathway and loss of that pontine on the derision center. And so with this, what we see is that bladder is having to work hard against that dysenergic sphincter. And as that muscle works hard, we can see hypertrophy of that muscle. That hypertrophy muscle can lead to stiffness of the bladder. So we can have not only that really high pressure void, but we can also develop compliance losses as part of it. So that's going to put that patient, if we see this, into the higher risk category. The other thing we can see is very, very high pressure neurogenic detrusor overactivity. And so this is going to be the patient that's having phasic contractions at very low volumes. This is the patient, some of these folks are going to have contractions to 80, 90, 100 centimeters of water at 50 milliliters. So obviously, they're going to be at a higher risk of developing some problems comparatively to somebody that has a low pressure NDO event, maybe at 300 mils of installation. And then other things we want to worry about are anything that can make the bladder empty. So if they're not emptying well, if they're having bladder stones, if they're having hydro, if they're having worsening function of imaging. Those are all things that are going to put patients into that higher risk category that are going to warrant a lot closer following than someone without any of these underlying risk factors. And so we're going to wrap up here, so we have time for questions. And so what I hope that you've gotten from this is an understanding of the neural control of micturition. If you understand that, then my hope is you can then translate that into what you may see. And then if we understand that, then you can understand who we need to have a heightened level of suspicion for patients that are coming to us with neurologic disease. But then lastly, understanding that not all patients that come to you with that diagnosis of neurogenic bladder kind of need that kit and caboodle workup. So it's really using our common sense, using our risk stratification on those who are going to warrant this versus those that we can just treat symptomatically. And with that, I'll end. And this is a picture of my favorite place in the world. This is Salvo, North Carolina on the Outer Banks. If anybody ever wants a beautiful place to go, please go and visit. And so thank you very, very much for all of your attention. And Padma, I'm not sure if there's any questions that we can see in the chat. Yeah, thank you so much. I was totally like urology, neuro urology, nerd girl, fangirling you, because this was just an amazing discussion and such a great review. So we have a couple of questions in the audience. Do you use the severity or activity of multiple sclerosis symptoms to determine the dose of Botox for urgent continence, or do you automatically start at 200 units? That's a great question. And so a lot of it's going to depend on the patient. Obviously, the FDA, as I said, 200 units is the starting dose. But with that 200 units is going to come that increased risk of cath. So a lot of that is going to be what our patients are hoping to get. Now, I am very strict when I do Botox in that I'm not willing to do it if the patient cannot demonstrate that they can cath to me. And so then I'll have that shared decision making with them. I think, obviously, 200 is going to have a lot better chance of working in them, but they have to be willing to accept that increased retention risk. On patients that are cathing, it's a no-brainer. I'm going to go right to 200 right off the bat. Another question from the audience is, are MSA and DHIC, detrusor hyperactivity with impaired contractility, age-related covariance? All right. So that was a very intelligently asked question, and I will probably answer it stupidly. So we definitely see DHIC increase as folks age. We can see that, especially in some of our female patients, they develop overactivity with impaired contractility. MSA is not going to be the same. So we definitely don't see MSA maybe have that age correlation, if I'm answering that correctly. And likewise, it doesn't tend to happen. In patients with MSA, there's not a predictable rate of change that we'll see that progression. Some patients with more aggressive disease, we're going to see that go a lot more quickly. Now, I think the biggest difference there is that predictable stress incontinent issue that we'll get with MSA patients, that may not particularly be there with our DHIC patients. So I think we're going to have that as a confounding variable. I hope that answers your question. If it doesn't, please yell at me in the chat. And just as a reminder, if you have any questions, please place them in the Q&A function of the webinar. One of the things I actually had a question for is, I think as urogynecologists, we are pretty comfortable managing the superprontine low-risk neurogenic bladder. But for people who may be considering evaluating and managing bladder dysfunction in the central portion of the CNS, where you could have dysinertia and autonomic dysreflexia, do you keep an autonomic dysreflexia emergency kit in your office in case a urodynamic procedure sets off? We do. Yeah, we do. Yeah, we do. So because I see these patients in all of our offices, we have nitro paste available in all of our PICSAs, so meaning the nurses and we all have ready access and available to that. It's not common that I have the nitro paste pulled and in the room. I've only done that a handful of times for patients that I was like, oh, this isn't going to go well. We're going to have this ready to go. But we have it available in every location that I am managing the spinal cord patients. We do, as a rule, we do bring and monitor blood pressure on every patient with risk. Now, as part of my notes, when I template notes out for my spinal cord injured patients, I have a separate dysreflexia section so that my nurses and residents know they can always go right to that and know what their concern level has to be. And I think if you do care for these patients, you should have a separate section in that so people can go and identify and identify that as an issue. I think that tends to be sometimes more of a problem maybe with my male patients because if they are calling because they can't cath, because they've got a stricture or a false passage, I need our staff to know how quickly this has to happen, right? Like in someone with bad dysreflexia, we can't sit on that. They need to come in, they need to get managed immediately. I think what's also a good idea to have is something indicating kind of what is their baseline blood pressure. So making sure that you understand what their baseline blood pressure is so that way you know when they're dysreflexic. And so, you know, if I know that their baseline pressures are 60s and 70s, then again, our residents know it's a question I need to ask is, well, if they're getting a call from the ER or from nursing staff, what's their blood pressure? And if they hear 120, they know that may not be normal. You know, so they've got to then go and look and see kind of what the baseline blood pressures are. And I think that's an important thing to understand because that's not going to flag as abnormal for the ER staff or, you know, kind of maybe for your nursing staff. That blood pressure 140 may be completely normal to them, but it may be twice as high as the patient is normally used to. And then always have a catheter ready to go. We also have two questions that are very similar to one another. So what are your thoughts on sacral nerve stimulation for neurogenic bladder, like Emahat's or Parkinson's or, you know, if Botox fails in these patients, I'm assuming for patients who have OAB neurogenic bladder, what are your thoughts on sacral nerve stimulation? So I use it in a lot of patients with Parkinson's. I think it, you know, it's, it, it, I love sacral nerve modulation because I have the ability to test it. You know, full disclosure, I only test with a formal two-stage approach. I don't do any P&Es. And I think that that may be more, more important also with these patients with neurogenic bladders. Botox, I have zero preference between the two, with the exception of sometimes it's a little bit harder for us to get interstim covered in patients with neurogenic bladder, especially government payers with, with multiple sclerosis just because of the neurogenic buzzword. But the, really the big kicker for Botox is I am not willing to do it if you are not able and willing to cath. And that unfortunately eliminates a lot of patients for, for Botox. And so, you know, I think that self-selects out a lot of folks for it. And I, sorry, let me pull up what the other question was. Any neurologic conditions causing OIB that may be reasonable candidates for trial of interstim? Yep, absolutely. So stroke, Parkinson's, those are the ones I use it very, very commonly in. Again, MS, I certainly have patients that we use it, especially now that, that, you know, that we have MRI compatible implants that I think that has really opened up a vast majority of patients that we can offer that to. But again, it's, it is off label. I have to say this for CME, right? It's off label when we think about it for neurogenic bladder. Well, Maria, I have reached the end of our webinar. And on behalf of OGGS, I'd really like to thank Dr. Borowski for this excellent discussion. Be sure to register for our upcoming webinars on July 17th. Join Dr. Julia Guinitz-Montan as she presents a webinar entitled, Your Gynecologic Considerations in Women with a History of Female Genital Circumcision slash Mutilation. Follow OGGS on Twitter and Instagram and check out our website for all upcoming webinars and information. And again, we really thank you, Dr. Borowski. This was an excellent talk and we hope to see you guys soon. Have a great evening. Thank you very much. Have a great night.

Neurophysiology

Micturation Cycle

Neurogenic Bladder

Efferent Pathways

Afferent Pathways

Cerebral Micturation Center

Pontine Micturation Center

Sacral Micturation Center

Neurologic Conditions