Ryuji Sakakibara: Thank you, Alan. I'm Ryuji Sakakibara from Chiba, Japan. And my topic is Parkinson's disease and multiple system atrophy, and different characteristics, different management strategies for lower urinary tract dysfunction. Parkinson's and multiple system atrophy. What should we know? PD and MSA are neurodegenerative diseases that manifest bladder dysfunction. PD is the brain disease affecting the basal ganglia, leading to gait and other disorders such as tremor, rigidity, et cetera. PD commonly shows overactive bladder, along with or after motor disorder. Dementia with Lewy bodies shares pathology with PD, but it's not uncommon in older individuals. The incidence is 1 in 15 in octogenarians, showing complex lower urinary tract manifestation due to dementia. MSA affects the brain and the spinal cord, therefore sometimes difficult to diagnose. Shown as urinary retention of unknown etiology, or a combination of OAB with post-void residuals, sometimes before motor disorder. If we look for the correct diagnosis along with proper tests, we can maximize the quality of life of these patients. Imaging. Here, MSA cerebellar is a hot cross bun sign, and the pontocerebellar atrophy in MSA, Parkinson's, basal ganglia atrophy. But imaging of sacral spinal cord is still challenging, and needs other tests. I'll show you later. Now, PD/DLB are MRI-negative, but can be detected of dopaminergic loss by dopamine transporter scan.
It looks like edge of the panda's eye, and we can memorize. This is neural system regulating the LUT. It's a bit complicated, but in general, the brain is thought to be inhibitory on the bladder. In contrast, lumbosacral spinal cord are thought to facilitate what's driving the bladder. In MSA, both are affected. In contrast, in PD, brain is affected. And this is a urinary storage in normal volunteers in [inaudible 00:04:07]. Several brain areas are activated, but in general, anterior part of the brain are activated, together with brainstem and the cerebellum. And this is the basal ganglia and the LUT. And this is also a bit complicated, but if you look at the center of the failure, a substantia nigra-pars compacta, it's orange area, send fibers via direct pathway to the micturition circuit via [inaudible 00:04:37] and collaterals in PD. And these circuits are damaged and leading to OAB. This is the guideline for the management of Parkinson's disease and other gait disorders was achieved. And then it is published in Neurology and Urodynamics in 2016. And now, next issue, 2025 issue by Glenn Werneburg, Sanjay Sinha is available now. Treatment of OAB due to Parkinson's include selective beta-3 adrenergic agonists, anti-muscarinics that do not easily penetrate the blood-brain barrier because most patients are older. And botulinum toxin injection in the detrusor muscle in severe cases.
How to differentiate early MSA from PD in order to avoid prostatic surgery. The first is ultrasound echography. Large post-void residual more than 100 milliliter in MSA is common, but it's extremely rare in PD. It's performed by a nurse, and this is the sacral spinal cord including the intermediolateral nucleus (IML). It is a driving nucleus for the bladder. The second is urethrocystography or video urodynamics open bladder neck in MSA. But it's rare in PD. It's performed by a urologist. This is not a DSD but open bladder during filling phase. And this is the reflection of lumbar spinal cord, including intermediolateral nucleus region. The third is anal sphincter electromyography, showing neurogenic EMG in MSA, but is also rare in PD by a neurologist. This is the typical field of MSA and multi-unit potential figures. And this is a reflection of region in the Onuf's nucleus. Dr. Onufrowicz was working in the New York City in early 20th century. This is a Movement Disorder Society criteria for the diagnosis of multiple system atrophy led by Gregor Wenning and Alessandra Fanciulli from Austria. And Jalesh Panicker is my friend in London, and me. And this criteria include unexplained voiding difficulties with possible urinary residual volume, more than 100 milliliter. And/or unexplained urinary urge incontinence. We are very glad to include this. And in other words, measurement of post-void residual should be performed, not only by neurologists but also urologists. And we are recommending this in neurology. And this is a CIC, clean intermittent catheterization, performed by a lady with MSA.
This is originally introduced by Jack Lapides in Rochester. This is references, and I would like to thank my friends in National Hospital for Neurology and Neurosurgery, Queen Square London and the Chiba University and the Toho University. And thank you for listening.
Alan Wein: Thank you so much for that review. So if a patient comes in then with neurologic symptoms that you really can't explain and also urgency incontinence, I mean what is the best single test that you can do to make the diagnosis, and let's include multiple sclerosis versus MSA versus Parkinson's disease? I mean, how do each of them present in the earliest stages?
Ryuji Sakakibara: From a neurological point of view, if you look at the gait, if you look at the easy forward gait, and there are two types of walking difficulty. One is Parkinsonian features, the other one is spastic features. Spastic features is very common in multiple sclerosis. And Parkinsonian features are seen in both Parkinson's disease or MSA. Then we move on to the bladder things. It is, I think to ask them, ask he or she if we have some problem in urgency or incontinence and also we can measure post-void residual by ultrasound. So it's a second step.
Alan Wein: Is neuromodulation ever used as a treatment for Parkinson's disease, the lower urinary tract symptoms or MSA? Is it effective at all?
Ryuji Sakakibara: Neuromodulation. And particularly of the sacral cord you mean?
Alan Wein: Yes. In other words, standard neuromodulation with the electrodes applied down at S2, S3 and the usual type of sacral neuromodulation.
Ryuji Sakakibara: And I think we have personally not many cases, but it is performed in spinal cord disorder such as spinal cord injury or severe cases of MS, Multiple Sclerosis. And in such cases neuromodulation is effective. But in Parkinson's and particularly in MSA, there are some reports, but it's sort of invasive and not many cases, I think not good option for the patients for brain disease. I think I recommend neuromodulation for spinal cord disease, because they're a difficult bladder dysfunction.
Alan Wein: Well, certainly it would make sense not to do a thing in Parkinson's disease. It is originally described as more of a brain disorder where MSA is actually brain and spinal cord.
Ryuji Sakakibara: Yes.
Alan Wein: Let's say in an elderly male, 70 years old who appears to have some bladder outlet obstruction, under what circumstances would you do, let's say a transurethral prostatic resection in a patient with Parkinson's? Is there any danger actually of making that person's urinary dysfunction worse by doing a TUR?
Ryuji Sakakibara: It's a very important question, because there are many patients with both Parkinson's disease and prostatic hyperplasia. But we think at this moment the surgery is safe for pure Parkinson's disease, because these are different diseases. And amelioration of the prostatic hyperplasia is very good for Parkinson's disease patients as well. But we have to be careful to differentiate or exclude MSA patients, because MSA patients are very difficult disease-progressive, and disease itself will lead to the urinary retention. So before going to surgery, we have to be safe to exclude the MSA by checking imaging or sphincter EMG or something like that.
Alan Wein: Yeah, so it looks like with MSA characteristically, those people have an open bladder neck at rest. So essentially they've already had an outlet reduction. So in other words, doing a TUR prostate on them, if you go too distal, you would risk really creating a situation where they were incontinent because of sphincter weakness, correct?
Ryuji Sakakibara: Yes, that's correct. Unfortunately, we have several patients who are referred patients, and they already have undergone prostatic surgery, but the effectiveness is only transient. They are incontinent or leading to severe urinary retention. So surgery is not working in those patients.
Alan Wein: Is MSA always progressive? I mean are there some people in whom the disease process just seems to stop at a certain point or did they all ultimately keep on progressing to that terrible state that you see where you're really almost powerless to do anything to help them from a urinary standpoint?
Ryuji Sakakibara: Yeah, professor, I think the answer is progressive. So no cure for the patients. But we have to keep the patient's quality of life. So start teach them to perform a CIC in the very early time. If you're going to need the CIC, we teach them very early time.
Alan Wein: Do the standard medications that the neurologist give for Parkinson's disease, do they help to lower urinary tract symptoms as well?
Ryuji Sakakibara: Yes. And in Parkinson's disease, at least in the initial stage, the levodopa ... levodopa is a specific drug for the Parkinson's disease. It's also effective on OAB. So we have to wait for sometimes to look at the amelioration of OAB by levodopa. If it's not working, we have to add on the anticholinergics or beta-3.
Alan Wein: Right. But you prefer the beta-3 because most of the patients are older and you don't want to get into any of the problems with progressive cognition issues?
Ryuji Sakakibara: Yes.
Alan Wein: And if you're going to give one, you mentioned you should give one, hopefully that doesn't penetrate the blood-brain barrier. So you're pretty much reduced to trospium then?
Ryuji Sakakibara: Yes, I agree. In our country at this moment, the first thing is mirabegron and vibegron. These are sort of modest but very good effect on treating OAB.
Alan Wein: Is there any standard way of managing the urinary symptoms in multiple system atrophy or not?
Ryuji Sakakibara: I think it depends on the stage. I think the very early stage, particularly first year from the onset, can be managed by some beta-3 or anticholinergics. But after one year, the post-void residual volume going up to more than 100 milliliter. So we have to change the strategy to start CIC.
Alan Wein: Well, those are very useful facts to remember, and we thank you for taking your valuable time to come on and especially speaking to us in Tokyo. But I hope to see you at some of the meetings soon. And thank you again so much for being with us.
Ryuji Sakakibara: Thank you very much.
Alan Wein: Great.