Hot Topic: Normal pressure hydrocephalus - Assessments for intervention, outcomes, and future directions

And today I have the pleasure of speaking with Dr. Joachim Krauss, who is both a movement disorders neurologist and neurosurgeon, I think a unicorn. Professor of neurosurgery and chairman of the Department of Neurosurgery at Hannover Medical School in Hannover, Germany, and also the chair of the NPH Study Group at the MDS.

Thank you so much for joining us today.

Dr. Joachim Krauss: Yeah. Hi. Welcome everybody. Thank you very much a nd it's a pleasure for me to speak [00:01:00] about normal pressure hydrocephalus.

Dr. Sara Schaefer: So we've talked about the clinical aspects of NPH and differential diagnosis, some of the pathophysiological thoughts regarding NPH and co pathology and controversies. What are the common ways patients with NPH are assessed or people with suspected NPH are assessed to determine if treatment is indicated?

And is this standardized? I've seen a lot of different ways that people do this. Sometimes with a bedside, large volume LP, sometimes with a lumbar drain, is there a standardized procedure or data to support one avenue for assessment over another?

Dr. Joachim Krauss: Yeah, this is has been a problem since many decades, I must say, because there are several different diagnostic measures and tests which can be performed. And of course when we say suspected normal pressure hydrocephalus we have to think about what [00:02:00] that means. And actually the patient should have the typical clinic and the patient should have a clinical imaging.

 Sometimes patients with suspected normal pressure hydrocephalus may have typical imaging, but not typical reasons or vice versa. And there the problem already starts. I've seen patients actually who were transferred for further diagnostics. With suspected normal pressure hydrocephalus who actually did not really have hydrocephalus.

Yeah. So hydrocephalus, there should be clear hydrocephalus, which can be defined by an Evans index. Yeah. Or some other measures. And these patients should have a typical imaging features. And I think that is now well established. Hydrocephalus blues a dash, disproportionately enlarged sachin spaces and tight high convexity, that means narrowed sulci over the paraseptal brain surface. [00:03:00] And if we do not have this imaging findings and gait disorder that might be disappointment later also with therapy. So I would say it is very important to have typical clinics. Gait disorder which is the main symptom.

Then maybe cognitive problems, urinary dysfunction and movement disorder, slowness of movement, bradykinesia and so on. But definitely we need a firm combination. And I think only when we have some of these combination we should go ahead because otherwise, if we do lumbar puncture, lumbar drainage, we most likely will not get a positive result.

Yeah. And when we look at the story of diagnostic procedures we also have to realize that normal pressure hydrocephalus is a hydrodynamic disorder. So it's not only a disorder of brain tissue, but also of brain fluid dynamics. And of course this disturbance [00:04:00] of brain fluid dynamics of CSF of course can be used as well for diagnosis.

And that has been forgotten a little bit, but I think there will be a comeback on hydrodynamic studies, resistance to outflow, for example. Then patients do not really have normal pressure. They have slightly elevated intracranial pressure. And for example, 20-30 years ago we had overnight recordings to measure intracranial pressure.

We had all of these hydrodynamic tests and now the main third diagnosed procedure actually is lumbar puncture or lumbar drainage. But there are many other tools that can be used. Okay. Let's talk a little bit about lumbar puncture. Lumbar puncture should be done in a standardized way, and the clinical symptoms should be also recorded in a standardized ways before lumbar puncture and after lumbar puncture, then a lot of questions arise.

Okay. [00:05:00] How much of CSF should you relieve with the tap test. And there's come an agreement, it should be 30 to 40 milliliters, but still some people do less. And then what is the result? Then the question is, when after lumbar puncture should we do the assessment? Same day in the evening, next day, two days later? And, we recently published a manuscript on that, and there's a huge diversity in what has been published. But definitely all patients with NPH who undergo the tap test should have a standardized assessment for gait, velocity, number of steps, predefined length, what the patient asked to go. And there are several possibilities.

And also of course, patients should be tested for cognitive abilities, MoCA or Mini-Mental score examination several different ways. And the highest [00:06:00] predictability, of course, is the improvement of gait. And not only gait, maybe also posture after the tap test.

Dr. Sara Schaefer: So it sounds like you agree that this should be standardized. Absolutely. That makes sense. But in terms of when things are done, which exact test is done, and whether multiple tests should be done an immediate and then a delayed. The jury's out on all of that. Is that correct?

Dr. Joachim Krauss: There have been several recommendations, guidelines, and they differ in details from guideline to guideline. Yeah. And of course the guidelines change over, over the years. And when we look 30 years back people said that the main symptom of NPH would be treatable dementia. So we are completely away from treatable dementia and we now talk about the treatable gait disorder mainly.

Yeah. And it would be great if we could have a unified [00:07:00] assessment that everybody would use, but I think we are far away from that. Because first of all, we have different habits, different fashions, I must say, different countries also. And, there is such a lot of literature favoring one method over the other that we are not there yet, that we have completely standardized assessment being performed in every place.

So I would say each unit who looks into the diagnosis of normal pressure hydrocephalus, should have a standardized assessment method that might be different from one unit to the other.

Dr. Sara Schaefer: And you mentioned all kinds of gait outcomes that you're looking at, a MoCA or an MMSE for cognitive outcomes as well. It sounds like with all of the gait parameters that you look at that a gait lab would be very helpful as opposed to just timing somebody walking down the hall. I wonder which outcomes may be [00:08:00] expected to be more long lasting versus temporary versus not expected to change with CSF diversion.

And how, for example, you said that it used to be thought of as a reversible cognitive disorder, and now it's thought of as a reversible gait disorder. So what's the utility of testing cognitive outcomes when you're evaluating whether or not somebody is gonna be a good candidate?

Dr. Joachim Krauss: Yeah. So you are right. That is a problem. So again, I would say the main symptom we look at after the tap test is gait. And the other tests are a little bit more problematic because if you use, for example the Mini-Mental state examination, if you have one day, then the next day, even if you have maybe a little bit of different version, but usually the same version you do, of course there is some practice so the patient know what is expected, so the patient might be better with the Mini-Mental State the next stage [00:09:00] just by knowing what he will be asked. Yeah. And also cognitive dysfunction does not respond that rapidly to a tap test, like gait. So with gait we see early improvement and the problem is if we don't see really improvement of cognition as measured by MoCA or something, the patient might still benefit on the long term from improvement in cognition. And there's also some symptoms of NPH we do not really test in a standardized way that is psychomotor slow slowness. So patient feel a little bit less energy, more lame.

Slow to respond. And that is not being tested with a standard test usually. 

Dr. Sara Schaefer: And do you ever consider the urinary dysfunction when you're doing these assessments?

Dr. Joachim Krauss: Yeah. We always,

Dr. Sara Schaefer: for diagnostic purposes, but for assessment of [00:10:00] intervention.

Dr. Joachim Krauss: Actually we consider a urinary dysfunction for both because we always ask the patient. What's the problem with urination within reason? And many patients will not tell you spontaneously, but if you ask do we have the urge to go to the toilet when you feel your bladder is full, they would say, oh yes, exactly that, that is it.

And sometimes after the tap test, patient would say I have less urge now for me to urination. But again, there's no standardized test really that includes this item, but I think it's important.

Dr. Sara Schaefer: Any movement clinician knows the number of suspected NPH patients, that may be called by neuroradiology. Consider NPH as a diagnosis, right? Is huge compared to the number who might ultimately be diagnosed. And published data demonstrates that potentially even smaller populations respond favorably to shunts with [00:11:00] sustained outcomes.

There may be some temporary outcomes. What should providers be thinking about to critically determine who might best benefit from an intervention?

Dr. Joachim Krauss: Yeah. We have to consider now that we have a lot of comorbidity in NPH. We have patients with cerebrovascular disease, which might be part actually of the diagnosis of NPH in some patients. For example, it's being thought that arterial hypertension might be a pre deposing factor for the development of iNPH.

On the other hand, we have a core morbidity with Alzheimer disease, Parksinon's disease or PSP. Maybe there's a subtype of PSP with more NPH like symptoms as well, and with enlargement of the ventricles. And now the problem is if you have a patient that [00:12:00] is more on the less comorbidity side of NPH, okay, it's clear.

We would offer a shunt when we have the typical symptoms and improvement of tap test. And the other question, of course, is if we have more comorbidity, huge amount of dementia, PSP-like symptoms, what should we do with this patient? Yeah. Should we offer shunt surgery or should we say we had only little improvement in the tap test, but still some.

Maybe this is comorbid PSP and should we refrain from shunting these patients? Very difficult question. I think it has not been solved yet. And especially if we look at the long term outcome data and difference. Remarkable differences. Yeah. So we have in some years we have long term follow up improvement of 50 to 80% of the three to five years.[00:13:00] 

Then we have other studies within long-term improvement, 30%, maybe even less. And I think the main reason for that is twofold. One is the comorbidity. So maybe this year are completely different. Yeah, some have more comorbidity, the other years less. And then of course, also it's the dedication to the shunt technology, which plays a role.

That is often being neglected.

Dr. Sara Schaefer: Can you explain that a little bit more?

Dr. Joachim Krauss: Shunt technology has evolved tremendously over the past 30 years. So the usual technique was the P shunt with a differential pressure valve. And in the meantime, of course we have programmable valves, we have gravitational anti-siphon devices in addition, and we can manipulate the CSF flow in certain [00:14:00] ways.

So I consider in a way shunting as a form of neuromodulation. Yeah. So the shunt in a way is like the DBS electrode. The programmable valve in a little bit like, like the pacemaker. And so we have to think more in that way also. And then of course, we can modify outcome in a way. And the future technology in my thinking is that we have artificial intelligence driven shunts that adapt themselves more to the state of the patient.

So like we could have external markers, but we could also measure intracranial pressure and regulate the outflow. And I think with that thinking this is completely different just like putting a valve with a fixed setting and then the patient improves or it doesn't improve. Yeah. 

Dr. Sara Schaefer: Smart valves or smart shunts.

Dr. Joachim Krauss: Smart shunts. Absolutely. I think that is the future. Yeah.

Dr. Sara Schaefer: Wow. That's really [00:15:00] cool. So it sounds like there's probably just a lot of shared decision making and going on when you're counseling patients, especially if they might have vascular disease or Alzheimer's pathology or other things in order to, temper their expectations.

But see whether the amount of improvement that you might expect, or the range of improvement you might expect is worth it for them. But that if somebody has co pathology, it's not off the table because there may be multiple things going on and you might be able to take that top layer off of their symptomatology.

Is that basically what you're saying?

Dr. Joachim Krauss: Yeah, exactly. Exactly. And you know, it's even in series when it is being said that there was only transient improvement for two years and then the clinical picture deteriorates in some patients. So then the discussion is, should these patients be excluded from shunting? [00:16:00] But you could also say, why not shunt these patients?

At least they have improvement for two years. And with current shunt technology, low complications rate, this is different than it was 30 years ago. 30 years ago there were some published studies and with horrendous complication rates, high morbidity, even high mortality, high morbidity.

And with the new valve technology, new valve generation, this is quite different. Yeah. So there should be actually no mortality with procedures and morbidity with a program from a valve should take care of under drainage or over drainage. So this is a different picture, but as it is with many other aspects of everything, people still will talk about data that is 20 or 30 years old. So when we talk about shunting, I think it doesn't really make sense to look at the data from the [00:17:00] nineties.

Dr. Sara Schaefer: There's a lot of staying power to that stuff. I understand. Absolutely. Thinking about co pathology and how that might change the calculus and also change the conversation with the patient. Do you think that patients who are being evaluated for possible shunt and surgical intervention should be automatically tested for at least the pathologies that we can test for at this time?

Amyloids, synuclein, tau is a little bit more difficult of course. But do you think, is that part of your normal protocol or only if they exhibit certain symptoms that might point you in that direction?

Dr. Joachim Krauss: Now we are touching, I think, on a very difficult topic because there has been a quest for the biomarker of NPH for many years, and people talk about the biomarkers of NPH now. I think it'll be difficult to have really a biomarker [00:18:00] for NPH, but what we have is biomarkers for co pathology. And then of course the question is how do we define NPH?

And I hope we will get rid of this idiopathic at some point of time. And then if we say this is co pathology. Of course this is completely different than if we say this is part of the spectrum. So should we say NPH is a spectrum disorder, which might include Alzheimer's disease, which might include patient with PSP, or should we say these are different entities coming together in a way and different combinations?

I think we have to start to collect biomarkers. But this should be done on a large scale with big data because again if we look at single center studies or even small cohort studies the investigators have different ways to select the patients or what they think they [00:19:00] should be shunt candidates or not. So it would be good if you have really big data, let's say 10,000 patients, and then I think this would be much easier to have some conclusion in the end what would be beneficial. And of course, patients with mainly gait disorder less co pathology, but still it would give a clearer picture for the many co pathologies.

When should we offer shunt surgery? And also at the timing of shunt surgery, I, should we do this early? Is it sometimes maybe too late to offer shunt? Does it not make sense any longer? And all of these questions basically remain partially unanswered.

Dr. Sara Schaefer: Okay, so you've touched on a couple of future directions or priorities that you think should be looked at in the field. A couple that you mentioned were the smart shunt as it were, large data collection, multicenter data collection of biomarkers maybe a [00:20:00] standardization of protocols.

What do you think are the next steps and what do you think should be prioritized or what is your study group prioritizing?

Dr. Joachim Krauss: Well, we just looked into the evolution of NPH. And that has been a neglected topic. And of course it would be great if we could find something to prevent the progression of NPH. So let's say we have a patient with a mild gait disorder, no dementia, no urinary dysfunction, but we have the typical imaging of NPH.

Then it would be great to find something to stop the evolution. Then maybe the patient never needs a shunt. But the problem is that we do not know what are the factors that facilitate the progression of the development of NPH? Yeah. Maybe one factor is arterial hypertension. So should we treat maybe hypertension more [00:21:00] thoroughly. This patient also have a sleeping disorder. Should we treat as sleeping disorder, and that is completely unclear. So that would be one of my future focuses, prevention of progression. Then as you said already, we need more data about the co pathology benefit of shunting in these patient groups and as we discussed briefly before, the smart shunt technology.

And last, not least, CSF fluid dynamics that will come back, I'm pretty sure. If we do a lumbar puncture, of course we have the possibility to investigate also fluid dynamics. Which is rarely being done now.

Dr. Sara Schaefer: Alright, you've given us a lot to chew on. Do you have any last thoughts for our listeners as we wrap up this hot topic series?

Dr. Joachim Krauss: Yeah, of course. I think it's very important to know the clinical [00:22:00] picture. It's very important that movement disorders specialists look into NPH because there are neglected issues like bradykinesia. Many patients who do not have concomitant Parkinson's disease or PSP have bradykinesia, and this bradykinesia could even also be used maybe as a predictor for shunt improvement.

There's so many unresolved issues and also I think we now approaching a phases of hope with NPH. Yeah, we know that we can help these patients and at least in some temporarily not forever. And I'm very glad that we have this podcast in the Movement Disorder Society because this gives more attention to this still, I would say enigmatic disease.

Dr. Sara Schaefer: It sounds like the perfect field for our bright-eyed and bushy-tailed junior [00:23:00] members and listeners to go into.

Dr. Joachim Krauss: Absolutely. Absolutely.

Dr. Sara Schaefer: All right. Thank you very much for your time. I appreciate the discussion.

Dr. Joachim Krauss: Thank you so much, Sara for your question and thanks to the audience for listening.