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He is the senior author of the recent paper published on movement disorders clinical practice entitled "The Clinical Features of Idiopathic Normal Pressure Hydrocephalus Critical Review of the Objective Findings". Welcome to the MDS Podcast, Dr. Martino, and many thanks for your time.
[00:00:53] Dr. Davide Martino: Many thanks for having me, Sarah. It's a pleasure.
[00:00:55] Dr. Sarah Camargos: Thank you. Doctor, can you share with us a little bit of the [00:01:00] background of your study and what your critical review adds to the field.
[00:01:03] Dr. Davide Martino: Sure. So the review is on normal pressure hydrocephalus, as you mentioned. And we know that this has been recognized as an entity for more than five decades. And, overall it's quite frequently suspected and even diagnosed particularly when there is a relatively rapidly progressive gait disturbance with a variable cognitive impairment or urinary dysfunction, and primarily in elderly people. However, if we consult the existing guidelines that come mostly from neurosurgical societies, we realize that the grading of the recommendations that are used to diagnose iNPH is not coupled to an objective assessment procedure that is standardized. Also the terminology used in these recommendations uses terms that are vague or often analogical.
Well, an example above all is magnetic gait, which do not appear to be reproducible. And if we look at the severity rating, then there is a widely used [00:02:00] grading scale that is based however, not on phenomenology, but on functional impairment. So the Movement Disorder Society Study Group for NPH, decided to start from a project zero. That was really going to go back to the literature to review critically the objective findings of clinical assessments to see how consistent the phenomenology of this clinical triad of NPH emerges from the clinical studies that have been published.
[00:02:27] Dr. Sarah Camargos: Perfect. Dr. Martino. It's very interesting because this kind of grading impoverished the specificity of the diagnosis as I understood. Please tell us what criteria you used to select these papers.
[00:02:42] Dr. Davide Martino: So we wanted to do a critical review, not really a systematic review in full. And this is because we really did not want to focus on some aspects that are key features of a systematic review. Like, for example, the risk of bias assessment that we have not conducted in full. But in any case, we followed the Prisma guidelines that are [00:03:00] well standardized for systematic reviews.
And we did this independently for the three key domains of gait dysfunction, of cognitive impairment and urinary dysfunction. And we decided to include only articles that described clinical findings related to at least one of these triad symptoms before treatment. And that documented through objective neurological examination or an instrumental testing that is included in routine clinical practice.
This type of finding. So for example, specific phenomena, characterizing gait abnormalities coming from neurological examination rather than, as summary scores on quantitative scales. And so in the same way for cognitive, we needed to include neuropsychometry and for urinary dysfunction, we needed to include urodynamic testing because we could not rely only on subjective reporting.
We do not want to rely only on that. These are the essential criteria that we use to select articles in our critical review.
[00:03:56] Dr. Sarah Camargos: So a subjectively reported [00:04:00] phenomenon were not included in this review?
[00:04:02] Dr. Davide Martino: No, we did not include them because unless we included papers that provided this type of subjective data, but papers to be included had to provide also objective data.
[00:04:11] Dr. Sarah Camargos: Perfect. So maybe this will improve the sensitivity of your study.
[00:04:17] Dr. Davide Martino: Well, we were interested in assessment procedures. Right? And moving forward towards the definition of assessment procedures that are needed to diagnose NPH.
[00:04:26] Dr. Sarah Camargos: Very nice. On the gait results, you pointed that the level of confidence rated as probable, possible, or definite was not specified in 22 out of 26 studies. Do you think we can be facing a potential bias on that?
[00:04:44] Dr. Davide Martino: Well, yes, I do. The bias isn't, not so much on our methodology, I think, but on the type of evidence that is out there. So definitely, yes. 22 of the 26 studies that provided objective gait findings did not report whether [00:05:00] patients had a probable or possible or definite level of diagnostic confidence for NPH.
But this is actually one of the salient points of the paper. We don't know the clear reasons for which this level of diagnostic confidence based on the recommendations was not reported in most clinical studies. Majority of these studies were observational studies, not RCTs.
I think one could assume that it could be because the grading is not felt to be useful or characterizing enough. And and there may even be concern from researchers that it might not be easily reproducible. But this however, does not surprise me. My view is really, again, it's linked to the difficulties that we have identified to describe a consistent phenotype of NPH based on objective findings.
[00:05:41] Dr. Sarah Camargos: Yes. And that's why you thought about this study, right?
[00:05:45] Dr. Davide Martino: Yeah, exactly.
[00:05:46] Dr. Sarah Camargos: I realized that there is a wide range of descriptors for each component of the triad. How do you feel about it?
[00:05:55] Dr. Davide Martino: Yes. the prevalence range for descriptors, particularly of gait dysfunction is pretty huge across [00:06:00] studies. And yeah, this makes me feel uncertain about consistency in which NPH is diagnosed. It makes me feel also that this diagnosis in routine clinical practice may actually be relying much more on the imaging picture than on a clinical picture. And also this variability in the prevalence of salient features like, for example, a widened stance. This variability may also mean simply that there is inconsistent recording or there is inconsistent reporting of the individual objective gait findings on examination.
Because a lot of studies simply reported the grading scale scores. But what are the key gait abnormalities that determine a specific grading scale score? That remains unclear in my opinion. And we will see if more consistency will come from another review that hopefully will be published soon from the Study Group that focused on laboratory supported gait analysis.
And so we will see how crucial it is to rely more frequently, even in routine [00:07:00] practice on gait analysis to confirm a diagnosis of NPH.
[00:07:03] Dr. Sarah Camargos: So the clinicians will be important in this field to describe the phenomenology of the gait disorders and cognitive profile.
[00:07:13] Dr. Davide Martino: Yeah.
[00:07:13] Dr. Sarah Camargos: Perfect. iNPH and other neurodegenerative disorders such as parkinson's and Alzheimer's disease are probably the most important limitations of studies in the field. Do you think of another limitation for this type of study?
[00:07:30] Dr. Davide Martino: Well I'm not sure that we can say that dual pathology per se is a limitation, but rather it's actually an additional very important layer of complexity to this area. But there is no doubt there are different challenges to advance the field here. But if I have to pick one, which I consider most important, is that, again, as I mentioned earlier, the vast majority of the literature on NPH is produced by neurosurgical teams, which if we exclude just as more a proportion of them, they do not really collaborate [00:08:00] too actively with movement disorders, clinical programs. And this is why our Study Group in the Movement Disorder Society is so important on this topic because when different specialties do not crosstalk on important subject that they both care about, then we have confusion in the nomenclature. We have confusion in the clinical criteria and even in the treatment practices, which is the most dangerous thing.
I find in this a similarity with a field of movement disorders and psychosis. And where there is still a discrepant nomenclature between psychiatrists and neurologists. And the same thing is happening probably between neurosurgeons and neurologists for NPH.
[00:08:32] Dr. Sarah Camargos: Yes, indeed. I agree with you. Your revision included only five articles on united dysfunction contrasting with 36 in gait and 52 in cognition. What are the possible reasons for this discrepancy?
[00:08:49] Dr. Davide Martino: Well, yeah. I was surprised and concerned about that. But then if we look at the criteria that we used to include articles, then it becomes quite easy to explain because objective [00:09:00] assessment of urinary dysfunction requires instrumental testing, requires urodynamic testing and urodynamic testing in these patients is way less used than, for example, neuropsychometry.
So this is why only a few studies have provided that. We could not consider sufficient for inclusion papers that reported the frequency of nocturia, the frequency of urgent continents, because those were subjective reports. Right? But as a result of this, I think that if this clinical domain of urinary dysfunction is confirmed to be relevant to diagnose NPH, then probably more instrumental testing will need to enter clinical practice for these patients.
So probably these patients will need to see the urologist more if we decide that we need urinary dysfunction or the urinary dysfunction is an important component of the diagnosis of NPH. If this is confirmed.
[00:09:50] Dr. Sarah Camargos: On the cognitive component you demonstrate that no cognitive dysfunction profile was described for iNPH. Do you [00:10:00] think that there isn't a cognitive signature of those patients or more than one neurodegenerative disease could be present masquerading the findings.
[00:10:09] Dr. Davide Martino: First of all, we have to keep in mind that not all patients who entered these studies has cognitive dysfunction or had to have cognitive dysfunction by definition. But in any case, to answer your question, I think that if there is an entity like idiopathic NPH or NPH, I think it will have a specific cognitive dysfunction profile. May be broad, but there will be.
But I also believe in, like you mentioned, that there is dual pathology in many cases with a diagnosed NPH so if the way we conceptualize NPH is correct, then I think it is fair to state that the greater the response to shuns surgery, the more likely a specific clinical feature is genuinely an NPH feature.
And this is why it is really so important, even more so if we are studying of reassessing treatment response to describe the [00:11:00] phenomenology in depth at baseline if not for other reasons, because the confounding effect of dual pathology is definitely very likely in these patients.
[00:11:09] Dr. Sarah Camargos: Perfect. Do you think the readers of your paper will be encouraged to describe in detail the phenomenology of gait, cognition, and urinary dysfunction to perhaps fill the gaps in the knowledge of this disease?
[00:11:24] Dr. Davide Martino: Well, I should hope so. Obviously, it means that the paper has had some form of impact, but I think that what's most important, and this is again, what the Study Group wants to achieve here is a cultural change. A cultural change that should, in this context, in the context of NPH, improve the quality of the interaction between neurosurgeons and neurosurgery and movement disorders neurology and cognitive neurology as well. Also because neurologists are likely the ones who will continue to follow up these patients for a long time, even after a shunt, right? And we know that, that this is gonna happen. So if this is [00:12:00] working for DBS, that neurosurgeons and neurologists work well together, why shouldn't it work also for NPH?
[00:12:06] Dr. Sarah Camargos: I agree. And maybe improving specificity, selecting properly, and defining the natural history of the disease. As you mentioned in the paper, as the time progresses. This is a beautiful paper. You diagnose a problem in the field and you addressed this problem and you came up with solutions, so thank you so much for that.
[00:12:31] Dr. Davide Martino: Thank you very much for your kind words. Let's hope it is well received.
[00:12:34] Dr. Sarah Camargos: It's not kind. It's objective findings.
Thank you again Dr. Martino for sharing your thoughts with us. And thank you to our listeners. Have a great week.
[00:12:45] Dr. Davide Martino: Thank you again.