Jan 20 2011
Electrovestibulography
I recently received this question in my Topics Suggestions page:
Dear Dr. Novella,
An interesting and rather weird neurological diagnostic technique…
http://www.abc.net.au/tv/newinventors/txt/s2909625.htm
I would be interested in hearing your thoughts.
dave, Melbourne Australia
Thanks for bringing this to my attention, Dave. Electrovestibulography, or EVestG, is a technique that measures and digitally analyzes the electrical signals produced by the vestibular system during certain manipulations, such as changes in head position. The vestibular system is that part of the brain and inner ear that senses the orientation of the head with respect to gravity, and also acceleration. The primary sensory organ is three semicircular canals, each oriented along a different three-dimensional axis. These canals are filled with fluid (endolymph) and are lined with neurons that project tiny hairs into the canals. When the fluid moves in response to head rotation they flow past the hairs, bending them and triggering neuronal activation. Separate structures, the otolithic organs, respond to gravity or linear acceleration. This information is processed by the brain to give us the subjective sense of our own position with respect to gravity and acceleration.
There already are standard tests for investigating vestibular function and localizing any dysfunction. Vestibular dysfunction usually results in vertigo – a subjective sense that either one is moving or the world is moving or spinning. (The colloquial term “dizzy” is often used to describe this sensation, but “dizzy” is a vague word with multiple meanings, so “vertigo” is the preferred technical term.”)
What these inventors appear to have done is devise a system that measures the electrical output of the vestibular system during tilting or other maneuvers and then analyzes that output in order to search for patterns of activity. I have not found the technical information online to know if this basic part of the claim is true or not, but it is plausible. Let’s assume that their machine does what they claim it does – measure and analyze the electrical activity of the vestibular system. This remains to be determined, but there is nothing surprising about this claim.
The question is – what are the clinical applications of this new diagnostic technology. The obvious application will be for diagnosing vestibular problems. This application is reasonably plausible, but cannot be taken for granted. Looking for patterns of electrical activity that act as a reliable marker for specific vestibular dysfunction is not easy, and requires a great deal of clinical study. We would need to know what the sensitivity and specificity of the test is in a variety of vestibular conditions, and then see if the test has validity – meaning that is predicts something. Do the results of the test correlate in any way with prognosis or response to specific treatments? Do they correlate with any gold standard tests already in use, or with any pathology that can be demonstrated in other ways?
I did a PubMed search on “Electrovestibulography” and came up with 6 papers. All six appear to be by the same team of researchers – the developers of the technology, which is a bit of a red flag. It could just mean that the technology is new and has not yet garnered attention from other researchers, and therefore there has not yet been any replication. This is fine – but means that we need to be very cautious about the claims until such replication can be done.
Of the six papers, three deal with vestibular disease, two in animals and one claiming that their technique can distinguish between Meniere’s disease and benign positional vertigo – two different vestibular diseases. Sorry - I only have access to the abstract at the moment, which states:
“Separation of Meniere’s disease and benign paroxysmal positional vertigo (BPPV) has been accomplished using a “DC” biomarker.”
The abstract does not give any details as to the type of study that was done, but the absence of any details is concerning – no methods, no results, just a claim. It seems like an introductory paper just outlining the technology, and not the presentation of a detailed study.
If this were the end of the story I would say that this is a new and interesting technology that requires some investigation and replication to determine if it works as claimed, and to see if it really does detect biomarkers of specific vestibular conditions. So far I am not impressed with the data being presented, and I would be concerned that the developers are going the commercial rather than the academic route. But I would keep an open mind until actual detailed studies are done.
But that’s not the end of the story. The developers of this technology then go on, from the most preliminary of data, to expand the potential clinical uses of their technology to the diagnosis of schizophrenia, depression, and bipolar disorder with suggestions that it may also work for Alzheimer’s disease and Parkinson’s disease. This would mean that there are discernible vestibular biomarkers not only for vestibular diseases, but a host of distinct and very different neurological disorders. Plausibility has now plummeted and the red flags are flying.
In one study of schizophrenia they look at 4 affected subjects and 10 controls, without any apparent blinding. This sample size is too small to be of any real use, and is questionable if it should even be published – especially given that their outcome is not something concrete (like death or survival) but is the very complex action of pattern recognition – distinguishing different patterns of activity between schizophrenics and normal controls. This type of analysis would require many more subjects (50 or more sounds about right) and blinded analysis before I would take it seriously.
I am concerned that before the developers of this technology have done extensive research to validate its use for the most obvious application – vestibular dysfunction – they have done pilot studies for depression, schizophrenia, and Parkinson’s disease. So now we have a small group of almost worthless pilot studies, rather than a series of increasingly tight and powerful studies for the most likely application. This is an odd way to proceed – unless one is trying to bolster the commercial appeal of a proprietary device by generating lots of low grade evidence for a wide range of applications.
Further – the evidence they have provided so far is akin to retrodicting – taking known quantities then looking for patterns. Astrologers can do this quite well – use astrology to “explain” why something happened in the past. But the real test of any system is its predictive power, and we have no data on that so far. The developers may be falling victim to simple pattern recognition and confirmation bias. They appear to be so impressed with the technical aspects of their device that they are neglecting the medical aspects – the plausibility of their claims and the type of data that would be needed to really substantiate them.
I predict that electrovestibulography will become just another fringe crank device with overblown and dubious claims. It seems to be heading rapidly in that direction. It may also have some genuine utility, but that is yet to be determined by proper studies. I would recommend to the developers that they focus on vestibular disease and perform (in collaboration with outside experts) large and well-designed studies to determine if it has true utility for such applications. Demonstrate first that the thing works and is useful. Then you can explore the more unlikely claims.
12 Responses to “Electrovestibulography”
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I can forward the paper to you if you’d like. Also, it’s a conference paper which means it’s not peer reviewed.
exactly what the world needs: more e-meters
Again, the paper is from a conference and therefore not peer-reviewed.
Draal,
Thanks. I did eventually find that these studies were not peer-reviewed. That makes it worse, but they are so thin as evidence it doesn’t really change the bottom line.
Draal, some conference organizers have a process of peer review to determine which papers to accept. So, strictly speaking, it’s being a conference paper doesn’t necessarily mean that it wasn’t peer reviewed. However, the standard of acceptance for a conference is usually much lower than it would be for a journal, so you right to be skeptical of the results of such a paper. Just sayin…
Stephen, I think you analysis is spot on. I’d be interested if you’d comment on their logic behind using their tech and using it to find biomarkers for Parkinson’s.
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A cause of Parkinson’s disease is known to be the progressive death of selected populations of dopamine secreting neurons. These are located in the midbrain region called substantia nigra which is part of the basal ganglia of the brain. The basal ganglia are a group of nuclei located deep within the cerebral hemispheres which play a major role in motor control [3]. Figure 1 shows the complex interconnected pathways between these nuclei. The basal ganglia receive inputs from the cerebral cortex and send outputs to upper motor neurons located in the cortex and the brainstem [3].
In Parkinson’s disease there is a degeneration of the ‘nigrostriatal pathway’. This dopamine path runs between two parts of the basal ganglia called the substantia nigra pars compacta (SNPc) and the striatum. It is composed of dopaminergic neurons located in the SNPc which project to the striatum [4].
Figure 1 shows the complex interaction of glutamate pathways from sensory organs with dopamine pathways. This indirect connection could cause the glutamate paths from sensory organs to be affected by the degeneration of the dopamine pathway in Parkinson’s disease. This could be one of the reasons for the poor balance experienced by people suffering from Parkinson’s disease.
The sensory organs which we have focused on
in this research have been the vestibular, which help
maintain our balance by sensing the position and
movement of the head.
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Figure 1: i51.tinypic.com/2r5rwvp dot jpg
excerpt from: Conf Proc IEEE Eng Med Biol Soc. 2008:4142-5.
EVestG: a diagnostic measure for schizophrenia.
@chrisj
I’m familiar of how some conference papers are accepted and published. I personally do not submit my papers to conferences because I’d rather have it peer review in a well-known journal (Impact Factor considerations). Also, if a study is published in one journal, it is not appropriate to publish in another later on. It also affects the timetable for when a patent can be filed. Once research is presented publicly anywhere (i.e. conferences, journals, ect.), you have just one year to file for a provisional patent. Further work might be needed and completing everything in one year is often impractical. Conferences are a good way to discuss preliminary results with your peers before all the lab work is complete.
The PI, Brian Lithgow, is publishing a number of these studies through the IEEE conferences. It also so happens that Brian Lithgow, is a Senior Member of the IEEE. In practical terms, he can have any work he’d like published through the IEEE conference. I know that the manuscripts were not peer-review because I have the papers in hand. The manuscripts only provide a received date (when the manuscript was first submitted) and not an accepted date (the date the manuscript is re-submitted following revisions based on reviewer comments).
Draal – I think the link to Parkinson’s is not impossible, but it’s very tenuous. I would be surprised if it pans out. The link to imbalance makes no sense, and Parkinsonism causes imbalance through postural instability, not vestibular dysfunction. These look very different on neurological exam. So I am not impressed with that hypothesis.
The link to depression, schizophrenia, and Alzheimers is even more tenuous – and the notion that all of these disorders would be manifest with such an analysis of vestibular function seems highly far fetched to me.
Thanks Steven!
And one last tid bit, Brian Lithgow has at least two patents filed.
Patent Application number: 12/602,456
Publication number: US 2010/0261978 A1
Filing date: May 30, 2008
Patent Application Number: 11/661,622
Filing Date: 09/01/2005
I have a somewhat different take on this. I don’t doubt that the authors would like to do larger and more rigorous clinical studies, but such things take money and obtaining funding is extremely difficult, especially in today’s investment climate. Small, unblinded pilot studies don’t cost very much to do. They also don’t demonstrate very much.
It doesn’t seem as though they are trying to scam the public with their device before it is tested.
http://www.todaymedic.com/other/electrovestibulography-new-technique-to-diagnose-mental-illness/
If you look up electrovestibulography on google, this blog post is the third hit. This is not something that looks like it is being peddled by quacks on the internet to scam people.
I am not sure how valuable this device would be, even if it was highly effective at diagnosing these different things. There aren’t treatments that are curative, these disorders are and likely will remain chronic life-long disorders (until my nitric oxide treatment becomes available
). Differential diagnosis is only useful for differential treatment. Major “treatments” for depression, Alzheimer’s, Parkinson’s include lifestyle changes, diet, exercise, stress reduction. You don’t need a differential diagnosis to suggest them. If a person has those disorders to such a sub-clinical level that it takes a highly sensitive (and expensive) machine to test for them (instead of a trained clinician), then it isn’t clear what (if any) treatment the patient should receive. Conventional treatments derive from conventional diagnoses.
Responses to pharmacological treatments are pretty idiosyncratic, a diagnosis from any test is very unlikely to be predictive of how that patient will respond to a specific drug.
If it could be used for something like monitoring nausea during chemotherapy (and titrating the chemotherapy dose via nausea), or to monitor other drugs that cause nausea, maybe it would be useful.
There is only a single patent application that I could find.
http://www.google.com/patents/about?id=OAnYAAAAEBAJ&dq=Publication+number:+US+2010/0261978+
Which does list what is meant by “DC offset”.
I don’t think this will be a successful innovation because I don’t think it does enough (even if it worked, which I doubt that it can). Some disorders are disorders of exclusion (for example Ménière’s). If they can’t explain the symptoms with something else, then you have Ménière’s. You would still have to go through the work-up to exclude the other things that it might be (and which might be treatable).
There isn’t any theory behind it (that is discussed in the patent). It is simply signal processing on the data and looking at (what are claimed to be) characteristic patterns in the signals that are characteristic of different neurological disorders. I think this is doubtful.
However, using a tilt-table may be influencing these things via a mechanism unrelated to the vestibular system (yes, nitric oxide).
There are variations in heat beat inter-interval time. In normal individuals these variations are chaotic, that is they do not exhibit a simple pattern. The pattern they do exhibit becomes more regular as individuals become sicker. These patterns also change when the subject is put on a tilt table and the table tilted. My explanation is that the changes in the hydrostatic pressure of blood in vessels due to the change in orientation results in changes in vessel tone, which is compensated for by changes in NO levels (the major regulator of vessel tone). I think it is these changes in NO due to changes in orientation that affect heart rate inter-interval variability.
NO is also a major neurotransmitter and does have effects on neuron firing in the brain.
Many neuropsychiatric disorders are characterized by low basal NO levels, so they would be sensitive to changes in basal NO from tilt-table movement. I don’t think this would be sensitive enough or specific enough to be used as a screening or diagnostic tool.
The invention is interesting in that it is attempting to measure some neurological degeneration in the types of medical patients specified. How do you explain the defects in normal processing of information in Alzheimer’s, Parkinson’s, schizophrenia/depression or bipolar affective disorders? For example, a cocaine addict/multiple substance abuser will experience degeneration in all senses. Wouldn’t it be useful to pinpoint reasons for inattention and progression of dementia in these disorders?
Does anyone else scan daedalus’ posts for the letters NO before deciding whether to read them