Multiple Sclerosis Research: Dr Leigh Charvet

INTERVIEW WITH DR LEIGH CHARVET – NYU LANGONE MULTIPLE SCLEROSIS COMPREHENSIVE CARE CENTER

BD: Brett Drummond, MStranslate
LC: Dr. Leigh Charvet, NYU Langone Multiple Sclerosis Comprehensive Care Center

BD: Alright, welcome everyone to our MStranslate interview, continuing on with our coverage of the American Academy of Neurology conference that’s recently been held in Vancouver, Canada.

Today we are very thankful to be joined by Dr. Leigh Charvet. Dr. Charvet is a researcher at the NYU Langone Comprehensive MS Care Center, and Dr. Charvet had a number of presentations that she was involved in that were presented at the AAN conference and she has been kind enough to join us very early in the morning in New York now to talk to us about those projects.

Dr. Charvet, welcome, thank you for joining us.

LC: Hi

BD: I wonder if you’d mind starting just by giving us a little bit of an introduction to you, and how you’ve gotten into this field and the work that you’re doing.

LC: Sure, so I’m a clinical neuropsychologist by training and have had a longstanding interest in MS, starting out with my clinical work over 20 years ago, and very interested to merge research, so very interested in the symptom of cognitive impairment, especially because it is such a major problem in living for so many individuals with MS and there’s really no available treatment or effective treatment that’s consistently effective at least for many people.

BD: Yeah, I think that was one of the things that caught my attention when I was looking through the abstracts of the conference is that you have a number of presentations that are looking at cognitive function in people with MS and how that can be impacted then improved and as you say cognitive function is one of those symptoms that is very common amongst people with MS but at the moment really no treatment that can help improve.

So, there’s a number of different presentations we’re going to talk about but we might just talk about a couple very briefly to begin with. So one of the presentations that you were involved in was regarding a tele-health mindfulness meditation project. Can you tell us a little bit about that.

LC: Sure, so mindfulness meditation is a really powerful tool to reduce stress and it’s something that’s accessible so almost anybody can learn the simple techniques and practise it so, you know, it’s like the tagline, you know – a few minutes to learn and a lifetime to master – so it’s practice over and over.

And we were interested, so a longstanding issue is stress and how stress influences illness and can just improve quality of life if you reduce stress and so we came to mindfulness in that way. We were interested in how it affected symptoms. so the severity and intensity of symptoms on a day to day basis. And, so one of the problems which is kind of a theme throughout our work is trying to deliver treatments to be accessible to people living with MS outside of the lab. So, we are here in New York City, but almost anywhere it is a real obstacle for people to come into the clinic weekly or especially every day if we are doing something else, some kind of more intense remediation, and so we were really interested to use technology to deliver these treatments to people outside of the clinic.

So this is where we took a standard Mindfulness program which has been established and converted it to a tele-medicine type of platform so basically here we just used the telephone and group conferences and so we took some mindfulness, involves some group learnings together and then group meditation and then individual practice and so we took the group part and the instruction and put it onto a tele-medicine platform.

And in that study, it was very interesting in that this was a really feasible way to reach people so participants really enjoyed being able to learn about mindfulness and be tied into a program in a much more convenient, feasible way and we also saw significant benefit with the STMT, which is a measure of cognitive processing speed. so it seemed to help a little bit and that is consistent with findings in the literature, that probably because it is reducing stress it just helps dial down the intensity of symptoms so we would think about it not only for cognitive impairment but for stress and fatigue, I’m sorry, fatigue and depression as well, some of those things.

BD: That’s fantastic and as you say I mean one of the difficulties that people with MS can face especially towards those more advanced stages. is having to travel somewhere to get these sort of therapies can be really difficult, so being able to deliver it via that tele-medicine platform and seeing the results you’ve seen is really interesting and fantastic.

So, one of the other studies that you presented or that you were involved in the presentation was looking at a marker of cognitive function in pediatric MS and looking at the impaired olfactory function. Can you talk to us a little bit about that study.

LC: Sure, so under the umbrella of our focus we are trying to find measures that are the most sensitive to MS, cognitive involvement in MS at its earliest point. It is ultimately much easier to prevent a decline than it is to repair or remediate impairment once it’s occurred. And so that’s kind of the end goal, to try to predict who’s at risk for impairment and then that’s where our interventions I think will ultimately be most effective.

And so, there’s a lot of interesting work in olfactory functioning, so smell identification, so these are just scratch and sniff tests, so that’s actually appealing in that these are very easy to administer, patients enjoy them so it is a low stress assessment that’s very friendly for routine assessment and olfactory identification, or smell identification, has been a powerful, early detector for cognitive impairment, both the presence of cognitive impairment and especially the risk for future cognitive impairment in other disorders such as Alzheimer’s disease, or Parkinson’s disease and some others.

So, we were interested to see if that smell detection also might be sensitive in MS, so there’s been a study or I think maybe a few studies that have shown that in adults with MS, smell does correspond to the degree of cognitive impairment so olfactory identification is effective in at least corresponding to cognitive impairment in adults. but with our pediatric patients, these are the patients that have the earliest onset of MS, and so we extended the assessment to these patients and we also, we saw in the study as well we’ve found, just as with adults that there is an impaired, a relative impairment so when we call it impairment, it’s not necessarily impaired but it’s a relative weakness and for smell identification but importantly that that was also corresponding to cognitive functioning in the pediatric sample.

So, this is, so we had the appeal of this type of test and what it may mean and also it may be a the predictive window into future risk for decline and that that’s corresponding even in this young sample that really has no truly measureable cognitive deficits at this point that it’s corresponding with cognitive performance.

So that is designed to, to continue to evaluate this measure and what it might mean specifically for use in MS across the lifespan.

BD: OK, I mean, I think one of the real advantages of using or looking into pediatric MS is we get people at that very early stage when we’re looking at what are the actual effects of MS and not necessarily the effects of having this longstanding inflammatory condition that we may be looking at when we are looking at adults.

Do you have any sort of idea as to what may be causing the link between impaired olfactory function and cognitive decline – is it site of lesions, amount of lesions?

LC: Right, so, there’s really no, no, it’s really not known in any of these disorders, it’s probably not the site of lesion, of the theories, I think that the olfactory system in general is just very sensitive, the neurons there are relatively amyelinated and they, it’s just, it’s a symptom of brain health overall so it’s just a sensitive part of the brain so that if there is global decline or whatever, disease processes happening, that olfactory functioning is going to be an early indicator.

BD: OK fantastic. So another study that we actually published a short article on during the conference and one that has gained a little bit of media attention already here was looking at adaptive computer-based training to help improve cognitive function.

LC: Right, yes, this study really excited, it’s a large clinical trial, so it’s controlled, randomised, with 135 patients Here, what we studied was, so these programs are coming out with technology allowing delivery of cognitive remediation through a web-based platform and what that allows are features that have never been able to be provided through one on one working with a clinician. So a web-based platform can provide rapid learning trials, really optimizing and driving learning and in addition they adapt in real time to how the user is performing so if I go a little bit slower it will slow down, a little bit faster it will speed up. That really drives learning because it maintains my engagement in the program.

And so there are these programs coming out and we really wanted to know if they would be helpful specifically for use within MS and then really the advantage of the programs because they are web-based they can be remotely accessed, that can be accessed from home and so in this trial we did a remotely supervised protocol so it’s different than just having people play and report back but we actually monitored them in real time and we used to compare the program that were ordinary computer games that might have face validity as something we all may think are cognitive enhancing or helpful so like you think word searches and crossword puzzles and just things like that but didn’t have any of these adaptive features or advanced designs that the target program did, which was Posit Sciences Brain HQ, developed for research purposes for us, so we picked the games or the training exercises that would be most targeted towards MS-specific deficits.

So we randomised participants, they all had some degree of cognitive impairment, and we randomised them to train in either that adaptive program or the control condition for 12 weeks, so we were targeting five days a week, an hour a day, for 12 weeks so targeted 60 hours of training and we did a neuro-psychological assessment at baseline and then we did that at the study’s end after 12 weeks and here we found the first, very exciting to us, that it was really feasible, this was a really doable type of delivery of cognitive remediation so participants really liked it, it was a rapidly enrolling trial, we rapidly recruited, it really speaks to how much of a need there is for treatment of cognitive impairment because so many people wanted to participate in the trial and we had very high compliance in both conditions, so they were able to follow procedures.

We found actually that that control condition was played more often than the adaptive condition but this is probably because it was easier, it’s really a workout to do the training condition but that being said the training condition led to significantly greater gains, that that adaptive, targeted program led to significantly greater gains in cognitive functioning so we used a composite of cognitive tasks that are sensitive in MS and that average we looked at, at baseline and then at study end. So they had significantly greater gains than the comparison group by study end and also in that condition, the more they played, the higher the gain they had. So it was a real indicator that again we can reach these, we reach people this way and provide cognitive remediation through this platform and that these features, this type of program may work specifically in MS.

So, we were really excited about this and looking forward to following up to find out who’s going to benefit and how we can really maximize that benefit and in some of the parameters so we can give some real world recommendations on what people can be doing to be most helpful.

BD: OK, that’s really interesting because I think, I mean we often say when it’s, we are doing physical training, and be this you know for people in the public or people with MS and we’ve done features before on ways that we can do physical therapy to help improve muscle function and things like that that you always look at doing things for increased resistance and build up that sort of muscle strength and it sounds like what you are saying is that the brain is no different. If we are really going to train the brain and get those sort of benefits, we need to keep increasing, increasing it, it’s not just a matter of doing the same sort of tasks over and over.

LC: Right, we use that exercise analogy all the time and it definitely, you know, seems to be applicable here.

End of Part 1.