Neuromodulation for COVID-19 Symptoms

Prof. Leigh Charvet

Professor, Department of Neurology at NYU Grossman School of Medicine

Professor Charvet is a neuropsychologist who has worked in neurology and primarily with people living with Multiple Sclerosis (MS) as well as other different types of neurologic conditions, with cognitive and psychiatric problems resulting from these conditions. She has done a lot of research around that area and always with the focus on what tools we can build to improve the quality of life and reduce the disease burden. She has conducted a large trial of cognitive remediation with people living with MS involving telemedicine, which brought her into the world of tDCS. About 8-9 years ago, Prof. Leigh was interested in pairing stimulation in the rehab setting, to boost the benefit of cognitive training. This is when she started partnering with biomedical engineers and started working in the field of telerehabilitation to administer tDCS at home for clinical applications.

Postdoctoral Research Fellow, Department of Neurology at NYU Grossman School of Medicine

Dr Pilloni is a biomedical engineer and she started working with Prof. Charvet in 2018. She arrived in New York from Cagliari, Italy as a visiting PhD student and joined the team last year. Her PhD was focused on the quantitative assessment of gait and balance with inertial sensor and she applied this technology to see if the rehabilitative intervention can improve gait and balance in neurological disorders and specifically in Multiple Sclerosis.

Dr Giuseppina Pilloni

How Can Neuromodulation Treat

COVID-19 symptoms?

Leigh: I think absolutely and it’s also driven by the accessibility, safety and tolerability of these tools. It’s a non-drug intervention that patients can have immediately and it can be applied anywhere. Our focus is on home use and if you look at the growing literature, there’s a lot of potential direction that can go for evaluation and application of these stimulation therapies and in managing Covid throughout, from acute through persistent symptoms and recovery.

We are not saying that this treats Covid. It treats the effects of Covid on the system and manages the sequel of what Covid does to somebody. I think that what it does in the acute infection and the persisting symptoms is really unknown and it’s still being characterized and so it’s just catching up to seeing if we can apply some of what we know in other syndromes and other situations here. But again we have to remind ourselves too that this is an accessible, tolerable, safe therapeutic approach and so there’s a call for research and evaluation. That’s really the point of our paper too, it’s just for it to be considered fitting in an area where we don’t have many other therapeutic options right now.

Are there any deleterious effects in the use of tDCS?

Leigh: Especially with transcranial Electrical Stimulation (tES), it comes from a really strong record of safety and tolerability and no serious adverse events have been reported in clinical trials to date. Certainly, in our high volume of experience, it’s really well tolerated. Everything has side effects, but they’re usually at the sight of the electrode, like discomfort. That’s not something that would prevent you from evaluating in a therapeutic context.

However, we’re learning more and more and we definitely need more evidence for sustained continued use of these therapeutics. A lot of the trials have been really limited to few applications and we really believe that there’s an accumulative benefit. So you need to repeat the application, ideally daily, for extended periods of time to have that benefit. We just don’t have the full body of evidence that we need to really guide dosing parameters and what we would expect for long-term use. But with that, there’s nothing yet that would make us think or anticipate a worry about the continued use. We’re cautiously moving forward, but I do want to always note that there’s caution and that more evidence is really needed especially for dosing guidance and parameters in this field.

How can neuromodulation be used to treat COVID-19 symptoms and what are the engineering challenges?

Jonathan: It seems to be quite a lot of encouraging empirical evidence that this stuff works and works quite well in contexts like Covid and actually many different aspects of the disease. You discuss in your paper that it can be used in the early stages when there’s an acute inflammatory response, it can also apparently help with supporting respiration through vagal nerve stimulation, with neuralgia, the chronic pain syndromes that may be associated with long Covid -if indeed that exists beyond a psychiatric phenomenon-. So it’s a very powerful tool. However, there’s so much ignorance too, like you said, we don’t really know how this stuff is being affected.

Giuseppina: Transcranial Direct Current Stimulation (tDCS) is a really technical area and especially with all the modelling of the electric field. We need to give answers to how the electric field propagates in the brain, which is the best target area to reach the optimal benefit, how the brain activation changes with current intensity, if we should increase the current intensity or not, how long the treatment has to be, 20 minutes or more for example? There are a lot of unknown things that we are actually investigating. We are combining, for example, the real-time effect of tDCS on our brain with MRI protocol and so there is a lot of interest.

Can neuromodulation be administered at home?

Leigh: That’s how we actually started with tDCS, because of the handheld portability of the devices and my background in telemedicine. We know from almost every rehabilitative therapy you need a consecutive near-daily application for extended periods of time. So tDCS or tES can be therapeutic on its own for certain uses, but also you compare it to boost the learning that occurs with a simultaneous learning activity, whether it’s physical or cognitive rehabilitation for instance. With that angle, especially home-based therapy is really important to provide the ongoing daily sessions. We do it remotely, supervised through telehealth so it’s very structured and guided, and the technology is sent to patients at home and they’re guided through it in that way. We actually had eight years of development of a whole system for it to be able to reach patients in their homes and deliver tDCS. With Covid we were suddenly moved to telemedicine. Across the world, patients were isolated in need of treatment. So it really lends itself well to that model, to both reach patients in need and also to provide that ongoing daily type of therapeutic activity to boost recovery.

It’s a very major topic, because everybody’s trying to think of what can we do therapeutically to help all of the patients with Covid and particularly those with persisting symptoms. We work with patients with neurologic disorders who then get Covid, so there’s just a tremendous therapeutic need across the world and it was positioned in that way. We also have, through NYU Langone here, an innovative care policy that allows us to have a clinical service where we provide tele-tDCS to patients in their homes therapeutically or clinically and we began to get people recovering from Covid. So that informed a lot of our thought trying to optimize their rehabilitation and recovery and to help them in that way.

Can neuromodulation be administered asynchronously at patients’ homes?

Leigh: Our primary activity here is research and so we are driven by all the rigour of research and also from the abundance of caution. These are patients often with a high level of neurologic impairment who are self-administering tDCS in their homes and it can be complicated. There’s technology involved and so we built a system around live video connection at every point and, especially important, if we’re pairing it with an ongoing therapeutic activity, we can just really enable that. So I wouldn’t say it’s necessary for a clinician to be in the tele-session. I think there is definitely technology and models where people can self-administer it. I do think though that especially in the beginning it lends itself really well to a daily-contact therapeutic model, both for safety and clearance checks, but also just to checking in and reaching a patient at home every day is very powerful, which can also ensure adherence to the therapy and make sure everything’s going okay. So there’s a lot of soft therapeutic benefits around that daily connection model too. That being said, the technology is for self-administration which can still be clinician-guided at a lower level than live video connection and I definitely think that that’s where we’re going. But again we need that guided use and we always want to come from an abundance of safety precaution, especially in somebody’s home for their use.

What are the technical challenges in the field of neuromodulation that we will face in the next few years?

Giuseppina: As a biomedical engineer, for sure being able to be more specific in the stimulation of the target in the brain. We are using electrode montage that is on a standard measure, however, there’s a lot of difference between patients and so I think the next step will be to reduce this variability in between subjects. In this way, maybe you will get a better response in terms of uniformity.

Leigh: I would agree with Giuseppina, in that we’ll have technology that’ll drive individualization of the therapeutic use and also it will be combined across different stimulation therapies, both invasive and non-invasive. We’re still very early and there are a lot of exciting advances on the forefront with all of this.

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