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Francois Bethoux, MD, and Hubert Fernandez, MD, discuss the individualized approaches needed to deliver neurotoxins for an array of neurological indications.

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Challenges in Neurotoxin Delivery

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: April 15, 2024

Expiration Date: April 15, 2025

Estimated Time of Completion: 34 minutes

Challenges in Neurotoxin Delivery

Hubert Fernandez, MD and Francois Bethoux, MD

Description

Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

  • Review up to date and clinically pertinent topics related to neurological disease
  • Discuss advances in the field of neurological diseases
  • Describe options for the treatment and care of various neurological disease

Target Audience

Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

ACCREDITATION

In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

CREDIT DESIGNATION

  • American Medical Association (AMA)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

  • American Nurses Credentialing Center (ANCC)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

  • Certificate of Participation

A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

  • American Board of Surgery (ABS)

Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Credit will be reported within 30 days of claiming credit.

Podcast Series Director

Imad Najm, MD
Epilepsy Center

Additional Planner/Reviewer

Cindy Willis, DNP

Faculty

Hubert Fernandez, MD
Center for Neurological Restoration

Francois Bethoux, MD
Physical Medicine and Rehabilitation Center

Host

Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

Challenges in Neurotoxin Delivery

Hubert Fernandez, MD and Francois Bethoux, MD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

Francois Bethoux, MD

IPSEN

Consulting

GW Pharma

Advisor or review panel participant

Springer International Publishing

Intellectual property rights (Royalties or patent sales)

Amneal Pharmaceuticals Advisor or review panel participant
MedRhythms Inc Advisor or review panel participant
Research: Principal investigator on an investigator-initiated grant partially funded by MedRhythms
Qr8 Intellectual property rights (Royalties or patent sales)
Hubert Fernandez, MD

Acorda Therapeutics

Consulting
Other activities from which remuneration is received or expected: Research / Independent Contractor

Biogen Idec

Other activities from which remuneration is received or expected: Research / Independent Contractor

Elsevier

Other activities from which remuneration is received or expected: Received a stipend as Editor in Chief of Parkinsonism and Related Disorders

Michael J. Fox Foundation

Other activities from which remuneration is received or expected: Research / Independent Contractor

Parkinson Study Group Other activities from which remuneration is received or expected: Research / Independent Contractor
Kyowa Hakko Kirin Co. Ltd Consulting
Teaching and Speaking
Abbvie Pharmaceuticals Consulting
National Institutes of Health/National Institute of Neurological Disorders and Stroke Other activities from which remuneration is received or expected: Research / Independent Contractor
Bial Teaching and Speaking
Cerevel Consulting

Imad Najm, MD

Eisai

Advisor or review panel participant

NIH

Other activities from which remuneration is received or expected: Research Funding

LivaNova, PLC

Advisor or review panel participant

SK Life Science Inc

Advisor or review panel participant
Teaching and Speaking

Glen Stevens, DO, PhD

DynaMed

Consulting

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: Neuro Pathways Podcast April 15 2024 to log into myCME and begin the activity evaluation and print your certificate If you need assistance, contact the CME office at myCME@ccf.org

Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.

Introduction: Neuro Pathways: A Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: The growing number of indications for neurotoxin injections, increasing number of available neurotoxins, and the potential dangers of toxin injection may make the thought of delivering neurotoxins to patients a daunting one for today's providers. In today's episode of Neuro Pathways, we're tapping into the extensive expertise of two physicians with dedicated neurotoxin clinics who are taking us through the perils and pitfalls of neurotoxin delivery. 

I'm your host, Glen Stevens, neurologist, neuro-oncologist in Cleveland Clinic's Neurological Institute. And joining me for today's conversation are doctors Francois Bethoux and Hubert Fernandez. Dr. Bethoux is director of the Department of Physical Medicine & Rehabilitation, and Dr. Fernandez, the director of the Center for Neurological Restoration, both within Cleveland Clinic's Neurological Institute. 

Francois, Hubert, welcome to Neuro Pathways.

Francois Bethoux, MD: Thank you.

Hubert Fernandez, MD: Thanks for having us.

Glen Stevens, DO, PhD: So before we start, and I'll start with you, Francois, tell us a little bit about yourself, where you're from, how you made your way to Cleveland and what you do at the Clinic.

Francois Bethoux, MD: Of course, I was born in Paris, so I'm from France as my accent will tell you anyways. I actually came to Cleveland the first time to do a year abroad for an academic career in France. And then one thing led to the other and I left and came back to Cleveland to stay 26 years ago. So I've been at the Cleveland Clinic in the Neurological Institute since then.

Glen Stevens, DO, PhD: And Hubert?

Hubert Fernandez, MD: Yes, my accent might tell you, I'm a born and raised Filipino. I did all of my postgraduate here in the United States. I did my internship at Penn, my neurology residency at Boston University and my fellowship in movement disorders at Brown University. That's where I learned how to use neurotoxin injections. In my assistant professor years, I spent at Brown, my associate professor years I spent at the University of Florida, and most of my professor years here at the Cleveland Clinic.

Glen Stevens, DO, PhD: Well, we're thankful to have both of you here and all the work that you do. And I'm Canadian, so we have a very international panel here today.

Francois Bethoux, MD: That is great.

Glen Stevens, DO, PhD: So today we're going to talk through the practical challenges that providers are faced when delivering neurotoxins to patients with neurologic disorders. And Hubert, I'll get you to start first, but can you start our conversation by describing the neurotoxins currently available for neurologic patients and how they work primarily with the ones that you're using?

Hubert Fernandez, MD: Sure. I think the use of neurotoxins in movement disorders is probably the most diverse because all commercially available neurotoxins are used in movement disorders. So we have now about four commercially available ones. We have onabotulinum toxin, which is Botox. We have incobotulinum toxin, the trade name is Xeomin. We have abobotulinum toxin, the trade name is Dysport. And then we have a type B. All the first three are type A neurotoxins, and then we have one type B, which is rimabotulinumtoxin, and the trade name is Myobloc. We have one that was just recently FDA approved, which is daxibotulinumtoxin. We haven't used it yet because it has yet to be commercially available, although already approved. So we'll have five in total in the next few months. But for now we have four.

Glen Stevens, DO, PhD: And the mechanism of action are the same for all of them or do they vary? Can you tell us and go through the mechanism of action?

Hubert Fernandez, MD: What a kind of a tamed botulinum toxin does is it prevents the contraction of muscles where it is injected. And so the muscles consequently relax and maybe weaken if it's too much of a dose. And all four toxins really work on the same mechanism except that they bind with a different complexing protein. The net effect is very similar.

Glen Stevens, DO, PhD: And they all work at the neuromuscular junction, I take it?

Hubert Fernandez, MD: Yes.

Glen Stevens, DO, PhD: So I don't know if there's any good anecdotal stories with the first person that ever decided to inject these medications, but the person must have been pretty nervous injecting botulinum toxin into someone for the first time.

Hubert Fernandez, MD: From the historical perspective, the very first indication of botulinum toxin was for strabismus in children. So these are children who had a lazy eye or they looked a different way from where they intended to look. And the first doctor who ever used this really was trying to develop ways of correcting the gaze, the primary gaze, to make sure that they look normal other than surgery. So by relaxing the muscle, it is able to correct that. And so at that time, the name of the botulinum toxin was oculinum for eyes, ocu meaning eyes. But then that was the start. But now it's used in pretty much almost any skeletal muscle in the body. We are able to use it to relax it.

Glen Stevens, DO, PhD: And Francois, anything else to add to this in your area?

Francois Bethoux, MD: It is actually very similar to what Hubert just said. We have the same toxins available. Only one of them, the famous toxin B actually has not been approved by the FDA in the US for the treatment of spasticity. But otherwise, the mechanism of action is the same. The doses may be slightly different. So I treat patients with spasticity after a stroke, or MS, or with cerebral palsy, and they tend to require higher doses of the toxins to tame their tone, their spasticity. But other than that, there are really no major differences in the mechanism of action or the approach we take.

Glen Stevens, DO, PhD: So if you watch TV these days, you'll hear these terms used all the time, people using botulinum toxins. So I think within the general public, they're quite comfortable with it. I'm sure that was very different many years ago when they first came out. But are they dangerous, Hubert?

Hubert Fernandez, MD: Well, they can be. Of course in the wrong hands at the wrong dose, they can be. In fact pound for pound, botulinum toxin is the world's most powerful toxin. Thankfully it's very difficult to be used as a weapon of mass destruction because it's not through the air. It has to be injected and it's not contagious or infectious. So it is a very individual dosing mechanism. But if you give too much, then you could really paralyze and weaken the entire body. And there have been unfortunate instances where the calculations have been off or a horse strain or an animal strain of botulinum toxin because horses also can benefit from this, race horses, for example, when they have a muscle contraction. So people that are trying to save money and recycle those for human consumption, and if you're a decimal point off, that could be dangerous.

Glen Stevens, DO, PhD: Francois, anything else to add to that in terms of toxicity?

Francois Bethoux, MD: I would concur that from a perception standpoint, I can remember that before, botulinum toxin was used for wrinkles and the after. Before I had to do a lot of explaining to convince people that yes, it is a toxin, but when we use it properly, it is overall safe and we know how to minimize the risk of side effects. After it became a household name, basically I had much less convincing to do. Actually, I have to remind my patients that it is a toxin and actually no, their arm or leg is not going to look 10 years younger and there could be side effects. So it's a very different approach.

As far as the risk goes, some of the risks could be dose dependent, so the higher the dose and maybe the higher the risk of some side effects. Again, in my patient population, we tend to use pretty high doses, so we have to keep this in mind. The location, of course, you can imagine that an injection not too far from where the swallowing muscles are is more at risk of causing swallowing problems even though some of the side effects are really remote, like I could possibly inject in one arm and have remote effect in a totally different part of the body.

Glen Stevens, DO, PhD: Hubert, your duration of the effect?

Hubert Fernandez, MD: Well, the standard duration of effect that we aim for is 90 days. And in part that is a regulation that insurance will not really pay for anything sooner than 90 days. And so we try our very best to make it last and find the dose that will keep them happy for 90 days, but not too high of a dose that will make the limb or whatever body part, too weak for them. So it's a balancing act. Now the newest FDA approved botulinum toxin may last longer than 90 days, but this is yet to be seen, yet to be published, and also experienced by clinicians.

Glen Stevens, DO, PhD: Is there an antidote if patients receive too large an injection?

Hubert Fernandez, MD: That's one of the limitations is that we don't really have an antidote. Fortunately, they don't last forever. As I said, the effect hopefully lasts for three months and then it wears off. And so if the patient inadvertently got too high of a dose, we have to simply wait, wait it out until their muscle function recovers. And then at the next injection we know better and we're going to reduce that dose.

Glen Stevens, DO, PhD: But of course, if we start looking at drugs with longer half-life, greater risk.

Hubert Fernandez, MD: Yes, there is a pro and a con for every advantage.

Glen Stevens, DO, PhD: So tell us the disorders that you treat and then we'll go to what Francois is treating. What are the common disorders you're using botulinum toxin for?

Hubert Fernandez, MD: Sure. I am a movement disorders neurologist, so I treat patients with abnormal movements, those who move too much or who move too little such as Parkinson's disease. So the major indication for botulinum toxin in my area is a disorder called dystonia, D-Y-S-T-O-N-I-A. It is a disorder, a general disorder where two muscles that are supposed to be complementing each other are actually fighting each other. And so it results in an abnormal posturing of that body part and virtually any body part could be involved. And so the most common form of dystonia is the neck dystonia called cervical dystonia. That's the most common focal dystonia, so that's our biggest indication. But the eyelids can also be dystonic and that's called blepharospasm. The wrist muscles can also be dystonic. It's called writer's cramp, and then other body parts and pretty much any body part could be dystonic, but it's also used by my colleagues in other muscles. It's a very good treatment for chronic migraine, so we inject the scalp muscles for that. It's used by the urologists for hyperactive bladder and Francois uses it for his patients, so he'll tell you about that.

Glen Stevens, DO, PhD: Well segue over to you then, Francois.

Francois Bethoux, MD: Very nice segue Hubert, thank you. I would say there's significant overlap between the patients that Hubert treats and the ones I treat. I tend to focus more on people who have spasticity. I guess the main difference between spasticity and dystonia is that spasticity often comes from significant damage to the brain or the spinal cord, and so often along with the spasticity, which is that tone. And that tone tends to be, I would say more fixed in a way than the dystonia, but there's also weakness along with it.

So imagine injecting with a toxin that can potentially cause weakness, somebody who already has weakness. So that extreme care given to the person's goals and making sure we don't inject the wrong muscle that would result actually in a loss of function, even if it's only for a few weeks, that would be devastating to the patient, obviously. And my patients tend to have a disability, and so they are also more frail in general. So combined with the fact that they tend to require a higher dose of the botulinum toxin, we have to be careful, carefully assess the goals and really individualize the treatment plan. That's really what we do.

Glen Stevens, DO, PhD: Do you utilize EMG for placement of your botulinum toxin?

Francois Bethoux, MD: Yes. Yes, it's recommended by the FDA and now it's widely accepted in the field that the injections are safer and more accurate if we use some form of guidance. So it can be EMG, it can be electrical stimulation where we stimulate the muscle to see it contract before we inject it. And also one mode of guidance that has gained a lot of traction is ultrasound. So we literally visualize the muscle and we can visualize the botulinum toxin going into the muscle, which really guarantees 100% accuracy in the injection.

Glen Stevens, DO, PhD: Hubert, do you guys utilize these techniques?

Hubert Fernandez, MD: Yes, in our field I would say some still do anatomical localization meaning no guidance, no external guidance other than the anatomical landmarks of the body. I think for some indications, that might be okay. But it is clinician's preference. And so at our center we do at the very least, EMG guided botulinum toxin. So the muscle involved emits a certain sound, and so when we hear that sound, then we are assured that this is the right muscle and we inject. But even better than hearing, at least in my opinion, is seeing the muscle itself and seeing the needle and seeing the botulinum toxin spread within that muscle. And so at least for my own practice, I have mainly transitioned already to ultrasound guided botulinum toxin injections, but this is not for everyone. There is some technical expertise and a little bit of lag time that is required for ultrasound guided botulinum toxin injections. So it takes some practice before one becomes efficient with it.

Glen Stevens, DO, PhD: So Francois, you kind of intimated this earlier that if someone's already so weak, if you give them botulinum toxin, you could worsen that weakness and then that could affect their ability to ambulate. But who's a good patient for you? How do you define a good candidate for neurotoxin?

Francois Bethoux, MD: It is a great question. Basically, somebody first who has spasticity, there's a clinical diagnosis there. We have to ensure there is spasticity present and then that spasticity causes a problem that we can improve by injecting botulinum toxin. I know it's very vague as a definition, but to give you the range of patients that I treat, I just injected a patient who actually is able to run long distances but does have spasticity, and I have patients who are wheelchair bound or possibly bed bound and that benefit from spasticity. So the range is very wide. It's really about the goals to say this is where spasticity causes a problem. And often unfortunately, it's several muscles and we think that by relaxing these muscles but leaving the others alone, then we can help that person be more comfortable or be better positioned or be easier to care for if they need a caregiver or also function better, move better. As Hubert was mentioning, some muscles with spasticity tend to contract at the same time when they should nicely collaborate with each other. If we can relax one, then it could lead to better function as well. So quite a great range of possible advantages. Again, being careful about the potential side effects.

Glen Stevens, DO, PhD: And how many treatments would somebody require before you might say they're not going to get a response? Do you treat them once, if they don't get the response that you figured you would treat them a second time and if not, then you wouldn't continue?

Francois Bethoux, MD: It's a rule I've built over time. So if there is absolutely no response, which honestly is pretty rare, if there's absolutely no response twice and I'm sure I've hit the right muscles, then I say it's probably not going to be helpful for you. I don't want to just inject and cause pain for no results. But if there is some improvement, then every time we meet with the patient again, we try to refine it. And at the end, honestly, the patient will be the judge, either benefit enough to warrant repeat injections or not. So we do have quite a few patients who come back for more injections over several years, but I'm very careful about this is an expensive treatment. This is also a treatment that requires causing pain to someone by injecting. So I want to make sure that it is worth doing and repeating over time.

Glen Stevens, DO, PhD: Hubert, any additional thoughts?

Hubert Fernandez, MD: Well, from the dystonia standpoint, the more targeted the muscles are, that is the more ideal the patient is. So because obviously there is only a limited amount of dosing that we can inject that is within safety guidelines. And so the more we can focus on a group of muscles and the lower the dose that can be used for that, the better. You'll have patients, for example, with what we call generalized dystonia, when the whole body is twisted like a pretzel. That's not a good candidate because they will require botulinum toxin injections for the entire body, which will be above the required safety limit. So the more focused the muscle groups that we need to target, the more ideal it is.

And also this is where the art and the science blends together because you want to give a dose that is sufficient enough to work but not too high to cause weakness. So we have to start somewhere. The general rule is we start on a lower dose and then when we see them again in three months for their next injection, we review the response and if there is room for improvement, we increase. If there's a side effect, we decrease. If it's just right, we stay on the same dose.

Glen Stevens, DO, PhD: Francois, you mentioned the injections can cause discomfort. How much discomfort is there?

Francois Bethoux, MD: It's a needle in the muscle and not only just a needle in the muscle, but that muscle is tight, may actually spasm around the needle. And sometimes also the area is hypersensitive because of the brain damage or spinal cord damage. So immediately there may be some amount of pain. We do everything we can to minimize that pain. Sometimes people can take a medication they take for common pain beforehand, we can use a cold spray to numb the skin. So we do take precaution to diminish that pain.

And then similar to what happens when we get a flu shot or other immunization, the muscle can remain sore for a few days. And so again, generally this is temporary for a couple of days and also can actually be treated with common treatments for pain that everybody would take. To me, it generally is not a tremendous amount of pain. Also keeping in mind that the medication does not kick in right away. It takes about a week to kick in. Sometimes the patient may see some of these temporary side effects first before they see the benefit. So I encourage them to be patient and see how it unfolds over a period of two to four weeks.

Glen Stevens, DO, PhD: Well, like a lot of things that we do, education is the most important in a lot of ways. So Hubert, you mentioned multiple different formulations for botulinum toxin. How do you decide which one to give? Is it what their insurance will cover?

Hubert Fernandez, MD: Well, sometimes it'll come to that. The good and the bad of this is that most of the medications that are FDA approved for botulinum toxin, they have been compared to placebo. And so they have been shown with class one evidence that they work but not against each other. So we do not have a dosing equivalence between one toxin to another, and we have no evidence of consistent superiority of one toxin over the other. So I guess the good effect or consequence of this is that the clinician and the patients can decide together which one would be the most cost-effective for that patient and his or her situation.

Glen Stevens, DO, PhD: Do you ever switch to a different drug?

Hubert Fernandez, MD: Sometimes. Sometimes. Just like any drug, for example, you'll have a patient who likes ibuprofen, but another one like Naprosyn, although they're very similar, they have a preference. So occasionally you will have a patient who responds better to one or another. In general, botulinum toxin type A medications are all very similar and you have one that's type B. So in theory, if one develops partial or complete resistance from type A, which is now very rare because we have our production processes much more refined compared to the early 1980s, you could shift them. We are able to shift them to a type B and then they have a good response and vice versa. If we start with type B and their response starts waning off after several months or years, then they could be in theory injected with type A and they'll have a fresh kind of response to that medication because it works in a different ... It binds a different complexing protein.

Glen Stevens, DO, PhD: And is a resistance antibody directed?

Hubert Fernandez, MD: Yes, it is an immune resistant. This has been a lot more documented and is more common in the early 80s up to the early 90s, and after that the purification process has been so much improved that the incidence of immune resistance is really less than 5%. And so at our center, we actually see a lot of "botulinum toxin failures." And so we see them because their clinicians think that they develop immune resistance. And from our experience, far and away, when someone comes in our clinic for botulinum toxin failure, the major reason is the wrong dose was injected at the wrong muscle. And if you get the right dose and the right muscle, usually they will respond.

Glen Stevens, DO, PhD: So I've decided that I'm going to go do a weekend course to learn how to inject toxins. How do I get certified to do that? Can I do that type of a thing? What's the process? Francois?

Francois Bethoux, MD: It's very interesting because there is not, to my knowledge, an official certification, like a board certification for botulinum injections. There are many, many workshops, some given at national and international conferences, others given separately. So there are many opportunities to get trained to the correct technique and muscle selection. Of course, there's a lot of clinical training that's given during residency, during fellowship, which is very important because that's where we learn who are the good candidates. As we were discussing earlier, which muscles are the best, what doses are more appropriate, or that experience through actually clinical practice. So there are many opportunities and I see more and more interest actually from physicians in training and physicians who are beyond their initial training to do that. And I think that's great.

As Hubert mentioned, the indications for botulinum toxin have grown, which is as always a blessing and not so much of a blessing at the same time because now I have patients who may get botulinum toxin for migraine, spasticity, and their bladder and the FDA wants us, and rightfully so, to consider the overall dose that they're getting between the three indications. And that can run the doses to a pretty high range. And so the downside of more indications and more specialists doing these injections is that we have to be even more mindful about proposing it because we don't want to create another dangerous situation.

Glen Stevens, DO, PhD: Hubert, anything else to add on your side?

Hubert Fernandez, MD: I think the danger of not having a uniform certification of this, a clinician doesn't need an exam that they have to pass or a minimum number of procedures like surgeons would have to do because of the lack of that standard procedure. It can be the Wild West out there. And so patients will need to be very diligent about asking their doctors, "How many have they done? Is this what you do for a living?" And assess really the comfort level of that clinician. There are clinicians that might be doing more than they're comfortable with and others are very comfortable, but they're very conservative and they want to do less even if they're actually fully trained for it. So finding the perfect fit is a homework for the patients for sure.

Glen Stevens, DO, PhD: Is certification coming or you don't see it?

Hubert Fernandez, MD: We don't see it because the indications are just growing, but there are some guidelines we could certainly recommend for patients. So it depends on the indication. If your indication, for example, is you want to consider botulinum toxin for spasticity, then you might want to see a physiatrist, a rehab specialist for this because this is what they do. If they have dystonia or a movement disorder, then you want to see a movement disorders neurologist. The eyes. So a lot of eyelid twitching is a shared indication for both the ophthalmologist and the neurologist. So it really depends. And of course for wrinkles, it'll be the dermatologist or the plastic surgeon. So the indication sometimes guides the patient as to where to go.

Glen Stevens, DO, PhD: So it looks like we're getting towards the end here, but what's on the horizon? I know you mentioned maybe a longer acting botulinum toxin. What else? For spasticity, for dystonia?

Francois Bethoux, MD: I think we're all very interested in potentially longer acting toxins because again, thinking of my patient population where they have a disability, difficulty traveling to an appointment. If we could have fewer appointments for injections during the course of the year, that is absolutely not trivial because it's often a hardship and a considerable expense for them.

Other than that, I'm very excited that we're looking more and more at how these botulinum toxins not only relax the muscle because we know now, it's been proven again and again that they do relax the muscles very well. But the real goal is not that. The real goal is does it make the person more comfortable? Do they function better? It's actually evidence that is hard to gather. And I see more and more studies, and I think that if we can figure out how to combine, say, botulinum toxin rehabilitation, sometimes even more cutting edge procedures like deep brain stimulation you could imagine, or other procedures to maximize the level of function, then that will really be progress in our field and we'll know which patients are more likely to benefit. So it's not going to be just personal experience. Right now, as Hubert said, we have guidelines which are already great, but then in the future I think we'll be way more targeted because targeted medicine is really on the up and up and rightfully so.

Glen Stevens, DO, PhD: Hubert?

Hubert Fernandez, MD: Yeah, I probably would just add, we continue to learn how to properly use botulinum toxin. The indications are ever so expanding. This is like a new frontier being discovered every so often, and not only for neurological disorders, but for other things. We also need to still learn how to compliment botulinum toxin with our medications. It is also being used prior to operations, prior to say, at least in being investigated in preoperative low back pain, for example, to hasten the recovery postoperatively. And so there's a lot of investigations coming along, and we're really excited about that.

Glen Stevens, DO, PhD: Francois, final takeaways?

Francois Bethoux, MD: I would say to summarize what I've said, basically again, it's a great treatment option, and it just again requires, as Hubert said, the right dose in the right muscles, but also the right treatment plan. In my practice, botulinum toxin is rarely the only treatment. And so to ensure success, we often pair it with physical or occupational therapy, also exercise and stretching done by the person or with the help of their family or loved ones. So it's really like a whole treatment plan where we engage the person, the patient, as the most important part of the team. And so that's really the message I try to carry to my patients. It's not the magic cure. It's a great treatment for the right patients and in the right management plan. I would say that's the way I would summarize it.

Glen Stevens, DO, PhD: Hubert, final comments?

Hubert Fernandez, MD: Yeah, just to second the statement that botulinum toxin injection is a very individualized treatment. We have four and soon five makers and drugs to choose from and choosing which one to use over the other requires some expertise. It only works if it's at the right dose and at the right muscle and at the right indication. And so this is a treatment where the art blends with the science, and therefore patients should really find the most comfortable and clinically trained injector before they subject themselves into this treatment.

Glen Stevens, DO, PhD: Well, Francois and Hubert, I appreciate all your insights and expertise in this area. Thank you very much.

Hubert Fernandez, MD: Awesome.

Francois Bethoux, MD: Thank you.

Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.

Neuro Pathways
Neuro Pathways VIEW ALL EPISODES

Neuro Pathways

A Cleveland Clinic podcast for medical professionals exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neurorehab and psychiatry. Learn how the landscape for treating conditions of the brain, spine and nervous system is changing from experts in Cleveland Clinic's Neurological Institute.

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