Managing Peripheral Neuropathy after Transplant
July 16th, 2020
Presented at the Celebrating a Second Chance at Life Survivorship Symposium 2020
Presenter: Sasha Knowlton, MD, Assistant Director of Cancer Rehabilitation, Massachusetts General Hospital
Presentation is 28 minutes with 14 minutes of Q&A. Download Speaker Slides
Summary: Evaluates the risks for developing neuropathy after transplant, and strategies to manage the weakness and pain associated with neuropathy.
- Peripheral neuropathy, caused by chemotherapy, is very common after transplant.
- The risk factors for making the neuropathy worse are smoking, poor kidney function and diabetes.
- Neuropathy should be managed by a physiatrist, neurologist, or neuro-oncologist.
- Nearly 1 in 5 who develop neuropathy from chemotherapy will experience a fall.
- Duloxetine has been found to be the most effective drug treatment.
- Exercise is very important for managing neuropathy and pain associated with it.
01:57 Neuropathy is damage of the peripheral nerves and affects how nerves feel sensation, and their ability to tell where the body is in space.
06:55 Typical symptoms of neuropathy include burning or stabbing pain, hypersensitivity, and numbness.
08:17 Goal of treatment should include pain management, maintaining independence and or vocation.
10:05 A typical evaluation should include evaluation of sensation, balance, and strength.
13:04 Chemotherapy agents that cause neuropathy include platinum agents, Taxol and many more.
18:33 If a patient experiences increasing neuropathy while taking chemotherapy, the oncologist may be able to reduce the dosage or frequency of the chemotherapy treatment.
24:00 Talk to your doctor before starting an exercise program. A personalized exercise plan is key to prevent injury. All medications and conditions should factor into the physician-prescribed exercise plan.
25:15 Working with a physical therapist can help address balance and dexterity.
26:20 Proper training with a physical therapist is needed before using a TENS unit for sensation issues.
27:08 Compression socks, braces or ankle foot orthotics can be helpful for those experiencing foot drops or who have the inability to tell where their feet are in space.
27: 20 Canes, walkers, and rollators are extremely helpful to prevent a fall.
Transcript of Presentation
00:00 [Moderator] Speaker Introduction: Welcome to the workshop, Managing Peripheral Neuropathy after Transplant. My name is Sue Stewart and I'm the Executive Director of Blood & Marrow Transplant Information Network, and we are your hosts for today.
It is my pleasure to introduce to you Dr. Sasha Knowlton. Dr. Knowlton is an instructor and the Assistant Director of Cancer Rehabilitation in the Department of Physical Medicine and Rehabilitation at Harvard Medical School. She is board certified in physical medicine and rehabilitation. Dr. Knowlton's interests include cancer rehabilitation with a goal of improving the function and quality of life of cancer patients during all aspects of cancer treatment and survivorship. Please join me in welcoming Dr. Knowlton.
00:51 [Knowlton] Overview of presentation: So, thank you for that kind introduction. I'm happy to be here today with all of you virtually. And today I'd like to talk to you about the number one diagnosis that I see and treat as a cancer rehabilitation physician, which is often known as a physiatrist. And, so, my introductory slide is entitled, What You Need to Know about Chemotherapy-Induced Peripheral Neuropathy, otherwise known as CIPN. So, I do not have any disclosures other than I work at Mass General, a Spaulding Rehabilitation hospital and Harvard Medical School.
So, in terms of the overview of this talk, first what I'd like to do is really define what, exactly, is chemotherapy-induced peripheral neuropathy. There's a lot of misnomers out there, there's a lot of misunderstanding about what this diagnosis actually is. And, so, I hope to give you a better understanding of what it actually is.
I also, want to review with you the risk factors of CIPN or chemo-induced peripheral neuropathy, the prevalence of it, and the common culprits [drugs that often cause neuropathy] of it.
I also, want to discuss the symptoms of it and also, review treatment strategies.
01:57 What is neuropathy? And so, to start off, I'd like to get back to the basics, and for those of us who don't have a medical background, really explain what is neuropathy. Neuropathy breaks down, essentially, to disease or damage of the peripheral nerves. Nerves allow us to feel different sensations, whether that's hot sensation, cold sensation, pain, soft touch, or light touch, the ability to tell where a body is in space, which is also, called proprioception, and I'll get back into that a little bit later on.
Additionally, it allows us to move our muscles, and it also, controls our autonomic system, which includes our blood pressure, heart rate, and other autonomics.
This diagram demonstrates to you, in a cartoon fashion, what a neuron looks like. These are the little tiny microscopic structures that form the backbone of the peripheral nervous system. As you can see, there are different components. There's the cell body. There is the axon where the nerve signals jump from one to another to pass along through the nerves.
03:01 So, how common is neuropathy after chemotherapy? Well, this was a study done a few years ago, but overall it showed that after completing the last cycle of chemotherapy for the common culprit [the drug that may cause neuropathy], overall, almost 70% of people experienced some level of neuropathy. Three months after completing the last cycle of chemotherapy, that number dropped to 60%. And even at the end of six months, 30% of people who had had chemotherapy, that included one of the common culprits, so, to speak, up to 30% of them experienced some form of neuropathy. So, as you can tell, it is quite common.
03:40 What are the risk factors for peripheral neuropathy? So, really it breaks down to, how much at risk are you for development of it? Do you have a baseline neuropathy?
And surprisingly, chemotherapy-induced peripheral neuropathy is not the most common cause of peripheral neuropathy. Diabetes is. And, so, if someone has a history of diabetic neuropathy, then they're more likely to develop symptoms of worsening neuropathy during chemotherapy or afterwards. Additionally, unfortunately, the more life experience you have, or the older you are, the more likely you are to experience neuropathy.
If you're a former smoker or if you're currently smoking, that also, puts you at higher risk of developing neuropathy. Decreased creatinine clearance, an overall reflection of your renal function or your kidney function, also, plays a factor. The worse your kidneys are, the worse the chances of you developing neuropathy, unfortunately.
And also, if you develop some sensory changes during chemotherapy, for example, if you develop numbness or tingling in your fingertips or toes, then that also, makes you at higher risk for developing chemotherapy-induced peripheral neuropathy.
So, why does it happen? Overall, people aren't really sure to be totally honest. It does have something to do with the axon, as I demonstrated to you. It also, has something to do with the myelin as I demonstrated in the prior diagram. But overall people, aren't really sure why some people are more susceptible to it than others. There has been a lot of research into how each of these chemotherapy drugs does cause neuropathy and which parts of the neuron it affects and whatnot, but overall, why it happens, people aren't 100% sure and there's lots of ongoing research.
05:22 Symptoms of neuropathy: So, overall, in terms of the symptoms of neuropathy, people generally can either develop an acute or slowly progressive onset and symptoms. And what does that mean?
Sometimes people will wake up one morning and they've got significant neuropathy in their feet and hands. But more generally, they develop what's called a length-dependent phenomenon whereas people will start to develop symptoms first in their toes, followed by creeping up towards their ankles. And then when it gets to about the mid shins, they'll start developing symptoms in their fingertips.
Generally it's a slow process. Like I said, some people do wake up and they have significant symptoms overnight, but overall it tends to be more of a gradual process.
And this is a question that I ask of my residents when they rotate with me, but just to give you a better idea of why sensory nerves, the nerves that allow us to feel things, are affected more than the motor nerves or the nerves that allow us to move our muscles.
Why do we experience more sensory changes rather than weakness? The reason is based on our anatomy. And that's because the cell body, that big lobe, what I showed you before in that neuro diagram, is located in the dorsal root ganglion, which is outside of the blood-brain barrier. The motor nerves, and this might be getting a little bit too technical, the cell bodies for those nerves are located inside the blood-brain barrier. So, they have an extra layer of protection, whereas the sensory nerves, unfortunately do not.
06:53 Positive and negative symptoms of neuropathy: And so, what do people develop? When people come to see me in clinic, and like I said, this is probably the number one diagnosis that I see and treat, I typically explain to them that there are positive symptoms and negative symptoms of neuropathy. And what do I mean by that?
So, when I talk about positive symptoms, I talk about things that unfortunately are added on to your experience with neuropathy. Typically, the most common thing is pain. And that pain can be described as a burning pain, a stabbing pain, a shocking pain. It can be described as a hypersensitivity.
So, if I touch a foot or if I touch a hand where it's affected, people tend to jump back because the area's really sensitive, when just touching with my fingertip or touching with the cotton swab really shouldn't be painful. They can have tingling and it can also have a sensation of stickiness or cramping.
When I talk about negative symptoms, it means things that are lacking. So, in the sense of sensory, when you have lack of sensation you experience numbness. When you have the the inability to sense where your body is in space, the fancy word for that is called proprioception, and there's ways to test that on exams, your balance is affected. So, you have lack of the ability to tell where your body is in space. You can also, have lack of strength, which is weakness. And a lot of times, unfortunately, risks we have are foot drops.
08:17 Clinical evaluation: When I see patients in clinic, and anyone who's seen me before can attest to this, I spend a lot of time talking with patients. I want to get a good understanding of what their symptoms are. Are they experiencing pain? What type of pain are they experiencing? Are they experiencing hypersensitivity? Are they experiencing numbness? Is their balance off?
And why do I care? Because I want to treat it adequately because they care about pain management of course, but I also really care about their functional status.
And, unfortunately, a lot of times when I see people in clinic and I start asking really detailed questions about functional status, it's a self-realization. They'll say, "Oh yeah, now that you mention it, my balance has been off a bit since I started experiencing neuropathy," or "I do have more difficulty with buttons and zippers and other fine motor tasks. My handwriting is worse. I am dropping things more." And functional status, for me as a rehab physician, is really important because I care about maintaining people's independence and keeping them going at what they like to do vocationally and aid vocationally as much as possible.
I also, want to get a good understanding of comorbidity. Like I said earlier, the number one cause of neuropathy is not chemotherapy, it's actually diabetes. Is there undiagnosed diabetes lurking in their history? Is there a strong family history of it? And, unfortunately, I have diagnosed a few people with nuance of diabetes as a result of testing. And is there a family history of any neuropathy or neurologic diseases? Because sometimes that can contribute.
Tests for sensation: In terms of the exam, when I'm examining someone, in terms of a neuropathy evaluation, I check their sensation and there's different aspects of the sensational tests. There's light touch, there's pinprick or the sensation of pain. You can also, test temperature. You also, want to check balance and see how someone is walking. Because a lot of times people will develop a more protected gait because they can't sense where their body is in space. Again, going back to that proprioception piece of information, it sets them up at risk for falls.
Also, I check their strengths. And too, I may also, refer them for a nerve conduction study or an EMG which is demonstrated here in this picture, to see how severe the neuropathy is. My exam, I can detect a lot of things, but in terms of the severity, the EMG or the nerve conduction study is really the best test.
10:54 Diagnosing neuropathy: Overall and I tell people this all the time, it's a diagnosis of exclusion. There's no direct test to say with 100% certainty, "Your symptoms of neuropathy of numbness, tingling, burning, etc, are due to chemotherapy." Overall, I will send at least a screen of different tests, which includes looking for diabetes, looking for vitamin deficiencies or toxicity, checking the fibroids in addition to less common things, depending on what someone's history presents. If I send my screen and the story doesn't add up 100%, then a lot of times I will often refer them, the patients, to my neuro-oncology colleagues to see if there's any other lab tests that I'm missing ,just to make sure we completely exclude anything else because a lot of times those things are treatable and I want to make sure that we are treating things adequately.
And when I say that if someone has more of an atypical story, an atypical story is someone who had chemotherapy a while ago and had one of the common culprits [a chemotherapy that can cause neuropathy], which I'll get into in a bit. And had symptoms five years ago, and symptoms resolved. And over the past six months started noticing development of neuropathy. That's atypical. Chemotherapy-induced peripheral neuropathy is a time dependent thing. It usually starts within the first month or couple months after chemo and then hits a peak and then gradually starts to improve because the insulting injury or the chemotherapy essentially is stopped after completion of treatment and so, you're taking the offending agent away.
Things like diabetes are always there, unfortunately, high sugars are always there. Vitamin deficiencies or toxicities are there unless you treat them. Thyroid issues are there unless you treat them. So, when someone comes in years after completing chemotherapy and hasn't had any recent chemotherapy with symptoms, to me that raises a red flag that says this probably isn't chemotherapy-induced peripheral neuropathy, it's probably something else. Then why do I send this again? Because I want to treat it adequately. And in order to do that, I have to diagnose it adequately.
13:04 Which chemotherapy drugs cause neuropathy? So, here is a not inclusive an list but a pretty substantial list of the most common offenders. So, vincristine, platinum agents, taxol or taxoids in addition to others that are listed here, And there are others, like I said, but these are the most common ones. They each cause neuropathy in a slightly different manner and a lot of research is ongoing into this just because it's becoming much more recognized and much more prevalent with improved survival after cancer. And so, I'm sure more will be added to this list in time.
13:41 Who manages neuropathy? So, people like me, so, physiatrists, who are physicians. We are not physical therapists or occupational therapists, because I get that question a lot. We're physicians that do subspecialty training in a field of medicine called physical medicine and rehabilitation. And a lot of times a number of us who specifically work with cancer patients or cancer survivors, like myself, go on to do additional training and fellowship in this area. Neurologist or neuro-oncologists are also quite equipped to manage neuropathy.
14:14 Why care about neuropathy? Now, I alluded to this a little bit earlier. And the reason why you should care about it is because, as I mentioned, almost 70% of patients experience neuropathy a month after completing their last cycle. And six months out, so six months after completing that last cycle with chemotherapy, 30% of patients reported ongoing symptoms. So, it's prevalent, and unfortunately it's under-recognized to a certain extent.
And again, why care about it? Because it affects people's quality of life. When you're in constant pain or you're falling all the time because you have no idea where your feet are in space, or you're unable to button a blouse, or you're unable to find your name on a document, it affects your function and it affects your quality of life. And, also, because it sets you at higher risk for falls, it really affects your safety. And I was telling my patients, as a rehab doctor, I really care about safety. The last thing I want to happen is someone to fall, break a hip, hit their head, have a bleed, etc, especially after completing treatment for cancer.
And so, again, why care about it? So, there's actually been a number of studies published about quality of life after chemotherapy-induced peripheral neuropathy. And a couple of studies that I cited here were in colorectal cancer, but I think it, overall, represents what people experience.
People who have neuropathy from chemotherapy report a worse quality of life. And the more symptoms of neuropathy you have, the worse quality of life that means. Which really makes sense, because if you have pain, in addition to persistent numbness, in addition to weakness, in addition to fall, in addition to constant worrying about your balance, it adds up and unfortunately there've been studies on this that it does cause the worse quality of life.
In terms of function, not surprisingly, people with neuropathy from chemotherapy do worse on functional tests. When people's function declines, they unfortunately have a higher risk of falling. As I had mentioned, when someone has neuropathy and they're walking, you can tell right away, they walk wider, they walk slower. And that adaptive gait, which is called a conservative gait or conservative way of walking, results in more time with two feet on the ground, rather than one foot on the ground. And you can compare slow walking with running, in terms of the time of two feet on the ground versus one foot on the ground. And overall that results in increased fall risk.
And as I had mentioned, when people can't feel things, they can't feel where their body is in space, they have a reduced independence with activities of daily living. Activities of daily living are formally recognized as things like getting dressed, taking a shower, etc. And when you require more assistance with that, understandably, it's because you have worsening function and it can also, do a number on your quality of life.
17:12 Approximately 17%, almost 20%, almost one in five of people who have neuropathy from chemotherapy fall. There's an increased odds for falling by anywhere from almost two to three times compared to people who don't have a history of chemotherapy-induced peripheral neuropathy. So, it's a huge safety risk.
And who falls with chemotherapy-induced peripheral neuropathy? In terms of these numbers, almost 12% of people fall within three months. That's puts you at higher risk, as I had mentioned, things like the inability to tell where your body is in space or proprioception, if you're walking or your gait is affected.
And also, if you have foot drop. If you have foot drops, it caps your toes, and it sets you at higher risk for falls if:
- you have a higher total amount of chemotherapy
- you have a higher number of symptoms on certain scales, and there's a number of scales out there
- you've got more motor compared to sensory symptoms, motor meaning strength issues - and 27% of people with neuropathy from chemotherapy report functional impairment. I do think this number is maybe slightly under reported. But again, it's a pretty significant number.
18:33 How do you prevent neuropathy? So, another question I get asked all the time unfortunately, I'm a little bit late to the game as I tend to see people after they've already experienced neuropathy from chemotherapy, is, "Is there any prevention techniques? Or was there anything I could have done to prevent neuropathy from chemotherapy."
And short of saying, "Well, you could have prevented diabetes if you have diabetes or you could have gotten better control of your sugars or addressing the other risk factors," as I had mentioned earlier, the short answer is no. There's a lot of studies ongoing, the jury is out on vitamin E. There's one FDA approved drug, but there's very limited evidence that it actually helps or does anything. But there's a lot of ongoing research in this particular area.
When people start to develop symptoms during chemotherapy, a lot of times the medical oncologist will either do a dose reduction of the chemotherapy, so, overall reduced the administered dose, or they'll reduce the frequency of chemotherapy. So, keep the same dose, but space it out more. And if there is a contributing cause, as I have reiterated a few times through this presentation, treat the contributing cause.
19:48 How can you treat neuropathy? So, there's been a lot of research in this area and there was a practice guideline that came out six years ago now. But overall looking at all the drugs that are out there, the duloxetine was actually found to be the most effective.
Other antidepressants, including venlafaxine, amitriptyline, nortriptyline, can be used as well. But of course, everything has its side effects. And if someone's already on an antidepressant, you can't just add a second antidepressant. What I typically do is reach out to the prescribing physician and have a discussion about [the patient’s] history, etc, to see if they can switch over to duloxetine.
Another medication that has been studied and I do use is gabapentin. It used to be used as an antiseizure medication 30 plus years ago. Now it's used quite commonly to treat pain from neuropathy or neuropathic pain.
Pregabalin, there's a lot of commercials about this particular medication. Unfortunately, it hasn't really been shown to be all that helpful. I've used it in a couple of my patients and haven't found it to be helpful, so, I don't really prescribe it.
Topical medications can be helpful too. Medications like capsaicin, which is the active ingredient in hot peppers, can be helpful, but I strongly caution patients about using it because you do have to wear gloves and wash your hands really well after. Because the last thing you want to do is touch your face or eye after you applied this medication.
Topical lidocaine either as a cream, a gel, or a patch can be helpful. There are other mixtures out there, some of which have been investigated in research, and you can get them at compounding pharmacies. But I tell people with topicals, I'm happy to recommend them, but how they is work two-fold. One, the medication is the active ingredient, but also, the act of rubbing or applying the medication can be quite helpful, as well, as it's a massage technique.
So, in terms of other treatments, exercise is really, really important to treat neuropathy. It helps symptoms. The more exercise, the less the pain will be, the better your strength will be, you'll have a better ability to tell where your body is in space.
Anyone who's ever started practicing yoga realizes that, with practice, their balance gets better and better and better. And so, it's a good analogy for how exercise can help neuropathy. It also, improves quality of life, improves a number of other health factors, and it also, improves independence with activities of daily living.
There've actually been studies on this too, and they found that people who exercise during chemotherapy experienced less symptoms of neuropathy, and those who did experience symptoms experienced less severe symptoms compared to those people who were more couch potato like.
So, when I tell you to exercise, what do I mean by that? So, there are actually guidelines for people at all stages of cancer survivorship from the time of diagnosis forward. They were initially published back in 2010, so, 10 years ago now. The initial recommendations, which have since been updated as the end of last year, were to exercise at least 150 minutes of aerobic activity and include strengthening and flexibility exercises. So, in terms of updates, this was published at the end of last year, moderate to vigorous exercise was found to reduce cancer risk and symptoms. They upped the frequency a little bit, and 150 minutes or 30 minutes five times per week is a lot.
But I always tell people, reset the clock every week. If you didn't get it last week, try again this week. And the prescription recommendation is really to do it at least three times a week. So, not one 150 minute session, that would be a lot. But to break it up during the week and exercise for at least 30 minutes.
So, when I tell people to exercise, I try to write out a general exercise prescription. I try to highlight the recommendations, including the 150 minute mark, strength training session, flexibility session. But before you do any of this, before you start going out and start training for marathon, most importantly, you should be screened by a physician.
24:00 General Exercise Prescription: And why? You want to prevent injury. If you've had certain chemotherapy agents, if you've had treatments that affect your heart, affects your lungs, your exercise prescription is going to be different compared to someone else's exercise prescription. Additionally, if you have other heart issues, if you have lung issues, if you have what we call comorbidities or other diseases, it's important to really be screened to make sure that you are not going to hurt yourself.
Additionally, you want to tailor your exercise program to achieve your goal. For some people they want to get in better shape, for other people, they want to work on toning, for toning your muscles and getting stronger.
For people who are on chronic steroids, a toning or strengthening regimen is going to look completely different than for people who are not on steroids. Someone who's on a medication like a beta blocker for heart related issues, blood pressure issues, etc, isn't going to be able to achieve the recommended heart rate levels or target heart rate levels because that medication blocks the heart rate from getting too high. So, I can't reiterate enough, before you go out and start exercising, while I do recommend exercise, it's important to get screened by a physician.
25:15 Rehab interventions: So, in terms of rehab interventions, if I send you to a physical therapist, what are things that you're going to work on?
So, if the balance is off, first thing to start with is really what's called static standing, so, standing in one place, then adding some manipulation, then starting to walk, and then starting to manipulate while walking. So, you don't put the cart before the horse specifically. And working on walking training or gait training, strengthening in the legs, and the ability to tell where the body is in space, or proprioception, or other interventions that we can do as rehab professionals.
For people who have impaired dexterity or impaired fine motor tasks, hand therapy from specially trained occupational therapists can be helpful. What they do is strengthen the fine motor skill, re-educate the hands and fingers on how to do things, then, if needed, prescribe adaptive equipment.
Now not everyone has access to occupational therapists or has time to work with an occupational therapist. And so, I put this photo up here of knitting. I can't tell you how often I recommend my knitters to knit, my painters to paint, my sculptors, my pottery enthusiasts, to do their hobbies. And the reason why is all of those activities work on fine motor skills. For my grandparents that babysit their grandkids, I tell them they're going to put out Playdough and make all sorts of structures and sculptures with the Playdough. Playing with Playdough or clay is a quite common technique used by hand therapist as well.
So, other options, we have intervention desensitization for hypersensitive areas and TENS units or transcutaneous electric nerve stimulators that can also, be helpful. They actually sell these devices for TENS units on the TV or online. I do not recommend doing that. I recommend practicing it before you buy it. In other words, working with the therapist, trying out the leads, trying out the device before you go and spend money on it to see if it helps you.
Laser therapy, scrambler therapy are things that are being actively researched. No real recommendations right now, but there are trials to my understanding that are ongoing.
For some people who have foot drop or who have the inability to tell where their feet are in space, things like compression socks can be helpful and braces or ankle foot orthotics can be helpful as well. Ambulatory aids, although people don't like me talking about canes and walkers and rollators, can be extremely helpful, particularly for people who fall a lot. Like I said earlier, the last thing I want is for people to fall.
Additionally, acupuncture is getting a lot more research into it. I tell people as long as you don't have any bleeding concerns with the edema concerns, etc, I am all for trying acupuncture. I have no idea how it works. But if it works for you, great.
And lastly, just like a diabetic, it's extremely important to do regular skin checks. You don't want to step on a tack and not realize that. You don't want to have a nasty wound or sore that leads to all sorts of complications. So, regular skin checks are quite important as well. And with that, I will open it up to questions.
28:30 [Moderator] Thank you, Dr. Knowlton. That was an excellent presentation. I know I learned a lot and I'm sure others did as well. We have several questions if you'have a few minutes to answer them.
One person has asked, "Is there a way to tell if neuropathy in a specific area like a leg is from an old injury or from something more recent?"
28:53 [Knowlton] Yeah. Typically, neuropathy is bilateral, meaning it occurs in both legs rather than one leg. It can potentially occur in one leg, but through a physical exam, a physician would be able to decipher whether it's from a newer injury versus an older injury.
29:11 [Moderator] All right. Next question, you talked about laser therapy and scrambler therapy, can you describe those in a bit more detail?
29:19 [Knowlton] Sure. So, I'm probably not the best person to describe it to be totally honest. To be fair, I have not done a whole lot of reading on it as it's not yet recommended. There are, like I said, a number of trials that are ongoing. So, hopefully at a future event, I will be able to tell you more about them.
29:39 [Moderator] Okay. Another person has asked, "My neuropathy seems to be situated in my skin, what other areas of the body can be affected?"
29:49 [Knowlton] So, neuropathy can feel like it's in the skin. As I had mentioned, nerves allow us to do all sorts of things throughout our body, whether it's feel things, sensing, move our muscles, etc. So, it can really be affected all over.
In terms of neuropathy from chemotherapy, the textbook answer is that it typically affects the toes and feet followed by the hands because it's a length-dependent process and the legs are longer than the arms, and the longer nerves tend to be more susceptible to these types of injuries. But it can occur in other places as well.
30:30 [Moderator] Next question, are there any medications that you should not use once you've developed neuropathy?
30:37 [Knowlton] So, I have seen unfortunately, a couple of cases where people develop neuropathy, and right away are put on vitamin B12 and vitamin B6. That's not the right answer unless they have a vitamin deficiency. So, before someone is automatically put on those vitamin B supplements, they should have their B6, B12 levels checked because I have seen in a couple of cases where they came to me after being on these drugs and their vitamin levels were through the roof. And so, we had to go through a number of months weaning down those medications.
31:16 [Moderator] Another question, "Shortly after transplant, I developed neuropathy on the bottoms of both feet. I met with a neurologist who said it was not due to chemotherapy because the top of my feet were fine. He said chemotherapy-induced neuropathy would produce symptoms all around the foot. Do you agree?"
31:35 [Knowlton] So, good question. So, yes, typically neuropathy affects the entire foot, what's called a stocking glove distribution. But people's bodies don't always read the textbook. A lot of times people will say, "Oh, I only developed symptoms in my hand," but then when I actually do an exam on their feet, their feet are affected, too . And that's the reason why we pay attention a lot more to areas that we use more.
So, we tend to use the bottom of our feet more than the top of our feet because we're walking on them. We use our hands much more than our feet because we do things with our hands. And so, if there's something symptomatic in the hands, we tend to notice it before the feet. So, I respectfully question that as well because not everybody reads the textbook.
32:28 [Moderator] All right. We've had several questions, really, basically is the same question. And that is, how long does neuropathy typically last?
32:36 [Knowlton] Excellent question. So, I get this question all the time when I meet with patients. The good news is that neuropathy from chemotherapy does tend to improve. I give people a ballpark of 18 months to three years. And the reason why is because nerves regenerate. They don't regenerate in the same way as they did when we were two years old when our whole peripheral nervous system was fully developed with myelination. The central nervous system of the brain actually doesn't fully develop until much, much later, but the peripheral nervous system finishes its development around age two.
The nerves, they do regenerate. They regenerate all the way from the spinal cord, so, all the way up into your back, and have to reach all the way down into the feet. And so, they regenerate about a millimeter a day or an inch a month. And so, this is where someone like myself, who is short, has an advantage over someone who is tall because it's just a shorter distance for the nerves to have to travel.
Will symptoms 100% go away? That's a big, big question. It depends on which study you read and it depends on whom you ask. I will tell you, in my patient population through the years, there always seems to be a little bit of residual symptoms, it never fully goes away. But as time away from chemotherapy increases, symptoms do tend to improve.
34:07 [Moderator] All right. The next question is, "Can you explain what autonomic neuropathy is and whether it's reversible? I suffer from very low blood pressure spouts at different times, which make me very dizzy and I need to lie down."
34:22 [Knowlton] For sure. So, autonomic neuropathy is fortunately not something I see all that commonly in regards to chemotherapy-induced peripheral neuropathy. I don't, as I had said, really see those types of symptoms on a regular basis. Occasionally, will I refer someone? Yes. In those cases, I tend to refer patients just because I don't see it commonly at all. I do tend to refer them to my neuromuscular colleagues or my neurology colleagues for further assessment and workup. So, I'm sorry, I can't answer more of that as well.
35:04 [Moderator] All right. Next question, "I'm currently on a one milligram of prednisone and six milligrams of budesonide for GvHD. With exercise and diet, I hope that the neuropathies will go away. Will it help when I'm off of all steroids?"
35:20 [Knowlton] So, steroids as far as I'm aware, there hasn't really been any research studies really investigating the relationship with steroids and neuro recovery in this particular sense, which is neuropathy from chemotherapy. So, I don't think it really makes too much of a difference. I think what you're doing in terms of trying to exercise and eat right is more important than necessarily trying to get off the steroids as fast as possible.
35:53 [Moderator] All right. Next question, "Are there any supplements that you suggest taking for neuropathy in your feet?"
36:01 [Knowlton] No. As I had mentioned, there are some out there that I have seen some of my colleagues use, one of which is alpha lipoic acid. I don't know or have as much comfort using that particular supplement. I'm always of the mindset of, be more conservative and do no harm. And with a lot of supplements, they're not really regulated by the FDA and so, it's hard to say, compared to a medication, exactly how much for a particular supplement is in a pill. Like I had said earlier, unless you're deficient in vitamins, I don't recommend taking a vitamin B12 for this, or vitamin B6, or vitamin B1, etc.
36:46 [Moderator] Okay. Next question, Ryan says he had his transplant in 1996 when he was nine and started having migraines when he was around 11 years old. Are migraines an expression of neuropathy? Could the bone marrow transplant have caused these problems.
37:05 [Knowlton] That's a good question. Typically, we don't see neuropathy from chemotherapy as a migraine. Could there be other contributors as a result of your prior treatment? Yes. So, in that case, I would recommend maybe making an appointment with neurology.
37:25 [Moderator] All right. Next question, a questioner wants to know, "How does GvHD interact with neuropathy? Does it make it worse?"
37:35 [Knowlton] No. Not, that I'm ... I don't think there's been any research into that at all.
37:41 [Moderator] Okay. Scott is asking, "I have noticed that various nerves in my arms and legs fall asleep more easily than before transplant, but the problem is temporary whenever it happens. Is this an example of neuropathy?"
38:00 [Knowlton] So, no. That seems it would probably be more position-dependent or compressive mononeuropathy given that it's a certain position so, that it improves. More commonly neuropathy from chemotherapy is more of a persistent thing and not necessarily position-dependent.
38:22 [Moderator] Okay. Someone else asked, "Is sexual dysfunction in men an example of neuropathy?"
38:31 [Knowlton] So, the nerves that control sexual function can be affected, yes. There's lots of nerves that do control sexual function. I unfortunately would need to know more details to try to describe that a bit more. But there are other causes of sexual dysfunction, not just neuropathy itself, but actually higher up in the spinal cord. Sexual function is controlled by the sacral nerves, so, if there's an issue going on with the sacral nerves, that can also, cause sexual dysfunction from a nerve standpoint.
39:07 [Moderator] All right. Jean wants to know, "Can neuropathy affects a urinary tract? My husband finds it difficult to commence urination. Or is this likely from something unrelated?"
39:20 [Knowlton] So, again, I probably would need a little bit more detail. It may be related or it may not.
39:29 [Moderator] All right. Talal wants to know, "Once or twice daily, I get muscle cramps in my hand or foot and fingers with some pain. Is this neuropathy?"
39:41 [Knowlton] It could be. It could also, be more muscle related cramps. You can get cramps in the setting of low magnesium or other electrolyte disturbances as well. So, again, without more information, it's tough to say.
39:58 [Moderator] All right. Jennifer wants to know what the difference is between myopathy and neuropathy.
40:05 [Knowlton] Yep. So, neuropathy means disease of the nerves, myopathy means disease of the muscles. A lot of times they can mimic each other if there's weakness involved. Myopathy can also, be characterized by diffuse muscle cramps, muscle pain and profuse weakness, and may or may not necessarily have burning pain or numbness associated with it.
40:32 [Moderator] All right. Next question, "I've been in a wheelchair for three and a half years and have no sign of either neuropathy or myopathy going away. There have been slight improvements though. Could there still be hope?"
40:44 [Knowlton] Yes. As a rehab physician, I never lose hope, by any means, as I have seen improvements many, many years out. I think it's important to be connected with a physiatrist or a neurologist to make sure that everything that's being affected is being treated adequately. But I do think it's important as well to be realistic. The further you get out from an injury, the less likely it is that things are going to improve back to the way they were before injury. So, like I said, I think it's important to preserve hope, absolutely, and make sure that you're not missing anything at the same time.
41:29 [Moderator] All right. Next question, "I'm currently taking 10 milligrams of Revlimid 28 days, and I worry about the cumulative effect on worsening neuropathy in my hands and feet. Is there some lifetime limit or maximum dosage of Revlimid one should take?"
41:47 [Knowlton] So, that's probably not the best question for me, I would probably recommend that one of my medical oncologists answer that just because I don't prescribe the Revlimid.
41:57 [Moderator] Okay. And I believe that is our last question. Thank you, Dr. Knowlton. That was a very enlightening session. We thank you for your time. And I do thank everyone who submitted questions for Dr. Knowlton. I hope you found this presentation entertaining and interesting. And if you have any other questions, please don't hesitate to contact BMT InfoNet at help, H-E-L-P@bmtinfinite.org or by phoning us toll free at 888) 597-7674 or outside the United States at 847) 433-3313. Thank you and have a wonderful afternoon.
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