Practical Neuropathy Management with Dr. Marcus Pinto

Award winning educator Dr. Marcus Pinto joins us once again to give expert insight on neuropathy!

What do you do once you've made the diagnosis of neuropathy?

• why clear expectation-setting is important
• Practical steps to prevent falls and foot injuries
• Plus an evidence-based approach to neuropathic pain that focuses on realistic improvements

Transcript

Michael Kentris 0:05

Hello everyone and welcome back to the neurotransmitters. Uh we are continuing our chief concern series with part two of neuropathy. I'm joined today by my co-host, Dr. Galena Geikman. Galina, how are you?

SPEAKER_00 0:18

Hey Michael, thanks for having me back, and thanks for continuing the series. I'm doing well and I'm excited to keep the knowledge and learning going.

Michael Kentris 0:27

Yes, and we have a return guest, Dr. Marcus Pinto from Mayo Clinic, our neuropathy expert here with us today. So, Marcus, thank you so much for coming back. And uh we really appreciate you taking the time to talk with us more about your expertise in this area.

SPEAKER_01 0:42

Thank you, Michael and Galina, for inviting me back. Again, it's an honor to be here. And let's start.

Michael Kentris 0:48

Yeah, so Galena, fire us off.

SPEAKER_00 0:51

So, Marcus, last time you were here, you gave us like the complete landscape of neuropathy diagnostics from the questions to ask in clinic to the initial testing that you should and should not send. And so we thought we'd actually focus a little bit more on management this time, kind of dive in into, okay, so what? You've got the neuropathy, you've got the diagnosis, what can we do now? And how do you approach that in terms of, you know, talking to patients about it, educating them, but also what are the various elements in our armamentarium for managing neuropathy?

Safety Basics For Daily Living

SPEAKER_01 1:25

Yeah, I think it's a good way to start because neuropathy can be very frustrating for patients and for doctors. So we as physicians, we want to make people feel better. And uh we want patient symptoms to improve. And when we're talking about uh diabetic pediphone neuropathy, idiopathic periforneuropathy, inherited periforneuropathy, we are talking about probably three-fourths of the cause of neuropathy. I would say that around three-fourths, so three out of four patients with neuropathy, their neuropathy, you won't have any disease-modifying therapy available. So you won't be able to make them feel less paresthesia, less numbness, less chingling, and you're not gonna be able to make their sensation to improve. So it can be very frustrating. And I think that it's very important whenever you first see a patient with neuropathy and you do diagnostics, you diagnose then with neuropathy, you have diabetic neuropathy. And then you sit down with the patient and and and honestly tell them, you know, say, hey, now you have diabetic proof of neuropathy. And unfortunately, uh uh we do not have any magic pill to make your nerves to regrow, any magic pill to make your sensation to improve. And if you do have pain, then we're gonna talk about neuropathic pain management here, which is another important topic to discuss, because there is also so much frustration about neuropathic pain uh management uh for patients and doctors, and we're gonna talk later. And then doing the just general neuropathy education to the patient up front is very important because whenever you set up expectations, so then you know the patient feels better, the doctor feels better, your patient uh physician, you know, relationship, you know, keeps going well. And that's the first part of my when I diagnose someone. I there's not very often that I'm the first neurologist who see a patient with neuropathy, but sometimes it happens. And then I sit down with them and explain this uh first part to them. Then after I do this gender education, you know, it's also important to see, for example, are they falling from neuropathy? Do they have significant imbalance? So every patient who has falls and have a neuropathy, you know, I think they should be seen by a physical medicine and rehab specialists, you know, also a physical therapist, to see do they need a gate aid? What type of gate aid? Do they have a foot drop? Yes, or if they have a foot drop, they should be fitted for an ankle foot orthosis or AFO, so because that significantly impacts their ability to walk, that decreases false, you know, and false can be very dangerous for these patients. And the second thing that you I always talk to them, depending on their uh degree of sensation loss, is care of the feet. So, you know, diabetic patients usually know better because the endocrinologists are already educated on that, that they should always be looking at their feet every day, you know, front, uh, top, bottom, see there's anything sticking to it. Uh if the skin is very dry, use some cream, you know. Um and a care of the feet, fall prevention and general education of neuropathy. I think should be done in kind of every first neuropathy encounter.

Michael Kentris 4:41

You bring up an excellent point, and it's something I probably see like people as like the first neurologist, just because of like the neurology density in my area, further neuropathy. And a lot of times it's it breaks my heart a little bit because they'll say, like, oh, like what are you hoping to get out of this business? Like, I want you to fix memes. Like, I don't think that's in the cards for for what we likely have available. And so it is like a lot of what you're you're saying, counseling them, managing those expectations, and talking about like what are our our next, no pun intended, our next steps forward in terms of keeping them from developing any further comorbidities.

Metabolic Syndrome As The Driver

SPEAKER_01 5:16

Yeah, yeah, yeah. And the and this is a very important part, uh, Michael. And then you know, we I always talk with them about how to keep your nerves healthy. And then there is no specific diet for neuropathy, there is no specific supplement for neuropathy. It's very important to say out loud because given the frustration and the disappointment, there is a huge opportunity for people who want to steal your money, get advantage from you because you are desperate with just neuropathy that no one can fix. So it's very important for the patient, the doctors to know that laser therapy doesn't improve neuropathy. Putting your feet into vibratory kind of uh uh uh uh devices do not make your nerves to regrow or make your neuropathy better. Tense unit, scrambler therapy, that may help with your pain, and we're gonna talk about that in neuropathic pain management, but that does that not gonna make your neuropathy to improve, okay? So, and then talking about comorbidities is very important, especially if you have diabetic neuropathy or metabolic syndrome associated with neuropathy. And just before we go into, you know, it's very important to say there is growing evidence that metabolic syndrome is associated with neuropathy, mostly patients who have central obesity, and also patients who have high triglycerides. So the triglycerides have been strongly associated with neuropathy, and now they are hyperlipidemia, hypertriglyceridemia, central obesity, metabolic syndrome, they are considered risk factors for neuropathy. Okay, there is a growing uh concept, not very well accepted in the in yet in the neuropathy world, okay, that there is something called obesity-related neuropathy, right? Which is uh, and and that's why if you look at the pre-diabetes uh literature, right, and then there was uh even here where I'm from from Mayo Clinic, then my one of my mentors, you know, Dr. Peter Jick, the father, you know, was strongly against uh uh and even did a very nice work here showing that prediabetes doesn't cause neuropathy, which I think is correct, but it's not the prediabetes, it's what accompanies the prediabetes, what comes together with the prediabetes, which is the metabolic syndrome. And I disagree with Peter on that. Peter did not specifically look into metabolic syndrome, but I there is very strong evidence coming out from other places that I'm showing that uh obesity is in fact associated with neuropathy. And talking about diabetes, there's an important difference. Why? Because in type 1 diabetics, the DCCT and the 30 years of DCCT, DCCT, you know, for those who are not familiar, uh the pivoto trial post-New England Journal of Medicine, 1993, that showed that intensive glycemic control improves the microvascular complications of diabetes, prevents and also improves, you know, and neuropathy is one of the microvascular complications. So then uh controlling the blood sugars does help preventing the neuropathy of type 1 diabetics and also uh even can some patients improve symptoms in some other patients, and it can also slow the progression or stop the progression. But in type 2 diabetics, we thought this was the same, and it's not. So in type 2 diabetics, the evidence shows that the main driver is the metabolic syndrome. The hyperglycemia, yes, it can also have a modest effect in the patient developing neuropathy, but you probably have seen in your practice patients who have had an A with like a 7, 7 to 8 or something, they're not bad at diabetics, and they develop diabetic neuropathy, it's type 2 diabetics. And this is usually also because they have other comorbidities, they also have obesity and hyper epidemia. So then the comorbidities we're talking about, the importance of uh managing also, so there is no like class A evidence, like a randomized clinical trial showing that managing obesity, losing weight, and also working on lowering the triglycerides, improve neuropathy symptoms, or is low progression. But there is good prospective research studies showing what I just said. So we recommend to every patient who has proof of neuropathy and metabolic syndrome or diabetes that they should also work on their lipids with their primary care doctor. They should also exercise that is evidence, moderate degree level evidence that exercise, aerobic exercise, can improve uh neuropathic symptoms or slow progression of neuropathy. So, you know, usually people with neuropathy, because they have painful, if they have painful feet, they don't like to run, you know, some of them can't run. And also sometimes walking, the impact can make the pain worse. Walking, not gonna make neuropathy worse at all, but it can make maybe symptoms exacerbated and you can feel more. So, you know, swimming, like yoga, it's also a good one for even core. Yoga is not aerobic, but yoga can work with your core and your balance, it's important. So swimming and also cycling, you know, the elliptical, those can be used as uh exercise for people with neuropathy. And we also talk about diet. And the diet that is good for your heart is good for your nerves. A diet balanced, you know, fruits, grains, lean proteins, you know, avoiding junk food, um, uh using vegetables, you know, so everything is good for your heart will be good for your nerve as well.

SPEAKER_00 10:41

It's helpful to hear you say that as a neurologist and to give that counseling because I I think the same that some of my patients have told me that, you know, they get the diagnosis, but not so much the counseling. And I think we have a really important role to play, even if we're referring back and working in concert with our primary care colleagues, to say, like, hey, I really care about your diabetes, you know, as much as your primary care does, and really sort of try to emphasize the need for that management. And I do think while, as you said, frustrating that we may not be able to reverse it, I think trying, I always try to tell my patients that we can slow the progression, you know, we if we can control the the elements that are actually sort of the toxin to the nerve in this case.

SPEAKER_01 11:24

Yeah, yeah, that's very much true. You know, you we can we can try to correct the metabolic crisis that is happening in the nerves and also in your whole body, you know, and and controlling these risk factors for neuropathy, you know, also will hopefully and in some patients, you know, Galina, anadoctically, you know, they say that the symptoms improve, they feel less the parasitia, they feel less the pain, they you know, they uh feel overall they feel better. So I I highly recommend that to all my patients. And we also talk about you know that if they drink alcohol, so that alcohol is toxic to the nerve. We all know that. And some patients, for example, if they are drinking, there is no number for neuropathy, you know. So we use the same number that usually in general medicine, which is you should not drink more than two alcoholic drinks a day. But avoiding alcohol will be good for your nerves. Of course, if you drink eight beers a day, gosh, cut to four, maybe cut to two, you know. So, like anything you can do, because a lot of people drinking is part of their life. Some people are Somalias, you know, they they love wine and and they love the taste and all that. So it tells them, hey, now try maybe if you there is wine without alcohol, but these wines are not good, especially for just people who love wine. But uh the beer, you know, try of the eight you drink. Maybe you drink four that's you know, zero alcohol, or maybe all of them, you know, try something too. So I try to give uh the power to the patient and and tell them, empower them on what they can do to know to prevent a worsening of their uh neuropathy. And of course, you know, if they don't have diabetes, like avoid as much as you can developing diabetes, you know, uh also avoid gaining weight. If you can lose weight, you know, it's also disease usually good for neuropathy. And there are very nice uh kind of uh uh basic science studies done in rats, you know, showing that you know the the the obese rats, if they are put into an exercise program, they put in a low caloric diet, you know, it does uh reverse the metabolic problem in the accents and also in the neuronal cells and also in the schwann cells. Uh and so showing that there is very nice basic science evidence that kind of molecularly the change in the diet and the exercise, you know, um are impactful to the nerve health. So there is a nice research coming from the University of Michigan, you know, uh showing that there is uh one of my colleagues from the Periphen of Society, you know, Dr. Brian Callahan, Melissa Lafraze Eva Feldman, and also Stephanie Ige, they work with that. They put the little rats to do high-intensity interval training. And uh, yeah, so and then they then they get like a autopsy, sciatic biopsy of the rats, and show just very nice evidence. So just education is very important.

Lifestyle Changes That Protect Nerves

Michael Kentris 14:19

Excellent. I know you mentioned there's there's no specific magic pill. I I recall that uh some people, including myself, will recommend alpha lipoic acid to some patients. What's your opinion on that as a vitamin supplement alternative kind of thing for, especially like diabetic neuropathy?

SPEAKER_01 14:37

Yeah, yeah, Michael. Yeah, for diabetic neuropathy for sure, that's what we have the most evidence, you know. So it was very promising alpha lipoic acid, you know, in the 90s and also the early 2000s, especially, you know, in short term, and especially the IV form, which we don't use in practice. We use the oral, you know, 600 milligrams a dose. So I discussed with them, Michael. I tell them about the evidence. And as there is not much we can do for neuropathy, a lot of patients start taking, you know, especially those who like supplements, you know, to improve their health. It's not harmful, and it's also quite inexpensive they can buy off the counter. So I I have several patients who take it and it's uh 50-50. Some people say it makes no difference. Some people think it makes a difference. Whenever it makes a difference, you always wonder which is placebo or not, but it's a very harmless placebo, you know. So then I do not uh encourage them to take. I have like kind of a smart phrase that I discuss that. If they would like to take supplement, there is some evidence, you know, that that alpha lipoic acid would improve uh neuropathic symptoms and even you know slow down progression of neuropathy. The evidence that they did a large trial at four years, and at four years they did not see a difference comparing alpha lipoic acid, 600 milligrams daily, to placebo. But I also do know whenever a trial is negative, you also have to find why it was negative, right? So every single study in medicine, and the patients on the placebo arm did not significantly worsen. And then there was a thought that they did not worsen, so maybe that's why there was no such significant, because there was a difference, but not such significant. You don't reach the primary endpoint, but uh reached a few secondary endpoints. So, you know, so that is say some evidence. So it's not recommended by the American Diabetes Association, it's not recommended by the AAN, you know, the big kind of uh diabetic neuropathy uh kind of guidelines, but I think it's reasonable, you know, the patient interested to take. And uh and you can also sometimes use the placebo on the patient's behalf, you know, essentially. So anyway, so I have patients who take it and I discuss that evidence with them.

Michael Kentris 16:49

No, excellent. Thank you.

SPEAKER_00 16:51

Marcus, you mentioned that we've sort of been focusing a little bit on the diabetic neuropathy, which is, as you said, the probably the most common for those patients who have more of the sometimes you know genetic subtype, which often are not painful. I know they can be, but often aren't, um, or the idiopathic, which can be painful or non-painful. But let's focus on the non-painful neuropathies besides the safety counseling around checking your feet. Is there anything else you recommend specifically for those patients?

SPEAKER_01 17:20

So for the non-painful neuropathies, the yeah, the general education, you know, the care of the feet, the balance, you know, the need for AFO, you know, especially for the inherited, because CMG patients almost all they're gonna have foot drops.

SPEAKER_00 17:34

Yeah.

Alpha Lipoic Acid And Evidence

SPEAKER_01 17:36

Some of them also as, of course, I always check the vitamins of my patients, you know, with neuropathy first encounter. Uh I check vitamin B1, B6, B12, folate, and copper, you know, essentially every patient. I also like zinc. So the ones I said B1, folate, B12 with metamalonic acid, and copper and B6, they can be associated with neuropathy. You know, copper and B12, copper more of a large fiber, B12 also more of a large fiber. Also, both can cause subacute combined degeneration of the spinal cord, you know, but they can also cause some small fiber symptoms and small fiber damage as well. So these are five ones that I said, they can cause zinc is not associated with neuropathy. But zinc, you know, in a poor uh uh uh uh uh men's world, I think zinc is a nice parameter of your nutritional status. So I think zinc is a sensitive mineral, you know, to be deficient if you are malnourished, at least, you know, there is some evidence on that, and also in my experience. Why I like zinc to also because, for example, if I see someone who I suspect they have a nutritional neuropathy and all of them are normal, including zinc, I said, oh, it's likely not nutritional, you know, because there is a lot of questions regarding the thiamine assays, you know, especially for warnix encephalopathy, for example, right? We know from textbooks and also from some kind of uh real-world data that some patients with warnic encephalopathy are gonna have a normal thiamine on the available assay. So, but for nutritional neuropathy, that's why I usually all the, if you suspect that's a more broader panel. But and then with the when the when the vitamin, when of them is low, of course, if it's B12, for example, is low, right? And I always like to confirm with your malonic acid, especially those that are like kind of in the low normal range, you know. So, but then whenever they have a low vitamin B12, I usually also our panel here will include getting the antibodies for ponytious anemia, you know, and if they do have poniture's anemia, it's a lifetime subaccutaneous B12 replacement. If they do not have ponycious anemia, usually, and I believe the neuropathy is secondary to B12 deficiency, usually I supplement with uh subcutaneous B12. I do the protocol we do here, which we do like one milligram daily for seven days, then weekly for four weeks, and then monthly for five more months. After that, I transition them to oral B12 for the entire life. If they have low B6, low foliage, you know, depending on how low it is, I usually just give them a general multivitamin, okay? And I usually tell patients, it's an important point, do not buy the fancy multivitamin, vegan, paleo online. Don't do that. Buy the off-the-shelf ones, okay, at the anyway, supermarket you want, okay. But buy off the shelf. Uh, you know, I'm not gonna be mentioning names here, I'm not don't have any kickback, anything, but I'm not gonna be doing that. Uh, but but the the the general ones, they are well balanced. Okay, and the thing that's important, patients should see they should never take more than 50 milligrams of B6 a day. That's another very important point. And now, and also those who like to work out, you know, people who like, oh, I like to work out, I like to feel high when I work out, gonna pre-like the pre-workouts, it's pre-workout, some of them, and also some also some energy drinks, they have high content of B6. Okay, so there are several cases reported of people who develop B6, hypervitaminosis, B6 toxicity from energy drink and pre-workout uh powder. Uh so be careful with that. And also those who bought who bought super vitamins online, okay. So they you should never take more than 50 of B6 a day if it's not directed by your physician.

Michael Kentris 21:32

Oh, that's great. I know uh when I was a fellow, I was working crazy hours and I was having to drive at night a lot, and I was drinking like one to two, five hour energies a week. And I realized like halfway through the year, I'm like, oh man, these have like I forget, somewhere between two and four hundred milligrams of B6.

SPEAKER_01 21:48

It's crazy. It's crazy, Michael. It's crazy, you know. And you and you have no idea only if you check. So then uh and and the B6 also business, just to talk a little more about that. So usually when the B6 is Don't know it's very high, usually above 400, 500 in the serum assay. So when it's associated with more of a large fiber sensory neuropathy picture, okay, can also cause, of course, as a sensory neuropathy, small and large fiber dysfunction, but it's more of a sensor neuronopathy uh picture. So uh the high B6, the it's a little controversial if it can cause kind of a chronic length-dependent peripheral neuropathy. It's usually more of an acute sub-acute onset sensory neuropathy. But of course, if you have if you have neuropathy, you don't want the B6 to be high. So patients ask whenever they come to see us and they have a chronic length-dependent neuropathy, a gistosymmetric poly neuropathy. We check the B6 and come back like in the 100s, 180, 200s. They ask, was this damaging my nerves? We say, we don't know. But I think well helping. Helping was not. So no, let's change this multivitamin, let's stop that and uh and get one that will have kind of a more normal, not normal, but lower levels of B6. And most of the general ones, like off the shelf, they have two, four, six milligrams of B6. So it's a very balanced kind of a good quantity.

SPEAKER_00 23:14

Marcus, you mentioned copper, so I want to ask you a question I've been wondering about. I know the teaching is, you know, that copper deficiency can cause the same type of presentation as a uh kind of like a myeloneuropathy or subacute combined generation. And I'm curious, I've seen a couple cases where people come in with these almost what I would call almost like a small fiber kind of like scintillating paresthesias. Um, and then the lo and behold, copper comes back a little negative. Have you seen that? Do you do you replete the copper there? Um what's been your experience?

SPEAKER_01 23:47

Yeah, I know. Yeah, that's a that's a good question. So usually, so my in my experience, copper deficiency in neuropathy, myelopathy is very rare. Uh so when the copper is just mildly low, it's not copper deficiency in neuropathy or myelopathy. You know, the copper used to be like substantially low. And I would say probably what, maybe 30, 40% lower than the lower limit of normal, something like that, you know, kind of significantly low. Uh and uh and and then whenever I that is you know the protocol, you know, here there is a neurologist here, a mayor called Niraish Kuma, who I think published, you know, the few kind of uh the the in the first works on copper deficiency myelopathy. And we have a protocol that we do um we do copper like eight milligrams for one week, six for one more week, four one more week, then two lifelong a day. But unfortunately, these patients do not get much better. So, you know, it's uh it's an interesting, I think, uh uh disorder. They do not get much better, but some of them do get a little better, you know, and usually it's uh it's more clear when they have the correct phenotype, which is just kind of a dorsal column myelopathy and also a sensory neuropathy. Okay, if they only have small fiber symptoms, no large fiber, normal EMG, it's hard to believe that this could be copper deficiency. But again, to know this could be, for example, multivitamin deficiencies, okay? I have seen several patients with nutritional neuropathy, not only copper, but also, and that's why usually Galina, I also ordered all these vitamins. Oh, you're crazy, you order so many tests. Yeah, I order them, but I can't say I'm crazy. But I feel that getting like a full panel of vitamins, I also do vitamin D, vitamin A, vitamin E, because then you have a better understanding of what's going on with the patient's metabolism. And uh it's not only one vitamin, you know, there are usually multiple vitamin deficiencies causing, you know, the patient's symptoms.

SPEAKER_00 25:46

Yeah, I had a a sad case of a patient treated for scurvy and her neuropathy was attributed to the vitamin C deficiency, and I was like, I think it was the other vitamins that were gone. Like there was no B12 in that in that serum, you know, and and she, upon you know, digging into the records, did have pan essentially deficiencies, but it was helpful even for her in our conversation because she's like, I don't understand how this happened. I read up all you know a chat over with ChatGPT and it doesn't fit. And um, it was you know doing a little bit of counseling around uh the severity of her nutritional deficiencies at the time.

Vitamin Deficiencies And Replacement

Michael Kentris 26:25

Yeah, that's very important. So I think we need to talk about the the elephant in the room, right? So, you know, everyone's always like uh a lot of times when we get the patients coming to us, they've been told, here's your gabapentin, go see neurology, and it works, it doesn't work, sometimes it's dose isn't quite right. So what's what's your approach when we do have someone with with a neuropathic pain, diabetic related or not? What's your approach if they're coming to you kind of you know blank slate as far as your opening moves?

SPEAKER_01 26:56

Yeah, yeah, Michael, yeah, that's a great question because it's so common. And I always also start with counseling, you know. So I tell them, say, hey, you have neuropathic pain. Neuropathic pain is different than essentially all other types of pain. And why? Because if you have a headache, you take Tylenol, if you have migraine, you take max out, and your pain goes away. The pain goes away. But neuropathy pain doesn't go away. You have a shoulder pain, Tylenol, take some tordol, or put some cream, oh great, my shoulder is feeling well, have no pain. So we you know our brain is wired that if you have pain, the pain needs to be fixed. And that's why neuropathic pain drives everyone crazy because it doesn't go away. You go to the doctor and the doctor gives you a medicine who causes you all sort of symptoms, you know, and doesn't fix your pain. So we want our pain fixed. And and and whenever I see a patient that has never started or or or or if it's already on a medication or improving, I do this type of counsel and say, hey, the clinical trials, the outcome, the primary endpoints of a clinical trial, which is this drug work or doesn't work based on that number, is what they were 40 or 30 percent improvement of the pain. We don't talk, we're not talking about resolution of the pain. We're talking about 40 to 30 or 30, and the most recent ones were 30 percent. So this is very far from 100, 30, okay. So then I tell them say, hey, and this is not fixable, we will work together to try to get your pain under control, get your pain under an acceptable level. And and I also ask them about their mood, anxiety, and sleep. Okay, because if you do not rest at night, if you have undiagnosed OSA or that you have chronic insomnia, you're gonna have more pain because the brain amplifies the pain. Okay. And I always talk to them also in my generous pu I talk to them about when you go on vacation, what happens to neuropathic pain? You know, most of them will say, Oh, I feel less pain when I go on vacation. And I say, Well, I can't prescribe you a vacation, but it's important for you to know that it's because your brain is able to block the neuropathic pain signals going to it. And the brain is very powerful, and I always also introduce to them this concept, you know, for them to understand that how come the brain can amplify or the brain can block the pain signals because it's very important for them to know. And so I always do over an oxymetry test to screen for OSA. I always ask about a mood and anxiety, which is usually it's a problem in people with pain because they have pain. So they're gonna be anxious and gonna feel sad about it. So and and and and it started with that. And then I usually don't know. So the evidence shows to us that we have three, four classes of drugs that to work for the repathic pain. We have the galvapentinoids, galvapentine, and pregaboline. We have the tricyclic antidepressants that we usually don't use that much nowadays because of the side effects, especially with the elderly and all that. We have the estuloxygen and there's velafaxine and velafaxine, and we have the sodium channel blockers, okay? Carbamazepine, oxcobazepine, lacosamide, lamotrogen. These four, they work. And I try to see in the patient comorbidities, their age, their lifestyle, which one would be the better one for them? If they come to me and they are anxious and depressed, so usually start with, you know, do oxygen. If they come to me and their mood is good, they're just a little anxious. And and a lot of people also, it's important to ask, I always ask, have you been on antidepressants? You know, because a lot of people have strong opinions against antidepressants. And you guys always probably of course know that. So, and uh anyway, and it's very important to disclose that the medication you're giving them is an antidepressant because they can get mad at you if you don't tell them and then you find out later. And duloxychene and the SNRI is very important to also disclose the risk of suicides, you know, that can happen with that. Say, hey, so I'm having weird thoughts, let me know. You know, but I usually try to see uh if they have epilepsy, you know, so then you know that the sodium channel blockers, you know, would be a great because they're great anti-epileptic medications, you know. Lacosamide, for example, I think is a promising drug for neuropathic pain. Insurance a lot of times doesn't approve, you know, because it's expensive and all that. But it doesn't come with the problem of lamotrogine, which is a wonderful drug, but the uptitration is so hard for many patients. And oxcarbazipine and caramazepine caused hyponatremia, right? And especially the older folks. So I try to see based on the patient comorbidity and then during the encounter what I feel about them, and then I offer one of them. And then when you offer, you offer again with that, hey, my goal is to improve 30%. We're gonna uptitrate the dose, okay? Whenever you reach the 30% at uh at part of the uptitration, they tell them, say, hey, you can probably stop, you know, and at the up titration, and then whenever we see the patient back, and then we could discuss again, continue going up. Okay. I always tell them, say, hey, this is not like a one or two-day thing. It will be like a six to twelve week process. You should not give up on the medication too soon. Even if you have side effects, try to push it through a little bit. Okay, of course, if you develop hives, you know, an athlax, sure, stop right away and go to the ER. But if you develop some dizziness, some kind of a stomachache, you know, some mild issue. Hey, keep going. Because you know, we should not fire one of these medications prematurely, you know, because first we don't have many. And and you know, and and second, we want to give you the best shot at all these medications. That is also continuing on this. So whenever they improve 10-15%, you got the maximum, a maximum tolerable dose. So that is very good research showing that combination therapy is very helpful, okay, especially of SNRIs and GABA pentoids. Okay, so they usually are my go-to, SNRIs and GABA pentenoids. You know, I usually reserve solutions blockers for folks with epilepsy or for folks who have very refractory pain, or folks who have pain that's more kind of a like a like a neuralgic or kind of a joke type of pain, like to general neuralgia, right? Of the legs and hands. So uh these patients sometimes can do better with solutions blocker. But that are the two classes I usually use. I very rarely use TCAs, it's recyclics nowadays. I don't remember last time I prescribed. But all of these four classes, they have good evidence. And the combination therapy, you know, you can do two or even of three drugs later, but each of them improving the pain some amount.

Michael Kentris 33:57

No, that was that was a great rundown. And I was I'm really glad you talked about the combination therapy. I find that you do find, like you have these people who the first sign they take it a day or two and then they just say, Oh, I don't feel good, and they stop taking it. And I think we see that with with almost any neurologic condition, whether that's you know, neuropathy, seizures, migraines, you know, fill in the blank. And it is that counseling, like laying the groundwork for that really you know gets them to you know st steal their loins, if you will. And it's it's really important. Yeah, nothing is a quick turnaround. So uh I appreciate you emphasizing that point today.

SPEAKER_00 34:35

Yeah, I just wanted to add, Michael, that it's it reminds me of our conversation around uh like headache management. Like when how many minutes into the headache are you taking, you know, the suma tripton? And same with the neuropathic pain agents. I think some of my patients, whether I do understanding or my probably my miscommunication, maybe start maybe take it PRN, like you were saying, like the shoulder hurts, and I take an Adevilan and the feet are tingling, and I take a GABA pensin and trying to counsel them on the regularity. Um, and then also small adjustments, like I've sometimes find, you know, I usually recommend uh deluxetine in the morning because it's sort of activating and some of my PHJK at night and then having trouble sleeping. Even a switch of let's move it to the morning, maybe then this can become a winner, vice versa, with the TCAs doing it at night because they can't be produced a little somnolence. So trying to do this kind of like little adjustments and little tweaks in addition to the uptitration around the timing and optimizing for them.

Neuropathic Pain Mindset And Targets

SPEAKER_01 35:31

Yeah, that's very important, you know, try to use the medication, the side effects pro-patient, right? Yeah. So it's that that's uh very important to counsel them. And whenever I think you do good counseling, I think you have better outcomes, you know, with the patients. Because if they know that they should continue taking and not stop it early, you know, they will try though, you know, and you you're partnering with them to achieve the better outcomes possible. Anyway, and and also one very important point to say is to not take opioids for neuropathic pain. That is very strong research showing that opioids for neuropathic pain only work in the very, very short term. In the long term, it worsens pain. And this drives patients nuts because in the beginning that was helping, but then their pain just continued to worsen. So opioid causes what's called opioid uh induced allogenia, opioid-induced neuralgia. So the pain worsens, the neuropathic pain worsens on opioids, which with many other disorders that doesn't happen that much, but but in the nerve pain, that does happen. And people also sometimes ask about topicals. You know, what topical can we use? So I you know, I usually only use topicals for those who have pain only below the ankle, or the pain concentrates more below the ankle. And usually the topical, I usually try them to try first, is the lidocaine 4% cream over the counter. So they get off the shelf and they try it on their feet. Uh, you know, to see, and I usually tell them, those who have a lot of pain at night, I tell them to do like a foot routine that every day before going to bed, they soak their feet in lukewarm water with an epsilon salt. And it's an important thing. If they do that, they should not discard the epsilon salt like the like the water on a sink. They should do it on a toilet because the epsilon salt can clog the sink. And so they have to say that's important to say a patient of mine complained about that. So, okay, good. So then I started saying that. But doing that for 30 minutes, soaking the feet, and then after that, they dry their feet, they put some cream, some vena cream, some lubricant, and then they apply Lidocaine in the feet and go to bed. Uh, that's usually helpful. Some people and some places I hear now, institution, we have a triple cream that they combine. It's a compound cream. They do amitriptyline, ketamine, and uh gabapentin cream that's also some patients' life, but it's expensive because the compound insurance does not cover. And now there is an FG-approved therapy for that for neuropathic pain. It was main diabetic, but I've seen insurance approved for diabetic, non-diabetic, which is the capsysane 8% patches that they use like four times a year. It's a need to go to a uh to a to a pain medicine office, they put on the feet for 30 minutes, and there is also some patients with some good results with that.

Michael Kentris 38:23

How's that experience for patients?

SPEAKER_01 38:26

Well, some patients it worsens in the beginning, yeah. You know, uh because capsisane will deplete the substance pin neurotransmitter, you know, in the in the like down in the in the nerve. But uh, but some of them have improvement. And then it left the so the pharmaceutical company data, right? So I have like a couple, two pages on that, and both of them they're still doing, so they like it. Uh, that said their data say that 70% of patients keep using, you know, after one year. So yeah, so it's anyway. So I think it's another resource for those who reflect neuropathic pain, you know. And also for those with that, they all should go to a pain doctor, you know. I think neurologists should try to manage them with with medication. But there is also FGA, I think it's FG approved, you know, but uh spinal cord stimulator for diabetic, painful diabetic performanopathy, you know. But patients usually try to shy away from spinal cord stimulator because you know it's a procedure, it can have complications and all that. But but whenever your patient has a refracting neuropathic pain, I think asking a pay medicine physician to see them, I think it's recommended.

Michael Kentris 39:26

Excellent. I would like to get your opinion in the last couple of minutes we have. Gabapentin, I think, is right, everyone knows it as like the nerve, nerve pain drug, uh, even lay people. In terms of dosing, I find that that's probably one of the more misunderstood medications we have in terms of like frequency and how high to escalate it before transitioning to something else. What's your general approach in someone who's, let's say, coming on, coming to you who's maybe only on 100 or 300 milligrams three times a day and having an ineffective response?

SPEAKER_01 40:02

Yeah, my yeah, that's a very common issue in the office. So I think usually uh I I usually start when I got a pension, depending on the patient's age. So if they are like uh you know kind of a below 70, you know, I usually will do like uh if the pain is severe, okay. If the pain is severe, below seven, I'm starting. I usually start with 300 once a day, and I up titrade every three days. So, but if there's an older person, I do 300 every week. Okay, and with three times a day, that's I think the pausology should be done. And and and the and the the question is where to go, where up to up to how much you go before you switch, you know? And and uh uh so usually, okay, if the person is uh uh below 70, uh normal weight person, you know, not like a very skinny 50 kilograms person. So I usually go up to 2.7 grams or 2700 to see if there is any improvement. If they do feel there is improvement, then usually go to 3600, which is usually the maximum I use. I've used it more for folks who have felt significant improvement, you know, all the way along. I have no side effects, you know. But usually I think that if you do not see improvement at 2.7 grams, like no improvement at all, they say it's just like sugar, uh, for for uh like a younger than 70-year-old person. And if the older than seven, usually go to 1.8, like 1800 a day. If there is no improvement at all, you know, usually I would switch to lyrica, I would switch to lyrica uh if they're interested, or I would try another agent, you know. Uh but but this is this is the literature, this is kind of uh to be defined. The clinical trials, of course. Whenever we do a clinical trial, you have the clinical trial team, this infrastructure is so different than in you yourself and your patient, maybe a nurse to help out, you know. So uh but it's usually they need to go to 1800 or more for you to say, okay, there was no benefit at all. This is my opinion.

Michael Kentris 42:03

Yeah, no, I I would agree 100% with that. I I find the biggest right is that uh that bioavailability per dose with like the escalating doses, what you just get a lower and lower percentage of what you actually take in. Um and that's that's been my experience as as well. So I'm glad to hear that it's the same across the board.

SPEAKER_01 42:21

Yeah, no, yeah. And and one thing that I do know, and people also know that, but it's important to say that galapensin and lyrica, they are you know very similar molecules. So if you want to switch a patient due to side effects like brain fog, dizziness and ballast to lyrica, you can divide the galapensin dose by six and then start them on the same dose of lyrica the next day.

Michael Kentris 42:41

Perfect. Gotta love those fast transitions.

SPEAKER_00 42:44

Well, Marcus, thank you so much for another whirlwind. I feel like I learned something new from you every time. And it's actually really cool to hear someone like yourself who does this day in and day out because it gives some reassurance to me. Like I I've never heard kind of those numbers, but that's kind of what I've been doing. And it's nice to know that you know I've been sort of doing it at least, at least right according to Marcus Pink Pinto, which I think in my opinion is a sufficiently uh sufficiently high caliber. But I really appreciate you giving us that overview for the metabolic neuropathies for the most common diabetic neuropathy management and and uh idiopathic as well, and again, touching on PT, on AFOs and AIDS, and then also most importantly, that neuropathic pain and what we what we can do, even amongst so many things we can't.

Michael Kentris 43:30

Absolutely. Thank you so much, Marco. Marcus, really appreciate it. And if people want to find you online, where should they check you out? Uh where's where's the best place to track you down?

SPEAKER_01 43:40

Yeah, so I usually uh so I I the only social media I use for uh neuropathy related work is my Twitter, so Marcus V Pintel uh on X. So find me there, can ask me questions and all that, and I will do my best to respond.

Michael Kentris 43:54

Thank you so much. And you can always find us on X also at neuro underscore podcast. And on Our past work at the neurotransmitters.com. Thank you everyone for listening, and we'll catch you all again next time.