PETER GAILEY: Good afternoon, and thank you for joining us for the Neurosurgical Interventions for Pain webinar today. We're very glad to have you with us, and we're looking forward to a great discussion this afternoon. I'm pleased to introduce the speaker for today's webinar. Please join me in welcoming Rushna Ali, M.D.
Dr. Ali is an associate professor and Director of the Stereotactic and Functional Fellowship in the Department of Neurological Surgery. She's a board certified neurosurgeon with expertise in all salient aspects of stereotactic and functional neurosurgery, including advanced surgical treatments to treat chronic and cancer-related pain, facial pain, and other neuralgias-- I'm sorry, neuralgias-- movement disorders, stroke rehabilitation and recovery, as well as surgical management of epilepsy. Today, she'll be discussing neurosurgical interventions for patients experiencing chronic and cancer-related pain. Doctor, I'll turn it over to you.
RUSHNA ALI: Thank you for that very introduction, Peter. It's a pleasure to be here today and talk to the audience about a topic that's close to my heart. I have no relevant disclosures. And what we'll try to achieve today is identify why there is a need for any type of surgical intervention when it comes to managing medically refractory, chronic, as well as cancer-related Pain we'll go through the indications, a surgical procedure, and outcomes that are associated with the various treatment modalities that are available for both chronic and cancer-related pain, including neuromodulation as well as lesioning procedures.
So the neuromodulation procedures that I'll be talking about include spinal cord stimulation, dorsal root ganglion stimulation, peripheral nerve stimulation, intrathecal drug delivery, as well as motor cortex and deep brain stimulation. All of these therapies are aimed at delivering a small amount of electricity or a small amount of intrathecal medication that can interrupt the pain circuitry. These are used when we want the therapy to be reversible and titratable.
The lesioning procedures that I'll focus on today are cordotomy, mylotomy, and dorsal root entry zone lesioning procedures. There are very specific indications for these, which are limited to a certain subset of patient populations. And I'll be going over that as well. And then finally, we'll wrap up with the thought process behind having a large, multidisciplinary team that can holistically manage a patient who is suffering from chronic or cancer-related pain.
So why should we care about pain anyway? Well, we should care because chronic pain is endemic in the United States. It has a prevalence of about 30%, affects over 23 million adults, costs us $635 billion to society, and is the most common reason people will see any physician. It leads to an increase in long-term opioid use. And as neurosurgeons, we see a fairly large population of patients because back pain is the most common subtype of chronic pain that people will seek out therapy for.
When we look at cancer pain, or pain associated with a known malignancy, it is also a very predominant issue in those who are already suffering. There are about 9 million people that suffer from cancer-related pain each year. And about 50% report inadequate pain control, and about a quarter of them actually die while still in pretty significant pain. So as surgeons, we need to do a better job of contributing to helping this particularly vulnerable population in achieving appropriate pain control and lessen suffering.
The pain relief ladder is what has typically been used in the past when managing particularly cancer-related pain, where you start off with non-opioid analgesics like Tylenol, Motrin, other NSAIDs. Then you progress to weaker and then stronger opioids. And the top of that ladder is the various procedures that I discussed.
There is an impetus to ensure that it is not considered a last tier type of therapy, or where it's considered-- a neurosurgical intervention it's considered sort of an end-of-the-line type of therapy. Because a lot of times, by the time these patients reach us, they're so debilitated, and they're having so many issues, and side effects from the multiple medications and opioids that they're on that they might not even meet surgical candidacy because they reach us very late in the process. So over the course of the talk, I will be making an argument associated with supporting data that after trying an appropriate trial of medical therapy, these patients shouldn't wait too long to be referred to a neurosurgical specialist who can help with surgical interventions for chronic pain.
Now how do we decide what therapy we offer to a patient? Well, it's a very well thought out process, and it depends on where in the particular pain pathway we think that the pain is coming from. In humans, there are three very well-defined pain pathways. The first is the lateral pain pathway, which is responsible for us feeling sharp pain, pain that is associated with a certain sensation.
So you get cut by a knife, the pain travels up from the periphery, into the spinal cord, synapses in the thalamus, and then goes to the processing area of the brain known as the somatosensory cortex, which tells you that this is a sharp, bad pain. And you respond accordingly. You pull your hand away if it's a situation where you can pull away, et cetera. Or you let out any sort of verbalization that allows other people to intervene and help you.
The medial pathway is very interesting because the medial pathway is associated with the suffering that comes along with the sensation of pain. And as you can see, there are different parts of the brain circuitry that are involved. We feel the painful sensation. But then, the neurons that transmit this sensation go to different parts of the brain-- deeper and more superficial. And we find that after studying this particular pain pathway, we associate the suffering that comes with this pain with interventions in this particular pathway.
And then the descending pathway actually starts off in the brain, and works its way down through the brain stem and the spinal cord, and actually suppresses painful sensations. And it's typically an imbalance of these pain pathways that leads to chronic pain becoming a long-term issue.
When we are trying to figure out what part of this pain pathway and which pain pathway we should intervene on, we look at what the pain generator is. And typically, we can figure that out if we understand how the pain started, what the features of the pain syndrome are. And that informs us on where we should be intervening.
So it's typically a three-- it's a rather simplistic view. But in most situations, we can boil it down to a three-step chain where the first order neuron starts in the periphery, synapses in the dorsal ganglion, and then goes up to the level of the dorsal horn. The second order neuron will then take it up to the thalamus, and then the third order neuron goes from the thalamus to the cortex.
And if we're able to localize this pain generator, we can then determine what we need to do and where we need to intervene to best help the patient. If we're intervening at a level below where that injury or insult has occurred, we will not be able to break the pain circuitry enough to cause good long-term benefit for these patients.
And when trying to decide between lesioning-- which is a permanently injuring part of this pain pathway, depending on where the pain generator is-- and neuromodulation where we use electricity to disrupt the circuit, there are some characteristics that come into play. For lesioning procedures, we typically save it for patients who have a limited life expectancy or who have malignancy-related pain. There's easy access to the pain generator pathway. And the reason for doing this is because typically, the surgical risk is higher when we try to intervene on second and third order neuron pathways.
Neuromodulation is a good long-term solution. So it works well for patients who have a good long-term life expectancy, or there's poor access to the pain generator, or it's diffuse. We aren't able to pinpoint exactly which order neuron the pain is coming from, so we can access a larger circuitry with these procedures. And they typically are involved with a lower surgical risk profile.
So some of the common neuromodulation techniques that we use include spinal cord stimulation, which has been around for a long time. And the theory is that large fibers, which carry normal sensation when stimulated in the dorsal part of the spinal cord, can suppress the smaller fibers, which carry pain sensation. So if you overwhelm the pain sensation in the spinal cord with a bigger, more powerful stimulus, it fools your body into thinking that the sensation that you're feeling is not pain, but something else.
The principal is electrodes or wires are placed on top of the spinal cord outside of the dura in the epidural space. And there is a cathode and an anode. The cathode depolarizes, or activates the neurons, and the anode hyperpolarizes, or blocks the neurons. With conventional spinal cord stimulation, there are different parameters that can be changed or modulated based on the patient's response, including amplitude, which is how strong the stimulus feels, the pulse width, which is how far the stimulus spreads, and the frequency, which is how smooth that sensation is.
It is indicated and FDA approved for chronic pain conditions like post laminectomy syndrome or persistent spinal pain syndrome, non-surgical back pain, complex regional pain syndrome, arachnoiditis, peripheral neuropathy, and more recently, painful diabetic neuropathy. But we also use it often with very good success for neck pain, cervical radiculopathy, plexopathy, pain associated with non-operative critical limb ischemia pain, and non-operative angina pain. These are patients who can no longer have multiple revascularization procedures done. And the goal is not to help with their circulation, but just be able to manage the pain that is associated with these conditions.
For cancer pain, spinal cord stimulation is indicated to treat neuropathic cancer pain that can occur when a tumor is involving larger nerves or a plexus of nerves, as well as helping with radiation- or chemotherapy-induced pain. Smaller trials have been conducted which have shown good results, where most patients receive at least 50% or more improvement in their pain. Some common complications include spinal fluid leaks, infections at about 5%, and then hardware issues like the wires moving out of place or fracturing leads-- anywhere from 5% to 10%.
The way the surgery is done is it can be done both as a percutaneous needle approach, or through an open laminotomy after making an incision in the middle of the back. Where we place the wires depends on where the pain is located. And we use dermatomal anatomy and physiology to inform us on the level at which the spinal cord should be stimulated in order to get patients the best relief. We use intraoperative X-ray to make sure that we are in the correct region. The wires are placed in the epidural space, which is the space between the lining of the spinal cord and the bone.
With all of these neuromodulation procedures, we have to do a trial before doing a permanent implant because it doesn't work for everybody. And during the trial, what we're looking for is a 50% or more improvement in the painful symptoms. And if we achieve that goal, then we can proceed with a permanent implantation of the device. If the trial is unsuccessful, or if the patients don't obtain that degree of relief, then we remove the electrodes or we remove the wires, and we don't proceed with the permanent implant because it wouldn't make sense to implant hardware in somebody where it's unlikely to make a meaningful difference to them.
Now in addition to conventional spinal cord stimulation that I discussed a few slides ago, we now have a lot of different waveforms or software technology that can be tried. There are several open loop systems which use conventional or tonic square wave stimulation patterns. There are waveforms that can mimic the way our thalamus fires, and it can match that frequency with the help of burst stimulation. There's high frequency stimulation, upwards of 10 kilohertz. And there is a multiwaveform stimulation that not only stimulates neurons, but also stimulates the glial cells, and helps to improve the neuroinflammatory profile in the area, and is thought to play a big role in the way these therapies help patients.
We now also have closed loop systems available, which can respond and change the amount of stimulation that is being delivered in an automatic, artificial intelligence-based algorithm. Currently, because this technology is very new, it's only responding to the strength of the response by the spinal cord. So remember, it stimulates or depolarizes certain fibers in the spinal cord. These systems can record that response and then change the next output accordingly.
So some similar complaint-- some complaints that we get from patients with spinal cord stimulation is as they move around, the amount of stimulation they feel changes because the amount of spinal fluid between the device and their actual spinal cord changes with positions. This therapy allows to make minute adjustments based on those positional changes so that patients can get a more smoother delivery of current.
There is good evidence supporting each of these new paradigms in the form of multiple randomized controlled studies that have been conducted for high frequency stimulation. The high frequency paradigm was compared with traditional spinal cord stimulation and was found to be superior similarly for the birth stimulation, which mimics the thalamic firing. It also showed improved pain control, both in back and leg pain when compared to traditional or conventional spinal cord stimulation.
The differential target multiplex stimulation, which focuses on activating not just neurons, but also the surrounding glial structures also when compared with conventional stimulation was associated with better outcomes, both for back and leg pain. And lastly, the closed loop stimulation showed that-- the initial trial where closed loop stimulation was compared with open loop stimulation showed more patients achieving more than 50% improvement in their pain in the closed loop group. And a subsequent trial showed similar results at two years as well.
When it comes to cancer pain, spinal cord stimulation has been shown to be effective, both in the short term and in the long term when it is used in the appropriately selected patients, which are patients who have neuropathic pain associated with their cancer or subsequent cancer-related therapies.
And time to intervention matters. Going back to that ladder that I was discussing initially, we should not consider these therapies to be end of the line. What does that mean? That means that patients should certainly try appropriately selected medications, physical therapy, pain interventions such as nerve blocks, epidural injections, facet injections, based on what type of pain they're having and what the location of that pain is.
But after a trial of appropriately selected medications and therapy, if within three to six months you're not seeing significant improvement, that is the time to refer these patients over for more involved therapy if they're interested. Simply because we find that the longer patients have chronic medically refractory pain, the success rate for any neuromodulation intervention falls steeply, probably because chronic pain rewires our circuitry and ends up becoming much harder to treat any time we try to interrupt that circuitry with external stimulation. So referring these patients once they've had an appropriate trial of medical therapy and physical therapy four, three to six months is very appropriate.
Once again, something to remember is that if they've had a spinal cord stimulation trial but didn't do well with it, that doesn't mean that if their pain has progressed-- and especially now since technology has progressed-- that we can't try a different modality. If they have failed a percutaneous approach, then we can do an open approach with a paddle lead. That can provide a more dense and focused area of stimulation. So certainly, if patients have failed trial spinal cord stimulation in the past doesn't mean that they won't be candidates currently, especially if those trials occurred a few years ago because technology has significantly changed and progressed.
Dorsal root ganglion stimulation also became recently available. And it is indicated and works really well for pain that is more localized in distribution. So targeting certain anatomical areas that are difficult to treat with spinal cord stimulation, like just pain in the pelvis, or the groin, or the knee, or the foot, and the ankle. These devices work phenomenally. They can be used either with or without paresthesias. The lead is placed along the dorsal root ganglion itself. And because there's less spinal fluid in that area, there's less postural change that's associated with the stimulation. And it is performed as an outpatient percutaneous procedure, which the patients tolerate really well.
There's once again good, high level, level one data to recommend its use. When this type of device was compared with traditional spinal cord stimulation, it produced better results at improving focal leg pain. Now remember, this is comparing DRG stimulation to traditional spinal cord stimulation, not the newer paradigms that we just talked about. So it's an area of ongoing study if the newer parameters that are associated with spinal cord stimulation now might produce equivalent results. But we typically tend to favor DRG stimulation when the pain is fairly focal.
As mentioned, this is a percutaneous procedure. We access the epidural space through a needle. We pass the wire along the dorsal root ganglion. We make a hairpin strain relief loop so the wire doesn't get pulled out of place easily. Once again, we have to do a trial. And if the trial is successful, we do a permanent implant. And with this current system that's available, we can put four leads in at one time.
And in those patients who are not candidates for percutaneous procedure-- either they've had prior surgery that makes access harder or they have some local arthritis in the area that doesn't allow us to put the dorsal root ganglion stimulator in-- open approaches have been tried and attempted. We typically try not to do this because that's not what the device is on label for, but certainly something that can be done successfully.
Pumps or intrathecal drug delivery therapy is also a very, very powerful tool. There are two main sort of categories that this is used for. Baclofen. Intrathecal baclofen is used for spasticity that's associated with spinal cord injury, stroke, cerebral palsy, traumatic brain injury. It can be a very, very life-changing therapy for patients who have a lot of spasticity that's medically refractory. And then, morphine or ziconotide is FDA approved for treatment of chronic pain that is either related to cancer-- which is the most common indication to use these pain pumps-- in patients with cancer-related pain who have a life expectancy of more than three to six months, chronic neuropathic pain, diffuse visceral pain all responds well to this therapy.
Once again, we have to do a trial. The trial here is through an injection done through a lumbar puncture. And after that, the response is measured by testing either the pain scores or the level of spasticity. If the patients have a 50% or more improvement in their symptoms, then we proceed with a permanent implant. Once again, it's a simple outpatient surgery. The pumps can then be transcutaneously filled when they're about to empty out. They can be programmed wirelessly, where the dose delivered can be changed, where the frequency can be changed.
The medications can be switched out. Let's say somebody isn't responding to morphine. You can, in the office, transcutaneously change the medication and try ziconotide instead without having to redo another surgery. And it's a good therapy both for cancer-related pain and chronic pain, where the PACC guidelines-- the more recently updated guidelines-- are recommending this therapy as a category 1 recommendation for both localized and diffuse cancer-related pain.
Patient selection. As I mentioned, patients with advanced stage cancer, life expectancy of three months or more, who have a pain score of 5 or more, and have been tried on appropriate doses of opioids, and are simply not responding.
And we have good data to suggest that it works really well. It improves pain reduction when compared to continued medical therapy and is associated with fewer side effects such as fatigue, impotence, pruritis, grogginess, reduced consciousness. All of these side effects are lower if you're delivering these medications intrathecally as opposed to orally.
But as with any surgical therapy, it comes with complications. Again, thankfully, as the technology and our skill at implanting these devices has gotten better, so have the rates of complication. But things to look out for would be infections, seromas in the pump pocket, spinal fluid leaks, catheter malfunction, loss of efficacy. And then, based on the medications that are being used, overdose and withdrawal symptoms should be recognized and managed appropriately as well.
And it's cost-effective. A lot of time, we deal with nihilism when it comes to treating chronic or cancer-related pain because, why would you go ahead and implant an expensive device in somebody who might not be alive for a very long time? Well, it has been shown that this therapy is indeed cost-effective where, after the pump was implanted in patients who had more than three months to live, it saved over $3,000 per episode. So these patients were making fewer visits to the emergency department. Their medical management costs were lower. Their quality of life was improved.
Peripheral nerve stimulation is another modality to help manage chronic pain. Typically, not something we use for cancer-related pain, but this is more for chronic pain. Peripheral nerve stimulation targeting either the medial branch nerves or placed subcutaneously in an area that is painful due to neuropathic pain, or direct placement into the multifidus muscles in patients with chronic low back pain has shown success.
Similarly, patients who have headaches, atypical facial pain, or occipital neuralgia that is not responding to medications can have these wires implanted subcutaneously, which means we make a very small little puncture and then thread the wires along their pain distributions. We do a trial. If this trial is successful, then these wires are tunneled down and hooked up to a generator that's just under the skin. But these can be very, very effective therapies for those who are dealing with chronic headaches, migraines, occipital neuralgias, and other types of atypical facial pains that are not responsive to medical therapy, or facial pain that is not the typical trigeminal neuralgia pain that can be addressed with the more traditional approaches.
And lastly, intracranial neuromodulation is something that is reserved for central neuropathic pain patients, or chronic pain patients who have pain because of a spinal cord injury, a stroke, trauma or traumatic brain injury, multiple sclerosis, and some very resistant trigeminal neuropathies. Evidence suggests that there's about an improvement of about 50% of pain symptoms in 60% of patients. So not the greatest results, but still something very valuable for patients who have this very refractory type of central neuropathic pain.
Multiple targets have been explored. The best evidence exists for motor cortex stimulation and thalamic stimulation currently. Although, anterior cingulate and other parts of the pain circuitry are being studied for its role in managing central neuropathic pain.
Now those were sort of the workhorses of the various neuromodulation procedures that we have available to us at this point in time to treat both cancer, and some only for chronic neuropathic pain. Lesioning procedures come into place where we are either dealing with cancer-related pain where life expectancy is limited, or where long-term benefit can be achieved with a limited risk profile.
So dorsal root entry zone lesioning is one such procedure that can be life-changing for patients who have pain, particularly pain associated with brachial plexus or lumbar plexus avulsion injuries where the nerve roots have basically been disrupted, or pulled out, or injured, and they have this diffuse pain in their arm or their leg associated with this injury. It's also used in patients with spinal cord injury who have persistent neuropathic pain, or pain that develops after a peripheral nerve lesion, spasticity associated pain, and less frequently, pain associated with a malignancy that involves the brachial plexus or the lumbar plexus.
It's a technique where the goal is the destruction of the most superficial layer of the dorsal horn, which is where the nerves come in and take a deeper dive into the center portion of the spinal cord. It provides unilateral pain relief localized to the level of the lesioning. So we have to determine exactly which dermatomes are involved and lesion those.
And there's good outcomes. Although most of the large studies have looked at predominantly pain associated with brachial plexus injuries, some studies have included pain due to multiple other etiologies. And based on that, the results are pretty reasonable, where there's about more than 75% relief in half or more of the patients who were included in these studies.
Complications can certainly occur because this is very high stakes real estate. We are going in in a very small part of the spinal cord and trying to lesion a small portion of it. So if you see here, this is where we want to make the lesion. But right next to it are areas that control balance. Right next to it over here are areas that control movement. And the deeper you go, then we get areas and centers that control bowel and bladder function as well. So all things that we need to be very, very cognizant about.
Cordotomy is a procedure where we injure part of the spinal cord. That is reserved for patients who have cancer-related pain. Lesioning procedures have been performed for a very long time. In this particular procedure, we're destroying the lateral spinothalamic tract, which is responsible for conducting the pain sensation from the periphery all the way up to the thalamus and the somatosensory cortex in the brain. And this disrupts pain and temperature sensation from the opposite side of the body that is below the level of the lesion. So we save it for intractable, unilateral, somatic pain, or nociceptive pain. Patients who have bilateral pain, midline pain, or pain above the level of C5 in the cervical spine are not candidates for this.
The way we do the surgery is traditionally, we would do it do an open approach where we would do a couple of levels of laminectomy, release the dentate ligaments that are tethering the upper spinal cord to the sides of the spinal canal, rotate the spinal cord, and make an incision, or a lesion, or a burn just in front of where the spinal cord was attached to the spinal column. Because we know that's where, based on anatomical studies, that's where this particular tract lives. And as long as we're staying in front of the dentate ligament right over here that is tethering the spinal cord to the inner portion of the spinal canal, we'll be safe. And we'll only be disrupting the spinothalamic tract, and not causing any major side effects.
As you can imagine, it's not a surgery that's performed commonly because it's reserved for a specific group of patients. But in the smaller studies that have been performed, it does lead to significant pain improvement in a majority of these patients. One reason that we reserve it for patients with the limited life expectancy is if you follow these patients out, at about the two-year mark, you start to see some pain recurrence occur because the tracks are starting to repair themselves.
More recently, a safer and quicker approach to this has been developed, which is a percutaneous way of conducting the same type of lesioning procedure where we perform a myelogram. And then, using fluoroscopic techniques, we insert a small lesioning probe into the spinal cord. Instead of opening things up and visualizing it directly, we visualize and use myelography to guide this and make a stereotactic lesion instead.
Again, very good results associated with it. And the complications that do occur tend to be mostly temporary.
And lastly, myelotomies are used when we are dealing with cancer pain patients who have diffuse visceral pain or midline pain. What this basically does is it disrupts the pathway where the pain fibers are crossing, and thus helps with any pain that is associated with primarily being present in the midline or deep in the viscera, because the visceral fibers cross in this commissural area as well that is being transected and disrupted.
The way we perform the surgery is, based on where the pain is, we do a multi-level laminectomy. We identify the midpoint of the spinal cord dorsally after finding the midpoint between the two dorsal root entry zone areas. There's typically a vein running along the center that is mobilized. And then, either with a knife or lesioning probe, we essentially make an incision in the midline and go all the way to the front so that we are disrupting all of these fibers that are crossing in the midline.
It's associated with good pain relief in patients. However, the side effect profile or the complication profile isn't insignificant. And a lot of these patients exhibit a new weakness, or urinary issues, difficulty with proprioception, et cetera, which led to the development of the punctate myelotomy, where a smaller lesion is made. And it's a very focused lesion where, if you have pain in the upper abdominal viscera, we limit the lesion to T3, T4. If the pain is limited to the pelvic viscera, then we make a small lesion at T6 to T8. And compared to the control myelotomy that we looked at, the disruption is minimal. It's not as long, and it's not as deep.
And it still works really well. We can make a smaller opening, and either with a angiocath or lesioning probe, we go in to about a five-millimeter depth. It's something that we can measure on pre-surgical MRIs as well, so we can be quite precise. And essentially rotate this so we're making a lesion in all four quadrants in this area. But once again, it's a focal lesion. It's less than a millimeter in width, and causes less disruption, and therefore leads to a lower risk profile while still being able to achieve good surgical outcomes.
But none of these surgeries would produce good, reproducible, and successful long-term benefit if it were not for the efforts of a large, multidisciplinary team. A neurosurgeon is just one part of this entire spectrum. It is very, very important that it's a large group of experts who are part of the decision-making that helps us determine who is a good candidate for any of these surgeries, and why.
So services to be involved should include oncology, neurology, pain management, palliative care, neuropsych, pain medicine and rehab, a nurse navigator, a care management specialist so that we can look at each and every individual patient and determine their candidacy, evaluate specific risks and benefits, determine the surgical target and the surgical approach, make sure we're optimizing them pre-surgically, and most importantly, track our post-surgical outcomes to make sure that we're doing the right thing, and having the necessary and appropriate impact.
So in conclusion, collaboration instead of working in silos is what's going to help us bridge this gap and help this very vulnerable patient population by offering them the appropriate therapies. The optimal intervention should be determined by a large, multidisciplinary team of experts like the ones we have at Mayo Clinic. And what it all boils down to is the patient selection is crucial. And if we make it a patient-centric approach, we are most likely to achieve the best outcomes. Thank you. And I'll take any questions.
PETER GAILEY: Well, Dr. Ali, thank you very much for a wonderful presentation this afternoon. We have a handful of questions that have come in. So I'll go through them one by one, and we'll get through as many of them as time allows. The first question that came in is, "What is the value of spinal cord stimulation in peripheral neuropathies which are not painful? Just paresthesias, numbness, tingling, et cetera."
RUSHNA ALI: It's a very timely question because currently, a clinical trial is being designed to look at specifically that-- to see if spinal cord stimulation makes a difference in the sensory profile of these patients with peripheral neuropathies. Because there is some anecdotal evidence to suggest that in patients who had a painful neuropathy and had a spinal cord stimulator implanted, one of the secondary outcomes that were seen was not only an improvement in their pain, but their sensory profile. But because it was never a primary outcome, it wasn't studied in depth. It wasn't measured very, very objectively preoperatively or post-operatively.
So there is work underway to study the impact of spinal cord stimulation only on the sensory effects in peripheral sensory neuropathies that are not painful. So I would say, stay tuned and let's see what the data tells us. Right now, it's mostly just anecdotal, which seems to suggest that they may improve the sensory profile. But it's only been studied in patients who have a painful sensory neuropathy.
PETER GAILEY: OK. Well, thank you very much for that answer. The next question that came in is, "Do you have any experience with midline myelotomy? For example, cancer pain?"
RUSHNA ALI: Yes. So if we go back, midline myelotomies are used, typically for either midline or pain that is associated with visceral pain that can happen with diffuse cancer, either in the abdomen or pelvic area. In the appropriately selected patients, it can work really well.
PETER GAILEY: OK. The next question is, "If my patient is still receiving chemotherapy or radiation, are they a candidate for these surgical pain interventions?"
RUSHNA ALI: The short answer is yes, they would be a candidate for lesioning procedures because the time to heal-- depending, once again on what type of lesioning procedure we're doing-- is possible. However, we do want them to have completed or be in a little bit of a reprieve from their chemo and radiation before we do a hardware implant because ongoing chemo and radiation significantly increases their infection risk. So if there is, let's say, a six to eight week period where their chemo and radiation can or will be held for whatever reason, that is the optimal time to do this. So they have a good six to eight weeks to heal from their intervention.
PETER GAILEY: OK the next question here writes, "Some of my patients with colorectal cancer experience lower back pain due to the position of the tumor, some so severe they are unable to lay in a single position for radiation treatment without severe pain. Would spinal cord stimulation be an option for them to help them undergo the rest of their treatment plan?"
RUSHNA ALI: So in that situation, because the pain is actually referred pain from the viscera that is then being referred to the low back area, actually, intrathecal drug delivery systems would be a better solution for these patients. So a pain pump where they can undergo a quick trial through an LP and, if they respond, get a permanent implant done would be a more sort of-- will get you more bang for your buck than spinal cord stimulator because this is referred pain from the viscera and not primarily low back pain.
PETER GAILEY: Thank you. The next question is, "Are these interventions more for patients now in remission?"
RUSHNA ALI: So for those patients who-- we have both options. So we reserve the lesioning procedures for patients who have a limited life expectancy because we don't want to implant hardware, and have them go through multiple trials, et cetera when they have a limited life expectancy. But the neuromodulation options that exist exist for patients who have-- they don't necessarily need to be in remission, per se.
But we should have an idea of whether or not their life expectancy is going to be three months or more. And if the answer to that is yes, then they would certainly be considered for neuromodulation procedures. But if they have ongoing, severe pain with disease that is certainly not in remission with a limited life expectancy, then lesioning procedures can certainly be considered for them.
PETER GAILEY: Thank you. And Dr. Ali, we still have some questions coming in. So if you have a few more moments--
RUSHNA ALI: Of course.
PETER GAILEY: --I'd like to continue through. "How do I know my patient is a good candidate for these interventions?"
RUSHNA ALI: Oh. So that would be a very, very lengthy answer. And I would say some-- like a basic rule of thumb would be, does your patient have chronic or cancer-related pain? Have they tried appropriate medications and physical therapy? And some intermittent pain interventions, depending on what type of pain they have. Because some of these you can do some pain interventions for, like try a nerve block, or an epidural steroid, et cetera. But for some, there really aren't very many interventional pain options.
So again, it would depend on the type of pain, the etiology of the pain. But if they've tried medications, they've tried physical therapy, they've tried any indicated pain interventions, and within three to six months you're not seeing a meaningful improvement in their pain symptoms, and their pain scores are still consistently 5 or more, then I would say, refer them to a specialist and let them make the assessment. Because there are a lot of nuances to this that we do need to consider based on the type of pain, the location the pain generator, their response to certain therapy, the presence of a certain disease phenotype, et cetera can play into our decision. But for any referring providers, that's what I would recommend.
PETER GAILEY: All right, thank you. And "What is the optimal time for pain intervention for a patient? Is time to intervention important for all the different intervention methods, or just for spinal cord stimulation?"
RUSHNA ALI: For all intervention methods. Because chronic pain, regardless of where in the three-step order neuron chain we're dealing with, changes the pain circuitry. And as it changes, it becomes more resistant to any intervention. So time to intervention matters for all neuromodulation interventions.
PETER GAILEY: And "What is the optimal time for pain intervention for a patient?"
RUSHNA ALI: I would say, if they've tried medications, physical therapy, and any indicated pain interventions for at least three to six months and you have not noted any significant improvement in their symptoms, that's the time to refer.
PETER GAILEY: OK, thank you. And "How long does a referral and evaluation process typically take?"
RUSHNA ALI: Again it depends on what type of pain they have what therapy we're considering. But typically, at the Mayo Clinic, once we receive a referral, it's routed to the appropriate surgeon. We review it within a few days and make the determination on whether or not this is somebody who is appropriate to be seen. We certainly can make sure that we prioritize patients who have a more urgent need, but we try and get them in as quickly as possible. And then we take care of any associated imaging, or further testing, et cetera that might be needed prior to us intervening on them.
PETER GAILEY: OK. And then the final question that came in, and we may have partially answered this previously was, "How long should I have my patient manage their pain with medication before considering them for a referral for surgical intervention?"
RUSHNA ALI: Yeah. So three to six months. Again, appropriate trial of medications, physical therapy, et cetera. And if you're not seeing improvement, then that's the time to do it.
PETER GAILEY: OK. Well, Dr. Ali, that is the end the questions that we've received for the program. We do appreciate your time today, and your insight, and appreciate you sharing your time with us.
RUSHNA ALI: Of course. Thank you for having me.
PETER GAILEY: Thank you. And to all of you who are watching today, we thank you for joining us today. We hope that you found the presentation informative, and we look forward to seeing you next time. Thank you for your time. And we wish you all a very, very nice day.