Living Better With Spina Bifida: Opportunities to Improve Detection, Intervention and Long-Term Care While medical advances mean most patients with these anomalies are living into middle age, doctors often fail to address issues that impact quality of life. After offering a refresher on spina bifida types and early intervention techniques, Nalin Gupta, MD, PhD, chief of UCSF’s pediatric neurosurgery division, discusses management challenges and the value of specialty care – for problems ranging from incontinence and limited mobility to pain and depression.
no disclosure is relative to this particular talk. So, um, the subject of spinal this racism and I deliberately chose spinal disc racism and not spina bifida because I want to talk about actually spina bifida, which is what we call my, you know what there's a late term for my learning to seal, but also other dis traffic conditions. And I'm going to try to split the time roughly between those two entities and and and talk a little bit about some of the problems these kids have and some of the major things that we look for and are trying to deal with in this patient population. I'll also spend a little bit of time talking about the imaging and investigations for some of these patients that have some of these cutaneous anomalies of the, of the midline. So from a, from a perspective of, you know, biology, why is why are spinal list race six states interesting. They're interesting because they really relate to the formation at a very early stage of the entire nervous system, both spinal cord and brain. And you know, you obviously I always remember from medical school that the neural tube is really one of the formation of the neural tube is one of the first things that happens in the patterning of the embryo and abnormalities in that patterning from a very early timeframe are what lead to these anomalies and it's quite common. It's one of the communist um Survivable central nervous system abnormalities that we know about one in 2000 live births. And it's really what it is is it's a window into new regulation. Regulation is the formation of the central nervous system from the neural tube. And the nomenclature of what we call these entities is very confusing. And part of the reason for that is that it predates the modern era of imaging and also that I think the modern era of the repair and outcome of these patients. We have terms that we use that date back probably a few generations. And I try not to get too bogged down in those except that I try to um, you know, really separate these things into a couple of broad categories in my mind. Now, all of these have to do with some abnormality of how the neural tube forms or is or differentiates. And I'm not going to talk a lot about primary no relation, secondary manipulation except simply to say these are all sort of fall into into abnormalities of how the neural tube itself forms. And what's probably most useful is to think about um spinal dystrophy is um is really those and those abnormalities that are what are called paper to our open. Okay, that part is the old word for open and we call these open neural tube defects versus local to or closed neural tube defects. And there are a couple of examples there, but I think if you keep that sort of concept or that that sort of to um uh that sort of separation between those two entities, then it's a little easier to sort of think about the things that happen because each of these, whether it be open or closed, um, they may or may not be open ones require surgery, but they, how these patients, that outcome and what we look for is very different. So I'm not gonna spend a lot of time in embryology. I don't want to put you all asleep. Um, but it is important to understand that this is a something that happens extremely early. Often the process of variolation. The actual patterning of the neural tube is one of probably one of the very first things that occurs in the embryo, from a cellular molecular standpoint and the closure. In other words, the formation enclosure of the neural tube is probably complete by about 24 25 days after fertilization. So often, well before the mother knows that she's even pregnant, the neural tube closure is formed. And, you know, a lot of mothers will ask me, especially in the prenatal setting, you know, is there something they did? Is they defaulted? There's it's not it's a it's a segmental random abnormality of development that we don't actually know what is the actual trigger for most, for most cases. Okay, And all of you remember this cartoon of the schematic, but this is kind of what we're talking about. This. This patterning of the neural tube is what's happening really at about 10 to 12 days. And then the formation of this tube enclosure, the closure of the tube and separation from the ectodermal. This is a key step this step where the neural tube separates from the overlying ectodermal. And the reason I mentioned that is because it will become apparent to you when I talk about closed neural tube defects about wet when that actually happens. But as I said, this process, in other words this E. M. Shows you this this this isn't a mouse. Obviously it's not a human, but it's exactly the same in humans. This formation of the neural tube and separation from the overlying ectodermal is done by about Between 3- four weeks. Okay, these are this is just a classification of how we look at these things and I'm not gonna dwell on these except to tell you that, you know, the the abnormal maladies of primary manipulation, what we what we call spina bifida, or mile a minute to seal. Um, This is actually the Communist. It's also the most severe because it is associated with other anomalies. And this is because of the fact that it's open. The spinal cord is open, the back of the baby is open during pregnancy to the amniotic fluid. And these other entities occur after the ectodermal closed. So they're happening to them happening there, there an abnormality that happens after the ectodermal, the skin closes over it. So this is a, you know, this is a photograph of a baby and newborn. Uh, typical mile a minute to seal unrepaired. This is in the operating room and you can see the large sack. The sack is not solid. It's filled with fluid or CSF, the mid line right here is the unfolded neural plaque. Of what we call the plaque. Oh, really? What it is. It's the neural the neural tube that hasn't even folded. So this is not really you know people say it's a failure of closure. It's actually not even a failure of closure. It's before that. It's a failure of the neural tube patterning and folding. And so as I said this is something probably that Is a failure that happens in the first week or two. Even after conception. This baby has the typical features that will affect you know you know effect the infant for the rest of his or her life. Um You can see the club feet, the reduced tone and bulk and the cafs the spatulas anus indicating the fact the baby is not going to have continents. And you can see the sensitivity to some of the E. K. G. Leads that that sensitivity skin sensitivity they have at birth. So the incidents of newborns with my limited responsibility has fallen by about 50% in the last 20 years. And the it's believed that part of that explanation as folic acid prophylaxis. Um there is a landmark paper and land set several decades ago that illustrated the role of that folic acid is in most flour products and that we consume and that's contributing to it. Plus the fact most mothers are encouraged to take full of gas and supplementation during pregnancy. But the other factor that does play a role is early termination and that's been a depending upon the areas that people live that early so early diagnosis in mid mid gestation in the second trimester and termination also has affected the incidents of newborns with this. So the visible defect. What I showed you is really one aspect of the entire abnormality. Um The treatment that we focus on that, I'm sure all of you are aware of is early repair of that, of that sack of that lesion. But the misconception that people have is that we're doing something that's going to improve their function and that's not true. The the opening in the back is really if if uncorrected leads to infection and leads to meningitis and if you don't do anything than a high percentage of these Children will actually die from infectious complications. So the purpose of closure is really to protect the central nervous system. It's not restoration of neurologic function. So the associated anomalies are what really caused the from a neurologic perspective and I'll talk a little bit about some of the other things as well, but these are the things that cause problems moving forward for these kids in the long run. And obviously the first one is the loss of mobility and depending upon the level, the level plays a key role in determining that impact and mobility. So a child with a sacral mile amending seal is going to have problems with bowel and bladder control, maybe some foot weakness, but could still be emulating and have a very good functional motor level. Now, somebody who has a mile a minute to seal that extends up into the upper lumbar area is going to have a very significant motor deficit often and probably will be in a chair for their life. So that lower extremity dysfunction is a, is a major determinant in terms of impact In the prenatal setting. That's actually one of the commonest questions or things that parents want to know is my child going to be able to walk. And the ultrasound that we obtain in mid gestations 18-20 weeks gives us a reasonably good idea of level, but it's not exact because the spinal segments aren't fully formed at that point. So we have to be a little cautious about what we recommend. What we tell families about function. The extremes are easy. So if we have a a mom whose fetuses has a very high lesion, then you know, we're gonna we're gonna definitely tell them, look, you know, there's gonna have major impacts on lower extremity function, whereas a lesion that's in the sacral area, we can be more confident about mobility. Um The other two things that we deal with on an ongoing basis, one of them, and as I'm sure you're aware of is the hydrocephalus. So babies born at term anywhere from about 60, depending on the study, up to 80% will develop hydrocephalus and we'll need a shunt and once you have that shot, then we we recognize that that's a burden for both the patient and the family in terms of monitoring future shunt failures, complications. And it's something that has since I've been in practice. People have changed their approach in that, in when I first started, you know, we used to play shunts really on all of these babies right at birth, but now we we actually try to wait that out as long as possible, so that if there is even 10 15% That can avoid an additional 10 or 15% that can avoid being getting a shunt. We try to we try to achieve that. Um these open neural tube defects like spina bifida, it's not just the spinal cord that's affected. Um it's the whole brain that's affected and hydrocephalus is one manifestation of that. The chiari two, which is the descent of the cerebellum is another one that causes significant issues and problems in terms of swallowing upper extremity function. You can have abnormalities of the brain stem that can also affect their function with respect to also swallowing speech and sometimes other lower cranial nerves. Um Most kids with spina bifida mile a minute to seal will attend normal schools but they're mean or median I. Q. Is shifted by about 10 to 15 points. So what that means is that what are viewed as learning disabilities? Performance issues in school are going to be more common in this population. And and hydrocephalus not surprisingly is an independent predictor of more kids having a poor outcome. Um uh in terms of their intellectual and cognitive performance and as I mentioned that there's on top of that these kids also have the other associated um abnormalities which include orthopedic issues, sometimes club feet, sometimes hip hip dislocation, spinal deformity, Urologic and bowel management is an ongoing issue for a lot of these kids in terms of trying to achieve um continents and social control through a variety of techniques. I think the urologists have actually gotten very, very good over the last couple of generations in terms of finding a route or a path for most kids to either have continents through intermittent intermittent catheterization if they have good sphincter function, um and if they don't have center function, they'll often end up with procedures that they can have a artificial bladder that they can cast themselves through a stone mama. But the goal there is really to achieve social continents in a in a in a variety of ways. The last thing which I think we've underestimated and frankly don't have good tools for, I mentioned to some of the cognitive issues, but the the burden of having a chronic disease and chronic illnesses is something that we have not dealt with in an effective way. And there's many reasons for this. You know, we could have a separate talk just to discuss that aspect of it, but it is definitely a gap in our in our care of these patients. We we do take care of these kids in a multidisciplinary setting, as do most centers that spina bifida clinics but a deficiency is our ability to help these kids with their psychological and psychiatric illnesses. This, just to remind me to talk, mentioned you already, this is the MRI of a chiari two. You can see the cerebellum is really abnormal, it's squashed way down into the upper cervical cord. This brainstorm itself is elongated and and if you look carefully the brain itself looks abnormal. So this is spina bifida. My limiting steel is really an abnormality that affects the entire central nervous system. It's not just the lower back and the and the legs. I'm gonna talk a little bit about what I think is important is called burden of disease in these kids. And some of these, some of these data I think are a little bit older and I think we're probably doing a little bit better, but um, they're instructive because they tell us about, you know, what happens to these kids. These two studies looked at a cohort, one from sick kids, one from actually both from Canada. That looked at long term outcomes of these kids and they could do that because they're care was regionalized. So they looked after all the kids and that either in the province of british Columbia or in southwestern Ontario, and the mortality rates were not insignificant. They ranged anywhere, Um, you know from 8% up to 18% over that study period. So there's a there's a substantial burden of mortality in this group that that I think we we also don't know that we underestimate. This is a review of young adults with spina bifida and this talks about the extent of disability. And this was a group of patients from the U. K. I believe. And they and they looked at the patients that they had been following. And actually I think that they probably underestimated some of the things like wheelchair dependence and shunting because they may have had a group of patients that had survived through the young adulthood. But as you can see very substantial number of issues related to both lower extremity function, catherization, things like renal function. A big problem that I'm going to mention only briefly is that we also do really, I think an adequate job of transitioning patients from there, pediatric care providers to adult setting and there this is a gap that we people have. We've had numerous efforts to try to address it at both here, but also at a national level with quite honestly varying degrees of success and a lot of obstacles related to that management. Um there was some papers that talked a little bit also about life expectancy. Um the these kids are living longer. Um They do have a reduced life expectancy but certainly we would expect that in the current era these patients will live the majority of patients will certainly live through to middle age and possibly late middle age and certainly even longer than that. Um there is a higher incidence as I said of of chronic illness in this, in this patient group. As you as you can imagine. Yeah. Um this one i rhe already mentioned, sorry. So there was a um mm this is just remind me to give you a number in terms of this was a group of patients with spina bifida um young adults. So they most of them had spina bifida appear to, in other words what we call spina bifida a mile a minute to seal. And only a quarter. Um We're what they ultimately and there was a detailed sort of assessment of this group, but only a quarter were satisfied with their lives. So the majority of three quarters, um we're not happy with what what the kinds of obstacles and challenges they faced. Some of the things that we that they deal with in terms of long term issues. Um This is one that in particular is a problem and I've worked with my adult colleagues in the spine side. A lot of these patients will have ongoing issues with either delayed related to the tether cord. All these patients will have scarring of their abnormal spinal cord to the area of the repair, and a lot of them will develop delayed symptoms of either progressive weakness, often pain, neuropathic and debilitating pain and sometimes changes in bladder function as well. Oh the presentation of this condition can vary in Children and young Children is usually a change in urinary function and sometimes lower extremity deformities, club feet that worsen in in a little bit older group that they what we start to see our changes in gait, worsening bladder function or new sensory changes. And these are a lot of the things we monitor in spina bifida clinic. It's very difficult sometimes to sort that out because patients may not be fully kids may not be fully aware of some of those changes. And then there are changes that occur in this population as they get older. Their weight increases and that weight can have a big impact in terms of their mobility. What they What a child could do when there were £30 or 40 lb. Um they can't do when they're £80 or 90 lbs. And then there's also just a question of ease of mobility. A lot of these kids once they reach school age will prefer to be in a chair because it allows them a greater degree of mobility than if they had walkers or canes or things that makes it very difficult for them to get around at school. Okay. Um And then in terms of, you know, the young adult population, we generally see pain as a bigger problem. Both lower extremities, neuropathic pain in this in this group. So the patients that have these tethered cord, it's a real challenge. The indications for surgery usually include new neurologic deficits. Um, we will in the past have done direct uh untether ring operations and have had very mixed results with that. My colleagues in the spine surgery world have done a number of these big operations but actually staying away from the spinal cord and doing what are called vertebral body receptions where they actually will remove a vertebral body to reduce the tension on the spinal cord. And there's early data that that approach is actually successful in relieving some of these symptoms related to tension or torch in on the spinal cord. A large number of these kids will go on to develop scoliosis that will require surgical fusion at some point in their lives, probably as high as 60%. So the the ongoing problems that we face from that child to adult transition. And we've had meetings, you know, with our adult colleagues to try to facilitate that both through urology, um neurosurgery and orthopedics. But the the the biggest factor or gap is there isn't really a medical coordinator or or home for these kids, for these kids have become young adults, there isn't someone who in a sense quarterbacks their care and there. And even though there's an effort to make available some of these multidisciplinary clinics like we have in the paediatric side, it's a real, it's a real challenge to get people plugged into the appropriate specialists for that care. And as I said, a lot of that time that includes ongoing issues with shunting and hydrocephalus spinal deformity, which often requires fusion and then the urologic management, which is a problem, I will say there's a big shout out to my colleague. Hillary cop who's one of our pediatric urologists. She's actually taken upon herself to go to the adult congenital neurology neuro uh neurologic clinic to see along with one of her colleagues and adult urology these patients, particularly young adult patients. And I think that kind of model has actually been really good because she brings her skill set into that clinic and she and she actually helps and works with the adult urologist and some of these cases. So I think that's actually an ideal that I think the rest of us need to aspire to. Um So I'm gonna actually let's see here, gonna skip through some of this. Um There's a just will say that there's a lot of movement in our field towards trying to address some of the some of these complications long term complications and one of the ways is through fetal surgery. We do we now do offer and have been doing for about 20 years, fetal interventions for spina bifida where we can actually open the gravity uterus and we can identify the baby's back. This is an example of open neural tube defect with the plaque code, much easier to see before the second half of gestation tends to obscure some of the anatomy. And we can we can actually close those in utero. Um I'm going to shift gears now and talk to you a little bit about closed neural tube defects. So what I've been talking about so far and again, just to repeat is really the open neural tube defect and the Communist one, There are rare forms of the Communist one is my limited to seal closed neural tube defects happened because what happens with the neural tube is forming, it pulls away from the ectodermal directed, um closes over it, but the neural tube stays open, or part of it doesn't completely close. And you have anomalies that form as a result of that, the Communist is this abnormality called the spinal cord like poma that we see. But these these have varying effects and function, but typically it always has a associated anomaly of the skin. The skin is closed, but there is an abnormality because even though skin forms over it, you'll get a hit an echo or or a little clue that there's something going on deeper to that. Okay. And as I said, these really, the old term is part of a cult or closed neural tube defect. And these are the ones that almost always, I wouldn't say 100%, but probably 90% will have what the associated cutaneous anomaly of the midline spine. And so what are those anomalies? So so these are the five. So um the these are the things that you know that when they are present you have, so when they are present you have almost a 100% confidence that there's something going on inside. And one of them is a is what we call a segmental hemangioma. So this is a him and it's a very clear hemangioma. Um You can see that it obeys or follows probably a segment a segmental area. And that's because the skin overlying the abnormal segment becomes abnormal. You can see also this trial is a deviated gluteal cleft and we'll talk about that in a second. But this is a very clear segmental hemangioma. This is an appendage. So extra little skin tag coming out of the middle of the, of the lumbar area may be off a little bit to one side. This almost always has, say always. I haven't seen one that hasn't, it has an abnormality of the poster elements of the spinal cord. So this is a this is a mid lumbar dimple and with a little bit of a hemangioma around it. So as I said, we'll talk a little bit more about dimples in a second. But if you see a dimple way up here, here's a gluteal cleft, here's the dimple way up here that almost always has a associated abnormality with it. Um This is a harry patch and a child that had previous surgery. This is a good example of its like this division is coming back for surgery, but this is a really nice example. It's a it's a very clearly defined area of course, you know, very coarse and very prominent hair. Sometimes kids will have a little bit of fine, you know, this kid can barely see it has some fine hair in the lower back. I don't think that's abnormal, this is clearly abnormal. And this always has something associated with it inside more commonly with split cord malformations. Um This is the classic spinal cord like poma also with a little bit of a segmental hemangioma around it or are involved with it. You can see a very clear mass underneath the skin, it's all fat and the skin over it, even though there's a man Joma though is normal. Okay. And that's why that all of these are distinguished as closed neural tube defects. So if I see any one of these things, I'm pretty confident there's something going on structurally in the spine. Um I will say the other thing about all of these lesions compared to smile a meaningless shell is that more times than not these kids will have normal neurologic exams. Sometimes they'll particularly these kids will like palmas they may have a little bit of asymmetry in their muscle bulk. Sometimes they'll have a little difference in how their foot moves but often it's very subtle. Um A lot of times these the spinal cord is actually very functional and quite normal. Okay so there's an example in M. R. Scan of that like coma these lesions, as I said our problems of closure of the neural tube. So you'll you'll have a defect in the fashion and the muscles and that like coma extends into the spine and then at this point goes into the dura and then it terminates. This is a this shows the relationship better. This is actually the fat, this is the CSF. But you can see how the spinal cord terminates in that distal cord. And when we when we untether these cases, what we have to do is we have to separate all of this fat from all of this fact. We don't have to remove all of this fat. We just have to separate this from this, thereby um tethering the cord. Okay this is a normal sinus tracts. So these single dimples way up high. Um This is actually a track that goes all the way through to the spinal cord. This is that little skin ellipse. And you can see it, it's an obvious track that can be followed um goes through the dura and usually terminates at the end of the spinal cord because the spiral the neural tube um carried that connection with it from early development. This is another example of the spinal cord lipo. I wonder well and that too too much. This is that appendage. And you can see that appendage continues on as a fibrous track through the dura into the up to the spinal cord. We will remove that appendage but also remove that tracked. Okay, this is a split cord malformation. We don't have to talk to that too much. Okay, so let's talk a little bit in the time um that we have remaining about dimples. So this is, you know, I see a lot of these patients that are seeing. There is a literature in terms of the significance of um the where the location is of the dimple. So what I would tell you is that a dimple that is clearly um you know, clearly above the sacrum. So something that's in the lumbar area, like the picture that I showed you, that's that's going to be abnormal. And there's gonna be something inside that tracks from that down to the spine. That kid needs an MRI scan. Um I need, you know when I was to see that kid and the kid needs an MRI scan. Yeah. At the other end of the extreme arcoxia Jill dimples. So if you have a dimple that is very low meaning that if you put your finger on the dimple and you feel the end of the tailbone so you can you you feel that the coccyx then you know segment aly. What that means is that dimples related to really related to the tailbone is related to the coccyx. And so and we don't have a neurologic, other primates do, but we don't have a neurologic um correlate or structure that corresponds to the coccyx anymore, it has regressed. So a dimple that is cox Egil is typically not something that we would recommend additional imaging or investigations for. Now these are isolated cox Egil dimples. If you have a cocky little dimple and like home at the top then it's irrelevant that there's a small dimple there because you're going to image that child because of the light coma. Now the complicated ones are the ones where the dimple is higher than the light homa but still could be low sacral and then there are what I call the gray zone abnormalities, one of which is a deviated gluteal cleft. Another one is a shallow pair dimple. Um Sometimes you'll get a dimple, you're not sure is it low sacral as a cox jail. So those, those low cycle ones I think are a little tricky. People make a point of, well if you move the dimple, the ones that point upward are the ones that are worrisome, the ones that point downward or not. And what I mean by that is that if you go back to this structure because the spinal cord is typically shorter than the spine, these these dimples usually point up usually extend upwards, meaning that they where they start in the skin they head upward. So if you, if you pull them remove them theoretically, you should be able to tell that, okay, if there's something that heads upward that's going to be more concerning, I have to be honest with you, I've never felt confident about that particular physical exam sign and it's hard for me to know the significance of that. Um The true sort of cock schedule dimple, if you try to shift it upward will not move because it actually extends down to the tip of the coccyx. So I think sometimes you get some confidence in that, but as I said, it's not what I would say is a reliable sign if you have a child in that gray zone. Okay. So not absolutely clear cut abnormality or not. A. Mhm. Sorry, I'm just looking at the questions. Um Yeah, I'll try to get to those and let me let me just finish my training, that one thought and then I'll I will uh answer those questions. So the if you're not sure, sorry. Yeah. Yes. Oh. Oops. Forward. Okay. So if you're not sure meaning that it's one of those gray zone anomalies, then I think a reasonable screening test as an ultrasound and you should definitely get it before three months of age. Before after three months of age. It's really tough to it's tough to see a lot of things anyway. But it's really tough to see after three months earlier. The better the the information that the ultrasound is going to give you, it's going to give you two pieces of information. It's going to give you the position of the colonies relative to the vertebral bodies. And that you can you can you have a reasonable you have a reason a lot of confidence is the cone as normal. Or what position is that the one caveat with that is that at birth you're so normal. Conus position as well known as L. One L. Two. On average. Um There's uh I can send you a paper but people have looked at you know sort of incidental scans and in older kids and adults. There's obviously a range in the population everywhere from T. 12 to bottom of L2. Which in normal people. But the in newborns that the position of the Conus is sometimes half half a segment, sometimes a full segment below. What it will be between three and six months of age. And what that just means is that the cord actually sends a little bit more in those first few months of life. So an early ultrasound will give you the cones position. But the caveat you have to have with that is that if you see a kona set You know L Let's say L. two, it may not actually be low because in a newborn that could could very well be normal. Um The second piece of information the ultrasound will give you is is if there's a major anomaly, Okay so if you have a big spinal cord like poma filling half the canal. You're going to see that an ultrasound now having said that you're gonna have a pretty high suspicion of that anyway. But it's going to pick up something major. The ultrasound is going to miss small things. It's going to miss a little bit of thickening of the file and its gonna miss some subtle findings. However there is a lot of controversy as to whether some of those small or subtle findings are actually relevant. So I still think that it's a reasonable um It's a reasonable thing to get as a screening tool if it's totally normal. Um And you have a kid with a mildly sort of deviated gluteal cleft or a shallow dimple that you think is not really that significant will give you some confidence. And I if I have a normal ultrasound in that setting then I don't I don't do any further imaging after that. Now obviously the ultrasound shows something or is inconclusive then you may have to end up with an M. R. Scan. And we do also do these um We also do these things called, this is what I've been talking about. We also do what are called rapid MRI scans which are analogous to the rapid brain scans. The disadvantage of course with them is that even though they give you a little bit better a little bit more information than an ultrasound they're limited by their resolution. So often subtle things which are going to be much more common with these gray zone anomalies are are going to be missed by both the ultrasound and the rapid M. R. So I think that if I can tell you one thing is that if if you have a gray zone anomaly I would screen with ultrasound or rapid M. R. If they're totally normal then you know I wouldn't do anything further. If they clearly show something abnormal they're going to need a diagnostic. Um are often with anesthesia if they're inconclusive which happens, radiologist will say could not visualize could not be sure. Then you have to have a conversation with the parents about whether it makes sense to do actually a diagnostic M. R. And I'm happy to see those patients and talk to them because there's some pros and cons in terms of whether that's necessary or not. Um I work with a lot of people. I this is the font is too small to read but this is just to tell you there's a lot of people I work with and I'm very appreciative to them. Um You know it takes a village and I'm very I'm privileged to have a large number of people that I work with that are exceptional in what they do.