Good morning, everyone. This is Dr. Judith Owens. I'm the Director of Sleep Medicine at Boston Children's Hospital and a Professor of Neurology at Harvard Medical School. And I'm going to be speaking with you today about restless legs and periodic limb movement disorder in the pediatric population. And you may be aware that restless legs, and in the last couple of years that kind of renamed Willis-Eckbom disease after the physicians who originally described the disorder. But I'm going to use the more common phraseology of a restless leg in this presentation. So the objectives are, first of all, to list the core diagnostic features of RLS and PLMD in children, which share many characteristics with these entities in adults, but have some unique features as well. I'm going to talk about the relationship between RLS, PLMD, and neurobehavioral outcomes in children, including symptoms which are consistent with attention deficit hyperactivity disorder, which makes us somewhat unique in terms of this type of relationship with neurocognitive and neurobehavioral outcomes. And then I'm going to talk about the various components of both behavioral and pharmacologic management for children with RLS and PLMD. So first, a typical case, and I happen to have seen three children presenting in my clinic in the last couple of weeks with very similar constellation of symptoms. So this is a 12-year-old girl, Fidgety Fiona, who does have a diagnosis of ADHD. Mostly inattentive symptoms, as is often the case in girls with ADHD. Her medical history is consistent with a past history as a toddler preschooler of iron deficiency anemia, and she also has this history of growing pains, which disrupted her sleep in the past. Her mother has a diagnosis of restless legs, and the presenting symptoms are complaints of difficulty falling asleep and funny feelings in her legs at night, relieved by movement. She wakes up, her bed is disheveled, bedclothes all over the place, and reports still feeling tired in the morning despite getting an adequate night's sleep. So before we move on, I just want to remind the listeners that you can post questions. I think we will hold on answering the questions until the end of the presentation, because some of those may get answered as we go along, but please feel free to do so. So the definition, and this is from the International RLS Study Group in 2003, and what is contained in ICSD-3, basically characterizes RLS as a neurological sensory motor disorder that often has significant disruptions on sleep, and is a clinical diagnosis that consists of these following features. The urge to move the legs, so that's primary. I think a lot of people think of the leg discomfort as being the primary symptom, and that usually does company this urge to move the legs, but the urge, which may be described a little bit differently in the pediatric population, is really paramount here. These sensations and this urge begins or worsens during periods of rest or inactivity, and there's a circadian characteristic to this in that they're worse or only occur in the evening or at night, and this urge and this discomfort is partially or totally relieved by movement, hence the term restless legs, and that the features are not solely accounted for by other conditions. There are specifiers for the clinical significance of RLS in that the expectation, particularly in regards to treatment, is that the symptoms cause significant distress or impairments, not only in sleep, but in other aspects of life, functioning on social or educational level affects on behavior, cognition, and mood. The urge to move the legs can be present without these uncomfortable sensations, and sometimes the arms or other parts of the body are involved in addition. When symptoms are severe, this relief by activity may not be noticeable, and worsening in the evening or night may not be noticeable, but must have been previously present. So there are a number of conditions which are referred to as RLS mimics that produce symptoms that are very similar to restless leg, but restless leg can also occur with any of these conditions, but you require a clear delineation of the RLS-specific symptoms from these other conditions, and these clinical course criteria do not specifically apply for all pediatric cases and in certain adult situations like pregnancy or drug-induced RLS. So some of the special considerations that have been put forward for the diagnosis of pediatric RLS is that the child must describe the symptoms in his or her own words, and of course that's not always possible in pre-verbal or children who have language deficits, but by the same token, you have to be aware of the kinds of words and phrases that children and adolescents may use to describe their symptoms, and I'll talk about that a little bit later. So language and cognitive development determine the applicability of the diagnostic criteria rather than chronological age per se. It is not entirely known if adult specifiers for the clinical course that I mentioned earlier equally apply to children, but as an adult, you see a significant impact on sleep, mood, cognition, function, et cetera, but as you might expect, the impairments are more often in the behavioral and educational domains. You may see periodic limb movement to sort of precede the diagnosis of RLS, and even young children, infants, may present with kicking, crying, hitting the legs on waking or on falling asleep which oftentimes is not identified as RLS symptoms. So following features, although not essential for diagnosis in children, is closely associated with pediatric RLS, and these include PLMs more than five per hour, a family history of RLS among first-degree relatives, a family history of PLMs greater than five per hour, and a family history of PLMD among first-degree relatives as well. Not always easy to elicit, but if it's there, it's very helpful. So the diagnosis of PLMs is similar to adults in that this is a PSG diagnosis consisting of repetitive stereotypic limb movements that are a specific number of seconds in duration, a minimum amplitude, and they occur in a sequence of four or more minutes separated by an interval of more than five seconds and less than 90 seconds. And as I mentioned earlier, exceeding five per hour is considered clinically significant. In order to be diagnosed as PLMD disorder, you have to have this associated clinically significant sleep disturbance or impairment, and they cannot be better explained by another condition, particularly PLMs that occur at a termination of apnea. So in terms of RLS, what's termed primary RLS is a highly genetic disorder with a postulated six to seven times increase in first-degree relatives. The mode of inheritance seems to be quite complex, and there have been several genetic loci identified and no single candidate gene. And there's some interesting evolving evidence to suggest that the genetic components, the loci involved in RLS may differ according to the phenotype. I will be talking about the pediatric rest study, which is the largest study from an epidemiological standpoint that has looked at the prevalence of RLS in children. And this study, which was published about 10 years ago now, showed that 70 to 80% of children who met definite RLS criteria had at least one biological parent with RLS. So that's very high percentage, obviously, and 16% had both parents. And there's some, what I think is more speculation, that quote-unquote early-onset RLS may be a more chronic and progressive disorder, but I think we still don't know enough about the natural history of this in children. What's termed secondary RLS is in many cases due to iron deficiency because tyrosine hydroxylation is a rate-limiting step in the synthesis of dopamine, and RLS and PLMD are hypodopaminergic conditions. In particular, serum ferritin level of less than 50, and I'll talk a little bit more about the target for serum ferritin levels in treatment because that's changed a bit over time, but at a level of 50, we know that the iron stores in the basal ganglia, cerebral spinal fluid are reduced, and that these are very commonly found in a high percentage of children with RLS. Interestingly enough, low iron levels are also found in association with ADHD, and in particular with children who have both ADHD and RLS. On the other hand, if a simple CBC is done in these children, you may not see anemia because anemia is typically associated with ferritin levels that are less than 12. They're around 10 to 12 or less. It's also important to remember that serum ferritin is an acute phase reactant, which may be elevated during illness and may give you essentially a false negative, and you can also consider to kind of support ferritin levels to do iron and transfer them as well as total iron binding capacity levels, and this is just a schematic representation of this rate-limiting step that is required, that requires iron in order to synthesize dopamine. So other secondary risk factors that have been described in the literature in children, including peripheral neuropathy, uremia, end-stage renal disease, leukemia, type 1 diabetes, post-cardiac surgery. There was a case report on that, which probably had mostly to do with blood loss. There've been a couple of case reports which have reported the onset of symptoms with infections like group A strep and mycoplasma. There are certain conditions, congenital conditions, particularly increase in PLMs has been described in a congenital neurodevelopmental disorder called Williams syndrome, and maybe medication-related as well. In particular, tricyclic antidepressants, SSRIs, sedating antihistamines, dopamine receptor antagonists can exacerbate these symptoms. There seems to be an increase in PLMs, in particular in sickle cell disease, and some question about an increase in celiac disease and also in young children who have a history of prematurity, which may be a reflection of low iron levels. So the Pediatric Rest Study is, as I mentioned, our best guesstimate of what the prevalence of RLS is. This was a study of 10,000 patients. It was a telephone survey of children between age 11 and 12 and 17. They used the 2003 NIH consensus definition, and they found that 2% of those 10,000 plus patients had symptoms, definite symptoms more than once a month, which represents some 980,000 children in the US. So this is not a rare disorder, but it's oftentimes overlooked. And a smaller but still substantial percentage had symptoms much more frequently, more than twice a week. There didn't seem to be any gender differences. They did find that about a third of the patients reported impacts on daytime functioning and sleep. 25 to 50% qualified for having moderate to severe symptoms, and sleep disturbances were very common, but they were also quite common in children who did not meet criteria for RLS. So I think overall, we know much less about the prevalence of PLMD in children because it is a PSG-driven diagnosis. But in referral populations, sleep clinic referral populations, for example, the prevalence ranges from five to 25, a quarter of patients. In survey studies, which again, are not diagnostic for PLM, but the prevalence of symptoms is eight to 12%. They occur in up to 25% of children with ADHD. And with the exception of children with sickle cell disease, it seems to be increased in Caucasian versus African-American populations. So we know from some older studies that a substantial percentage of adults with RLS recall the onset of symptoms before the age of 20, and even almost 20% before the age of 10 years old. The peak age of the range of symptoms onset is in adolescence but the childhood onset RLS is associated very clearly with both primarily sleep onset, but also sleep maintenance insomnia, and also with inattentiveness as the daytime symptoms. And PLMs are associated with leg discomfort at night or in the morning, sleep onset and maintenance insomnia. And at least one study has suggested an increase in partial arousal parasomnias, perhaps because of the disruption and increased arousals associated with PLMs. So growing pains is defined as unexplained limb discomfort. It does seem to be associated with the later development of RLS symptoms in adults. At least in one study, a small study, the vast majority of children who had a history of growing pains met criteria for RLS, but these children also had a family history, they had an ADHD history, but they were significant enough that they actually required treatment with a number of different pharmacologic interventions. And in the pediatric rest study, there was a history of growing pains in a very large percentage of children who met criteria for RLS, but it was not a distinguishing feature because some 60 to 65% of children who did not meet criteria also had this history of growing pain. So it's a little unclear how helpful that history is. So the pain or discomfort associated with RLS in children is typically of low severity, can be symmetric or asymmetric, it's typically in the lower part of the legs. As opposed to adults, excessive daytime sleepiness is uncommon, and that's a very similar situation with obstructive sleep apnea in children. Excessive sleepiness is not a common presenting symptom, but similarly to OSA, it is associated with ADHD-like symptoms like inattention, hyperactivity, difficulty sitting still. Some children complain of symptoms primarily during the day, when they're sitting for long periods of time in class, for example. Physical descriptions may be challenging to elicit, as we mentioned earlier. And PLMs, especially in older children, are often unwitnessed. And you really have to question parents about this because they don't spontaneously volunteer that their child is kicking at night, although they may very well describe the restless sleep that were mentioned earlier. So we did a study a few years ago with children who had definite RLS, and the children were interviewed and we looked at the kinds of words they used, phrases they used to describe their symptoms. So needing to having to move or kick their legs. Children will sometimes describe that these are painful or they hurt, they can't get comfortable. A common description is bugs or ants crawling on my legs, tingling, pins and needles. My legs feel wiggly, itchy, restless, shaky. I feel like there's a soda bubbling through my veins was a particularly colorful description of the symptoms. And we also looked at how children depicted their symptoms in drawing. My legs feel weird. They want to kick. I'm in bed. My legs really, really hurt. So I say, help, mom. I need you. This is me in my bed and moving my legs. It's like a bruise. I'm trying to stretch my legs out, but at the same time, it's sort of hurting. It's like my legs are wiggly. And sometimes it feels like tiny nails poking in my legs. The SIT or suggested clinical immobilization test is a standardized series of instructions to a patient to try to essentially elicit symptoms of RLS. There has been some work done on adaptation of the SIT test for the pediatric population. But the question that I like to ask is sort of informal, and sometimes you can actually see the children in the exam room fidgeting and moving their legs around. I had one patient who actually fell asleep during my discussion with the mom and immediately started to have clear PLMs. But that's rare that you get that lucky. So a good question to ask is, if I asked you to lie perfectly still sitting on your bed at bedtime, would you be able to do it? And children with RLS will just roll their eyes and say, oh, no, absolutely not. I could not do it. And so they sort of understand that relationship. In terms of PLMD, there's been some work suggesting that there may be a possible screening role for essentially ankle actigraphy. And particularly because there's night-to-night variability in PLMs, even if you do a sleep study, you may not necessarily capture an adequate PLM index on the night of the study. In looking at these kinds of screening tools, you may need a higher threshold. For example, a PLM index of 10 per hour instead of 5 per hour. In a very recent study, what was quite interesting in that they tried to distinguish between what they term restless sleep disorder versus restless legs versus controlled children. Because my child is a very restless sleeper is a very, very common complaint from parents who come to sleep clinics. And they found that they were able to distinguish this RSD versus RLS because they were total body movements rather than specifically legs in all sleep stages. But they also found that this entity seemed to be associated with low ferritin levels. So how that will play out, whether there's really a phenotypic distinction and maybe a genetic distinction between restless sleep and RLS, I think is an interesting story that will play out. So we know that the vast majority of adults with RLS have PLMD. We don't really know so much about what that correlation is in children. There was one interesting study which suggested that PLMs are associated with familial short stature and constitutional growth delay. These are children who refer to an endocrine clinic for slow linear growth. And they did find that a substantial percentage had symptoms of RLS and increased PLM index. So whether the role of growth, there may be a role for growth hormone in all of this kind of raises an intriguing possibility. So associated sleep disorders, you may see these children presenting with sleep onset maintenance insomnia as well as significantly reduced sleep time. There does seem to be an association between sleep disordered breathing and increased reports of restlessness, restless-like symptoms, and growing pains. So that is an interesting association that I think is important to remember. If you have children presenting with sleep disordered breathing, not only may they also have PLMs that you need to look for, but you may see improvement in the PLMs with treatment of the sleep disordered breathing. And of course, narcolepsy is associated with an increase in PLMs as well. So some of these mimics I mentioned earlier, positional discomfort, overuse of muscles, ligament or tendon injuries, transient positional ischemia, nerve compression, dermatitis, and some other less common issues, including Osgood-Schlatter's, which is an orthopedic disorder involving the tibial tuberosity. So it's much more specific in terms of the location of the discomfort. And most of these other entities are reasonably easy to distinguish between RLS, but not always. And achestesia is an increase in really more total body movements that may be associated with a number of drugs. And formication is a description of feeling like insects or ants in particular are crawling on your legs, which may be a little bit hard to distinguish from RLS, but it doesn't just occur in the evening, is not worsened by rest, but is also associated with a number of conditions and drugs. Growing pains, we mentioned in terms of differential diagnosis, motor tics, chronic motor tics can occur during sleep, but are not associated with increased movements of the legs in general. Exercise related muscular pain, nocturnal leg cramps can be associated with electrolyte disturbances, neuromuscular disorders. I mentioned Osgood-Schlatter's. Chondromalacia patella is a fairly common orthopedic condition. But again, most of these other conditions are not exacerbated by rest. They're oftentimes exacerbated by movement and are oftentimes fairly easily distinguishable from RLS. So just a quick overview of the studies that have looked at the relationship between RLS and ADHD. So a number of studies now have shown that patients diagnosed with ADHD are more likely to have RLS symptoms and also to be diagnosed with periodic limb movement disorder. So this is a pretty well documented relationship at this point. Looking at directionally of children who are diagnosed with ADHD and then looking whether they have RLS symptoms or they have PLMD on PSG. And this is a study, the first one is a study looking at PLMs in particular and found that there was a significant increase in the prevalence in children with ADHD. And this is a little bit older study now, but this was a meta analysis of PSG studies and ADHD. And in that particular, at that time, they did not even find an increase in sleep disordered breathing in these PSG studies in children with ADHD, but they did see an increase in PLMs. And in fact, it was the only significant finding. So there clearly is this relationship with both RLS and PLMD. And it goes in the other direction as well, that children diagnosed with RLS, a substantial percentage of them have at least one comorbid psychiatric disorder, in particular disruptive behavior disorders such as ADHD. And we don't know what the mechanism is, but some of the theories that have been postulated is that the sleep disruption associated with RLS and PLMD results in manifestations of excessive daytime sleepiness in children, which essentially are very similar to ADHD symptomatology. That children who have RLS during the day, particularly when they're in school, they may look like they're hyperactive, like they're fidgeting, like they're moving around a lot. And that may be interpreted as ADHD. By the same token, ADHD symptoms in the evening, you know, in many children, they're on stimulants all day, which wear off around dinnertime, and they're essentially unmedicated in the evening hours. And so they may have an increase in movements and hyperactivity that may mimic RLS, but they typically will not have the associated discomfort. I think maybe an interesting and probably more plausible explanation may be that there's a common CNS pathology. We know that both ADHD and RLS are associated with dopaminergic, hypodopaminergic states and iron deficiency. And it may be that there is a co-inheritance of both ADHD and RLS, PLMD. So in terms of treatment, it's important to know that there are no double-blind controlled medication treatment studies in children, and there are no medications approved by use by the FDA for children under the age of 18. There are some case reports, which have shown improvement, for example, in ADHD symptoms with medication treatment for RLS and PLMD. But again, no double-blind placebo-controlled randomized studies. So we talk about treatment aims, AIMS, and so the first is avoidance of drugs and substances which can exacerbate RLS. And probably the most common that we see are children, or mostly adolescents, who are on antidepressants, particularly SSRIs and tricyclic antidepressants, but also any drugs that are dopamine antagonists, sedating antihistamines, antiemetics, can be associated with exacerbation. But typically those drugs aren't taken on a chronic basis, where obviously the antidepressants may be. Caffeine, nicotine, and alcohol can also exacerbate the symptoms, so that's important to look for in the adolescent population. Iron supplementation, I'm going to talk about that in more detail in just a minute. For some children, association with muscle activity, massage, or application of heat or cold can be helpful. There's some anecdotal reports to suggest that biofeedback might be helpful, muscle relaxation in the evening hours, and certainly good sleep hygiene. Having a regular sleep schedule, which ensures an adequate duration of sleep for the child's age, and just good sleep hygiene in general. The kinds of considerations to keep in mind are the severity of the symptoms, how frequently they occur, is the timing largely relegated to the evening hours, are there associated sleep complaints like sleep onset insomnia, what's the presence or suggestive symptoms of comorbid sleep problems like OSA, and in general, what's the impact on daytime dysfunction are all important considerations. In terms of oral iron therapy, we typically recommend ferrous sulfate, and this is either a tablet or a liquid, and the usual recommendation is for three to six milligrams per kilogram of elemental iron per day for three months period. And it's important to take this with vitamin C on it, preferably on an empty stomach to increase absorption and to avoid the co-administration of calcium-containing foods, which can actually slow absorption. So the goal in terms of ferritin level currently is 15 nanograms per ml in children. And the more recent recommendations in adults are more like 75 micrograms per liter. And this is where getting an iron, a measure of iron saturation may be helpful because in adults it should be less than 45 to avoid hemochromatosis. I don't think this is really much of a consideration in children. And in adults the duration of therapy is a bit unclear, but I think three months, as long as patients are adherent, is a reasonable ballpark to then retest the ferritin level. So there is some evidence to suggest that ferrous sulfate at three milligrams per kilogram per day results in improvements in PLMs and increased ferritin levels for at least two years. But there are challenges in oral iron. It doesn't taste very good, particularly in children. Getting them to swallow a tablet or capsule may be quite challenging. GI side effects, particularly constipation, are pretty common. And evidence suggests, recent evidence, that at least in adults the administration of oral supplement for ferritin levels greater than 75 to 100 is likely ineffective because at these higher levels absorption goes down. So the consensus right now is oral iron treatment for three months is considered likely effective in reducing clinical sleep disturbance in children with RLS and PLMD. And I will tell you that the vast majority of children that we do these ferritin levels in are hypoferrenic. Now what about IV treatment? This is really rarely used in the pediatric population. And even in adult adults, it's, you know, the usual tactic is to start with oral iron. But in particularly, ferric carboxymaltose has been used in adults with moderate to severe RLS symptoms. Another study showed that low molecular weight iron dextran is clinically effective in adults. So those are the two formulations of IV iron that have been used in adults. To my knowledge, there's only been one small study of children with pediatric RLS PLMD who were treated with iron sucrose at three to four milligrams per kilogram over two hour infusion period. There was a significant increase in mean ferritin and subjectively improved sleep. One of the big concerns with IV iron is the possibility of anaphylaxis. So I think most clinicians who go down this road would suggest pretreatment with IV diphenhydramine. So the potential advantages of iron, IV iron therapy are the rapid response, you don't have to worry about malabsorption issues, tolerance, compliance issues. But we really know almost nothing about how frequently you have to reinfuse, how long these effects last in children. So right now, the recommendation is that, you know, certainly, children with mild symptoms would not be candidates for IV iron, but those with moderate to severe RLS, if there's a medical contraindication, and you can interpret that however way you want, but for the use of oral but not IV iron. And this is an algorithm from a study that was published, a paper that was published just last year in Sleep Medicine, and I would highly recommend it. I think it was a very nice review of the empirical evidence, which in most cases is not strong enough to, to make recommendations based on that. But there were, it was a consensus of clinical experts, who kind of went through and created these algorithms. And this in particular, is what the suggestion is in terms of iron therapy for children, and when to consider IV iron. And you'll notice that the target ferritin level is still considered 50 here. But I think many clinicians, including myself, if a child continues to be symptomatic, we might really consider trying to get up around that 75 level. So I'm sure you're aware that in adults, again, these, this does not pertain to the pediatric population, because none of these are indicated for use in children by the FDA. Dopaminergic agents, dopamine agonists, pergolide is not used at this point. Opioids obviously have their own very significant drawbacks. Benzodiazepine, including on azepam, have been used for RLS. There was one study which suggested that that resulted in sustained subjective and PSG improvement in PLMs in patients with Williams syndrome. Again, this is a very small, non-randomized controlled trial. Clonidine is interesting because it is kind of the go-to drug for children with ADHD who have sleep onset problems. And one wonders if some percentage of those children who are successfully treated for their quote, unquote, insomnia with Clonidine are actually having their RLS symptoms improved. And bupropion has been studied in, in some, in adults. Gabapentin is a relatively newer, I think, proposed treatment for RLS in adults. And we do see, particularly our neurology colleagues are quite comfortable using gabapentin for children with RLS. And then, you know, a variety of different other medications have been used. The role of vitamin B12 deficiency in RLS, I think, in adults, it has been explored. I personally have started to get vitamin B12 levels, particularly in my patients who have refractory or severe symptoms. In general, they, I find them to be normal. And typically targeting the iron is really more effective. So these are just small studies of children who were treated with medication. This first one was Premopexil, found subjective improvement in PLMs, as well as resolution on PSG. The second study was the Open Label Trial of children with RLS plus or minus PLMs and ADHD who were treated with either L-DOPA or Pergolide, which found subjective improvements, improvement in parent reported behavior. This particular study also conducted some neuropsychological testing and found improvement. And interestingly enough, you know, almost half of those children no longer met ADHD criteria. But again, these are Open Label Trials. We really need randomized control trials to assess that. So I thank you for your attention. I want to remind you that in about two weeks, I believe, this presentation will be available on the AASM website. So if you want to re-review it, or if your colleagues did not have an opportunity to sit in on this presentation, it will be available. So if anybody has any additional questions, I'm sorry, I'm just looking at the one question that I've got. So why family history question of PLMs more than five per hour, when adults in that child's family will only be recognized if PLMs are more than 15 per hour? So I think that some of these studies were older studies, where five per hour in adults was considered potentially significant. Absolutely, you're correct in saying that the cutoff for PLMs in adults is higher than it is in children. And if, you know, that study was to be redone with the higher threshold, you know, that may show a different relationship. But, you know, the issue is that I think most, even most adults with RLS, or many of them may not have ever had a confirmatory sleep study, which showed how many, you know, what their PLM index is. So I would say that that is a less important additional factor in terms of family history to consider. And again, I want to emphasize that getting a definitive history of even RLS in first degree relatives of children who present with symptoms is quite challenging, because, as I'm sure you well know, many of these adults never get diagnosed with RLS, but may have symptoms. And that's worth questioning about. So it doesn't look like there are any other questions. I'll give things a few more minutes. I know that was a quick run through. But what's interesting to me is that I see a lot more children who have particularly RLS symptoms, whose pediatricians recognize the relationship between RLS and low iron, and particularly low ferritin, and have actually already done a ferritin level on these children. The problem is that if you look at the laboratory parameters for determining low ferritin levels, if you have a ferritin level of 30, that's considered normal by labs. And so if the pediatrician is going by that and not recognizing this 50 cutoff, I find many of these families were told by their pediatrician that the ferritin level was, quote unquote, normal. The other thing that happens is that the child will have a CBC done and will have a normal hemoglobin and hematocrit, because their ferritin level is not low enough to actually be anemic. So if you only do that as your screening test, then you may miss a substantial number of these children. So another question, would it be okay to advise parents to give the liquid iron mix and orange juice for kids who have difficulty taking iron? You could. I don't think that would be problematic, except that I don't honestly find that orange juice is terribly effective at masking the taste. There are some brands of liquid iron, which seem to be much more palatable for children. I'll mention one. I don't have any stock in the company, but there's a brand called Nova Ferrum, which has a raspberry grape flavoring to it that actually seems to go down much more easily. It's also, I would advise, if you're using oral iron, to go for the highest concentrated form so that the amount that, and remember it's elemental iron that is important to keep in mind. So, for example, for ferrous sulfate, a 325 milligram tablet has only 65 milligrams of elemental iron. So that, you know, a more concentrated form is going to be helpful. The other thing is that iron can stain the teeth. So usually we advise that if a child is going to take oral liquid iron, that they take that through a straw and that they also rinse out their mouth afterwards to avoid that issue. So it looks like we don't have any additional questions. Thank you for your attention. You're certainly welcome to contact me at this email address if you come up with any other issues or comments or questions, but thank you and stay warm.

Dr. Judith Owens

Sleep Medicine

Boston Children's Hospital

Neurology

Harvard Medical School

restless legs

periodic limb movement disorder

pediatric population