Oncology treatments save young lives but impact neurocognitive development and psychosocial health, potentially causing problems such as IQ, memory, and hearing deficits, as well as depression, anxiety and social difficulties. Pediatric neuropsychologists Gina Pfeifle, PhD, and Shannon Lundy, PhD, explain the harms of specific cancer therapies, how pediatric providers can be alert to problems in survivors, and the merits of specialized evaluation for a kid who’s struggling academically or emotionally.
mm. Thank you all for joining us today we are going to talk about as tabatha announced the neuro cognitive and psychosocial lead effects in oncology patients. We have a few objectives. We're going to talk about late effects and what they look like in the pediatric oncology population with a primary focus when we say oncology on a little and or leukemia patients as well as pediatric brain tumor patients, the role that pediatric neuropsychology plays. Um and an overview of neuropsychological evaluation in that process and what that looks like as well as referral and management guidelines. Again, thank you so much for having us here today. I'm going to start off and talk about the late effects and then I'm dr faithful will go ahead and jump in and do the latter part in terms of the pediatric neuropsychological evaluations, the utility of this type of assessment and overall referral and management guidelines. So when we talk about late effects, um, you know, most of you are really kind of familiar with what that is but kind of the definition of elite effect issues that arise following a medical condition that lead to complications, disability and possible adverse outcomes. Um, they can occur when we, you know physically and so um that's important to think about those tend to happen right away. But one thing about late effects as they can occur months, two years following the completion of treatment. Um Typically we say anywhere from right when treatment starts to happen and or the um represents itself to five years and sometimes even more out physical are things like cardiac endocrine dysfunction, gross and fine motor problems. Um, sensory issues that have arisen visual field, cut sand or hearing loss. And many survivors are really kind of unaware of these risks. And that isn't to say that families have been made aware of the potential risks related to treatment. But there's just so much going on in the immediacy of such a difficult diagnosis and there's such energy put and really trying to save the child and manage all the different treatments and their needs that I think a lot of that can sometimes be lost. Um, it's just hard to process and understand everything when you're when you're living day to day and thinking about long term, what does all of this mean? And then we look more in terms of, you know, the neuro cognitive social and psychological ones physical kind of appear right right away. But these are things that really emerge over time and development of a child. Um, and I think that we really see that because certainly for Children who are diagnosed at younger ages with development, there is expectation to master increasingly complex cognitive tasks, but also take on higher level experiences from a social emotional and psychological perspective, late effects. When you look at the literature and the pediatric oncology population are real and significant to about a three survivals, survivors will experience at least one late effect. four out of 10 survivors will experience multiple effects. One out of four survivors survivors will experience really severe late effects and certainly late effects are most apparent and prevalent in the cNS directed therapy. So the pediatric brain tumor population is kind of most at risk for some of these. And I think what's really hard is we don't know at this point how to reliably predict in advance which patients will develop cognitive late effects and which ones will not, they're just really not well understood at this point in time. So here is just a nice model from a developmental perspective, looking at all the factors involved in their cognitive late effects. Um First you look at the child themselves, genetics certainly in that profile play a role not only from pre morbidly genetically what they potentially have issues that are already existing. If there's a family history, for example of things like dyslexia and or significant mood issues and or A. D. H. D. Also genetics matters when you're starting to look at different treatment options. Um depending on the type of cancer, the age and gender can really mattered. Things also like tumor type and or leukemia, high risk, low risk all these kind of factors really play a role. When you look at direct cNS therapy in terms of like location size of tumor if the child has had hydrocephalus. Um that can certainly make them more at risk than for earlier on developing cognitive issues. Um short term memory attention, Executive function problems are highly associated with hydrocephalus. um and also um in terms of just kind of treatment itself that they have, you know, surgery, there's complications treatment that they need radiation chemotherapy. What type, how is it going to be administered if they're going to end up meeting a bone marrow transplant? Any complications that arise from any of those treatments, all of those things certainly play a role. And then other associated issues are the psychological, what is the child's life environment? What is the child's world context? There's going to be huge periods of time where there's a lot of isolation from a social perspective, there's a tremendous amount of pressure and strain put on family systems, um parents, siblings, um and then social socialization in general, kids have a lot of isolation. They're not getting to do normal. Typically developing things that they would be doing um and they're not getting to participate in any of those types of experiences. So these are all factors that play a role and development. You will certainly know this. But in the brain, what changes with development? Lots and lots of different things, You know, new systems are coming online all the time. There is certainly increasing sophistication of brain systems over development, there is more interactions among systems throughout the course of brain development. Um Systems that support a skill at one age, certainly at younger ages are not going to be the same systems that are supporting those skills at a later date. Um so what's happening in a five year old's brain from a language perspective looks much different na adolescence brain and there's a lot of increasing specificity and integration across development with all the networks that are being created. And there's additional change created by the fact that this child has become sick. So the task of formulating strategic adaptive responses to the injury and insult itself becomes very important from a developmental perspective in terms of factors to keep in mind. Kind of getting more into some of the neuro um cognitive challenges and the nitty gritty of what things like surgery, neurosurgery challenges, kind of how those impact overall development and these late effects. Sometimes a complete resection is certainly not feasible. Uh There are many neurological andro sensory deficits that can be associated with three sections. Children can certainly for brain tumors end up developing something called posterior fossa syndrome and cerebral are mutism syndrome. And even though they can recover, they may have ataxia, They may end up having mutism. They may have a lot of emotional ability and these things can certainly resolve all over a period of time, usually 4-8 weeks after. In general. These Children tend to have a much worse outcome from a neurocognitive perspective than um they're the group who doesn't have proposed area fossil syndrome. So that's important and then cranial radiation challenges. We um during this time of therapy, we have rapidly developing systems that are certainly more vulnerable to injury. And we know for a fact with a lot of research to back it up, that younger Children are much more vulnerable if they're going to have radiation to having long term impact of our cognitive issues. Um and just in general, I mean you're reading a young brain and the volume of white matter when you are younger and you're having whole brain radiation, the overall volume and reduction of what that white matter system is going to look like later on is definitely reduced. Um and white matter injury definitely occurs. You know, the linkedin joseph precursor cells are damaged. Those are the cells that take care of Myelin and that Myelin Ization process does not happen like it's supposed to and then hit the campus just really zapped during radiation and we know that the hippocampus is responsible for helping us learn and form and create new memories and or just learn new information and a lot of the cells are or die off as a result of radiation and we don't really have any good way to know how to make those certainly cells come back, how quickly and how much we can make the cell proliferation happen is something that we don't know how to control. And so really you just see from a developmental perspective that this effect on treatment and the normal white matter development is completely interrupted and therefore the complex information transmission network of what white matter systems do is forever kind of changed and derailed. From a developmental perspective, there is really some hope that with proton being radiotherapy, it's really a big advancement for brain tumor patients because the radiation is focused on the tumor itself. Therefore, therapy is kind of more sparing of surrounding areas. So you're not targeting the whole brain anymore, You're really just going into one section and there's a lot of hope that this is going to limit the neurocognitive impact. And there's some there's limited availability in terms of what we know if it's going to be positive or not. But so far the literature is looking very good. But having access to that. You know, this kind of therapy is not everywhere, not every institution has it. And so there is already kind of a bias in those families that are able to then go find this kind of treatment. It's not offered everywhere. So there's limitations in that. Um, as I said, the cognitive outcomes, we're just we don't know yet what that means, but there is hope that that's going to be better, you know, from the literature, we know that radiation, there's significant deficits in EQ, particularly for Children, um, that are rated under the age of six. Um, There's been a lot of Meta analysis reviews that happened throughout the 70s, into the late 80s, early 90s, looking at several different studies that showed significant deficits in patients who are radiated. Um Typically there's about a 10 point our reduction from baseline of IQ over time in terms of what you see. And there's also a lot of other deficits. There's kind of a course that of cognitive processes, processing speed, attention, and working memory that are um certainly tasked and can be very problematic, but there's also verbal and language abilities. They appear less likely to be impacted but certainly verbal learning and memory. That is not the case for. And all of these taken together really highlight um that there is going to be slowed learning across cognitive and academic domains because things don't get easier from a cognitive and academic perspective, they actually only get harder as a child advances in age, you know, when you look at chemotherapy alone um there is um typically um there's a kind of variable literature because there's a lot of different treatment protocols that are used, but methotrexate toxicity is often associated with damage to the cns white matter. It's called leukoencephalopathy. Um it's really been shown to reduce cerebral glucose metabolism resulting in cellular damage into the Violin nation. Again, it's the white matter systems. Um and despite the elimination of radiation for most allele treatment protocols into ethical insisted um systemic chemotherapy has have still been shown to cause acute and long term damage to the brain. Um you see um common changes from inner imaging perspective in white matter widening of the ventricles and results I and cerebral calcifications reduce preferential core tricks, cerebellum and cortical white volume matters are also reported and as the peak age of ale on so often time is during occurs during a period of pretty critical brain myelin nation within the provincial cortex. The timing of that method truck state administration and brain maturation. Um probably explain some of the reduction of the frontal white matter. Um and then the long term association with executive function deficits that we end up seeing from the late effects perspective. And at this point it's really unclear if mono therapy versus triple therapy will change any of this, but we certainly know that high dose treatment into ethical administration and also also a younger age, these Children are more at risk and then there are specific chemotherapy agents that are very well documented to cause certain types of late effects. So for some spotting it, so toxicity causing hearing loss, this is something that's monitored very closely now and then it has to be reduced but for certain protocols that can be really challenging for just overall treatment and cure of disease. Then Christine definitely associated with peripheral neuropathy. And another thing that is definitely closely followed. And then the use of politico corticosteroids, neural toxicity occurred regularly in the hippocampus. We really know this because this is a high concentration corticosteroid binding site. And so it's really not surprising that memory deficits for them later on scene from kind of a late term perspective, effective perspective. And with treatment that's been used for this there is some hope in terms of advancements advancements that are being made from a chemotherapy perspective. Um There's a lot of work being done to design therapies for specific gina types and there's a lot of hope that this is going to help lead overall to better outcomes and much less narrow toxicity. But there's you know that we're really in the early stages of that. You know when you look at chemotherapy alone those treated who are just getting chemotherapy not radiation, there are still very very much neurocognitive effects that we see during the acute treatment phase. Um There's definitely a reduction in motor speed and working memory. These tend to be the domains most commonly affected at that point. And then um by the end of therapy there is really a lot of Children tend to show lower performance and direct measures of attention and processing speed and a lot of this seems to be associated with the age of diagnosis and gender of the child. Um And then there are also from a long term changes among Children 2 to 5 years post remission. Um There have been shown to not have lasting of deficits necessarily in I. Q. But there are negative trends that do occur consistently in domains of visual motor integration, mass ability. Even though I like you kind of typically remains stable. Um And then the relationship right now between cognitive deficits and methotrexate appears to really be dose dependent. So both the number of doses and the cumulative doses have been associated with deficits in the visual motor spatial domains and overall global I. Q. Deficits into our reductions. And then for some of our leukemia patients who are high risk and the chemo therapies are not working. They need to have bone marrow transplants and there are cognitive effects of bone marrow transplants are certainly largely related to the preconditioning as well as the risk factors inherent in the disease process itself and all the treatment that's happened prior to that. And then there are obviously complications that can happen from a post transplant perspective that require additional pharmacological treatment and or lead to other medical morbidity ease and these then can further impact overall um neurocognitive defects but just quality of life and Children. And here's just a nice I think overall kind of graph when you're thinking about this idea of of emerging lead effects growing into deficits. These are kind of terms sometimes that are that are talked about especially for a younger patients because from a developmental trajectory it's not necessarily that they aren't making developmental progress on their own little line. But as you can see from this graph as things as they get older and things become much more complicated from a cognitive perspective that gap between them and their peers grew growing bigger and bigger and in general just kind of as a review. So you see impacting over like you increase academic difficulties, attentional problems as well as various executive function issues, working memory and processing speed, memory as well as fine motor and visual motor integration. Um and you also see the problems with just overall functional independence and activities of death of daily living. These are all areas that really impact that development and that widening gap as Children are compared to their peers over time. And then there are psycho, social or psychological impacts that are really important to consider. Uh there are many psychosocial and behavioral issues related to treatment. Um lots of symptoms of anxiety, depression, fear, anger wise, it's happening to me so many kiddos can have a lot of trauma associated with going to the hospital so many times and having so many procedures and what treatment in and of itself entailed. Um and all of these factors certainly impact their overall adjustment and sense of self. Um really there's also tons of social isolation that happens because they're not able to be interacting and doing the typical things with their peers that would be of a normal developing child. And so they're missing out on all of those experiences. Um and there can be a lot of physical changes that happen to them and their kiddos who can no longer participate in the things that they once found useful because of now physical deficits that they have and they're not able to integrate or interact in the same way with their peers that they once did. So it's forming new relationships, having new interests and that can be really, really hard. Obviously that can lead to self esteem issues, just struggles in general with knowing who they are in relation to their peers. And then I think more broadly from an adaptive functioning perspective, there can be lots of conceptual, practical and social concerns that arise. So even though Children may be on testing have intact or so, so it seems in many cognitively intact skills and or academic skills, their awareness conceptually of kind of how they navigate the world practicality in terms of getting up and doing remembering routines and things like that. Um can really be changed and altered with a lot of um support routines and kind of practice and rehearsal around those kinds of things after treatment is over. So really for these patients, there are a lot of long term challenges that they face. There is certainly an increasing number of adult survivors and there is definitely a diminished cognitive reserve associated with cns insult and we know that it's a heterogeneous population. The quality of life from a survivorship perspective is really faced with developmental challenges um that are part of adolescent and emerge into adulthood and they really require a lot of intervention and follow up over the lifespan, there's just lots of different kinds of issues that can arise even secondarily for some of these kiddos who are living because it's secondary issues like other malignancies, they can have great these endocrine issues that can really be on medications for the rest of their life for replacement therapies, the hearing and vision factors um Really will impact the way they integrate with the world going forward. Um and then all the psycho social things are also a huge part two. So now we're going to switch and dr faithful is going to spend some time talking about how neuropsychology plays a role in all of this. Hi everyone. Um So um when we think about pediatric neuropsychology in general, we feel like, you know, a lot of times it's helpful to do just like a little bit of an overview of what exactly it is um and how it can be useful in um situations of evaluating various medical disorders in this talk will talk specifically about pediatric oncology of course. So pediatric neuropsychology is a specialty within clinical psychology that is most concerned with the way the brain impacts behavior accepted training standards for specialization in pediatric neuropsychology includes specific graduate coursework and clinical training in neuro anatomy. Medical disorders and psychology, Including a pre doctoral internship in two year postdoctoral fellowship in pediatric neuropsychology specifically. Okay, the utility of pediatric neuro psychological evaluations within the medical sitting can include things like helping the medical team to clarify developmental and or psychological diagnoses in the context of the child's underlying medical disorder, helping family members and medical teams develop a better understanding of who the child is in the context of their specific situation, so their particular medical disorder, their family context and their cultural background and importantly to help guide interventions that are going to support and help the child over time. So these can be cognitive, academic or psychosocial in nature. Okay. The goal of a neuropsychological evaluation is to tell a story of who the child is to help foster understanding of their needs. So how do we do this First we obtain a comprehensive review of patient history, including an integrated presentation of family, medical, developmental, social, emotional and educational history. Next we evaluate the overall cognitive profile of the child, looking at a variety of domains and highlighting their specific patterns of strengths and weaknesses and then clinical analysis is conducted based on the collected data and the history in the context of the relative, the relative or relevant. Excuse me, medical diagnosis when it happened in development, what was affected, what was the treatment course? And how does that now play a role in who this child is. And finally, we make then appropriate recommendations and interventions tailored for the patient. This includes services and supports across all the settings that the child exists in. So neuropsychological assessment is really a process. The testing itself is really just one piece and the assessment is an overall process of clinical management. So we're going to look at each of these steps in just a little bit more detail. So first we have data collection which is a multi step process that includes history gathered in the parent intake observations of the child during testing and direct test results and scores from the evaluation. So within the history our goals are to determine what the child is bringing to the table. What have they been exposed to this far? What are their potential biological risk factors like? So getting a good family history Like is there a family history of language disorders, their dyslexia or anything like that? Has the child been able to take advantage of the learning exposures they've had so far? Like how have they done and what's their development in general looked like today. And then observations are a really large part of our clinical work in the room with a child beyond the direct test administration. So within the testing environment we're looking at how they interact in structured setting. How well do they engage, what's their activity level? How social are they importantly, what are their behavioral and problem solving styles? Under specific performance demands? Were also able to do some observations of their behavior and more natural environment. So what's their general appearance? How do they behave in the waiting room? What's their interaction like with their parents? Does this match what we heard in the interview process and so on. Yeah. The next step in data collection which is actually happening at the same time as a lot of our observational data is the testing itself. So a neuropsychological evaluation assesses the child's functioning across many domains, Things like overall like attention and executive functioning, language ability, visual processing, fine motor functioning memory, psychosocial functioning and adaptive abilities. The specific concerns raised by the parents and the treatment team, as well as the known cognitive risk factors of the child's medical condition will help guide how much testing is done in each area. So for example, um with a kid who has a. L. L. For example, you would want to make sure that you're doing a lot of assessment around attention, executive functioning processing speed because those are things we know are at risk in kids with pediatric oncology diagnosis. Um It's important to note that we do not typically assessed much academic achievement for multiple reasons. First and foremost, issues with academic achievement. Cannon should be assessed within the school setting. So because of this it is typically not possible to get insurance coverage for academic specific testing. Additionally, as neuropsychologist, we are more concerned with the underlying cognitive processes that cause academic achievement issues than the specific academic deficits that may be found. So within this context we will sometimes include targeted assessment of specific academic issues when they're relevant to a child's medical disorder. So for example, we may evaluate reading in a child with a l. L who missed a lot of early reading instruction due to school absences but we're not going to typically do a ton of academic testing in every assessment because of the factors that I mentioned before moving on to test interpretation. So when you're looking at a child's score tables, you could probably fairly easy pick out what domain the test assessed and how well the child did compared to age expectations. Were they performing at above or below what you might expect. But just looking at scores alone can be misleading. So many tests can be impacted by multiple cognitive and behavioral factors. So what we call like a one size fits all interpretation can often be incorrect for a specific patient in front of you. In general tests rarely assess one domain cleanly. Um So a lot of the tests require multiple sensory systems, visual motor auditory and second deficit in one domain may impact performance on a test designed to assess another domain. So for example, Children with weaknesses and attention and executive functioning often have variable performance on learning and memory tasks. But we would not then say that they have a memory deficit. So if they're not paying attention when you read them the story. If they can't remember the story later, that's really not their memory, that was their attention overall this is why it's important to have a comprehensive battery that assesses the demands from multiple angles. So you're not facing your interpretation on a single sub test or observation of behavior. Clinical analysis is the consolidation of all the data that you've collected in the context of your individual patient. So it's where we would synthesize the overall test data with relevant history and clinical presentation. It's here that we determine a child's strengths and weaknesses both within their own profile and compared to their same age peers. We then use this information to determine their pattern of performance as well as their overall developmental trajectory and following clinical analysis. You can then make the diagnosis as applicable for a given child. The final step in the evaluation process is management. So first we need to consider things like how this child's profile presents and how does it impact their daily functioning. So two Children can have the same profile but present quite differently and how their strengths and their weaknesses manifest and how pervasive the pervasive those weaknesses are. So the management approach may be different across different kids for that reason. And then also there are risks forgiven Children based on their specific history and presentation. So we want to think about all aspects of risk, cognitive, academic, social, emotional behavioral as well, both short term and long term risks. We can then develop recommendations to address and support these areas. So the goal is for us to help the child become a comfortable and competent child and adolescent and eventual adults. So when we talk about comfort, we're talking about like comfort emotionally, socially competent and when we talk about competence, we're thinking about that they are able to participate in their environment independently and take care of themselves, that academic and vocational achievement is successful. Um In general your recommendations need to be tailored to the individual patient and their context. So you want to consider the time required for given recommendations. The resources available to the family and the family's goals and circumstances. So private therapies are not available to everyone and resources are not just financial. So it's also about the time constraints and the needs of the whole family um within their family system. The information gathered during the evaluation, the diagnoses that are being made and the recommendations being provided are then communicated through a variety of means. So there's feedback with parents that's provided face to face or via telehealth. Um That's crucial to really communicate the main findings and priority recommendations. These appointments also allow opportunity for questions and interactive discussions with the family. Then there's a written report that documents the what, how, why and what to do next. And it can be helpful for parents schools and the medical team and then there can be school meeting participated participation. So for certain families um you may participate in this. This is sometimes hard for us to actually attend but when we can we like to um this can help to integrate findings for the school team, Help ensure that the recommendations make it into special education plans and also provide additional information in psycho education about how the child's medical history is really contributing to their needs, both short and long term at school. Yeah. So now that we've reviewed what a neuropsychological evaluation entails will discuss the overall referral guidelines for pediatric oncology patients. So overall recommendations for assessment, our baseline or pre treatment and then regular re evaluation every few years, notably baseline evaluations are pretty tricky. And oncology patients. So these are kids that are moving really quickly from diagnosis to treatment and a lot of times are already sick by the time of diagnosis, like there being diagnosed because they were already presenting the symptoms right? Um and because of that and the need for speed to start treatment. Typically if you are doing a baseline evaluation really close to diagnosis, it's not really a true baseline neuropsychological terms because it didn't occur prior to the development of the medical condition itself. Sometimes you're lucky and the kid had school testing prior to the development of their medical condition and then that would be a true baseline. Um The Children on Children's oncology group has a standard assessment battery and used for tracking their cognitive data over time and oncology patients. The lT this is a screening battery designed to be administered a designated time points. So um plus or minus a few months. So uh nine months, approximately 2.5 years and five years post treatment, the beginning of treatment um in the pediatrician's office. The goal would really to be ensure monitoring of the common complaints seen in Children following cancer treatment, remembering that some of these effects will become more prominent in the years following cessation of treatment. So essentially in any pediatric oncology patient, there should be a high suspicion of late effects of treatment for any cognitive complaints brought up by the parents. So things like increased complaints about academics, attention, executive functioning, processing speed, find vulnerability or memory um should be especially considered um of potential concern. Additionally, as we previously discussed, there's some common psychosocial presentations following treatment that could benefit from supports um including behavioral dis regulation, anxiety, pure difficulties in the A. L. L. Population in particular. Something that is often seen is that once they've made it through that sort of like initial phase of treatment, they're no longer worried about their child surviving and they're moving back into normal life. That can be like a really hard period of transition for the kids because they're kind of used to getting whatever they want. There's been like reduced expectations for them at home. And suddenly as their parents are starting to put inappropriate expectations again in the home setting, there's some challenge and tension there. So that's a common thing. You see a big component of support for these families and the pediatrician's office would be around resource provision for known late effects. So things like helping families to know their school rights and how to request will based evaluations is needed referrals for individual or family therapy to address any of the psychosocial issues that are being seen, potential medication management of attentional concerns and support for overall health. So guidance regarding the benefits of nutrition and exercise in general, there are some potential treatment options available for cognitively defects and we'll talk very briefly about the different options that are available and some of the benefits and drawbacks to these different options. So cognitive remediation programs are programs that generally look at one skill or small subset of skills and their direct um sort of training programs that try to address specific known cognitive problems. They're typically multidisciplinary in nature and includes support from school professionals, rehabilitation doctors and clinical psychologists. Um They're typically pretty intensive, individualized and expensive. And there aren't a lot of these programs available for this type of support. So there are certain programs known programs in the country that offer this type of support, but it's not something that's really commonly available at all hospitals. Um There are cognitive computerized programs that are more widely available and these include things like kogi state cognitive animosity et cetera. And these programs generally consist of sort of repetitive task specific training with increased difficulty over time in general. Within our field, there's lots of concerns for generalize ability with these programs and the ones that have best documented outcomes typically also require individual coaching or support some more um you know, uh more time invested into the program and more supports around the Children uh completing them. Pharmacological treatment consists of a few different strategies. So there are stimulants for attentional concerns in the oil population, stimulants are often typically less effective in the brain tumor population modafinil has been shown to have benefits for cancer related fatigue. Um Aricept has been shown to have some very preliminary E. F. And memory support for childhood survivors. And then Metformin is something that's being studied currently with the goal of brain repair and cognitive restoration. This is currently in clinical trials right now at hospital for sick Children. And finally there is some sort of like well established guidelines for exercise uh suggesting that this can have some beneficial effects um With no adverse concerns. And lots of positives that you know are just in addition to the to the effects uh the late effects support that they can provide. So um some of the less appreciated cognitive benefits of exercise include um some benefit to learning and memory, some delays in age related memory decline and some you know I think more well known as obviously the mood benefit to it. So that's the completion of our talk