Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations.

BACKGROUND: ATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. AIM: We aimed to describe the manifestations of early onset severe ATP1A2-related epileptic encephalopathy and its underlying mutations in a cohort of seven patients. METHODS: A retrospective chart review of a cohort of seven patients was conducted. Response to open-label memantine therapy, used off-label due to its NMDA receptor antagonist effects, was assessed by the Global Rating Scale of Change (GRSC) and Clinical Global Impression Scale of Improvement (CGI-I) methodologies. Molecular modeling was performed using PyMol program. RESULTS: Patients (age 2.5-20 years) had symptom onset at an early age (6 days-1 year). Seizures were either focal or generalized. Common features were: drug resistance, recurrent status epilepticus, etc., severe developmental delay with episodes of acute severe encephalopathy often with headaches, dystonias, hemiplegias, seizures, and developmental regression. All had variants predicted to be disease causing (p.Ile293Met, p.Glu1000Lys, c.1017+5G>A, p.Leu809Arg, and 3 patients with p.Met813Lys). Modeling revealed that mutations interfered with ATP1A2 ion binding and translocation sites. Memantine, given to five, was tolerated in all (mean treatment: 2.3 years, range 6 weeks-4.8 years) with some improvements reported in all five. CONCLUSIONS: Our observations describe a distinctive clinical profile of seven unrelated probands with early onset severe ATP1A2-related epileptic encephalopathy, provide insights into structure-function relationships of ATP1A2 mutations, and support further studies of NMDAR antagonist therapy in ATP1A2-encephalopathy.

Social impairments in alternating hemiplegia of childhood.

AIM: To evaluate presence and severity of social impairments in alternating hemiplegia of childhood (AHC) and determine factors that are associated with social impairments. METHOD: This was a retrospective analysis of 34 consecutive patients with AHC (19 females, 15 males; mean age: 9y 7mo, SD 8y 2mo, range 2y 7mo-40y), evaluated with the Social Responsiveness Scale, Second Edition (SRS-2). RESULTS: SRS-2 scores, indicating level of social impairment, were higher than population means (75, SD 14 vs 50, SD 10, p<0.001). Of these, 27 out of 34 had high scores: 23 severe (>76), four moderate (66-76). All subscale domains, including social cognition, social communication, social awareness, social motivation, restricted interests, and repetitive behavior, had abnormal scores compared to population means (p<0.001). High SRS-2 scores were associated with the presence of autism spectrum disorder (ASD) and epilepsy (p=0.01, p=0.04), but not with other scales of AHC disease symptomatology. All nine patients who received formal evaluations for ASD, because they had high SRS-2 scores, were diagnosed with ASD. INTERPRETATION: Most patients with AHC have impaired social skills involving multiple domains. ASD is not uncommon. High SRS-2 scores in patients with AHC support referral to ASD evaluation. Our findings are consistent with current understandings of the pathophysiology of AHC and ASD, both thought to involve GABAergic dysfunction. WHAT THIS PAPER ADDS: Most patients with alternating hemiplegia of childhood (AHC) have impaired social skills involving multiple domains. These impairments are significant compared to population means. Most patients with AHC have high Social Responsiveness Scale, Second Edition (SRS-2) scores. Patients with AHC with high SRS-2 scores are likely to have autism spectrum disorder.

Psychosocial Burden of Childhood Sickle Cell Disease on Caregivers in Kenya.

OBJECTIVES: To characterize the types and magnitude of psychosocial burden present in caregivers who have a child with sickle cell disease (SCD) in Kenya and to identify predictors of caregiver psychosocial burden, including disease severity and financial hardship. METHODS: Primary caregivers (N = 103) of children aged 1-10 years diagnosed with SCD completed surveys assessing multiple domains of caregiver quality of life (QOL), adjustment to child illness, mental health, and financial hardship. Descriptive statistics characterize psychosocial burden, and linear models assess associations. RESULTS: On indicators of QOL, caregivers report multiple difficulties across most domains, including daily activities and physical, social, cognitive, and emotional well-being. Daily activities emerged as most burdensome. On indicators of parental adjustment to chronic illness, guilt and worry emerged as the greatest concern, followed by long-term uncertainty and unresolved sorrow and anger; relative to these, they reported higher levels of emotional resources. Financial hardship was high, as caregivers reported moderate to major financial losses due to the time spent caring for their child. General linear model analyses revealed that level of financial hardship was a significant predictor of all negative psychosocial outcomes. CONCLUSIONS: Results document that Kenyan caregivers of children with SCD experience difficulties across multiple domains of functioning and that financial difficulties are likely associated with psychosocial burden. Results can guide intervention development for caregivers of children with SCD in low-resource, global contexts.

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype.

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes.

Cognitive, adaptive, and behavioral profiles and management of alternating hemiplegia of childhood.

AIM: To determine the neuropsychological abnormalities that occur in alternating hemiplegia of childhood (AHC) and report on our experience in managing them. METHOD: Patients underwent evaluations according to our standardized AHC pathway. Data were entered into our prospective AHC database and then analyzed. RESULTS: Of the cohort of 25 consecutive patients (ages 15mo-42y), eight had initial chief complaints about cognition, 14 language, five attention, and 11 behavior. As compared to population norms means, neuropsychological and behavioral assessment tools (including Child Behavior Checklist, Vineland Adaptive Behavior Scales, Peabody Picture Vocabulary, and Wechsler Intelligence Quotient tests) showed significant impairments in multiple domains: cognition, expressive and receptive language, executive function/attention, and behavior (p<0.05 in all comparisons). Evaluations generated management recommendations in all patients. Twenty had neuropsychiatric diagnoses: 10 attention-deficit/hyperactivity disorder (ADHD), seven disruptive behavior, and three anxiety disorder. Eight out of nine patients with ADHD who were prescribed medications responded to pharmacotherapy. INTERPRETATION: Patients with AHC have developmental difficulties related to impairments in multiple neuropsychological domains. This supports the hypothesis that the underlying AHC pathophysiology involves diffuse neuronal dysfunction. Testing generated recommendations to help manage these difficulties. Patients with AHC also have a range of neuropsychiatric diagnoses, the most common being ADHD which responds to pharmacotherapy. WHAT THIS PAPER ADDS: Patients with alternating hemiplegia of childhood (AHC) have developmental difficulties with underlying neuropsychological impairments. The findings in this study are consistent with an underlying AHC pathophysiology which involves diffuse neuronal, probably largely GABAergic, dysfunction. Patients with AHC have a range of neuropsychiatric diagnoses, the most common being attention-deficit/hyperactivity disorder.

Mobile health intervention for youth with sickle cell disease: Impact on adherence, disease knowledge, and quality of life.

BACKGROUND: Adherence to illness self-management among youth with sickle cell disease (SCD) positively impacts health outcomes and decreases overall healthcare costs. Despite this, children with SCD face several barriers to adherence, with adherence rates that remain moderate to low. The current feasibility study examined the Intensive Training Program (ITP), a mobile health (mHealth) intervention for youth with SCD designed to promote disease knowledge, adherence, and patient-provider communication. PROCEDURE: Youth with SCD prescribed hydroxyurea between ages 7-18 completed baseline disease knowledge and psychosocial assessments and then were provided with the ITP app. Youth participated in the 90-day ITP, during which they completed three education modules, tracked adherence through daily self-recorded videos on the app, and received video messages from providers. Participants completed poststudy knowledge, psychosocial, and feasibility questionnaires. Medication possession ratio (MPR) was obtained via pharmacy-refill rates. RESULTS: Thirty-two youths (mean age = 13.0 years) participated, with an average adherence tracking rate of 0.6 (standard deviation = 0.34). All participants demonstrated increased MPR (0.57-0.74, P < 0.001, d = 0.75) and disease knowledge (59.6-88.6%, P < 0.001). There was variable engagement in the ITP; completers demonstrated significantly better SCD-related functioning (P < 0.05), higher parent-reported treatment functioning (P < 0.05), and lower pain impact than noncompleters of the ITP (P < 0.05). CONCLUSIONS: Results support the ITP can feasibly be implemented to promote adherence among youth with SCD. All participants demonstrated increased adherence and disease knowledge. However, there was variable engagement and only intervention completers showed improvements in psychosocial outcomes. Further research is needed to evaluate long-term outcomes and ways to promote engagement in mHealth interventions among the youth.

Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. FINDINGS: Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10-8·98). Non-inferiority (p=8·82 × 10(-16)) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). INTERPRETATION: For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health.

Quinidine in the treatment of KCNT1-positive epilepsies.

We report 2 patients with drug-resistant epilepsy caused by KCNT1 mutations who were treated with quinidine. Both mutations manifested gain of function in vitro, showing increased current that was reduced by quinidine. One, who had epilepsy of infancy with migrating focal seizures, had 80% reduction in seizure frequency as recorded in seizure diaries, and partially validated by objective seizure evaluation on EEG. The other, who had a novel phenotype, with severe nocturnal focal and secondary generalized seizures starting in early childhood with developmental regression, did not improve. Although quinidine represents an encouraging opportunity for therapeutic benefits, our experience suggests caution in its application and supports the need to identify more targeted drugs for KCNT1 epilepsies.

Cognitive functioning one month and one year following febrile status epilepticus.

OBJECTIVE: The objective of this study was to determine early developmental and cognitive outcomes of children with febrile status epilepticus (FSE) one month and one year after FSE. METHODS: One hundred ninety four children with FSE were evaluated on measures of cognition, receptive language, and memory as part of the FEBSTAT study and compared with 100 controls with simple febrile seizures (FSs). RESULTS: Children with FSE did not differ dramatically on tasks compared with FS controls at one month after FSE but demonstrated slightly weaker motor development (p=0.035) and receptive language (p=0.034) at one year after FSE. Performances were generally within the low average to average range. Within the FSE cohort, non-White children performed weaker on many of the tasks compared with Caucasian children. At the one-year visit, acute hippocampal T2 findings on MRI were associated with weaker receptive language skills (p=0.0009), and human herpes virus 6 or 7 (HHV6/7) viremia was associated with better memory performances (p=0.047). CONCLUSION: Febrile status epilepticus does not appear to be associated with significant cognitive impairment on early developmental measures, although there is a trend for possible receptive language and motor delay one year after FSE. Further follow-up, which is in progress, is necessary to track long-term cognitive functioning.

Fatigue in Children With Sickle Cell Disease: Association With Neurocognitive and Social-Emotional Functioning and Quality of Life.

Children with sickle cell disease (SCD) report fatigue in addition to acute and chronic pain, which can decrease overall health-related quality of life (HRQL). The primary objective of the current study was to investigate the relationship between fatigue and HRQL. Given limited prior research, secondary objectives included investigation of associations between fatigue and functional outcomes, including child neurocognitive and social-emotional functioning. Children aged 8 to 16 years (N=32) and a caregiver completed measures of fatigue, HRQL, pain, and neurocognitive and social-emotional functioning. Controlling for pain and number of SCD-related hospitalizations, hierarchical linear regression models were used to determine the impact of child-reported and parent-reported fatigue on child HRQL. Correlational analyses were used to explore the relationship between fatigue and additional child outcomes. Data indicated that children with SCD experience clinically relevant levels of fatigue, which independently predicts lower HRQL. Fatigue was also associated with lower working memory, executive functioning, and higher levels of internalizing symptoms. Given its observed impact on HRQL and relationship to functional outcomes, fatigue may be an important target of clinical, home, or school interventions. This practice may attenuate the burden of fatigue in these patients, and in turn, help improve the quality of life of children living with SCD.

Prognostic factors that increase the risk for reduced white matter volumes and deficits in attention and learning for survivors of childhood cancers.

OBJECTIVE: In children, CNS-directed cancer therapy is thought to result in decreased cerebral white matter volumes (WMV) and subsequent neurocognitive deficits. This study was designed as a prospective validation of the purported reduction in WMV, associated influential factors, and its relationship to neurocognitive deficits in a very large cohort of both acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT) survivors in comparison to an age similar cohort of healthy sibling controls. PROCEDURES: The effects of host characteristics and CNS treatment intensity on WMV were investigated in 383 childhood cancer survivors (199 ALL, 184 BT) at least 12 months post-completion of therapy and 67 healthy siblings that served as a control group. t-Tests and multiple variable linear models were used to assess cross-sectional WMV and its relation with neurocognitive function. RESULTS: BT survivors had lower WMV than ALL survivors, who had less than the control group. Increased CNS treatment intensity, younger age at treatment, and greater time since treatment were significantly associated with lower WMV. Additionally, cancer survivors did not perform as well as the control group on neurocognitive measures of intelligence, attention, and academic achievement. Reduced WMV had a larger impact on estimated IQ among females and children treated at a younger age. CONCLUSIONS: Survivors of childhood cancer that have undergone higher intensity therapy at a younger age have significantly less WMV than their peers and this difference increases with time since therapy. Decreased WMV is associated with significantly lower scores in intelligence, attention, and academic performance in survivors.

Working memory abilities among children treated for medulloblastoma: parent report and child performance.

OBJECTIVE: We investigated the 5-year postsurgical developmental trajectory of working memory (WM) in children with medulloblastoma using parent and performance-based measures. METHOD: This study included 167 patients treated for medulloblastoma. Serial assessments of WM occurred at predetermined time points for 5 years. RESULTS: There was a subtle, statistically significant increase in parental concern about WM, coupled with a statistically significant decrease in age-standardized scores on performance-based measures. However, whole-group mean scores on both parent and performance-based measures remained in the age-expected range. Posterior fossa syndrome was consistently associated with poorer WM. Younger age at treatment and higher treatment intensity were associated with greater negative change in WM performance only. CONCLUSIONS: Most children treated for medulloblastoma display WM within the age-appropriate range according to parent report and performance. However, the subtle negative changes over time and identified subgroups at increased risk highlight the need for ongoing monitoring of this population.

Sluggish cognitive tempo in survivors of pediatric brain tumors.

The presence of neurocognitive late effects in survivors of pediatric brain tumors is well established. However, there remains some debate about how best to conceptualize these deficits. Sluggish cognitive tempo (SCT) is a proposed conceptual framework that has been used to describe a subset of children with ADHD who exhibit a particular profile characterized by lethargy, day dreaming and staring, and poor organization. Previous work has suggested that survivors of leukemia exhibit a similar profile, but it has not yet been examined in survivors of pediatric brain tumors. A sample of 65 survivors of pediatric brain tumors, 25 survivors of leukemia and 50 community controls completed the Child Behavior Checklist, with four items used to measure SCT. Survivors completed additional measures of neurocognitive functioning. Survivors of brain tumors demonstrated significantly greater symptoms of SCT than survivors of leukemia or controls. SCT was associated with attention problems and working memory deficits and the presence of a VP-shunt. Results provided conditional support for the presence of SCT in survivors of brain tumors, with further research needed to determine the clinical utility of the framework.

Working memory training in survivors of pediatric cancer: a randomized pilot study.

OBJECTIVES: Survivors of pediatric brain tumors and acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive deficits, but few empirically supported treatment options exist. We examined the feasibility and preliminary efficacy of a home-based, computerized working memory training program, CogmedRM, with survivors of childhood cancer. METHODS: Survivors of brain tumors or ALL (n = 20) with identified deficits in attention and/or working memory were randomized to either the success-adapted computer intervention or a non-adaptive, active control condition. Specifically, children in the adaptive condition completed exercises that became more challenging with each correct trial, whereas those in the non-adaptive version trained with exercises that never increased in difficulty. All participants were asked to complete 25 training sessions at home, with weekly, phone-based coaching support. Brief assessments were completed pre-intervention and post-intervention; outcome measures included both performance-based and parent-report measures of working memory and attention. RESULTS: Eighty-five percent of survivors were compliant with the intervention, with no adverse events reported. After controlling for baseline intellectual functioning, survivors who completed the intervention program evidenced significant post-training improvements in their visual working memory and in parent-rated learning problems compared with those in the active control group. No differences in verbal working memory functioning were evident between groups, however. CONCLUSIONS: Home-based, computerized cognitive training demonstrates good feasibility and acceptability in our sample. Children with higher intellectual functioning at baseline appeared to benefit more from the training, although further study is needed to clarify the strength, scope, and particularly the generalizability of potential treatment effects.

Pain and other non-neurological adverse events in children with sickle cell anemia and previous stroke who received hydroxyurea and phlebotomy or chronic transfusions and chelation: results from the SWiTCH clinical trial.

To compare the non-neurological events in children with sickle cell anemia (SCA) and previous stroke enrolled in SWiTCH. The NHLBI-sponsored Phase III multicenter randomized clinical trial stroke with transfusions changing to hydroxyurea (SWiTCH) (ClinicalTrials.gov NCT00122980) compared continuation of chronic blood transfusion/iron chelation to switching to hydroxyurea/phlebotomy for secondary stroke prevention and management of iron overload. All randomized children were included in the analysis (intention to treat). The Fisher's Exact test was used to compare the frequency of subjects who experienced at least one SCA-related adverse event (AE) or serious adverse event (SAE) in each arm and to compare event rates. One hundred and thirty three subjects, mean age 13 ± 3.9 years (range 5.2-19.0 years) and mean time of 7 years on chronic transfusion at study entry, were randomized and treated. Numbers of subjects experiencing non-neurological AEs were similar in the two treatment arms, including SCA-related events, SCA pain events, and low rates of acute chest syndrome and infection. However, fewer children continuing transfusion/chelation experienced SAEs (P = 0.012), SCA-related SAEs (P = 0.003), and SCA pain SAEs (P = 0.016) as compared to children on the hydroxyurea/phlebotomy arm. The timing of phlebotomy did not influence SAEs. Older age at baseline predicted having at least 1 SCA pain event. Patients with recurrent neurological events during SWiTCH were not more likely to experience pain. In children with SCA and prior stroke, monthly transfusions and daily iron chelation provided superior protection against acute vaso-occlusive pain SAEs when compared to hydroxyurea and monthly phlebotomy.

Health-related quality of life in sickle cell disease: past, present, and future.

Health-related quality of life (HRQL) is defined as the patient's appraisal of how his/her well being and level of functioning, compared to the perceived ideal, are affected by individual health. The study of HRQL in children and adults with sickle cell disease (SCD) has begun to flourish. Given the devastating complications of the disease and other co-morbid factors patients experience that influence HRQL, it is increasingly important to understand HRQL. The focus of this critical review was to examine past and current research in HRQL in SCD where a validated instrument was used. In addition, future directions for HRQL in SCD are explored.

Usability and Acceptability of the QuestLeukemia Mobile Application: A Pilot Study for An Educational and Psychological Intervention for Children with Chronic Illnesses.

It is widely accepted that educational interventions benefit children with chronic diseases (disease awareness and autonomy) or those undergoing medical procedures (decreased anxiety and improved satisfaction). Hematopoietic cell transplantation (HCT) is an intensive procedure to treat life-threatening diseases but is associated with multiple adverse medical experiences. QuestLeukemia (QuestED, Durham, NC) is a mobile app designed to educate pediatric patients preparing for HCT through age-appropriate videos and quizzes. Here we describe the results of the initial pilot study assessing acceptability and feasibility of QuestLeukemia app. Eligible participants were selected from a convenience sample (inpatient HCT unit and outpatient clinic). Participants spent 30-60 min using the app then completed a survey assessing the app for usability, accessibility, and user satisfaction. Participants identified the app as a useful tool for gaining disease-related knowledge and reported greater autonomy over their disease process. On average, patients indicated that the app was easy to use (M = 4.93), enjoyable (M = 4.79), and comprehensive (M = 4.71). Parents followed similar trends of satisfaction with the app. Pediatric HCT providers likewise reported that the app was easy to use (M = 4.22), enjoyable (M = 4.85), and educationally comprehensive (M = 4.77). The QuestLeukemia mobile application prototype provides an easy, enjoyable, and educational tool for pediatric patients undergoing HCT. This application was well received by patients, parents, and providers. These findings will be used to design future iterations of the game in clinical care.

How parents cope with their child's diagnosis and treatment of an embryonal tumor: results of a prospective and longitudinal study.

The current study reports longitudinal coping responses among parents of children diagnosed with an embryonal brain tumor. Patients (n = 219) were enrolled on a treatment protocol for a pediatric embryonal brain tumor. Their parents (n = 251) completed the Coping Response Inventory at time of their child's diagnosis and yearly thereafter, resulting in 502 observations. Outcomes were examined with patient and parent age at diagnosis, patient risk, parent gender and education as covariates. At the time of diagnosis, the highest observed coping method was seeking guidance with well above average scores (T = 61.6). Over time, younger parents were found to seek guidance at a significantly higher rate than older parents (P = .016) and the use of acceptance resignation and seeking alternative results by all parents significantly increased (P = .011 and P < .0001 respectively). The use of emotional discharge was also observed above average at time of diagnosis (T = 55.4) with younger fathers being more likely to exhibit emotional discharge than older fathers (P = .002). Differences in coping according to age of the patient and parent education level are also discussed. Results show a high need for guidance, and above average emotional discharge, especially among younger parents. It is imperative for the healthcare team to lead with accurate information so that these parents may make informed decisions about the care of their child. This need remains high years after diagnosis. Therefore it is critical to continue a consistent level of effective communication and support, even following treatment.