Key Questions on the Long-Term Utility of Methylphenidate in Paediatric Brain Tumour Survivorship: A Retrospective Clinical Case Series.

Methylphenidate has an established role in the management of attention-deficit hyperactivity disorder and attentional deficit secondary to brain injury. Increasingly, methylphenidate is considered for the attentional deficit in paediatric brain tumour survivors. A small number of studies have explored the benefit of methylphenidate in this population; however, studies are of short duration and do not address the impact of medium to long-term use of methylphenidate on intellectual function. We identified six patients who are survivors of a paediatric brain tumour aged 12-18 years with greater than three years of use of methylphenidate for inclusion in a clinical case series. We used this patient cohort to identify key questions to inform a future long-term cohort study. Linear mixed model and reliable change index analyses were performed on the data. Reliable change index analyses showed benefits to working memory (n = 3), processing speed (n = 2), and full-scale IQ (n = 4) performance for some patients. This exploratory case series suggests the potential medium to long-term benefit of methylphenidate in brain tumour survivorship, indicating the need for larger, appropriately powered studies. These patient data, alongside a discussion of learning points from our previously published studies, are used as a conduit for the identification of questions relating to the use of methylphenidate in a paediatric brain tumour.

Potential Anomalous Findings on the Cerberus Subtest of the TEACh 2 in a Pediatric Neuro-Oncology Cohort.

INTRODUCTION: The Test of Everyday Attention for Children 2 (TEA-Ch 2) is a rigorously tested measure of attention, often used in pediatric neuro-oncology settings. Data from one Primary Treatment Centre found a high proportion of children scored in the highest range on the Cerberus subtest. This brief report attempts to answer the question: Does the Cerberus subtest of the TEA-Ch 2 provide outlying scores in the pediatric neuro-oncology population? METHODS: Data representing 62 Cerberus assessments from four primary treatment centers were analyzed. RESULTS: Data showed a substantially higher level of performance on the Cerberus subtest compared to other TEA-Ch2 subtests. Scores were not only higher than expected relative to children's performance on other subtests but also higher than would be expected in the general population. DISCUSSION: Within our data, performance on the Cerberus subset of the TEA-Ch 2 yields somewhat questionable data from which to draw conclusions regarding sustained attentional ability in a pediatric neuro-oncology cohort.

The role of CNS tumor location in health-related quality of life outcomes: A systematic review of supratentorial vs infratentorial tumors in childhood survivorship.

Continued advancements in the treatment of pediatric brain tumors have resulted in a growing proportion of children surviving previously incurable diagnoses. However, survivors of pediatric brain tumors show reduced Health-Related Quality of Life (HRQoL) compared to healthy populations and non-CNS childhood cancer survivors. This review systematically evaluates the existing literature on the influence of supratentorial and infratentorial brain tumor locations on Health-Related Quality of Life outcomes in survivors of pediatric brain tumors. Five electronic databases were searched for relevant articles published between their inception and January 2022. A purpose-developed evaluative tool was constructed to assess the quality of eligible studies. 16 of the 5270 identified articles were included in this review (n = 1391). This review found little evidence relating to the impact of brain tumor location on HRQoL, with only one study finding a significant difference between supratentorial and infratentorial tumor survivors. Key limitations of the current evidence include poor statistical reporting, ambiguous construct definitions, and insufficient adjustment for confounds. Findings from this review show that recovery from a pediatric brain tumor extends beyond recovery post-treatment and that further study into the factors influencing survivor HRQoL, including the influence of tumor location, is necessary.

Barriers to the use of Methylphenidate in Pediatric Neuro-oncology Services.

BACKGROUND: Survivors of childhood CNS tumors are at a significant risk of chronic and multifaceted neurocognitive late effects. Recent findings indicate the potential utility of methylphenidate in addressing neurocognitive and academic plateauing and improving quality-of-life outcomes in this clinical population. However, the prescription of methylphenidate in neuro-oncology services remains inconsistent. OBJECTIVE: To explore the neurocognitive assessment and rehabilitative interventions (including the use of methylphenidate) offered to survivors of childhood CNS tumors within mainland UK. METHOD: We used a semi-structured questionnaire to gather qualitative data from clinical psychologists and neuropsychologists within National Health Service pediatric neuro-oncology principal treatment centers (PTCs) during May 2018. Thematic analytical methods were used to explore themes within the collected data. RESULTS: Eleven (58%) of the 19 PTCs returned the completed questionnaire. Respondents reported inadequate resource of psychology in many pediatric neuro-oncology PTCs, which limited the provision of methylphenidate to a restricted proportion of the patient group (i.e., those with the most profound neurocognitive difficulties). Respondents reported an interest in exploring the utility of methylphenidate in their patient group yet described a lack of appropriate evidence of its efficacy. In addition, respondents highlighted the need for the provision of accessible research summaries and treatment protocols addressing the use of methylphenidate. CONCLUSION: We anticipate that national collaboration between clinicians and researchers working in the cancer survivorship field will support the advancement of interventions such as methylphenidate for the growing clinical population of survivors of childhood CNS tumors.

[Formula: see text] The influence of methylphenidate on sustained attention in paediatric acquired brain injury: a meta-analytical review.

Impairment in sustained attention is a common consequence of childhood Acquired Brain Injury (ABI). Whilst methylphenidate provides promise in enhancing "attention" as a unitary construct, little work has explored its effectiveness upon individual attentional domains. The current systematic review and meta-analysis evaluates the utility of methylphenidate on sustained attentional performance across childhood ABI groups. Five databases (PsycINFO, MEDLINE, Embase, Scopus & Cochrane Library) were searched for relevant articles from their inception to March 2022. A purpose-developed evaluation tool was used to assess each study's research quality (QuEST:MAP). Nine of the 1600 identified articles were included within this review (n = 259). Meta-analytical findings reported an overall significant benefit of methylphenidate on sustained attention in childhood ABI (g = -0.33, 95% CI: -0.62 to -0.04). Associated summary effect sizes were relatively small, particularly when adjusting for outlier cases. Subgroup analyses identified a significantly greater benefit of methylphenidate in clinical subgroups with comorbid ADHD diagnoses (p < .01). The current evidence base is characterized by small-scale clinical trials with variable research quality and low generalizability. Further robust research is needed to quantify methylphenidate utility upon individual attentional domains in larger and more representative ABI samples.

Translating methylphenidate's efficacy on selective and sustained attentional deficits to those reported in childhood cancer survivors: A qualitative review.

Whilst an increasing number of children survive previously incurable cancers of the central nervous system (CNS), associated treatments often result in significant neurocognitive late effects. Methylphenidate provides some signs of alleviating cognitive difficulties in different pediatric groups; however, a minimal amount of systematic work has explored its effectiveness isolated to vulnerable attentional domains. The current review aimed to explore the effectiveness of methylphenidate isolated to two attentional domains (sustained and selective attention)-with an aim to substantiate its utility in childhood cancer survivors. Five databases were comprehensively searched for relevant articles. A purpose-developed tool was used to assess each study's robustness and research quality. Eleven out of 1,865 identified articles were included within the review. Studies drew upon five clinical populations. Individual attentional domains demonstrate variation in their response to methylphenidate. Sustained attention demonstrated the most consistent benefit of methylphenidate, reported largely in attention-deficit/hyperactivity disorder (ADHD) groups. Gains in selective attention and higher-order cognitive functions appeared to follow initial gains in sustained attention. Childhood cancer survivors report greater gains in selective attention compared to sustained attention. Higher doses may yield greater benefit for children with more diffuse attentional deficits. There is a need to improve the validity of current attentional measures before further methylphenidate trials are conducted.

Methylphenidate improves cognitive function and health-related quality of life in survivors of childhood brain tumours.

OBJECTIVES: The growing population of survivors of childhood brain tumors present the challenge of long-term quality of survival. The domains most affected by tumor and treatment are those implicated in development of typical intellectual functions: attention, working memory, and processing speed, with consequent effects upon function and quality of life. In this paper we present service evaluation data on the 12-month effect upon processing speed, visual and auditory attentional domains in 29 patients receiving methylphenidate aged 5-16 years (Mean=10.6). METHODS: Patients received immediate-release methylphenidate and were converted to modified-release as appropriate. Mean optimal dose of immediate-release methylphenidate was 0.34 mg/kg per dose (range 0.2-0.67). RESULTS: Patients showed a significant positive impact of methylphenidate on attention in all tests of selective visual attention from the Test of Everyday Attention for Children 2. A significant improvement was also shown on response time. Significant change was not found on psychometric measures of sustained auditory or visual attention, or selective auditory attention. Ratings of Health-Related Quality of Life showed a positive benefit of methylphenidate at 12 months. Side effects were minimal and not statistically significant. CONCLUSIONS: Survivors of childhood brain tumor with attentional and processing speed deficit show clinical benefit from methylphenidate.

"I Feel Happy Again": Methylphenidate Supports Health-Related Quality of Life in Survivors of Pediatric Brain Tumor.

BACKGROUND: The deleterious impact upon the cognitive development of survivors of pediatric brain tumors (PBT) is well documented. Impairment in cognitive function is associated with reduced health-related quality of life (HRQoL), such that survivors of PBT report difficulties in multiple distinct domains and an overall reduced quality of life. Studies of the use of methylphenidate in survivors of PBT to alleviate impairment in cognitive functions have shown some success. The current study aimed to explore the impact upon HRQoL in survivors of PBT of a trial of psychostimulant medication. METHOD: Data were collected from 12 pediatric neuro-oncology patients aged 7-17 years receiving methylphenidate treatment. HRQoL was measured using the PEDS QL quality of life self-report measure and a semi-structured questionnaire-based interview. RESULTS: Analyses of data demonstrates benefit to five domains associated with HRQoL: social, emotional, academic, physical, and cognition. CONCLUSION: Survivors of PBT reported favorable views as to the subjective benefit of methylphenidate on post-treatment impairment of HRQoL. This medication may offer the potential for restoration of a sense of 'normality' of function following cancer treatment in this clinical population.