Neurocognitive outcomes and functional independence in adult survivors of childhood medulloblastoma diagnosed over three decades.

BACKGROUND: Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown. METHODS: Adult survivors of childhood medulloblastoma (n=505; median[minimum-maximum] age, 29[18-46] years) and sibling controls (n=727; 32[18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI]≥30 Gy, no chemotherapy), standard-risk (CSI>0 to <30 Gy +chemotherapy) and high-risk (CSI≥30 Gy +chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver's license, marital/partner status. Multivariable models estimated risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence. RESULTS: Survivors in each treatment exposure group had 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval [CI] 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems and seizures were associated with 33%-34%, 25-26% and 21%-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with non-independence. CONCLUSIONS: Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.

The Use of Pressure Recording Analytical Method in Patients Undergoing Endovascular Repair for Abdominal Aortic Aneurysm: The Impact on Clinical Decisions for the Appropriate Postoperative Setting and Cost-effective Analysis.

OBJECTIVE: To analyze the use of the Pressure Recording Analytical Method (PRAM), an hemodynamic monitoring system, in evaluating intraoperative and postoperative hemodynamic instability in patients undergoing endovascular repair for abdominal aortic aneurysm, and to evaluate if the decision to refer patients to a ordinary ward or to a Cardiac Step-Down Unit (CSDU) after the intervention on the basis of intraoperative hemodynamic monitoring could be more cost-effective. MATERIALS AND METHODS: After preoperative clinical evaluation, 44 patients were divided in this non-randomised study into two groups according to their postoperative destination: Group 1-ward (N=22) and Group 2-CSDU (N=22). All patients underwent monitoring with PRAM during the intervention and in the 24 postoperative hours, measuring several indices of myocardial contractility and other hemodynamic variables. RESULTS: According to the variability of two parameters, Stroke Volume Variation and Pulse Pressure Variation, patients were classified as stable or unstable. Unstable patients showed a significant alteration in several hemodynamic indices, in comparison to stable ones. According to the intraoperative monitoring, eight high risk patients could have been sent to an ordinary ward due to their stability, with a reduction in the improper use of CSDU and, consequently, in costs. CONCLUSIONS: Hemodynamic monitoring with PRAM can be useful in these patients, both for intraoperative management and for the choice of the more appropriate postoperative setting, possibly reducing the improper use of CSDU for hemodynamically stable patients who are judged to be at high risk preoperatively, and re-evaluating low surgical risk patients with an unstable intraoperative pattern, with a possible reduction in costs.

Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma.

BACKGROUND: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown. METHODS: Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with or without chemotherapy and/or surgery]), and neurocognitive impairment. Latent class analysis with 5 indicators (employment, independent living, assistance with routine and/or personal care needs, driver's license, marital or partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, chronic health conditions, and functional independence. Statistical tests were 2-sided. RESULTS: Cranial radiation exposure decreased over time (51%, 1970s; 46%, 1980s; 27%, 1990s]. However, compared with siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (eg, memory: relative risk = 2.22; task efficiency: relative risk = 1.88; both P < .001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and nonindependent (22%). Cranial radiation was associated with nonindependence through impaired task efficiency (ß = 0.06), sensorimotor (ß = 0.06), and endocrine (ß = 0.10) chronic health conditions and through the associations between these conditions and task efficiency (each ß = 0.04). Sensorimotor and endocrine chronic health conditions were associated with nonindependence through memory. CONCLUSION: Most long-term glioma survivors achieve adult independence. However, functional nonindependence is associated with treatment-related neurocognitive impairment and chronic health conditions.

Social cognition and adjustment in adult survivors of pediatric central nervous system tumors.

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors are at risk for neurocognitive and social difficulties throughout childhood. This study characterized social cognition (perception and reasoning from social cues) and adjustment in adulthood. METHODS: A total of 81 adult survivors of pediatric CNS tumors (51% female; mean [SD] age, 28.0 [5.8] years), were recruited across four groups: (1) no radiation therapy (RT) [n = 21], (2) infratentorial (IT) tumors + focal RT [n = 20], (3) IT tumors + craniospinal irradiation [n = 20], and (4) supratentorial tumors + focal RT [n = 20]. Prevalence of social cognitive and adjustment impairments was compared to test norms. Multivariable models examined clinical and neurocognitive predictors of social cognition and its impact on functional outcomes. RESULTS: Survivors demonstrated elevated risk of severe social cognitive impairments (social perception Morbidity Ratio [95% CI] 5.70 [3.46-9.20]), but self-reported few social adjustment problems. Survivors of IT tumors treated with craniospinal irradiation performed nearly 1 SD worse than survivors treated without RT on multiple measures of social cognition (e.g., social perception: ß = -0.89, p = .004). Impaired executive functioning and nonverbal reasoning were associated with worse social cognitive performance (e.g., social perception: ß = -0.75, p < .001; ß = -0.84, p < .001, respectively). Better social perception was associated with higher odds of attaining full-time employment (odds ratio, 1.52 [1.17-1.97]) and at least some college education (odds ratio, 1.39 [1.11-1.74]). CONCLUSIONS: Adult survivors of CNS tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Better understanding of potential mechanisms underlying social cognitive deficits may inform intervention targets to promote better functional outcomes for at-risk survivors.

Emotional, behavioral, and physical health consequences of loneliness in young adult survivors of childhood cancer: Results from the Childhood Cancer Survivor Study.

BACKGROUND: Young adults in the general population are at risk of experiencing loneliness, which has been associated with physical and mental health morbidities. The prevalence and consequences of loneliness in young adult survivors of childhood cancer remain unknown. METHODS: A total of 9664 young adult survivors of childhood cancer (median age at diagnosis 10.5 years [interquartile range (IQR), 5-15], 27.1 years at baseline [IQR, 23-32]) and 2221 siblings enrolled in the Childhood Cancer Survivor Study completed a self-reported survey question assessing loneliness on the Brief Symptom Inventory-18 at baseline and follow-up (median follow-up, 6.6 years). Multivariable models evaluated the prevalence of loneliness at baseline only, follow-up only, and baseline + follow-up, and its associations with emotional distress, health behaviors, and chronic conditions at follow-up. RESULTS: Survivors were more likely than siblings to report loneliness at baseline + follow-up (prevalence ratio [PR] 2.2; 95% confidence interval [CI], 1.7-3.0) and at follow-up only (PR, 1.4; 95% CI, 1.1-1.7). Loneliness at baseline + follow-up was associated with elevated risk of anxiety (relative risk [RR], 9.8; 95% CI, 7.5-12.7), depression (RR, 17.9; 95% CI, 14.1-22.7), and current smoking (odds ratio [OR], 1.7; 95% CI, 1.3-2.3) at follow-up. Loneliness at follow-up only was associated with suicidal ideation (RR, 1.5; 95% CI, 1.1-2.1), heavy/risky alcohol consumption (RR, 1.3; 95% CI, 1.1-1.5), and new-onset grade 2-4 chronic conditions (RR, 1.3; 95% CI, 1.0-1.7). CONCLUSIONS: Young adult survivors of childhood cancer have elevated risk of experiencing loneliness, which is associated with future emotional distress, risky health behaviors, and new-onset chronic conditions.

Altered Cortical Gyrification in Adults Who Were Born Very Preterm and Its Associations With Cognition and Mental Health.

BACKGROUND: The last trimester of pregnancy is a critical period for the establishment of cortical gyrification, and altered folding patterns have been reported following very preterm birth (< 33 weeks of gestation) in childhood and adolescence. However, research is scant on the persistence of such alterations in adulthood and their associations with cognitive and psychiatric outcomes. METHODS: We studied 79 very preterm and 81 age-matched full-term control adults. T1-weighted magnetic resonance images were used to measure a local gyrification index (LGI), indicating the degree of folding across multiple vertices of the reconstructed cortical surface. Group and group-by-sex LGI differences were assessed by means of per-vertex adjustment for cortical thickness and overall intracranial volume. Within-group correlations were also computed between LGI and functional outcomes, including general intelligence (IQ) and psychopathology. RESULTS: Very preterm adults had significantly reduced LGI in extensive cortical regions encompassing the frontal, anterior temporal, and occipitoparietal lobes. Alterations in lateral fronto-temporal-parietal and medial occipitoparietal regions were present in both men and women, although men showed more extensive alterations. In both very preterm and control adults, higher LGI was associated with higher IQ and lower psychopathology scores, with the spatial distribution of these associations substantially differing between the two groups. CONCLUSIONS: Very preterm adults' brains are characterized by significant and widespread local hypogyria, and these alterations might be implicated in cognitive and psychiatric outcomes. Gyrification reflects an early developmental process and provides a fingerprint for very preterm birth.

Neuropsychological outcomes of children with Optic Pathway Glioma.

Optic Pathway Glioma (OPG) is a relatively common brain tumour in childhood; however, there is scarce understanding of neuropsychological sequelae in these survivors. In this study, 12 children with diagnosis of OPG before 6 years of age received a comprehensive standardised assessment of visual perception, general intelligence and academic achievement, using adjustments to visual materials of the tests, to examine the extent of concurrent impairment in these functional domains. Information about vision, clinical and socio-demographic factors were extracted from medical records to assess the associations of neuropsychological outcomes with clinical and socio-demographic factors. Children with OPG exhibited high within-patient variability and moderate group-level impairment compared to test norms. Visual perception was the most impaired domain, while scholastic progression was age-appropriate overall. For cognition, core verbal and visuo-spatial reasoning skills were intact, whereas deficits were found in working memory and processing speed. Visual function was associated with tasks that rely on visual input. Children with OPG are at moderate risk of neuropsychological impairment, especially for visual perception and cognitive proficiency. Future research should elucidate further the relative contribution of vision loss and neurofibromatosis type 1 co-diagnosis within a large sample.

Fine Motor Skills Predict Maths Ability Better than They Predict Reading Ability in the Early Primary School Years.

Fine motor skills have long been recognized as an important foundation for development in other domains. However, more precise insights into the role of fine motor skills, and their relationships to other skills in mediating early educational achievements, are needed to support the development of optimal educational interventions. We explored concurrent relationships between two components of fine motor skills, Fine Motor Precision and Fine Motor Integration, and early reading and maths development in two studies with primary school children of low-to-mid socio-economic status in the UK. Two key findings were revealed. First, despite being in the first 2 years of primary school education, significantly better performance was found in reading compared to maths across both studies. This may reflect the protective effects of recent national-level interventions to promote early literacy skills in young children in the UK that have not been similarly promoted for maths. Second, fine motor skills were a better predictor of early maths ability than they were of early reading ability. Hierarchical multiple regression revealed that fine motor skills did not significantly predict reading ability when verbal short-term memory was taken into account. In contrast, Fine Motor Integration remained a significant predictor of maths ability, even after the influence of non-verbal IQ had been accounted for. These results suggest that fine motor skills should have a pivotal role in educational interventions designed to support the development of early mathematical skills.