Long-term neuropsychologic outcome in children diagnosed with a low-grade astrocytoma

Central nervous system (CNS) tumors in children have a relatively high frequency. They are the second most common form of cancer in childhood only exceeded by acute lymphoblastic leukemia (ALL). However, prognosis is more severe and at present more children die because of CNS tumor than of ALL. The incidence of CNS tumors is estimated 3.5 per 100,000 in children below 15 years of age.1 Boys appear to be at greater risk than girls (1.1:1) and this ratio is even higher in primitive neuro-ectodermal tumor (PNET), plexus papilloma, and germinoma (2:1).1 The most frequently occurring histological tumor type is astrocytoma (40-50%) followed by medulloblastoma (15-20%), ependymoma (8-13%), and craniopharyngiomas (7-10%) as shown in Table 1.2 Astrocytomas are classified according to increasing malignancy grade as pilocytic, fibrillary, anaplastic astrocytoma, and glioblastoma. The most common variant in children is the pilocytic astrocytoma

Verbal and visual-spatial memory problems at adolescent age after neonatal extracorporeal membrane oxygenation

__Objectives__ To assess neuropsychological outcome in 17- and 18-year–old neonatal extracorporeal membrane oxygenation survivors. __Design__ A prospective longitudinal follow-up study. __Setting__ Follow-up program at the Erasmus MC-Sophia Children’s Hospital in Rotterdam, The Netherlands. __Patients__ Thirty adolescents 17 or 18 years old, treated between 1991 and 1997, underwent neuropsychological assessment. __Interventions__ None. __Measurements and Main Results__ Attention, memory, executive functioning, visual-spatial functions, social-emotional functioning, and behavior were assessed with validated instruments, and data were compared with reference data. Included predictors for analysis of adverse outcome were diagnosis, age at start extracorporeal membrane oxygenation, convulsions, and use of anti-epileptics. Adolescents’ performance (expressed as mean [sd] z-score) was significantly lower than the norm on short-term and long-term verbal memory (z-score = -1.40 [1.58], p = 0.016; z-score = -1.54 [1.67], p = 0.010, respectively), visual-spatial memory (z-score = -1.65 [1.37], p = 0.008; z-score = -1.70 [1.23], p = 0.008, respectively), and working memory (32% vs 9% in the norm population). Parents reported more problems for their children regarding organization of materials (z-score = −0.60 [0.90]; p = 0.03) and behavior evaluation (z-score = −0.53 [0.88]; p = 0.05) on a questionnaire. Patients reported more withdrawn/depressed behavior (z-score = −0.47 [0.54]; p = 0.02), somatic complaints (z-score = −0.43 [0.48]; p = 0.03), and social problems (z-score = −0.41 [0.46]; p = 0.04). Patients reported more positive feelings of self-esteem and an average health status. __Conclusions__ Adolescents treated with neonatal extracorporeal membrane oxygenation are at risk of verbal, visual-spatial, and working-memory problems. Future research should focus on 1) the longitudinal outcome of specific neuropsychological skills in adolescence and adulthood; 2) identifying risk factors of neuropsychological dysfunction; 3) evaluating to what extent “severity of illness” is responsible for acquired brain injury; and 4) effects of timely cognitive rehabilitation

Cardiac arrest in infants, children, and adolescents: long-term emotional and behavioral functioning

Very little is known about the psychological consequences of a cardiac arrest (CA) during childhood. Our aim was to assess long-term emotional and behavioral functioning, and its predictors, in survivors of CA in childhood. This long-term follow-up study involved all consecutive infants, children, and adolescents surviving CA in a tertiary-care university children’s hospital between January 2002 and December 2011. Emotional and behavioral functioning was assessed with the Child Behavior Checklist (CBCL), Teacher’s Report Form (TRF), and Youth Self-Report (YSR). Of the eligible 107 CA survivors, 52 patients, parents, and/or teachers filled out online questionnaires. Compared with normative data, parents and teachers reported significantly more attention and somatic problems (age range 6–18 years). Parents also reported more attention problems for age range 1.5–5 years. Twenty-eight percent of the children (n = 14) scored in the psychopathological range (i.e., for age range 1.5–18 years; p < 0.001) according to parent reports. Male gender, older age, and basic life support were significantly related to worse scores on the scales internalizing problems, externalizing problems, and total problems and subscale attention problems. Conclusion: Long-term deficits in attention and somatic complaints were reported. Attention problems after childhood CA can interfere with school performance. Long-term follow-up with neuropsychological assessment should be organized.(Table presented.

Long-term neuropsychological outcomes in children and adolescents after cardiac arrest

Purpose: Research into neuropsychological functioning of survivors of cardiac arrest (CA) in childhood is scarce. We sought to a

Can serial cerebral MRIs predict the neuronopathic phenotype of MPS II?

OBJECTIVE: To advance the prediction of the neurocognitive development in MPS II patients by jointly analyzing MRI and neurocognitive data in mucopolysaccharidosis (MPS) II patients. METHODS: Cognitive ability scores (CAS) were obtained by neuropsychological testing. Cerebral MRIs were quantified using a disease‐specific protocol. MRI sumscores were calculated for atrophy, white‐matter abnormalities (WMA) and Virchow‐Robin spaces (VRS). To distinguish between atrophy and hydrocephalus the Evans' index and the callosal angle (CA) were measured. A random effects repeated measurement model was used to correlate CAS with the three MRI sumscores. RESULTS: MRI (n = 47) and CAS scores (n = 78) of 19 male patients were analyzed. Ten patients were classified as neuronopathic and nine as non‐neuronopathic. Neuronopathic patients had normal cognitive development until age 3 years. Mental age plateaued between ages 3 and 6, and subsequently declined with loss of skills at a maximum developmental age of 4 years. MRIs of neuronopathic patients showed abnormal atrophy sumscores before CAS dropped below the threshold for intellectual disability (<70). White‐matter abnormalities (WMA) and brain atrophy progressed. The calculated sumscores were inversely correlated with CAS (r = −.90 for atrophy and −.69 for WMA). This was not biased by the influence of hydrocephalus as shown by measurement of the Evans' and callosal angle. Changes over time in the Virchow‐Robin spaces (VRS) on MRI were minimal. CONCLUSION: In our cohort, brain atrophy showed a stronger correlation to a decline in CAS when compared to WMA. Atrophy‐scores were higher in young neuronopathic patients than in non‐neuronopathic patients and atrophy was an important early sign for the development of the neuronopathic phenotype, especially when observed jointly with white‐matter abnormalities

Classic infantile Pompe patients approaching adulthood: A cohort study on consequences for the brain

Aim: To examine the long-term consequences of glycogen storage in the central nervous system (CNS) for classic infantile Pompe disease using enzyme replacement therapy. Method: Using neuropsychological tests and brain magnetic resonance imaging (MRI), we prospectively assessed a cohort of 11 classic infantile Pompe patients aged up to 17 years. Results: From approximately age 2 years onwards, brain MRI showed involvement of the periventricular white matter and centrum semiovale. After 8 years of age, additional white-matter abnormalities occurred in the corpus callosum, internal and external capsule, and subcortical areas. From 11 years of age, white-matter abnormalities were also found in the brainstem. Although there seemed to be a characteristic pattern of involvement over time, there were considerable variations between patients, reflected by variations in neuropsychological development. Cognitive development ranged from stable and normal to declines that lead to intellectual disabilities. Interpretation: As treatment enables patients with classic infantile Pompe disease to reach adulthood, white-matter abnormalities are becoming increasingly evident, affecting the neuropsychological development. Therefore, we advise follow-up programs are expanded to capture CNS involvement in larger, international patient cohorts, to incorporate our findings in the counselling of parents before the start of treatment, and to include the brain as an additional target in the development of next-generation therapeutic strategies for classic infantile Pompe disease. What this paper adds: In our long-term survivors treated intravenously with enzyme replacement therapy, we found slowly progressive symmetric white-matter abnormalities. Cognitive development varied from stable and normal to declines towards intellectual disabilities