Does dexamethasone induce more neuropsychological side effects than prednisone in pediatric acute lymphoblastic leukemia? A systematic review.

Steroid-induced neuropsychological side effects impact quality of life in children with acute lymphoblastic leukemia. Dexamethasone induces more metabolic side effects than prednisone. To evaluate whether dexamethasone also leads to more neuropsychological side effects, we reviewed all available literature. Randomized controlled trials with neuropsychological function as the primary or secondary outcome did not show clinically meaningful differences between dexamethasone and prednisone on cognition, mood or behavior.

Cognitive outcome of patients with classic infantile Pompe disease receiving enzyme therapy.

OBJECTIVE: Classic infantile Pompe disease affects many tissues, including the brain. Untreated infants die within their first year. Although enzyme-replacement therapy (ERT) significantly increases survival, its potential limitation is that the drug cannot cross the blood-brain barrier. We therefore investigated long-term cognitive development in patients treated with ERT. METHODS: We prospectively assessed cognitive functioning in 10 children with classic infantile Pompe disease who had been treated with ERT since 1999. Brain imaging was performed in 6 children. RESULTS: During the first 4 years of life, developmental scores in 10 children ranged from above-average development to severe developmental delay; they were influenced by the type of intelligence test used, severity of motor problems, speech/language difficulties, and age at start of therapy. Five of the children were also tested from 5 years onward. Among them were 2 tetraplegic children whose earlier scores had indicated severe developmental delay. These scores now ranged between normal and mild developmental delay and indicated that at young age poor motor functioning may interfere with proper assessment of cognition. We found delayed processing speed in 2 children. Brain imaging revealed periventricular white matter abnormalities in 4 children. CONCLUSIONS: Cognitive development at school age ranged between normal and mildly delayed in our long-term survivors with classic infantile Pompe disease treated with ERT. The oldest was 12 years. We found that cognition is easily underestimated in children younger than 5 years with poor motor functioning.

Long-term cognitive functioning in children and adolescents who survived septic shock caused by Neisseria meningitidis.

AIMS: To assess long-term cognitive functioning and its predictors, in children and adolescents who survived meningococcal septic shock (MSS) 4 to 16 years ago. METHODS: The Wechsler Intelligence Scale for Children-third edition was used to measure intellectual functioning and neuropsychological tests were used to measure attention, verbal memory, visual-motor integration, and executive skills. RESULTS: Overall, results of the total MSS sample (N=77) as to neuropsychological functioning were similar to those of normative reference groups. On social and practical reasoning and visual-motor integration, however, MSS children obtained poorer outcomes compared to normative data. Two children had mental retardation (estimated IQ<70) due to the MSS. The percentage of children with mental retardation or borderline intellectual functioning (15%) was similar to that in the general population (16%). Eighteen children (23%) had a z score<-2, indicating unusual poor functioning, on one or more domains of neuropsychological functioning (selective attention, sustained attention, and executive functioning). Compared to normative data, significantly more children had received special education services in the past. Older age at time of follow-up was the most important significant predictor of poorer long-term cognitive functioning. CONCLUSION: Overall, long-term outcomes as to cognitive functioning of the total MSS sample were similar to those of normative reference groups, but MSS children showed long-term impairments on social and practical reasoning, visual-motor integration, attention, and executive functioning. Older age at time of follow-up was a significant predictor.

Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families.

Four Dutch male patients, two brothers from unrelated families were referred for investigation of psychomotor and severe language/speech delay. All four patients showed growth deficiency over the years. Facial features and poor body habitus were quite similar in the patients and in their mothers. Brain MRI showed nonspecific periventricular white matter lesions. In all the patients neuropsychological tests revealed moderate mental retardation, attention deficit and hyperactivity with impulsivity, a semantic-pragmatic language disorder, and oral dyspraxia. This specific cognitive profile is different from other children with mental retardation syndromes and seems to be unique. Excretion of creatine to creatinine ratio in urine of the four boys was increased compared to controls and their creatine uptake in fibroblasts was deficient. In the two brothers from the first pedigree, DNA sequence analysis revealed a novel mutation in the splice donor site in intron 10 (IVS10 + 5G>C, c.1495 + 5G>C) of the SLC6A8 gene leading to skipping of exon 10. In the other sib pair a novel missense mutation (c. 1361C>T; p.Pro544Leu) was found. These are the first families reported, in which the clinical suspicion of a creatine transporter disorder was raised on clinical grounds, before a brain 1H-MRS suggested the diagnosis. Screening of apparently X-linked mental retarded patients with this somatic and behavioral phenotype by the biochemical assay of creatine to creatinine ratio in the urine or DNA sequence analysis of SLC6A8 is worthwhile even when 1H-MRS is not available.

Long-term sequelae in children after cerebellar astrocytoma surgery.

OBJECTIVE: To study long-term effects on neurologic, neuropsychological, and behavioral functioning in children treated for cerebellar pilocytic astrocytoma (CPA) without additional radio- and chemotherapy. METHODS: The authors assessed speech, language, nonverbal intelligence, attention, memory, executive skills, and visual (-spatial) functions in a consecutive series of 23 children. Neurologic and neuropsychological follow-up ranged from 1 year to 8 years and 10 months after resection. RESULTS: Long-term sequelae in the investigated domains were found in all children. Apraxia, motor neglect, and dysarthric features, as well as language, sustained attention, visual-spatial, executive, memory, and behavioral problems, were observed in various combinations and to different degrees. No clear pattern of neurocognitive disturbances could be discerned in this group. In addition, significant relationships were revealed between severity of preoperative hydrocephalus and visual-spatial skills. The high percentage of children who needed special education reflects the severity of the impairments. CONCLUSION: Despite the current opinion of a good quality of life after CPA treatment, careful long-term neurocognitive follow-up is needed in order to inform parents and teachers about the behavioral and cognitive sequelae and to contribute to timely social and educational intervention.