Intelligence and executive function are associated with age at insult, time post-insult, and disability following chronic pediatric acquired brain injury.

Background: Pediatric acquired brain injury (pABI) profoundly affects cognitive functions, encompassing IQ and executive functions (EFs). Particularly, young age at insult may lead to persistent and debilitating deficits, affecting daily-life functioning negatively. This study delves into the intricate interplay of age at insult, time post-insult, and their associations with IQ and EFs during chronic (>1 year) pABI. Additionally, we investigate cognitive performance across different levels of global function, recognizing the multifaceted nature of developmental factors influencing outcomes. Methods: Drawing upon insult data and baseline information analyzing secondary outcomes from a multicenter RCT, including comprehensive medical and neuropsychological assessments of participants aged 10 to 17 years with pABI and parent-reported executive dysfunctions. The study examined associations between age at insult (early, EI; ≤7y vs. late, LI; > 7y) and time post-insult with IQ and EFs (updating, shifting, inhibition, and executive attention). Additionally, utilizing the Pediatric Glasgow Outcome Scale-Extended, we explored cognitive performance across levels of global functioning. Results: Seventy-six participants, median 8 years at insult and 5 years post-insult, predominantly exhibiting moderate disability (n = 38), were included. Notably, participants with LI demonstrated superior IQ, executive attention, and shifting compared to EI, [adjusted mean differences with 95% Confidence Intervals (CIs); 7.9 (1.4, 14.4), 2.48 (0.71, 4.24) and 1.73 (0.03, 3.43), respectively]. Conversely, extended post-insult duration was associated with diminished performances, evident in mean differences with 95% CIs for IQ, updating, shifting, and executive attention compared to 1-2 years post-insult [-11.1 (-20.4, -1.7), -8.4 (-16.7, -0.1), -2.6 (-4.4, -0.7), -2.9 (-4.5, -1.2), -3.8 (-6.4, -1.3), -2.6 (-5.0, -0.3), and -3.2 (-5.7, -0.8)]. Global function exhibited a robust relationship with IQ and EFs. Conclusion: Early insults and prolonged post-insult durations impose lasting tribulations in chronic pABI. While confirmation through larger studies is needed, these findings carry clinical implications, underscoring the importance of vigilance regarding early insults. Moreover, they dispel the notion that children fully recover from pABI; instead, they advocate equitable rehabilitation offerings for pABI, tailored to address cognitive functions, recognizing their pivotal role in achieving independence and participation in society. Incorporating disability screening in long-term follow-up assessments may prove beneficial.

A population-based study of global outcome after moderate to severe traumatic brain injury in children and adolescents.

OBJECTIVE: The primary aim of this study was to evaluate the global outcome longitudinally over 5 years in children and adolescents surviving moderate to severe traumatic brain injury (msTBI) to investigate changes in outcome over time. The secondary aim was to explore how age at the time of injury affected outcome. METHODS: All children and adolescents (aged 0-17 years; subdivided into children aged 0-10 years and adolescents aged 11-17 years) with moderate (Glasgow Coma Scale [GCS] score 9-13) or severe (GCS score ≤ 8) TBI who were admitted to a level I trauma center in Norway over a 10-year period (2004-2014) were prospectively included. In addition, young adults (aged 18-24 years) with msTBI were included for comparison. Outcome was assessed with the Glasgow Outcome Scale-Extended (GOS-E) at 6 months, 12 months, and 5 years after injury. The effect of time since injury and age at injury on the probability of good outcome was estimated by the method of generalized estimating equations. RESULTS: A total of 30 children, 39 adolescents, and 97 young adults were included, among which 24 children, 38 adolescents, and 76 young adults survived and were planned for follow-up. In-hospital mortality from TBI was 7% for children, 3% for adolescents, and 18% for young adults. In surviving patients at the 5-year follow-up, good recovery (GOS-E score 7 or 8) was observed in 87% of children and all adolescents with moderate TBI, as well as in 44% of children and 59% of adolescents with severe TBI. No patient remained in a persistent vegetative state. For all patients, the odds for good recovery increased from 6 to 12 months (OR 1.79, 95% CI 1.15-2.80; p = 0.010), although not from 12 months to 5 years (OR 0.98, 95% CI 0.62-1.55; p = 0.940). Children/adolescents (aged 0-17 years) had higher odds for good recovery than young adults (OR 2.86, 95% CI 1.26-6.48; p = 0.012). CONCLUSIONS: In this population-based study of pediatric msTBI, surprisingly high rates of good recovery over 5 years were found, including good recovery for a large majority of children and all adolescents with moderate TBI. Less than half of the children and more than half of the adolescents with severe TBI had good outcomes. The odds for good recovery increased from 6 to 12 months and were higher in children/adolescents (aged 0-17 years) than in young adults.

Incidence and mortality of moderate and severe traumatic brain injury in children: A ten year population-based cohort study in Norway.

OBJECTIVE: In this study we wanted to estimate population-based rates of incidence and mortality of moderate and severe traumatic brain injury (TBI) in children in one specific region in Norway. METHODS: In the region there are seven acute care hospitals (ACHs) in addition to a Level 1 trauma centre. Of 702 869 inhabitants (2014), 145 395 were children aged 0-16 years. Data were collected during ten years (2004-2014). All children aged 0-16 years with moderate (Glasgow Coma Scale [GCS] score 9-13) or severe (GCS score ≤ 8) TBI admitted to the Level 1 trauma centre were prospectively included. Children treated outside the Level 1 trauma centre were retrospectively included from the ACHs. Children who died from TBI prehospitally were included from the National Cause of Death Registry. Poisson regression was used to estimate incidence rate ratios (with a 95% confidence interval) comparing age, sex, and time periods. RESULTS: A total of 71 children with moderate or severe TBI were identified. Crude incidence rates were 2·4 (95% CI 1·7-3·3) for moderate and 2·5 (95% CI 1·8-3·4) for severe TBI per 100 000 person-years (py). Mortality rate from TBI was 1·2 (95% CI 0·7-1·9) per 100 000 py, and 88% were prehospital deaths. CONCLUSION: The incidence rates and mortality of moderate and severe TBI were low compared to international reports. Most likely explained by successful national prevention of TBI.

[Juvenile-onset muscular diseases]. / Muskelsykdommer med debut i barnealder.

Children with muscular diseases constitute an important group in paediatric neurology. Some of the conditions are very serious and require extensive interdisciplinary treatment and facilitation. There is some degree of optimism regarding the possibility of causal treatment in some of the conditions.

Genes determining the severity of cerebral palsy: the role of single nucleotide polymorphisms on the amount and structure of apolipoprotein E.

AIM: Apolipoprotein E (apoE) influences repair and other processes in the brain, and the apoE4 variant is a risk factor for Alzheimer's disease and for prolonged recovery following traumatic brain injury. We previously reported that specific single nucleotide polymorphisms in the APOE or TOMM40 genes affecting the structure and production of apoE were associated with epilepsy, more impaired hand function and gastrostomy tube feeding in children with cerebral palsy (CP). This study explored how various combinations of the same polymorphisms may affect these clinical manifestations. METHODS: Successful DNA analyses of APOE and TOMM40 were carried out on 227 children. The CP Register of Norway provided details of gross and fine motor function, epilepsy and gastrostomy tube feeding. Possible associations between these clinical manifestations and various combinations of the APOEε2, ε3 or ε4 alleles and of the rs59007384 polymorphism in the TOMM40 gene were explored. RESULTS: Epilepsy, impaired fine motor function and gastrostomy tube feeding were less common in children carrying the combination of rs59007384 GG and APOEε2 or ε3 than in children with other combinations. CONCLUSION: Our findings suggest that specific combinations of genes influence the structure and production of apoE differently and affect the clinical manifestations of CP.

Child apolipoprotein E gene variants and risk of cerebral palsy: estimation from case-parent triads.

OBJECTIVE: To use case-parent triad data to investigate if cerebral palsy (CP) is associated with variants of the APOE gene, the rs59007384 SNP of the TOMM40 gene or combined haplotypes of the two genes. STUDY DESIGN: DNA was analyzed in buccal swabs from 235 children with CP, their parents and a sibling. The relative risks (RR) with 95% confidence intervals (CI) that the children would have a distribution of APOE genotypes, rs59007384 variants or combined haplotypes deviating from Mendelian inheritance were estimated. RESULTS: Children with CP were more likely than expected to carry the APOEε3 allele (RR 7.5; CI: 0.99-53.7 for heterozygotes and 10.3; CI: 1.4-79.6 for homozygotes), and to have the haplotype of APOEε3 and rs59007384 G (RR 2.4; CI: 1-5.7 for heterozygotes, RR 3.7; CI: 1.4-9.5 for homozygotes) whereas the distribution was as expected for rs59007384 alone. In the subgroup analyses the findings were confined to children born preterm. Among siblings the distribution of these genes was as expected according to Mendelian inheritance. CONCLUSION: We speculate that children with APOEε2/APOEε4 alleles are more likely to die following cerebral injury in utero, resulting in a higher than expected proportion of children with CP carrying the APOEε3 allele.

Gene sequences regulating the production of apoE and cerebral palsy of variable severity.

BACKGROUND: The apoE protein is the most important lipid transporter in the brain and has also been shown to have several regulatory functions in the central nervous system. The production of apoE is regulated by a number of genes and increases under certain conditions such as cerebral injury in adults. AIMS: Our aim was to study whether variations in genes regulating the expression of the APOE gene were associated with severity of cerebral palsy (CP). METHODS: Children enrolled in the Cerebral Palsy Register of Norway (CPRN) were invited to participate in this cross-sectional study; 281 of the invited 703 children (40%) returned swabs with buccal cells collected by parents. Six genetic variations thought to affect the production of apoE were genotyped and correlated with clinical data recorded in the CPRN. RESULTS: Compared with children carrying the GG allele, children with genotype GT or TT in a specific genetic variation (rs59007384 located in the nearby TOMM40 gene) had excess risk for worse fine motor function (Odds ratio (OR): 1.82; 95% Confidence interval (CI): 1.10-2.99; p = 0.019) and epilepsy (OR: 2.32; CI: 1.17-4.61; p = 0.016). There was no association between severity of CP and any of the other five genetic variations analyzed. CONCLUSION: Our findings suggest that genetic variations in one of the sequences regulating the expression of APOE, may be associated with worse clinical outcome in children with cerebral palsy.

Apolipoprotein E polymorphisms and severity of cerebral palsy: a cross-sectional study in 255 children in Norway.

AIM: The aim of this study was to examine whether the presence of the apolipoprotein E (ApoE) allele APOEε4 is associated with less severe manifestations of cerebral palsy (CP), consistent with the suggested beneficial effect of this allele on neurodevelopment in children. METHOD: ApoE genotyping was performed on buccal epithelial cells from 255 children (141 males 114 females; mean age 12y, SD 2y 3mo, range 9-17y) recorded in the Cerebral Palsy Register of Norway. The main outcome measure of CP severity was the Gross Motor Function Classification System (GMFCS). Secondary outcome measures were fine motor function, epilepsy, and the need for gastrostomy tube feeding (GTF). RESULTS: There was no association between the APOEε4 genotype and GMFCS levels (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.66-1.99). However, the APOEε4 genotype was more often present among children with epilepsy (OR 2.2; 95% CI 1.1-4.2) and/or receiving GTF (OR 2.7; 95% CI 1.1-6.6). Among children with unilateral CP, the presence of APOEε4 was associated with more severe fine motor impairment (OR 2.6; 95% CI 1.3-6.9). INTERPRETATION: Our main hypothesis that APOEε4 would have a protective effect on neurodevelopment was not supported. Instead, subgroup analyses suggested an adverse effect of the APOEε4 genotype on the developing brain after injury.