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Background: Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7–10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction. Methods: Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7–10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations. Results: The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (β = 0.488 p = 0.000) as well as reduced cognitive independence (β = − 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (β = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7–10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (β = − 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (β = 0.679, p = 0.010). Conclusions: Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS , 2019, 25 , 293–301) [ABSTRACT FROM AUTHOR]

Importance: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury.Objective: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury.Design, Setting, and Participants: Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL.Interventions: Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells.Main Outcomes and Measures: Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury.Results: There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009).Conclusions and Relevance: In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting.Trial Registration: clinicaltrials.gov Identifier: NCT00313716. [ABSTRACT FROM AUTHOR]

IMPORTANCE There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% Cl, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% Cl, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% Cl, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% Cl for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% Cl, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00313716 [ABSTRACT FROM AUTHOR]

Early deafness is thought to affect low-level sensorimotor processing such as selective attention, whereas bilingualism is thought to be strongly associated with higher order cognitive processing such as attention switching under cognitive load. This study explores the effects of bimodal-bilingualism (in American Sign Language and written English) on attention switching, in order to contrast the roles of bilingual proficiency and age of acquisition in relation to cognitive flexibility among deaf adults. Results indicated a strong high-proficiency bilingual advantage in the higher order attention task. The level of proficiency in 2 languages appears to be the driving force for cognitive flexibility. However, additional data are needed to reach conclusive interpretation for the influence of age of second language acquisition on higher order attention-switching ability and associated cognitive flexibility. [ABSTRACT FROM PUBLISHER]

After a review of Arthur Benton's conceptual and methodological contributions to the understanding of normal and pathological development, we discuss agenesis of the corpus callosum (CC), criteria for potential neuroanatomical compensatory mechanisms in CC agenesis, and the results of an examination of magnetic resonance imaging (MRI) data of the CC in 193 children with spina bifida meningomyelocele (SBM). There were 26 CC regional patterns. Although complete agenesis did not occur, partial agenesis was observed in 102 children and within 15 CC regional patterns. Only 4.1% had a normal CC. Quantitative assessment of the area of the CC in 26 NC children and 68 children with SBM revealed that all subgroups with CC anomalies had smaller areas than did a subgroup with a normal CC. Areas were especially small in rostral/splenial agenesis and splenial agenesis but larger with rostral agenesis. Subgroups with normal/hypoplastic regions or complete hypoplasia also had CC areas that were smaller than normal but larger than the areas for the splenial agenesis groups. The relative rarity of anterior commissure enlargement (3.1%) and longitudinal bundles of Probst (0.1%) suggest that these particular fiber tract anomalies are unlikely candidates for structural compensatory mechanisms. The hippocampal commissure, enlarged in 13%, may be a more promising candidate. Overall, however, the functionality of anomalous fiber tracts and commissures in SBM is yet to be determined. [ABSTRACT FROM AUTHOR]

This study addressed the incidence of Attention-Deficit/Hyperactivity Disorder (ADHD) subtypes in children with spina bifida meningomyelocele and shunted hydrocephalus (SBH) as well as differences in executive functions among these subtypes. Parent rating scales revealed that 31% of the group with SBH could be identified with AD/HD, mostly the Inattentive type (23%). The group with SBH differed from normal controls on cognitive measures of executive functions, but subtype differences were not significant. Multivariate tests showed that children with SBH were rated with greater difficulties on the Behavior Rating Inventory of Executive Function (BRIEF) compared to controls; those with SBH and any subtype of ADHD differed from those with SBH and no ADHD; and those with ADHD (Combined Type) differed significantly from those with ADHD (Predominantly Inattentive Type). Subtype differences on univariate tests in the latter comparison were significant on the BRIEF Inhibit scale, showing more disinhibition in those with SBH and ADHD (Combined Type), but no significant differences were apparent on the BRIEF Sustain, Shift, and Initiate scales. The results show that the incidence of ADHD in children with SBH exceeds the population rate, is represented by problems with inattention rather than with impulsivity and hyperactivity; and that as with non-brain injured individuals, subtype differences in cognitive function remain to more clearly delineated. [ABSTRACT FROM AUTHOR]

The current study investigated the efficacy of a Satz­Mogel type short form of the WAIS-R in a closed head injury (CHI) population and whether the short form's effectiveness varied by lesion site. Data were taken from the files of 79 CHI patients, 20 with left hemisphere damage, 15 with right hemisphere damage, 29 with bilateral damage, and 15 with only diffuse damage. Information about IQ scores and age-corrected subtests scores was examined. As expected, correlations between two forms, for both IQ scores and subtest scores were high. However, there was a remarkable percentage of deviation in scaled score pints and changes in intellectual classification for some of these scores. No evidence was found to support the notion that usefulness of the short form varied according to the location of lesion. [ABSTRACT FROM AUTHOR]