Duration of Prophylactic Levetiracetam After Surgery for Brain Tumor: A Prospective Randomized Trial.

BACKGROUND: Levetiracetam is commonly used as a prophylactic antiseizure medication in patients undergoing surgical resection of brain tumors. OBJECTIVE: To quantitate side effects experienced in patients treated with 1 week vs 6 weeks of prophylactic levetiracetam using validated measures for neurotoxicity and depression. METHODS: Patients undergoing surgical resection of a supratentorial tumor with no seizure history were randomized within 48 hours of surgery to receive prophylactic levetiracetam for the duration of either 1 or 6 weeks. Patients were given oral levetiracetam extended release 1000 mg during the first part of this study. Owing to drug backorder, patients enrolled later in this study received levetiracetam 500 mg BID. The primary outcome was the change in the neurotoxicity score 6 weeks after drug initiation. The secondary outcome was seizure incidence. RESULTS: A total of 81 patients were enrolled and randomized to 1 week (40 patients) or 6 weeks (41 patients) of prophylactic levetiracetam treatment. The neurotoxicity score slightly improved in the overall cohort between baseline and reassessment. There was no significant difference between groups in neurotoxicity or depression scores. Seizure incidence was low in the entire cohort of patients with 1 patient in each arm experiencing a seizure during the follow-up period. CONCLUSION: The use of prophylactic levetiracetam did not result in significant neurotoxicity or depression when given for either 1 week or 6 weeks. The incidence of seizure after craniotomy for tumor resection is low regardless of duration of therapy.

Patient-Reported Outcome of Functional Cognition for Traumatic Brain Injury: Item-Level Psychometrics.

A patient-reported functional cognition measure that can bridge neuropsychological tests and ecological validity is lacking. The purpose of this study was to present the initial item-level psychometrics of a functional cognition item bank, the Functional Cognition-Patient-Reported Outcome (FC-PRO). Confirmatory factor analysis, Rasch analysis, and convergent validity were conducted to establish item-level psychometrics of the FC-PRO item bank. Four of the six domains met essential unidimensionality criteria; all domains met rating scale criteria; domains had relatively few misfitting items (3%-13%); person reliability (.8-.92), and person strata (2.97-4.29) were satisfactory; the domains showed convergent validity for five of six domains. The FC-PRO showed adequate initial item-level psychometrics for researchers/clinicians to measure specific functional cognitive domains in patients with traumatic brain injury (TBI). This study provides the foundation for the development of future short forms, computer adaptive tests, and keyform recovery maps of patient-reported functional cognition to facilitate clinical utilization.

Predicting Clinical Outcomes 7-10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2.

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 (ß = 0.488 p = 0.000) as well as reduced cognitive independence (ß = - 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 (ß = 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 (ß = - 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (ß = 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.

The Role of Sleep-Disordered Breathing Symptoms in Neurocognitive Function Among Youth With Sickle Cell Disease.

OBJECTIVE: To examine associations between sleep-disordered breathing (SDB) and executive/attentional function in pediatric sickle cell disease (SCD). METHODS: Sixty youth with SCD ages 8-18 years and caregivers completed the Pediatric Sleep Questionnaire (PSQ), Delis Kaplan Executive Function System Trail Making Test (DKEFS TMT), Psychomotor Vigilance Test (PVT), and the Behavior Rating Inventory Of Executive Function, Second Edition (BRIEF-2) Parent Report. RESULTS: The PSQ significantly predicted the BRIEF-2 Parent Report, F(1, 58) = 44.64, p < .001, R2 = 0.44, f2 = 0.77. CONCLUSIONS: Sleep-disordered breathing symptoms may predict informant-rated executive dysfunction in pediatric SCD, but not performance-based executive function.

Examining the Item-Level Factor Structure of the Behavior Rating Inventory of Executive Function-Adult Version Within a Traumatic Brain Injury Sample.

OBJECTIVE: To conduct the first item-level exploration of scale and index structure of the self-report Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) in traumatic brain injury (TBI). DESIGN: This was an observational cross-sectional study design using secondary data. We conducted exploratory factor analyses (EFA) to explore the index structure and scale structure of the BRIEF-A. We conducted EFA with all 70 items of the BRIEF-A to examine the index structure. Based on the finding of index structure, we conducted EFA on the 30 items of the Behavioral Regulation Index (BRI) and the 40 items of the Metacognitive Index (MI). SETTING: Data were collected through 5 studies in outpatient and community settings in the southeast United States. PARTICIPANTS: Individuals (N=338) aged 18-89 years with a history of mild to severe TBI who were able to speak English fluently. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The BRIEF-A. RESULTS: The 2-factor structure aligned with the BRIEF-A manual at the index level. Scale structure for the MI (40 items) resulted in 1 factor, whereas the BRI (30 items) could be represented by either a 2- or 3-factor structure. The 2-factor structure of the BRI is more parsimonious and matched other factor analyses derived from the sum of scale items. CONCLUSIONS: We confirmed the manual designated index structure (BRI and MI) of the BRIEF-A but took precautions against using the 9 scales. Instead, we recommend using the 2 designated index scores and 2 newly identified composite scores representing Behavioral Control Trait and Emotional Control Trait.

Association of Serum Bilirubin with the Severity and Outcomes of Intracerebral Hemorrhages.

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, and it is often associated with a high mortality rate and significant morbidity among survivors. Recent studies have shown that bilirubin, a product of heme metabolism, can exhibit cytoprotective, antioxidant and, anti-inflammatory properties. However, little is known about the role of bilirubin in combating several pathophysiological pathways caused by intracerebral bleeding in patients with ICH. In this study, data were collected retrospectively on 276 patients with ICH who were admitted to a university hospital between 5 January 2014 and 31 December 2017. We assessed the relationship between levels of total, direct, and indirect serum bilirubin and assessments of initial stroke severity and clinical outcomes by using Spearman's rank correlation and Kruskal-Wallis H tests. A secondary examination of the carrier protein albumin was also undertaken. Our study found that higher levels of direct bilirubin were correlated with worse admission Glasgow Coma Scales (GCS) (rs = -0.17, p = 0.011), worse admission ICH Scores (rs = 0.19, p = 0.008), and worse discharge modified Rankin Scales (mRS) (rs = 0.15, p = 0.045). Direct bilirubin was still significantly correlated with discharge mRS after adjusting for temperature at admission (rs = 0.16, p = 0.047), oxygen saturation at admission (rs = 0.15, p = 0.048), white blood cell count (rs = 0.18, p = 0.023), or Troponin T (rs = 0.25, p = 0.001) using partial Spearman's correlation. No statistical significance was found between levels of total or indirect bilirubin and assessments of stroke severity and outcomes. In contrast, higher levels of albumin were correlated with better admission GCS (rs = 0.13, p = 0.027), discharge GCS (rs = 0.15, p = 0.013), and discharge mRS (rs = -0.16, p = 0.023). We found that levels of total bilirubin, direct bilirubin, and albumin were all significantly related to discharge outcomes classified by discharge destinations (p = 0.036, p = 0.014, p = 0.016, respectively; Kruskal-Wallis H tests). In conclusion, higher direct bilirubin levels were associated with greater stroke severity at presentation and worse outcomes at discharge among patients with ICH. Higher levels of albumin were associated with lower stroke severity and better clinical outcomes. Future prospective studies on the free bioactive bilirubin are needed to better understand the intricate relationships between bilirubin and ICH.

New cut-score to improve performance of the Memory Validity Profile (MVP) in heterogenous clinical populations.

The Memory Validity Profile (MVP) is a standalone performance validity test developed specifically for use with children. Prior research has demonstrated the MVP's strength in its ease of administration to children with a wide range of intellectual abilities. However, it has been found to lack sensitivity in detecting noncredible performance in select clinical populations using published cutoffs. The current study examines the MVP's performance in a diagnostically heterogeneous clinical sample and proposes a new cutoff for optimization of sensitivity and specificity. Archival clinical data were examined from 96 participants referred for a comprehensive neuropsychological evaluation (ages 6-18). Receiver operating characteristic analysis was used to assess the discriminative ability of MVP in detecting cases of noncredible performance defined as failures on both the Test of Memory Malingering and Reliable Digit Span. Using published cutoffs, the MVP demonstrated perfect specificity (100%) but suboptimal sensitivity (33.3%). Receiver operating characteristic analysis revealed strong discrimination using MVP Total score (AUC = 0.891 (p < 0.001)) and a MVP Total cut-score of ≤30 resulted in optimal sensitivity (89%) and specificity (63%). Our findings provide additional evidence that published MVP cutoffs may be too lenient to adequately capture instances of noncredible performance and indicate an MVP Total score cutoff of ≤30 may be more appropriate for use with heterogeneous clinical populations.

Making a Difference: Affective Distress Explains Discrepancy Between Objective and Subjective Cognitive Functioning After Mild Traumatic Brain Injury.

OBJECTIVE: To assess the relationship between subjective cognitive symptoms and objective cognitive test scores in patients after concussion. We additionally examined factors associated with subjective and objective cognitive dysfunction, as well as their discrepancy. PARTICIPANTS: Eighty-six individuals (65.1% female; 74.4% adult) from an interdisciplinary concussion clinic. METHODS: Subjective and objective cognitive functioning was measured via the SCAT-Symptom Evaluation and the CNS Vital Signs Neurocognition Index (NCI), respectively. Cognitive discrepancy scores were derived by calculating standardized residuals (via linear regression) using subjective symptoms as the outcome and NCI score as the predictor. Hierarchical regression assessed predictors (age, education, time postinjury, attention-deficit/hyperactivity disorder, affective distress, and sleep disturbance) of cognitive discrepancy scores. Nonparametric analyses evaluated relationships between predictor variables, subjective symptoms, and NCI. RESULTS: More severe affective and sleep symptoms (large and medium effects), less time postinjury (small effect), and older age (small effect) were associated with higher subjective cognitive symptoms. Higher levels of affective distress and less time since injury were associated with higher cognitive discrepancy scores (ß = .723, P < .001; ß = -.204, P < .05, respectively). CONCLUSION: Clinical interpretation of subjective cognitive dysfunction should consider these additional variables. Evaluation of affective distress is warranted in the context of higher subjective cognitive complaints than objective test performance.

Predicting long-term cognitive and neuropathological consequences of moderate to severe traumatic brain injury: Review and theoretical framework.

Prognostic modeling in moderate to severe traumatic brain injury (TBI) has historically focused primarily on the projection of crude outcomes such as the risk of mortality and disability. Initial work in this area has perpetuated the notion that prognosis after moderate to severe TBI can be measured as a single, static, and dichotomous outcome. However, more recent conceptualizations describe moderate to severe TBI as the initiation of a chronic disease state with high levels of inter-individual variability in terms of symptom manifestation and disease progression. Unfortunately, existing prognostic models provide limited insight into the extent of chronic cognitive and neurodegenerative changes experienced by moderate to severe TBI survivors. Though prior research has identified a variety of acute factors that appear to influence post-injury cognitive and neuropathological outcomes, an empirically supported framework for prognostic modeling of these injury-distal outcomes does not exist. The current review considers the literature on an expanded array of empirically supported predictors (both premorbid and injury-related) in association with long-term sequelae of moderate to severe TBI. We also provide a theoretical framework and statistical approach for prognostic modeling in moderate to severe TBI in order to unify efforts across research groups and facilitate important progress in this research area.

The Role of Executive Functioning and Academic Achievement in the Academic Self-Concept of Children and Adolescents Referred for Neuropsychological Assessment.

The current study evaluated a model of youth academic self-concept which incorporates practical executive functioning behaviors and academic achievement. Though greater academic achievement has been linked to both positive self-concept and better executive functioning, these constructs have not been examined simultaneously. It was hypothesized that academic achievement would mediate the association between problems with executive functioning and academic self-concept such that youth with more problems with executive functioning would have lower academic achievement and, in turn, lower academic self-concept. Clinical data was analyzed from a diagnostically heterogeneous sample of youth (n = 122) who underwent neuropsychological evaluation. Problems with executive functioning were assessed using the Behavior Rating Inventory of Executive Function. Academic achievement was assessed using the Woodcock⁻Johnson Tests of Achievement or Wechsler Individual Achievement Test. Academic self-concept was assessed using the youth-report version of the Behavioral Assessment System for Children. Surprisingly, findings indicate that academic achievement is not significantly associated with problems with executive functioning or academic self-concept. However, greater problems with executive functioning are associated with decreased academic self-concept. The overall model included several covariates and accounted for 10% of the variance in academic self-concept. Findings suggest that executive skills may be essential for aligning academic achievement with classroom performance. Though various child characteristic covariates were included, the model accounted for a small amount of variance suggesting that future studies should examine contributing contextual factors.

The Relationship Between Sleep and Cognition in Children Referred for Neuropsychological Evaluation: A Latent Modeling Approach.

Children with conditions affecting cognitive processes experience high levels of sleep disturbance, which may further compound the cognitive ramifications of their disorders. Despite this, existing studies in this area have been primarily confined to only particular diagnostic groups and/or a limited scope of sleep and cognitive parameters. The current study characterized the nature of sleep problems and examined the relationship between a wide range of sleep-related problems and cognitive functioning in a large (N = 103) diagnostically heterogeneous sample of youth (aged 6-16) referred for neuropsychological assessment. Structural equation modeling was used to examine the relationship between sleep-related problems (i.e., daytime sleepiness, sleep onset latency, sleep fragmentation, sleep time variability, sleep debt) and cognitive performance (i.e., executive functioning, sustained attention, memory, processing speed). Sleep fragmentation emerged as the most prominent sleep-related problem in the present sample. Structural equation modeling demonstrated a negative association between sleep-related problems and cognition that did not reach statistical significance (ß = -0.084, p = 0.629). The current statistical approach may be used as a conceptual framework for future work examining these multi-dimensional constructs in a parsimonious fashion.

Temporal Profile of Microtubule-Associated Protein 2: A Novel Indicator of Diffuse Brain Injury Severity and Early Mortality after Brain Trauma.

This study compared cerebrospinal fluid (CSF) levels of microtubule-associated protein 2 (MAP-2) from adult patients with severe traumatic brain injury (TBI) with uninjured controls over 10 days, and examined the relationship between MAP-2 concentrations and acute clinical and radiologic measures of injury severity along with mortality at 2 weeks and over 6 months. This prospective study, conducted at two Level 1 trauma centers, enrolled adults with severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring a ventriculostomy, as well as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 h following TBI and analyzed via enzyme-linked immunosorbent assay for MAP-2 (ng/mL). Injury severity was assessed by the GCS score, Marshall Classification on computed tomography (CT), Rotterdam CT score, and mortality. There were 151 patients enrolled-130 TBI and 21 control patients. MAP-2 was detectable within 6 h of injury and was significantly elevated compared with controls (p < 0.001) at each time-point. MAP-2 was highest within 72 h of injury and decreased gradually over 10 days. The area under the receiver operating characteristic curve for deciphering TBI versus controls at the earliest time-point CSF was obtained was 0.96 (95% CI 0.93-0.99) and for the maximal 24-h level was 0.98 (95% CI 0.97-1.00). The area under the curve for initial MAP-2 levels predicting 2-week mortality was 0.80 at 6 h, 0.81 at 12 h, 0.75 at 18 h, 0.75 at 24 h, and 0.80 at 48 h. Those with Diffuse Injury III-IV had much higher initial (p = 0.033) and maximal (p = 0.003) MAP-2 levels than those with Diffuse Injury I-II. There was a graded increase in the overall levels and peaks of MAP-2 as the degree of diffuse injury increased within the first 120 h post-injury. These data suggest that early levels of MAP-2 reflect severity of diffuse brain injury and predict 2-week mortality in TBI patients. These findings have implications for counseling families and improving clinical decision making early after injury and guiding multidisciplinary care. Further studies are needed to validate these findings in a larger sample.

Factor structure and item level psychometrics of the Social Problem Solving Inventory-Revised: Short Form in traumatic brain injury.

Social problem-solving deficits characterise individuals with traumatic brain injury (TBI), and poor social problem solving interferes with daily functioning and productive lifestyles. Therefore, it is of vital importance to use the appropriate instrument to identify deficits in social problem solving for individuals with TBI. This study investigates factor structure and item-level psychometrics of the Social Problem Solving Inventory-Revised: Short Form (SPSI-R:S), for adults with moderate and severe TBI. Secondary analysis of 90 adults with moderate and severe TBI who completed the SPSI-R:S was performed. An exploratory factor analysis (EFA), principal components analysis (PCA) and Rasch analysis examined the factor structure and item-level psychometrics of the SPSI-R:S. The EFA showed three dominant factors, with positively worded items represented as the most definite factor. The other two factors are negative problem-solving orientation and skills; and negative problem-solving emotion. Rasch analyses confirmed the three factors are each unidimensional constructs. It was concluded that the total score interpretability of the SPSI-R:S may be challenging due to the multidimensional structure of the total measure. Instead, we propose using three separate SPSI-R:S subscores to measure social problem solving for the TBI population.

Lateral Ventricle Volume Asymmetry Predicts Midline Shift in Severe Traumatic Brain Injury.

Midline shift following severe traumatic brain injury (sTBI) detected on computed tomography (CT) scans is an established predictor of poor outcome. We hypothesized that lateral ventricular volume (LVV) asymmetry is an earlier sign of developing asymmetric intracranial pathology than midline shift. This retrospective analysis was performed on data from 84 adults with blunt sTBI requiring a ventriculostomy who presented to a Level I trauma center. Seventy-six patients underwent serial CTs within 3 h and an average of three scans within the first 10 d of sTBI. Left and right LVVs were quantified by computer-assisted manual volumetric measurements. LVV ratios (LVR) were determined on the admission CT to evaluate ventricular asymmetry. The relationship between the admission LVR value and subsequent midline shift development was tested using receiver operating characteristic (ROC) analysis, and odds ratio (OR) and relative risk tests. Sixty patients had no >5 mm midline shift on the initial admission scan. Of these, 15 patients developed it subsequently (16 patients already had >5 mm midline shift on admission scans). For >5 mm midline shift development, admission LVR of >1.67 was shown to have a sensitivity of 73.3% and a specificity of 73.3% (area under the curve=0.782; p<0.0001). LVR of >1.67 as exposure yielded an OR of 7.56 (p<0.01), and a risk ratio of 4.42 (p<0.01) for midline shift development as unfavorable outcome. We propose that LVR captures LVV asymmetry and is not only related to, but also predicts the development of midline shift already at admission CT examination. Lateral ventricles may have a higher "compliance" than midline structures to developing asymmetric brain pathology. LVR analysis is simple, rapidly accomplished and may allow earlier interventions to attenuate midline shift and potentially improve ultimate outcomes.

Biomarkers improve clinical outcome predictors of mortality following non-penetrating severe traumatic brain injury.

OBJECTIVE: This study assessed whether early levels of biomarkers measured in CSF within 24-h of severe TBI would improve the clinical prediction of 6-months mortality. METHODS: This prospective study conducted at two Level 1 Trauma Centers enrolled adults with severe TBI (GCS ≤8) requiring a ventriculostomy as well as control subjects. Ventricular CSF was sampled within 24-h of injury and analyzed for seven candidate biomarkers (UCH-L1, MAP-2, SBDP150, SBDP145, SBDP120, MBP, and S100B). The International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) scores (Core, Extended, and Lab) were calculated for each patient to determine risk of 6-months mortality. The IMPACT models and biomarkers were assessed alone and in combination. RESULTS: There were 152 patients enrolled, 131 TBI patients and 21 control patients. Thirty six (27 %) patients did not survive to 6 months. Biomarkers were all significantly elevated in TBI versus controls (p < 0.001). Peak levels of UCH-L1, SBDP145, MAP-2, and MBP were significantly higher in non-survivors (p < 0.05). Of the seven biomarkers measured at 12-h post-injury MAP-2 (p = 0.004), UCH-L1 (p = 0.024), and MBP (p = 0.037) had significant unadjusted hazard ratios. Of the seven biomarkers measured at the earliest time within 24-h, MAP-2 (p = 0.002), UCH-L1 (p = 0.016), MBP (p = 0.021), and SBDP145 (0.029) had the most significant elevations. When the IMPACT Extended Model was combined with the biomarkers, MAP-2 contributed most significantly to the survival models with sensitivities of 97-100 %. CONCLUSIONS: These data suggest that early levels of MAP-2 in combination with clinical data provide enhanced prognostic capabilities for mortality at 6 months.

Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products.

The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.

UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A Single Center Pilot Study.

OBJECTIVE: We examined two potential biomarkers of brain damage in hypoxic-ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury). We hypothesized that the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. We further hypothesized that higher levels would be detected in serum samples of HIE neonates and would correlate with brain damage on magnetic resonance imaging (MRI) and later developmental outcomes.? STUDY DESIGN: Serum UCH-L1 and GFAP concentrations from HIE neonates (n = 16) were compared to controls (n = 11). The relationship between biomarker concentrations of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III) was examined using Pearson correlation coefficients and a mixed model design. RESULT: Both biomarkers were detectable in cord blood from control subjects. UCH-L1 concentrations were higher in HIE neonates (p < 0.001), and associated with cortical injury (p < 0.055) and later motor and cognitive developmental outcomes (p < 0.05). The temporal change in GFAP concentrations during (from birth to 96 h of age) predicted motor developmental outcomes (p < 0.05) and injury to the basal ganglia and white matter. CONCLUSION: Ubiquitin C-terminal hydrolase L1 and GFAP should be explored further as promising serum biomarkers of brain damage and later neurodevelopmental outcomes in neonates with HIE.

Cognitive predictors of verbal memory in a mixed clinical pediatric sample.

Verbal memory problems, along with other cognitive difficulties, are common in children diagnosed with neurological and/or psychological disorders. Historically, these "memory problems" have been poorly characterized and often present with a heterogeneous pattern of performance across memory processes, even within a specific diagnostic group. The current study examined archival neuropsychological data from a large mixed clinical pediatric sample in order to understand whether functioning in other cognitive areas (i.e., verbal knowledge, attention, working memory, executive functioning) may explain some of the performance variability seen across verbal memory tasks of the Children's Memory Scale (CMS). Multivariate analyses revealed that among the cognitive functions examined, only verbal knowledge explained a significant amount of variance in overall verbal memory performance. Further univariate analyses examining the component processes of verbal memory indicated that verbal knowledge is specifically related to encoding, but not the retention or retrieval stages. Future research is needed to replicate these findings in other clinical samples, to examine whether verbal knowledge predicts performance on other verbal memory tasks and to explore whether these findings also hold true for visual memory tasks. Successful replication of the current study findings would indicate that interventions targeting verbal encoding deficits should include efforts to improve verbal knowledge.

The item level psychometrics of the behaviour rating inventory of executive function-adult (BRIEF-A) in a TBI sample.

PRIMARY OBJECTIVE: To determine whether the psychometrics of the BRIEF-A are adequate for individuals diagnosed with TBI. RESEARCH DESIGN: A prospective observational study in which the BRIEF-A was collected as part of a larger study. METHODS AND PROCEDURES: Informant ratings of the 75-item BRIEF-A on 89 individuals diagnosed with TBI were examined to determine items level psychometrics for each of the two BRIEF-A indexes: Behaviour Rating Index (BRI) and Metacognitive Index (MI). Patients were either outpatients or at least 1 year post-injury. MAIN OUTCOMES AND RESULTS: Each index measured a latent trait, separating individuals into five-to-six ability levels and demonstrated good reliability (0.94 and 0.96). Four items were identified that did not meet the infit criteria. CONCLUSIONS: The results provide support for the use of the BRIEF-A as a supplemental assessment of executive function in TBI populations. However, further validation is needed with other measures of executive function. Recommendations include use of the index scores over the Global Executive Composite score and use of the difficulty hierarchy for setting therapy goals.