Head Control Contributes to Prediction of Emergence From the Minimally Conscious State in Children Admitted to Inpatient Rehabilitation.

OBJECTIVE: To examine the utility of head and trunk control, assessed using the Physical Abilities and Mobility Scale, for predicting emergence from a minimally conscious state (eMCS) among children with acquired brain injury admitted to inpatient rehabilitation in a disorder of consciousness (DoC). DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation hospital. PARTICIPANTS: Forty patients (2-21 years-old) directly admitted from acute care to pediatric inpatient brain injury rehabilitation in a DoC (average length of stay=85 days; N=40). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: State of consciousness (eMCS vs not) at discharge from inpatient rehabilitation. RESULTS: Forty-five percent of patients emerged from a minimally conscious state during inpatient rehabilitation. Admission state of consciousness and head control (but not trunk control) were significantly associated with eMCS and provided complementary prognostic information. Admission state of consciousness (ie, admitting in a vegetative state/unresponsive wakefulness syndrome) afforded the greatest negative predictive value (93.8%), whereas admission head control ability afforded the greatest positive predictive value (81.8% for any independent head control; 100% for maintaining head-up position for >30 seconds). Fifty percent of patients who emerged during the inpatient stay did not have independent head control at admission, highlighting the importance of exploring head control as a prognostic marker in conjunction with indicators with greater sensitivity (eg, state of consciousness at admission). CONCLUSIONS: A brief measure of head control at admission may contribute to identification of a subgroup of patients who are likely to emerge.

Screening for Delirium During Pediatric Brain Injury Rehabilitation.

OBJECTIVE: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in this population, and explore longitudinal trends in CAPD scores and their association with rehabilitation outcomes. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: 144 children (median 10.8 years) with ABI (N=144). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Percent compliance with twice daily delirium screening; prevalence of positive delirium screens; trajectories in CAPD scores and their relation with FIM for Children (WeeFIM) scores. RESULTS: Screening was feasible (mean 75% compliance for each of 144 children). Of 16,136 delirium screens, 29% were positive. 62% of children had ≥1 positive screen. Four primary patterns of CAPD trajectories were identified: Static Encephalopathy (10%), Episodic Delirium (10%), Improving (32%), and No Delirium (48%). Validity of these trajectories was demonstrated through association with WeeFIM and CALS outcomes. Younger age at admission was associated with positive delirium screens, and rehabilitation length of stay was significantly longer for the Improving group. CONCLUSIONS: Delirium occurs frequently in children with ABI during inpatient rehabilitation. Routine delirium screening provides clinically relevant information including the potential to facilitate early detection and intervention for medical complications. Longitudinal ratings of delirium symptoms may also have a role in developing a standardized definition for Post Traumatic Confusional State (PTCS) stage of recovery in children.

Rasch Properties of the Cognitive and Linguistic Scale and Optimization for Outcome Trajectory Modeling in Pediatric Acquired Brain Injury.

OBJECTIVES: To (1) determine if items on the Cognitive and Linguistic Scale (CALS) follow a Rasch distribution and (2) explore the relationship between Rasch-derived Cognitive Ability Estimates and outcome trajectory parameters using a nonlinear mixed-effects modeling approach. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation hospital. PARTICIPANTS: A total of 252 children (N=252) aged of 2-21 years (median, 11.8 [IQR, 6.4-15.9] years) consecutively admitted to an inpatient rehabilitation brain injury unit (2008-2014) for a first inpatient admission after acquired brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch-derived Cognitive Ability Estimates from the CALS and associated outcome trajectory parameters. RESULTS: The CALS demonstrates adequate interval-scale properties with removal of scores from the arousal and responsivity items. Rasch-derived Cognitive Ability Estimates were associated with age (ß=0.025, P<.001) such that older age was associated with a faster rate of recovery and more complete ultimate recovery. Slower recovery initiation was associated with a less complete overall cognitive recovery (Spearman ρ=-0.31; P<.001). CONCLUSIONS: The Cognitive Ability Estimates derived from the CALS and associated outcome parameters (eg, rate of recovery) may serve as an ideal outcome measure for clinical trials evaluating interventions for acquired brain injury in a pediatric rehabilitation setting.

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.

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.

Exploratory study of sport-related concussion effects on peripheral micro-RNA expression.

OBJECTIVE: Explore changes in micro-RNA (miRNA) expression in blood after sport-related concussion (SRC) in collegiate athletes. METHODS: Twenty-seven collegiate athletes (~41% male, ~75% white, age 18.8 ± 0.8 years) provided both baseline and post-SRC blood samples. Serum was analyzed for expression of miR-153-3p (n = 27), miR-223-3p (n = 23), miR-26a-5p (n = 26), miR-423-3p (n = 23), and miR-let-7a-5p (n = 23) at both time points via quantitative polymerase chain reaction (qPCR). Nonparametric analyses were used to compare miRNA expression changes between baseline and SRC and to evaluate associations with clinical outcomes (symptom severity, cognition, balance, and oculomotor function, and clinical recovery time). RESULTS: Participants manifested a significant increase in miRNA expression following SRC for miR153-3p (Z = -2.180, p = .029, 59% of the participants increased post-SRC), miR223-3p (Z = -1.998, p = .046, 70% increased), and miR-let-7a-5p (Z = -2.190, p = .029, 65% increased). There were no statistically significant associations between changes in miRNA expression and clinical test scores, acute symptom severity, or clinical recovery time. CONCLUSION: MiR-153-3p, miR-223-3p, and miR-let-7a-5p were significantly upregulated acutely following SRC in male and female collegiate athletes compared to baseline levels, though several athletes demonstrated no change or a decrease in expression. The biological mechanisms and functional implications of the increased expression of these circulating miRNA are unclear and require more research, as does their relevance to clinical outcomes.

Inter-rater Reliability of the Revised Physical and Neurological Examination of Subtle Signs (PANESS) scored using video review.

The Physical and Neurological Examination of Subtle Signs (PANESS) is a brief neuromotor exam designed for use in children. This study examined the inter-rater reliability of PANESS scoring using video review in 23 typically developing youth, aged 10-18 years, who were either never-concussed or evaluated following clinical recovery from concussion. Moderate to excellent inter-rater reliability was identified across PANESS subscores and total score. The strongest inter-rater reliability was observed for the Timed Motor portion of the PANESS (ICCs >.90) suggesting that this section in particular may be a strong candidate for video-based scoring or telehealth administration.

Randomized controlled trial of cognitive refocusing versus stimulus control treatment for college insomnia: feasibility of a brief, electronic-based, and peer-led approach.

OBJECTIVE: Performance of Cognitive Refocusing Treatment for Insomnia (CRT-I) relative to stimulus control treatment (SCT) remains unknown among college students. This pilot trial compared single-session, electronic-based, peer-led CRT-I to SCT, and as well as awareness-based (AC) and no-treatment (NTC) controls. PARTICIPANTS: College students (N = 82; Mage=18.59 [SD = 0.78]; 58% female; 61% White; 16% Hispanic) with insomnia symptoms were randomly assigned to CRT-I (n = 12), SCT (n = 14), and AC (n = 14) conditions, or non-randomly recruited to NTC (n = 42). METHODS: All participants completed baseline and one-month follow-up surveys, and reported daily task enactment (except NTC). RESULTS: Feasibility ratings were comparable across conditions. Within-group treatment effects revealed greater improvements in (a) insomnia symptom severity among CRT-I (d = 1.13) and SCT (d = 1.66) groups relative to AC (d = 0.90) and (b) pre-sleep cognitive arousal among CRT-I (d = 0.94) and SCT (d = 1.42) groups relative to AC (d = 0.75). CONCLUSIONS: Brief, electronic-based, peer-led CRT-I and SCT interventions appear feasible and potentially efficacious for college insomnia.

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.