Trajectories of Persistent Postconcussion Symptoms and Factors Associated With Symptom Reporting After Mild Traumatic Brain Injury.

OBJECTIVE: To examine the trajectories of persistent postconcussion symptoms (PPCS) after mild traumatic brain injury (MTBI) and to investigate which injury-related and personal factors are associated with symptom reporting. DESIGN: Prospective longitudinal cohort study. Follow-up at 3 and 12 months postinjury. SETTING: A level 1 trauma center and an emergency outpatient clinic. PARTICIPANTS: Patients with MTBI (n=358), trauma controls (n=75), and community controls (n=78). MAIN OUTCOME MEASURES: Symptoms were assessed with the British Columbia Postconcussion Symptom Inventory (BC-PSI). Participants were categorized as having moderate to severe PPCS (msPPCS) when reporting ≥3 moderate/severe symptoms or a BC-PSI total score of ≥13. BC-PSI total scores were compared between the groups and were further used to create cutoffs for reliable change by identifying uncommon and very uncommon change in symptoms in the community control group. Associations between symptom reporting and 25 injury-related and personal factors were examined. RESULTS: The MTBI group had a similar prevalence of msPPCS at 3 and 12 months (21%) and reported more symptoms than the control groups. Analyses of individual trajectories, however, revealed considerable change in both msPPCS and BC-PSI total scores in the MTBI group, where both worsening and improvement was common. Intracranial lesions on computed tomography were associated with a greater likelihood of improving from 3 to 12 months. Those with msPPCS at both assessments were more likely to be women and to have these personal preinjury factors: reduced employment, pain, poor sleep, low resilience, high neuroticism and pessimism, and a psychiatric history. CONCLUSIONS: Group analyses suggest a stable prevalence of msPPCS the first year postinjury. However, there was considerable intraindividual change. Several personal factors were associated with maintaining symptoms throughout the first year.

Personal Factors Associated With Postconcussion Symptoms 3 Months After Mild Traumatic Brain Injury.

OBJECTIVE: To describe personal factors in patients with mild traumatic brain injury (MTBI) and 2 control groups and to explore how such factors were associated with postconcussion symptoms (PCSs). DESIGN: Prospective cohort study. SETTING: Level 1 trauma center and outpatient clinic. PARTICIPANTS: Participants (N=541) included patients with MTBI (n=378), trauma controls (n=82), and community controls (n=81). MAIN OUTCOME MEASURES: Data on preinjury health and work status, personality, resilience, attention deficit/hyperactivity, and substance use. Computed tomography (CT) findings and posttraumatic amnesia were recorded. Symptoms were assessed at 3 months with the British Columbia Postconcussion Symptom Inventory and labeled as PCS+ if ≥3 symptoms were reported or the total score was ≥13. Predictive models were fitted with penalized logistic regression using the least absolute shrinkage and selection operator (lasso) in the MTBI group, and model fit was assessed with optimism-corrected area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: There were few differences in personal factors between the MTBI group and the 2 control groups without MTBI. Rates of PCS+ were 20.8% for the MTBI group, 8.0% for trauma controls, and 1.3% for community controls. In the MTBI group, there were differences between the PCS+ and PCS- group on most personal factors and injury-related variables in univariable comparisons. In the lasso models, the optimism-corrected AUC for the full model was 0.79, 0.73 for the model only including personal factors, and 0.63 for the model only including injury variables. Working less than full time before injury, having preinjury pain and poor sleep quality, and being female were among the selected predictors, but also resilience and some personality traits contributed in the model. Intracranial abnormalities on CT were also a risk factor for PCS. CONCLUSIONS: Personal factors convey important prognostic information in patients with MTBI. A vulnerable work status and preinjury health problems might indicate a need for follow-up and targeted interventions.

Cognitive Reserve Moderates Cognitive Outcome After Mild Traumatic Brain Injury.

OBJECTIVE: To investigate whether cognitive reserve moderates differences in cognitive functioning between patients with mild traumatic brain injury (MTBI) and controls without MTBI and to examine whether patients with postconcussion syndrome have lower cognitive functioning than patients without postconcussion syndrome at 2 weeks and 3 months after injury. DESIGN: Trondheim MTBI follow-up study is a longitudinal controlled cohort study with cognitive assessments 2 weeks and 3 months after injury. SETTING: Recruitment at a level 1 trauma center and at a general practitioner-run, outpatient clinic. PARTICIPANTS: Patients with MTBI (n=160) according to the World Health Organization criteria, trauma controls (n=71), and community controls (n=79) (N=310). MAIN OUTCOME MEASURES: A cognitive composite score was used as outcome measure. The Vocabulary subtest was used as a proxy of cognitive reserve. Postconcussion syndrome diagnosis was assessed at 3 months with the British Columbia Postconcussion Symptom Inventory. RESULTS: Linear mixed models demonstrated that the effect of vocabulary scores on the cognitive composite scores was larger in patients with MTBI than in community controls at 2 weeks and at 3 months after injury (P=.001). Thus, group differences in the cognitive composite score varied as a function of vocabulary scores, with the biggest differences seen among participants with lower vocabulary scores. There were no significant differences in the cognitive composite score between patients with (n=29) and without (n=131) postconcussion syndrome at 2 weeks or 3 months after injury. CONCLUSION: Cognitive reserve, but not postconcussion syndrome, was associated with cognitive outcome after MTBI. This supports the cognitive reserve hypothesis in the MTBI context and suggests that persons with low cognitive reserve are more vulnerable to reduced cognitive functioning if they sustain an MTBI.

Examining 3-month test-retest reliability and reliable change using the Cambridge Neuropsychological Test Automated Battery.

The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a battery of computerized neuropsychological tests commonly used in Europe in neurology and psychiatry studies, including clinical trials. The purpose of this study was to investigate test-retest reliability and to develop reliable change indices and regression-based change formulas for using the CANTAB in research and practice involving repeated measurement. A sample of 75 healthy adults completed nine CANTAB tests, assessing three domains (i.e., visual learning and memory, executive function, and visual attention) twice over a 3-month period. Wilcoxon signed-rank tests showed significant practice effects for 6 of 14 outcome measures with effect sizes ranging from negligible to medium (Hedge's g: .15-.40; Cliff's delta: .09-.39). The Spatial Working Memory test, Attention Switching Task, and Rapid Visual Processing test were the only tests with scores of adequate test-retest reliability. For all outcome measures, Pearson's and Spearman's correlation coefficients ranged from .39 to .79. The measurement error surrounding difference scores was large, thus requiring large changes in performance (i.e., 1-2 SDs) in order to interpret a change score as reliable. In the regression equations, test scores from initial testing significantly predicted retest scores for all outcome measures. Age was a significant predictor in several of the equations, while education was a significant predictor in only two of the equations. The adjusted R2 values ranged between .19 and .67. The present study provides results enabling clinicians to make probabilistic statements about change in cognitive functions based on CANTAB test performances.

Methodology Matters: Comparing Approaches for Defining Persistent Symptoms after Mild Traumatic Brain Injury.

Some people experience persistent post-concussion symptoms (PPCS) after mild traumatic brain injury (mTBI). A meaningful clinical classification and scientific progress are hampered by a lack of consensus regarding the phenomenology, assessment, and operationalization of PPCS. Here we demonstrate and evaluate how the methodology used to assess and define persistent symptoms after mTBI influences PPCS as a binary outcome. We present empirical data from 15 classification methods reflecting procedures found in the literature and clinical practice. In total, 221 patients with mTBI, 73 patients with orthopedic injuries, and 77 community controls were included in the study. The prevalence rate of PPCS in the mTBI group varied between 10% and 47%, depending on the method used to assess and define unfavorable outcome. There was generally low positive agreement between the different methods; even the two methods yielding the most similar prevalence rates (89.2% overall proportion agreement) agreed on less than half (45.5% positive agreement) of the PPCS cases. Using a liberal but not uncommon threshold for symptom severity, there was a considerable misclassification rate of PPCS in both comparison groups. Our results highlight the importance for researchers to be aware of the limitations of using binary approaches for classification of PPCS. The poor agreement between methods should be considered when (1) interpreting the heterogeneity in the existing PPCS literature and (2) developing new improved methods. An empirically informed consensus regarding classification of PPCS should be a priority for the research community.

Developing Cognition Endpoints for the CENTER-TBI Neuropsychological Test Battery.

Background: Measuring cognitive functioning is common in traumatic brain injury (TBI) research, but no universally accepted method for combining several neuropsychological test scores into composite, or summary, scores exists. This study examined several possible composite scores for the test battery used in the large-scale study Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Methods: Participants with mild traumatic brain injury (MTBI; n = 140), orthopedic trauma (n = 72), and healthy community controls (n = 70) from the Trondheim MTBI follow-up study completed the CENTER-TBI test battery at 2 weeks after injury, which includes both traditional paper-and-pencil tests and tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Seven composite scores were calculated for the paper and pencil tests, the CANTAB tests, and all tests combined (i.e., 21 composites): the overall test battery mean (OTBM); global deficit score (GDS); neuropsychological deficit score-weighted (NDS-W); low score composite (LSC); and the number of scores ≤5th percentile, ≤16th percentile, or <50th percentile. Results: The OTBM and the number of scores <50th percentile composites had distributional characteristics approaching a normal distribution. The other composites were in general highly skewed and zero-inflated. When the MTBI group, the trauma control group, and the community control group were compared, effect sizes were negligible to small for all composites. Subgroups with vs. without loss of consciousness at the time of injury did not differ on the composite scores and neither did subgroups with complicated vs. uncomplicated MTBIs. Intercorrelations were high within the paper-and-pencil composites, the CANTAB composites, and the combined composites and lower between the paper-and-pencil composites and the CANTAB composites. Conclusion: None of the composites revealed significant differences between participants with MTBI and the two control groups. Some of the composite scores were highly correlated and may be redundant. Additional research on patients with moderate to severe TBIs is needed to determine which scores are most appropriate for TBI clinical trials.