Investigating cognitive reserve, symptom resolution and brain connectivity in mild traumatic brain injury.

BACKGROUND: A proportion of patients with mild traumatic brain injury (mTBI) suffer long-term consequences, and the reasons behind this are still poorly understood. One factor that may affect outcomes is cognitive reserve, which is the brain's ability to maintain cognitive function despite injury. It is often assessed through educational level or premorbid IQ tests. This study aimed to explore whether there were differences in post-concussion symptoms and symptom resolution between patients with mTBI and minor orthopedic injuries one week and three months after injury. Additional aims were to explore the relationship between cognitive reserve and outcome, as well as functional connectivity according to resting state functional magnetic resonance imaging (rs-fMRI). METHOD: Fifteen patients with mTBI and 15 controls with minor orthopedic injuries were recruited from the emergency department. Assessments, including Rivermead Post-Concussion Questionnaire (RPQ), neuropsychological testing, and rs-fMRI scans, were conducted on average 7 days (SD = 2) and 122 days (SD = 51) after injury. RESULTS: At the first time point, significantly higher rates of post-concussion symptoms (U = 40.0, p = 0.003), state fatigue (U = 56.5, p = 0.014), and fatigability (U = 58.5, p = 0.025) were observed among the mTBI group than among the controls. However, after three months, only the difference in post-concussion symptoms remained significant (U = 27.0, p = 0.003). Improvement in post-concussion symptoms was found to be significantly correlated with cognitive reserve, but only in the mTBI group (Spearman's rho = -0.579, p = .038). Differences in the trajectory of recovery were also observed for fatigability between the two groups (U = 36.5, p = 0.015). Moreover, functional connectivity differences in the frontoparietal network were observed between the groups, and for mTBI patients, functional connectivity differences in an executive control network were observed over time. CONCLUSION: The findings of this pilot study suggest that mTBI, compared to minor orthopedic trauma, is associated to both functional connectivity changes in the brain and concussion-related symptoms. While there is improvement in these symptoms over time, a small subgroup with lower cognitive reserve appears to experience more persistent and possibly worsening symptoms over time. This, however, needs to be validated in larger studies. TRIAL REGISTRATION: NCT05593172. Retrospectively registered.

Cognitive Reserve, Early Cognitive Screening, and Relationship to Long-Term Outcome after Severe Traumatic Brain Injury.

The objective was to investigate the relationship between early global cognitive functioning using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and cognitive flexibility (Trail Making Test (TMT), TMT B-A), with long-term outcome assessed by the Mayo-Portland Adaptability Index (MPAI-4) in severe traumatic brain injury (sTBI) controlling for the influence of cognitive reserve, age, and injury severity. Of 114 patients aged 18-65 with acute Glasgow Coma Scale 3-8, 41 patients were able to complete (BNIS) at 3 months after injury and MPAI-4 5-8 years after injury. Of these, 33 patients also completed TMT at 3 months. Global cognition and cognitive flexibility correlated significantly with long-term outcome measured with MPAI-4 total score (rBNIS = 0.315; rTMT = 0.355). Global cognition correlated significantly with the participation subscale (r = 0.388), while cognitive flexibility correlated with the adjustment (r = 0.364) and ability (r = 0.364) subscales. Adjusting for cognitive reserve and acute injury severity did not alter these relationships. The effect size for education on BNIS and TMT scores was large (d ≈ 0.85). Early screenings with BNIS and TMT are related to long-term outcome after sTBI and seem to measure complementary aspects of outcome. As early as 3 months after sTBI, educational level influences the scores on neuropsychological screening instruments.

Behavioural problems in the first year after Severe traumatic brain injury: a prospective multicentre study.

OBJECTIVE: To investigate the occurrence of behavioural problems in patients with severe traumatic brain injury during the first year after injury and potential associations with outcome. An additional post hoc objective was to analyse the frequency of behaviours with need for intervention from staff. DESIGN AND SETTING: In a prospective population based cohort study 114 patients with severe traumatic brain injury were assessed at three weeks, three months and one year after injury. MAIN MEASURES: Assessments included clinical examination and standardised instruments. Agitation was assessed with the Agitated Behaviour Scale, the course of recovery by the Rancho Los Amigo Scale and outcome by Glasgow Outcome Scale Extended. RESULTS: Agitation were most common at 3 weeks post injury and 28% ( n=68) of the patients showed at least one agitated behaviour requiring intervention from staff. Presence of significant agitation at 3 weeks after injury was not associated with poor outcome. At 3 months agitation was present in 11% ( n=90) and apathy in 26 out of 81 assessed patients. At 3 months agitation and apathy were associated with poor outcome at one year. CONCLUSIONS: Most agitated behaviours in the early phase are transient and are not associated with poor outcome. Agitation and apathy are uncommon at three months but when present are associated with poor outcome at one year after injury. In the early phase after a severe traumatic brain injury agitated behaviour in need of interventions from staff occur in a substantial proportion of patients.

Extended Anatomical Grading in Diffuse Axonal Injury Using MRI: Hemorrhagic Lesions in the Substantia Nigra and Mesencephalic Tegmentum Indicate Poor Long-Term Outcome.

Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I-hemispheric lesions, stage II-corpus callosum lesions, stage III-brainstem lesions, and stage IV-substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).

Associations between care pathways and outcome 1 year after severe traumatic brain injury.

OBJECTIVE: To assess associations between real-world care pathways for working-age patients in the first year after severe traumatic brain injury and outcomes at 1 year. SETTING AND DESIGN: Prospective, observational study with recruitment from 6 neurosurgical centers in Sweden and Iceland. Follow-up to 1 year, independently of care pathways, by rehabilitation physicians and paramedical professionals. PARTICIPANTS: Patients with severe traumatic brain injury, lowest (nonsedated) Glasgow Coma Scale score 3 to 8 during the first 24 hours and requiring neurosurgical intensive care, age 18 to 65 years, and alive 3 weeks after injury. MAIN MEASURES: Length of stay in intensive care, time between intensive care discharge and rehabilitation admission, outcome at 1 year (Glasgow Outcome Scale Extended score), acute markers of injury severity, preexisting medical conditions, and post-acute complications. Logistic regression analyses were performed. RESULTS: A multivariate model found variables significantly associated with outcome (odds ratio for good outcome [confidence interval], P value) to be as follows: length of stay in intensive care (0.92 [0.87-0.98], 0.014), time between intensive care discharge and admission to inpatient rehabilitation (0.97 [0.94-0.99], 0.017), and post-acute complications (0.058 [0.006-0.60], 0.017). CONCLUSIONS: Delays in rehabilitation admission were negatively associated with outcome. Measures to ensure timely rehabilitation admission may improve outcome. Further research is needed to evaluate possible causation.

WebRehab: a Swedish database for quality control in rehabilitation.

BACKGROUND: The healthcare sector needs to deliver evidence-based care and be cost-effective. This can be monitored in part via a national quality registry containing individualized data concerning patient problems, medical interventions, outcomes of treatment, and patient-reported outcomes. With this aim, WebRehab Sweden was launched in 1997 and has been available online since 2007. The aim of this paper is to discuss the design, some results, and possible use of such a registry. METHODS: Data entered into the registry online since 2007 were used in this paper. The registry contains information from 7,458 patients. Data from the first 3 years were used to show differences between genders and among diagnostic groups. Non-parametric statistics were used to analyse the differences between groups. RESULTS: The registry coverage of the country is 95%, and completeness is 81%. Data from hospitals/units have been accessible to the general public since 2009, but no data from individuals can be accessed. Length of stay has varied over the years, becoming significantly shorter between 2007 and 2012. CONCLUSION: A quality registry presents an opportunity to improve rehabilitation processes at participating units, provides data for use in benchmarking between units, and enables hospital management to utilize resources wisely.

Brain pathology after mild traumatic brain injury: an exploratory study by repeated magnetic resonance examination.

OBJECTIVE: To explore brain pathology after mild traumatic brain injury by repeated magnetic resonance examination. DESIGN: A prospective follow-up study. SUBJECTS: Nineteen patients with mild traumatic brain injury presenting with Glasgow Coma Scale (GCS) 14-15. METHODS: The patients were examined on day 2 or 3 and 3-7 months after the injury. The magnetic resonance protocol comprised conventional T1- and T2-weighted sequences including fluid attenuated inversion recovery (FLAIR), two susceptibility-weighted sequences to reveal haemorrhages, and diffusion-weighted sequences. Computer-aided volume comparison was performed. Clinical outcome was assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Hospital Anxiety and Depression Scale (HADS) and Glasgow Outcome Scale Extended (GOSE). RESULTS: At follow-up, 7 patients (37%) reported ≥ 3 symptoms in RPQ, 5 reported some anxiety and 1 reported mild depression. Fifteen patients reported upper level of good recovery and 4 patients lower level of good recovery (GOSE 8 and 7, respectively). Magnetic resonance pathology was found in 1 patient at the first examination, but 4 patients (21%) showed volume loss at the second examination, at which 3 of them reported < 3 symptoms and 1 ≥ 3 symptoms, all exhibiting GOSE scores of 8. CONCLUSION: Loss of brain volume, demonstrated by computer-aided magnetic resonance imaging volumetry, may be a feasible marker of brain pathology after mild traumatic brain injury.

Internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire.

OBJECTIVE: To investigate the internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) by Rasch analysis of data from a national cohort of patients with mild traumatic brain injury. METHODS: Data collected at 3 months after mild traumatic brain injury from 2,523 patients were analysed using the partial credit model, describing rating scale structure, local dependency, age and gender differential functioning, dimensionality and model fit. RESULTS: Categories did not work in a consistent manner; however, collapsing of Categories 1 and 2 yielded ordered thresholds. Local dependency of items was present and 2 item pairs were combined. There was no differential item functioning by gender or age. The Rasch factor explained 47.7% of the variance and the first contrast explained 12.4% of the unexplained variance (eigenvalue 1.9). Further analysis indicated 3 or more dimensions. Person measure had a mean of -2.16, showing poor targeting of persons to items. Person reliability was 0.71 and person separation index was 1.56. CONCLUSION: According to this Rasch analysis of data from a representative sample of mild traumatic brain injury, the RPQ may not be optimal for this population. Even after reducing the number of categories and collapsing items with local dependency, unidimensionality was not reached, which argues against summation of a total score. However, the scale is unbiased for gender and age. :

Prevalence and structure of symptoms at 3 months after mild traumatic brain injury in a national cohort.

OBJECTIVES: To describe symptom prevalence and structure after mild traumatic brain injury (MTBI) in a population-based cohort. METHODS: Symptoms data were collected at 3 months post-MTBI by use of the Rivermead Post-concussion Symptoms Questionnaire (RPQ) at follow-up of 2602 patients attending 39 Swedish hospitals. Spearmans rank correlation analysis was used to explore correlations between symptoms and structural equation modelling (SEM) was performed by use of several fit indices to explore if data were compatible with one or more factors. RESULTS: Questionnaires were received from 2523 (97%) patients with a mean age of 31 years (median 22, range 6-96). A majority of the respondents (56%) reported no remaining injury related symptoms, 24% reported three or more symptoms and 10% reported seven or more symptoms. All symptoms exhibited strong positive inter-relations and SEM provided strong support for a single or two factor solution. Fit indices were only slightly weaker for three and four factor solutions. CONCLUSIONS: A significant minority of patients reported multiple symptoms to persist at 3 months after MTBI. The observed structure of symptoms according to RPQ demonstrates a common factor for all symptoms, but also sub-groups of symptoms as previously suggested.