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.

An observational study of trait and state fatigue, and their relation to cognitive fatigability and saccade performance.

AIM: Different fatigue measurements and their relation to saccadic functions were investigated in 15 patients with a mild traumatic brain injury (mTBI) and 15 orthopedic controls. MATERIALS & METHODS: State fatigue was measured with the Fatigue Severity Scale and trait fatigue with the question on fatigue in the Rivermead Post Concussion Questionnaire and fatigability as decreased performance over time on a neuropsychological measure. RESULTS: Patients with an mTBI scored significantly higher in state fatigue and showed more fatigability compared with the orthopedic controls. Among patients with mTBI, state fatigue correlated with prosaccade latency and cognitive fatigability, while trait fatigue correlated with anxiety and antisaccade latency and variability. CONCLUSION: This pilot study indicates that saccade measurements might, in the future, be useful in the understanding of fatigue and in the search for prognostic factors after mTBI.

Emotional reserve and prolonged post-concussive symptoms and disability: a Swedish prospective 1-year mild traumatic brain injury cohort study.

OBJECTIVE: Prolonged post-concussive symptoms (PCS) affect a significant minority of patients withmild traumatic brain injury (mTBI). The aetiology is multifactorial depending on preinjury as well as peri-injury and postinjury factors. In this study, we examine outcome from an emotional reserve perspective. DESIGN: Prospective cohort study. SETTING: Patients were recruited from three emergency departments in major university hospitals in Stockholm, Sweden. Follow-up data were collected in an outpatient setting at one of the recruiting hospitals. PARTICIPANTS: 122 patients with a history of blunt head trauma (aged 15-65 years; admitted for mTBI within 24 hours after trauma (Glasgow Coma Scale score of 14-15, loss of consciousness <30 min and/or post-traumatic amnesia <24 hours). Exclusion criteria were other significant physical injury and other major neurological disorder, including previous significant head injury. PROCEDURE: Recruitment in three emergency departments. Initial assessments were made within 1 week after the injury. Patients were mailed the follow-up questionnaires 1 year postinjury. OUTCOME MEASURES: A psychiatric assessment was performed at 1 week post injury. The participants also completed a personality inventory, measures of psychological resilience, depression, anxiety and post-traumatic symptoms. One-year outcome was measured by the Rivermead Post Concussion Symptoms and the Rivermead Head Injury Follow-Up questionnaires. RESULTS: The psychiatric assessment revealed more symptoms of anxiety, depression and post-traumatic symptoms in the acute stage for patients who later developed PCS.After 1 year, 94 participants were still in the programme (male/female 57/37) and 12% matched the extended criteria for PCS (≥3 symptoms and ≥2 disabilities). PCS patients reported more preinjury and concurrent psychiatric problems, lower level of functioning before the injury and experienced more stress. They showed higher somatic trait anxiety, embitterment, mistrust and lower level of psychological resilience than recovered participants. CONCLUSION: Intrapersonal emotional reserve shape the emergence and persistence of PCS after mTBI.

Longitudinal changes in oculomotor function in young adults with mild traumatic brain injury in Sweden: an exploratory prospective observational study.

OBJECTIVES: To assess (1) whether visual disturbances can be demonstrated with objective measures more often in patients with mild traumatic brain injury (mTBI) than in orthopaedic controls and non-injured controls, (2) whether such objectively demonstrated disturbances change over time and (3) whether self-reported visual symptoms after mTBI correlate with objectively measurable changes in visuomotor performance. DESIGN: A prospective, controlled, observational study, with assessments planned 7-10 and 75-100 days after injury. SETTING: Emergency department of a general hospital in Sweden. PARTICIPANTS: 15 patients with mTBI, 15 patients with minor orthopaedic injury, 15 non-injured controls, aged 18-40 years. OUTCOME MEASURES: Visual examination, including assessment of visual acuity, accommodation, eye alignment, saccades and stereoacuity. Symptom assessment using Convergence Insufficiency Symptoms Survey (CISS) and Rivermead PostConcussion Symptoms Questionnaire. RESULTS: Assessments were performed 4-13 and 81-322 days after injury (extended time frames for logistical reasons). No statistically significant difference was found between the mTBI and control groups regarding saccade performance and stereoacuity at any time point. The accommodative amplitude was significantly lower in the mTBI group compared with non-injured controls at baseline. 6 out of 13 patients with mTBI had accommodative insufficiency at follow-up. Near point of convergence in the mTBI group was receded at baseline and improved statistically significantly at follow-up. At baseline, patients with mTBI had significantly higher CISS score than orthopaedic and non-injured controls. For patients with mTBI, the CISS score correlated with fusional vergence. CONCLUSION: There were some transient measurable visual changes regarding convergence in patients with mTBI during the subacute period after the injury. Our findings of persistence of accommodative insufficiency in a considerable proportion of patients with mTBI suggest that this visual function should not be overlooked in clinical assessment.

No effect of an early intervention after mild traumatic brain injury on activity and participation: A randomized controlled trial.

OBJECTIVE: To evaluate measures of activity, participation and quality of life 3 months after mild traumatic brain injury and the effect of an early intervention for patients with an estimated high risk for problems after mild traumatic brain injury. PATIENTS: Consecutive patients attending the emergency room with mild traumatic brain injury. DESIGN: Randomized controlled trial. METHODS: Patients reporting < 3 symptoms after 10 days were considered to have a low risk for prolonged problems. Patients with ≥ 3 symptoms (high-risk patients) were randomized to a visit to a physician or treatment-as-usual. Data on self-reported limitations in activity, restrictions in participation, and quality of life were collected for all patients at 3 months. RESULTS: At 3 months post-injury, low-risk patients reported good quality of life and significantly fewer problems in everyday life compared with high-risk patients. The intervention had no effect on activity, participation or quality of life. CONCLUSION: Patients who report few symptoms early after mild traumatic brain injury are likely to have a good outcome regarding activity and participation. The intervention offered in this study, focusing on reassurance of a good outcome and treatment of comorbidities, had no effect.

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.

Disorders of consciousness after severe traumatic brain injury: a Swedish-Icelandic study of incidence, outcomes and implications for optimizing care pathways.

BACKGROUND: Very severe traumatic brain injury may cause disorders of consciousness in the form of coma, unresponsive wakefulness syndrome (also known as vegetative state) or minimally conscious state. Previous studies of outcome for these patients largely pre-date the 2002 definition of minimally conscious state. OBJECTIVES: To establish the numbers of patients with disorder of consciousness at 3 weeks, 3 months and 1 year after severe traumatic brain injury, and to relate conscious state 3 weeks after injury to outcomes at 1 year. DESIGN: Multi-centre, prospective, observational study of severe traumatic brain injury. INCLUSION CRITERIA: lowest (non-sedated) Glasgow Coma Scale 3-8 during the first 24 h; requirement for neurosurgical intensive care; age 18-65 years; alive 3 weeks after injury. Diagnosis of coma, unresponsive wakefulness syndrome, minimally conscious state or emerged from minimally conscious state was based on clinical and Coma Recovery Scale Revised assessments 3 weeks, 3 months and 1 year after injury. One-year outcome was measured with Glasgow Outcome Scale Extended (GOSE). RESULTS: A total of 103 patients was included in the study. Of these, 81% were followed up to 1 year (76% alive, 5% dead). Three weeks after injury 36 were in coma, unresponsive wakefulness syndrome or minimally conscious state and 11 were anaesthetized. Numbers of patients who had emerged from minimally conscious state 1 year after injury, according to status at 3 weeks were: coma (0/6), unresponsive wakefulness syndrome (9/17), minimally conscious state (13/13), anaesthetized (9/11). Outcome at 1 year was good (GOSE > 4) for half of patients in minimally conscious state or anaesthetized at 3 weeks, but for none of the patients in coma or unresponsive wakefulness syndrome. These differences in outcome were not revealed by prognostic predictions based on acute data. CONCLUSION: Patients in minimally conscious state or anaesthetized 3 weeks after injury have a better prognosis than patients in coma or unresponsive wakefulness syndrome, which could not be explained by acute prognostic models.