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.

Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity.

OBJECTIVES: The therapeutic effects of botulinum neurotoxin (BoNT) are well documented in upper limb spasticity. However, several factors may influence treatment efficacy, including targeting of neuromuscular junctions (NMJs). We examined whether NMJ-targeted BoNT injections were non-inferior, in terms of efficacy, to current injection practices. DESIGN: Open-label prospective evaluator-blinded study. SETTING: Conducted across 20 medical centres in Denmark, Finland, Norway and Sweden (24 September 2012 to 11 March 2015). PARTICIPANTS: Aged ˃18 years with upper limb spasticity (Modified Ashworth Scale [MAS] score of 2 or 3) following stroke or traumatic brain injury, had received ≥2 consecutive BoNT-A treatment cycles (the latest of which was abobotulinumtoxinA [aboBoNT-A]) and needed BoNT-A retreatment (same modality as previous cycle). Patients requiring aboBoNT-A doses >800units were excluded. In total, 88 patients were randomised (intention-to-treat [ITT] population), most were male (n=58/88, 65.9%) and 54/88 (61.4%) completed the study (per protocol [PP] population). INTERVENTIONS: Randomisation (1:1) to receive a single dose of aboBoNT-A (≤800 U) according to either current clinical practice (300 U/mL) or as an NMJ-targeted injection (100 U/mL). PRIMARY OUTCOME MEASURE: Proportion of patients with a ≥1 level reduction from baseline in MAS score at week 4 post-injection (responders). RESULTS: In the ITT population, the proportion of responders at elbow flexors was 72.7% in the current practice group and 56.8% in the NMJ-targeted group (adjusted difference -0.1673 [95% CIs: -0.3630 to 0.0284]; p=0.0986). Similar results were observed in the PP population (69.0% vs 68.0%, respectively, adjusted difference 0.0707 [-0.1948 to 0.3362]; p=0.6052). CONCLUSIONS: Owing to the limited number of participants, non-inferiority of NMJ-targeted injections could not be determined. However, there was no statistical difference between groups. Larger studies are needed confirm whether the two techniques offer comparable efficacy. TRIAL REGISTRATION NUMBER: NCT01682148.

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.

Ten-year mortality after severe traumatic brain injury in western Sweden: a case control study.

PRIMARY OBJECTIVE: Life expectancy may be substantially reduced for many years after severe traumatic brain injury (TBI). This study investigated the patterns of the short- and long-term all-cause mortality and the rates of primary causes of death in patients with severe TBI. SUBJECTS: This study was of 166 consecutive patients (6-82 years) with severe TBI admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, from 1999-2002. The control group consisted of 809 subjects from the community, matched to the TBI cohort for age, gender and postcode area at the time of the injury. METHODS: Survival outcome and cause of death were ascertained 10 years after the injury from the Swedish National Board of Health and Welfare register. The cumulative death rates and causes of death in cases and controls were compared. RESULTS: The risk of death was increased for at least 10 years after severe TBI. The distribution of the causes of deaths differed between cases and controls in the first year of follow-up, but not between 1-year survivors and controls. CONCLUSION: Further research will be required to determine how to improve treatment so as to lower late mortality among survivors of severe TBI.

A history of unemployment or sick leave influences long-term functioning and health-related quality-of-life after severe traumatic brain injury.

PRIMARY OBJECTIVE: The consequences of pre-morbid factors in adults with severe traumatic brain injury have not been widely addressed. This study aimed to determine whether being unemployed or on sick leave before injury influences long-term health-related quality-of-life (HRQoL) and functioning in patients with severe traumatic brain injury. SUBJECTS: Fifty-one consecutive patients were studied; aged 16-65 years, with severe traumatic brain injury who were admitted to Sahlgrenska University Hospital, Gothenburg, from 1999-2002. METHODS: The patients were assessed once, 2-11 years after trauma. Data from the time of injury were combined into a validated prognostic model to adjust for injury severity. Data on sick leave and unemployment before injury were gathered from the Swedish social insurance agency. Outcomes were measured with the Short Form-36 Health Survey, the Glasgow Outcome Scale-Extended, and a self-report questionnaire specifically designed for this study to measure functioning. RESULTS: In a multivariate analysis, a history of sick leave/unemployment predicted a worse long-term global outcome, more problems with personal activities of daily living and worse HRQoL. CONCLUSION: These results should be considered when refining outcome predictions and optimizing rehabilitation interventions for patients with severe traumatic brain injury.

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.

Early intervention for patients at risk for persisting disability after mild traumatic brain injury: a randomized, controlled study.

STUDY OBJECTIVE: To investigate the effect of an early intervention visit in addition to written information and treatment as usual for patients with an estimated high risk for persisting disability after a mild traumatic brain injury (MTBI). RESEARCH DESIGN: Randomized controlled trial. METHODS: One hundred and seventy-three patients, aged 15-70 years with a Glasgow coma scale of 14-15 were included. All received written information about MTBI. Ninety-seven patients who reported three or more symptoms according to the rivermead post-concussion symptoms questionnaire (RPQ) at 10 days after the injury were considered as high-risk patients and were randomized to either early visit to a doctor or to treatment as usual (TAU); all patients including the 76 low-risk patients were followed-up at 3 months. Completion rate was 83%. Outcome measures included RPQ and the hospital anxiety and depression scale. RESULTS: RPQ symptoms decreased significantly in both randomized groups, but were not significantly different in the groups at 3 months. At 3 months, anxiety and depression scores did not differ between groups. CONCLUSIONS: An early intervention, offered to patients with an estimated high risk for persisting disability, had no additional effect on symptom level at 3 months after MTBI as compared to TAU.

Pituitary function and functional outcome in adults after severe traumatic brain injury: the long-term perspective.

Post-traumatic hypopituitarism (PTHP) has been linked to disability and decreased quality of life. However, no studies have addressed the long-term consequences of PTHP in adults with severe traumatic brain injury (TBI) only. In this study, we evaluated the relationship between pituitary function, quality of life, and functioning in 51 patients (16-65 years of age) with severe TBI who were admitted to Sahlgrenska University Hospital, Gothenburg from 1999 to 2002. The patients were assessed once, 2-10 years after trauma. Data from the time of injury were collected retrospectively to adjust for injury severity. Outcome measures included hormonal testing, the Short Form-36 Health Survey, the Glasgow outcome scale-extended, and a self-report questionnaire specifically designed for this study and based on the International Classification of Functioning, Disability and Health. Of 51 patients, 14 (27.5%) presented with PTHP, and 11 (21.6%) had isolated growth hormone deficiency. Patients with PTHP were more often overweight at follow-up (p=0.01); the higher body mass index was partially explained by PTHP (R2 change=0.07, p=0.001). Otherwise no significant correlation was found among PTHP, functioning, or patient-reported quality of life. This study-which is unique in the homogeneity of the patients, the long follow-up time, and the use of injury severity as an outcome predictor-did not confirm results from previous studies linking PTHP to a worse outcome. Therefore, screening for PTHP might be restricted to specific subgroups such as overweight patients, indicating growth hormone deficiency.