Chronic immunosuppression across 12 months and high ability of acute and subacute CNS-injury biomarker concentrations to identify individuals with complicated mTBI on acute CT and MRI.

BACKGROUND: Identifying individuals with intracranial injuries following mild traumatic brain injury (mTBI), i.e. complicated mTBI cases, is important for follow-up and prognostication. The main aims of our study were (1) to assess the temporal evolution of blood biomarkers of CNS injury and inflammation in individuals with complicated mTBI determined on computer tomography (CT) and magnetic resonance imaging (MRI); (2) to assess the corresponding discriminability of both single- and multi-biomarker panels, from acute to chronic phases after injury. METHODS: Patients with mTBI (n = 207), defined as Glasgow Coma Scale score between 13 and 15, loss of consciousness < 30 min and post-traumatic amnesia < 24 h, were included. Complicated mTBI - i.e., presence of any traumatic intracranial injury on neuroimaging - was present in 8% (n = 16) on CT (CT+) and 12% (n = 25) on MRI (MRI+). Blood biomarkers were sampled at four timepoints following injury: admission (within 72 h), 2 weeks (± 3 days), 3 months (± 2 weeks) and 12 months (± 1 month). CNS biomarkers included were glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and tau, along with 12 inflammation markers. RESULTS: The most discriminative single biomarkers of traumatic intracranial injury were GFAP at admission (CT+: AUC = 0.78; MRI+: AUC = 0.82), and NFL at 2 weeks (CT+: AUC = 0.81; MRI+: AUC = 0.89) and 3 months (MRI+: AUC = 0.86). MIP-1ß and IP-10 concentrations were significantly lower across follow-up period in individuals who were CT+ and MRI+. Eotaxin and IL-9 were significantly lower in individuals who were MRI+ only. FGF-basic concentrations increased over time in MRI- individuals and were significantly higher than MRI+ individuals at 3 and 12 months. Multi-biomarker panels improved discriminability over single biomarkers at all timepoints (AUCs > 0.85 for admission and 2-week models classifying CT+ and AUC ≈ 0.90 for admission, 2-week and 3-month models classifying MRI+). CONCLUSIONS: The CNS biomarkers GFAP and NFL were useful single diagnostic biomarkers of complicated mTBI, especially in acute and subacute phases after mTBI. Several inflammation markers were suppressed in patients with complicated versus uncomplicated mTBI and remained so even after 12 months. Multi-biomarker panels improved diagnostic accuracy at all timepoints, though at acute and 2-week timepoints, the single biomarkers GFAP and NFL, respectively, displayed similar accuracy compared to multi-biomarker panels.

The prognostic importance of traumatic axonal injury on early MRI: the Trondheim TAI-MRI grading and quantitative models.

OBJECTIVES: We analysed magnetic resonance imaging (MRI) findings after traumatic brain injury (TBI) aiming to improve the grading of traumatic axonal injury (TAI) to better reflect the outcome. METHODS: Four-hundred sixty-three patients (8-70 years) with mild (n = 158), moderate (n = 129), or severe (n = 176) TBI and early MRI were prospectively included. TAI presence, numbers, and volumes at predefined locations were registered on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging, and presence and numbers on T2*GRE/SWI. Presence and volumes of contusions were registered on FLAIR. We assessed the outcome with the Glasgow Outcome Scale Extended. Multivariable logistic and elastic-net regression analyses were performed. RESULTS: The presence of TAI differed between mild (6%), moderate (70%), and severe TBI (95%). In severe TBI, bilateral TAI in mesencephalon or thalami and bilateral TAI in pons predicted worse outcomes and were defined as the worst grades (4 and 5, respectively) in the Trondheim TAI-MRI grading. The Trondheim TAI-MRI grading performed better than the standard TAI grading in severe TBI (pseudo-R2 0.19 vs. 0.16). In moderate-severe TBI, quantitative models including both FLAIR volume of TAI and contusions performed best (pseudo-R2 0.19-0.21). In patients with mild TBI or Glasgow Coma Scale (GCS) score 13, models with the volume of contusions performed best (pseudo-R2 0.25-0.26). CONCLUSIONS: We propose the Trondheim TAI-MRI grading (grades 1-5) with bilateral TAI in mesencephalon or thalami, and bilateral TAI in pons as the worst grades. The predictive value was highest for the quantitative models including FLAIR volume of TAI and contusions (GCS score <13) or FLAIR volume of contusions (GCS score ≥ 13), which emphasise artificial intelligence as a potentially important future tool. CLINICAL RELEVANCE STATEMENT: The Trondheim TAI-MRI grading reflects patient outcomes better in severe TBI than today's standard TAI grading and can be implemented after external validation. The prognostic importance of volumetric models is promising for future use of artificial intelligence technologies. KEY POINTS: Traumatic axonal injury (TAI) is an important injury type in all TBI severities. Studies demonstrating which MRI findings that can serve as future biomarkers are highly warranted. This study proposes the most optimal MRI models for predicting patient outcome at 6 months after TBI; one updated pragmatic model and a volumetric model. The Trondheim TAI-MRI grading, in severe TBI, reflects patient outcome better than today's standard grading of TAI and the prognostic importance of volumetric models in all severities of TBI is promising for future use of AI.

The Epidemiology of Moderate and Severe Traumatic Brain Injury in Central Norway.

INTRODUCTION: Few studies account for prehospital deaths when estimating incidence and mortality rates of moderate and severe traumatic brain injury (msTBI). In a population-based study, covering both urban and rural areas, including also prehospital deaths, the aim was to estimate incidence and mortality rates of msTBI. Further, we studied the 30-day and 6-month case-fatality proportion of severe TBI in relation to age. METHODS: All patients aged ≥17 years who sustained an msTBI in Central Norway were identified by three sources: (1) the regional trauma center, (2) the general hospitals, and (3) the Norwegian Cause of Death Registry. Incidence and mortality rates were standardized according to the World Health Organization's world standard population. Case-fatality proportions were calculated by the number of deaths from severe TBI at 30 days and 6 months, divided by all patients with severe TBI. RESULTS: The overall incidence rates of moderate and severe TBI were 4.9 and 6.7 per 100,000 person-years, respectively, increasing from age 70 years. The overall mortality rate was 3.4 per 100,000 person-years, also increasing from age 70 years. Incidence and mortality rates were highest in men. The case-fatality proportion in people with severe TBI was 49% in people aged 60-69 years and 81% in people aged 70-79 years. CONCLUSION: The overall incidence and mortality rates for msTBI in Central Norway were low but increased from age 70 years, and among those ≥80 years of age with severe TBI, nearly all died. Overall estimates are strongly influenced by high incidence and mortality rates in the elderly, and studies should therefore report age-specific estimates, for better comparison of incidence and mortality rates.

Obesity Does Not Protect From Subarachnoid Hemorrhage: Pooled Analyses of 3 Large Prospective Nordic Cohorts.

BACKGROUND: Several population-based cohort studies have related higher body mass index (BMI) to a decreased risk of subarachnoid hemorrhage (SAH). The main objective of our study was to investigate whether the previously reported inverse association can be explained by modifying effects of the most important risk factors of SAH-smoking and hypertension. METHODS: We conducted a collaborative study of three prospective population-based Nordic cohorts by combining comprehensive baseline data from 211 972 adult participants collected between 1972 and 2012, with follow-up until the end of 2018. Primarily, we compared the risk of SAH between three BMI categories: (1) low (BMI<22.5), (2) moderate (BMI: 22.5-29.9), and (3) high (BMI≥30) BMI and evaluated the modifying effects of smoking and hypertension on the associations. RESULTS: We identified 831 SAH events (mean age 62 years, 55% women) during the total follow-up of 4.7 million person-years. Compared with the moderate BMI category, persons with low BMI had an elevated risk for SAH (adjusted hazard ratio [HR], 1.30 [1.09-1.55]), whereas no significant risk difference was found in high BMI category (HR, 0.91 [0.73-1.13]). However, we only found the increased risk of low BMI in smokers (HR, 1.49 [1.19-1.88]) and in hypertensive men (HR, 1.72 [1.18-2.50]), but not in nonsmokers (HR, 1.02 [0.76-1.37]) or in men with normal blood pressure values (HR, 0.98 [0.63-1.54]; interaction HRs, 1.68 [1.18-2.41], P=0.004 between low BMI and smoking and 1.76 [0.98-3.13], P=0.06 between low BMI and hypertension in men). CONCLUSIONS: Smoking and hypertension appear to explain, at least partly, the previously reported inverse association between BMI and the risk of SAH. Therefore, the independent role of BMI in the risk of SAH is likely modest.

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.

Risk Factors for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage in a Prospective Population-Based Study.

Background and Purpose- We wanted to evaluate potential risk factors for unruptured intracranial aneurysms (UIAs) and aneurysmal subarachnoid hemorrhage (aSAH) in a large, prospective study of the general population with risk factors collected before the detection of UIA or aSAH. Methods- All residents ≥20 years were invited to the HUNT (The Nord-Trøndelag Health Study). In this study, 89 951 participants were included. The study included standardized measurements of blood pressure and self-administered questionnaires. Cases of UIA and aSAH from 1999 to 2014 were identified using hospital records and the Norwegian Cause of Death Register. Hazard ratios with CIs were estimated using Cox regression analysis. Results- The detection rate of UIA was 8.2 per 100 000 person-years (97 patients). Current smoking (hazard ratio, 4.1; 95% CI, 2.4-7.1) and female sex (hazard ratio, 2.8; 95% CI, 1.7-4.5) were associated with markedly increased risk of UIA, but we found no association with systolic blood pressure (P for trend 0.62). The incidence of aSAH was 9.9 per 100 000 person-years (117 patients). The most important risk factors for aSAH were current smoking, female sex and increasing blood pressure (P for trend 0.006 for systolic blood pressure). Conclusions- In contrast to previous studies on risk factors of UIA, we found no association with systolic blood pressure. However, there was a strong association between systolic blood pressure and aSAH in the same population. Current smoking and female sex were associated with both diseases.

Diffusion kurtosis imaging in mild traumatic brain injury and postconcussional syndrome.

Aims of this study were to investigate white matter (WM) and thalamus microstructure 72 hr and 3 months after mild traumatic brain injury (TBI) with diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI), and to relate DKI and DTI findings to postconcussional syndrome (PCS). Twenty-five patients (72 hr = 24; 3 months = 23) and 22 healthy controls were recruited, and DKI and DTI data were analyzed with Tract-Based Spatial Statistics (TBSS) and a region-of-interest (ROI) approach. Patients were categorized into PCS or non-PCS 3 months after injury according to the ICD-10 research criteria for PCS. In TBSS analysis, significant differences between patients and controls were seen in WM, both in the acute stage and 3 months after injury. Fractional anisotropy (FA) reductions were more widespread than kurtosis fractional anisotropy (KFA) reductions in the acute stage, while KFA reductions were more widespread than the FA reductions at 3 months, indicating the complementary roles of DKI and DTI. When comparing patients with PCS (n = 9), without PCS (n = 16), and healthy controls, in the ROI analyses, no differences were found in the acute DKI and DTI metrics. However, near-significant differences were observed for several DKI metrics obtained in WM and thalamus concurrently with symptom assessment (3 months after injury). Our findings indicate a combined utility of DKI and DTI in detecting WM microstructural alterations after mild TBI. Moreover, PCS may be associated with evolving alterations in brain microstructure, and DKI may be a promising tool to detect such changes.

Frequency and prognostic factors of olfactory dysfunction after traumatic brain injury.

OBJECTIVE: To assess the frequency and factors associated with posttraumatic olfactory dysfunction, including anosmia, in a follow-up of patients with moderate and severe traumatic brain injury (TBI). METHODS: The setting was a cross-sectional study of patients that were consecutively included in the Trondheim TBI database, comprising injury-related variables. Eligible participants 18-65 years were contacted 9-104 months post trauma and asked olfactory-related questions. Those reporting possible posttraumatic change of olfaction were invited to further examination using the Sniffin' Sticks panel. RESULTS: Of 211 eligible participants, 182 (86.3%) took part in telephone interviews and 25(13.7%) were diagnosed with olfactory dysfunction. 60% of these, or 8.2% of all participants, had anosmia. In age-adjusted logistic regression analyses, fall (OR 2.5, 95% CI 1.0-6.2), skull base fracture (OR 2.9, 95% CI 1.2-7.1) and cortical contusion(s) (OR 6.0, 95% CI 2.1-17.3) were associated with olfactory dysfunction. In an analysis of anosmia, fall (OR 3.4, 95% CI 1.1-10.6) and cortical contusion(s) (OR 19.7, 95% CI 2.5-156.0) were associated with the outcome. CONCLUSION: Of the study participants 13.7% had olfactory dysfunction and 8.2% had anosmia. Higher age, trauma caused by fall and CT displaying skull base fracture and cortical contusion(s) were related to olfactory dysfunction.

Headache following head injury: a population-based longitudinal cohort study (HUNT).

BACKGROUND: Headache is the most frequent symptom following head injury, but long-term follow-up of headache after head injury entails methodological challenges. In a population-based cohort study, we explored whether subjects hospitalized due to a head injury more often developed a new headache or experienced exacerbation of previously reported headache compared to the surrounding population. METHODS: This population-based historical cohort study included headache data from two large epidemiological surveys performed with an 11-year interval. This was linked with data from hospital records on exposure to head injury occurring between the health surveys. Participants in the surveys who had not been hospitalized because of a head injury comprised the control group. The head injuries were classified according to the Head Injury Severity Scale (HISS). Multinomial logistic regression was performed to investigate the association between head injury and new headache or exacerbation of pre-existing headache in a population with known pre-injury headache status, controlling for potential confounders. RESULTS: The exposed group consisted of 294 individuals and the control group of 25,662 individuals. In multivariate analyses, adjusting for age, sex, anxiety, depression, education level, smoking and alcohol use, mild head injury increased the risk of new onset headache suffering (OR 1.74, 95% CI 1.05-2.87), stable headache suffering (OR 1.70, 95% CI 1.15-2.50) and exacerbation of previously reported headache (OR 1.93, 95% CI 1.24-3.02). The reference category was participants without headache in both surveys. CONCLUSION: Individuals hospitalized due to a head injury were more likely to have new onset and worsening of pre-existing headache and persistent headache, compared to the surrounding general population. The results support the entity of the ICHD-3 beta diagnosis "persistent headache attributed to traumatic injury to the head".

Traumatic axonal injury: Relationships between lesions in the early phase and diffusion tensor imaging parameters in the chronic phase of traumatic brain injury.

This prospective study of traumatic brain injury (TBI) patients investigates fractional anisotropy (FA) from chronic diffusion tensor imaging (DTI) in areas corresponding to persistent and transient traumatic axonal injury (TAI) lesions detected in clinical MRI from the early phase. Thirty-eight patients (mean 24.7 [range 13-63] years of age) with moderate-to-severe TBI and 42 age- and sex-matched healthy controls were included. Patients underwent 1.5-T clinical MRI in the early phase (median 7 days), including fluid-attenuated inversion recovery (FLAIR) and T2* gradient echo (T2*GRE) sequences. TAI lesions from the early phase were characterized as nonhemorrhagic or microhemorrhagic. In the chronic phase (median 3 years), patients and controls were imaged at 3 T with FLAIR, T2*GRE, T1, and DTI sequences. TAI lesions were classified as transient or persistent. The FLAIR/T2*GRE images from the early phase were linearly registered to the FA images from the chronic phase and lesions manually segmented on the FA-registered FLAIR/T2*GRE images. For regions of interest (ROIs) from both nonhemorrhagic and microhemorrhagic lesion, we found a significant linear trend of lower mean FA from ROIs in healthy controls to ROIs in patients without either nonhemorrhagic or microhemorrhagic lesions and further to transient and finally persistent lesion ROIs (P < 0.001). Histogram analyses showed lower FA in persistent compared with transient nonhemorrhagic lesion ROIs (P < 0.001), but this was not found in microhemorrhagic lesion ROIs (P = 0.08-0.55). The demonstrated linear trend of lower FA values from healthy controls to persistent lesion ROIs was found in both nonhemorrhagic and microhemorrhagic lesions and indicates a gradual increasing disruption of the microstructure. Lower FA values in persistent compared with transient lesions were found only in nonhemorrhagic lesions. Thus, clinical MRI techniques are able to depict important aspects of white matter pathology across the stages of TBI. © 2016 Wiley Periodicals, Inc.

Headaches in patients with previous head injuries: A population-based historical cohort study (HUNT).

Background Headache attributed to head injury is claimed to be among the most common secondary headache disorders, yet available epidemiological evidence is scarce. We evaluated the prevalence of headache among individuals previously exposed to head injury by a comparison to an uninjured control group. Methods This population-based historical cohort study used data from hospital records on previous exposure to head injury linked to a large epidemiological survey with data on headache occurrence. Participants without head injury, according to hospital records, were used as controls. The head injuries were classified according to the Head Injury Severity Scale (HISS) and the International Classification of Headache Disorders (ICHD-3 beta). Binary logistic regression was performed to investigate the association between headache and head injury, controlling for potential confounders. Results The exposed group consisted of 940 individuals and the control group of 38,751 individuals. In the multivariate analyses, adjusting for age, sex, anxiety, depression and socioeconomic status, there were significant associations between mild head injury and any headache, migraine, chronic daily headache and medication overuse headache. Conclusion Headache was more likely among individuals previously referred to a hospital for a mild head injury compared to uninjured controls.

Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function.

This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations.

Intracranial Pressure During Pressure Control and Pressure-Regulated Volume Control Ventilation in Patients with Traumatic Brain Injury: A Randomized Crossover trial.

INTRODUCTION: Mechanical ventilation with control of partial arterial CO2 pressures (PaCO2) is used to treat or stabilize intracranial pressure (ICP) in patients with traumatic brain injury (TBI). Pressure-regulated volume control (PRVC) is a ventilator mode where inspiratory pressures are automatically adjusted to deliver the patient a pre-set stable tidal volume (TV). This may result in a more stable PaCO2 and thus a more stable ICP compared with conventional pressure control (PC) ventilation. The aim of this study was to compare PC and PRVC ventilation in TBI patients with respect to ICP and PaCO2. METHODS: This is a randomized crossover trial including eleven patients with a moderate or severe TBI who were mechanically ventilated and had ICP monitoring. Each patient was administered alternating 2-h periods of PC and PRVC ventilation. The outcome variables were ICP and PaCO2. RESULTS: Fifty-two (26 PC, 26 PRVC) study periods were included. Mean ICP was 10.8 mmHg with PC and 10.3 mmHg with PRVC ventilation (p = 0.38). Mean PaCO2 was 36.5 mmHg (4.87 kPa) with PC and 36.1 mmHg (4.81 kPa) with PRVC (p = 0.38). There were less fluctuations in ICP (p = 0.02) and PaCO2 (p = 0.05) with PRVC ventilation. CONCLUSIONS: Mean ICP and PaCO2 were similar for PC and PRVC ventilation in TBI patients, but PRVC ventilation resulted in less fluctuation in both ICP and PaCO2. We cannot exclude that the two ventilatory modes would have impact on ICP in patients with higher ICP values; however, the similar PaCO2 observations argue against this.

High-level mobility in chronic traumatic brain injury and its relationship with clinical variables and magnetic resonance imaging findings in the acute phase.

OBJECTIVES: To compare high-level mobility in individuals with chronic moderate-to-severe traumatic brain injury (TBI) with matched healthy controls, and to investigate whether clinical variables and magnetic resonance imaging (MRI) findings in the acute phase can predict high-level motor performance in the chronic phase. DESIGN: A longitudinal follow-up study. SETTING: A level 1 trauma center. PARTICIPANTS: Individuals (N=136) with chronic TBI (n=65) and healthy matched peers (n=71). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: High-Level Mobility Assessment Tool (HiMAT) and the revised version of the HiMAT performed at a mean of 2.8 years (range, 1.5-5.4y) after injury. RESULTS: Participants with chronic TBI had a mean HiMAT score of 42.7 (95% confidence interval [CI], 40.2-45.2) compared with 47.7 (95% CI, 46.1-49.2) in the control group (P<.01). Group differences were also evident using the revised HiMAT (P<.01). Acute-phase clinical variables and MRI findings explained 58.8% of the variance in the HiMAT score (P<.001) and 59.9% in the revised HiMAT score (P<.001). Lower HiMAT scores were associated with female sex (P=.031), higher age at injury (P<.001), motor vehicle collisions (P=.030), and posttraumatic amnesia >7 days (P=.048). There was a tendency toward an association between lower scores and diffuse axonal injury in the brainstem (P=.075). CONCLUSIONS: High-level mobility was reduced in participants with chronic, either moderate or severe TBI compared with matched peers. Clinical variables in the acute phase were significantly associated with high-level mobility performance in participants with TBI, but the role of early MRI findings needs to be further investigated. The findings of this study suggest that the clinical variables in the acute phase may be useful in predicting high-level mobility outcome in the chronic phase.

Improvement in Functional Outcome from 6 to 12 Months After Moderate and Severe Traumatic Brain Injury Is Frequent, But May Not Be Detected With the Glasgow Outcome Scale Extended.

The aims of this study were (1) to report outcome and change in outcome in patients with moderate and severe traumatic brain injury (mo/sTBI) between 6 and 12 months post-injury as measured by the Glasgow Outcome Scale Extended (GOSE), (2) to explore if demographic/injury-related variables can predict improvement in GOSE score, and (3) to investigate rate of improvement in Disability Rating Scale (DRS) score, in patients with a stable GOSE. All surviving patients ≥16 years of age who were admitted with mo/sTBI (Glasgow Coma Scale [GCS] score ≤13) to the regional trauma center in Central Norway between 2004 and 2019 were prospectively included (n = 439 out of 503 eligible). GOSE and DRS were used to assess outcome. Twelve-months post-injury, 13% with moTBI had severe disability (GOSE 2-4) versus 27% in sTBI, 26% had moderate disability (GOSE 5-6) versus 41% in sTBI and 62% had good recovery (GOSE 7-8) versus 31% in sTBI. From 6 to 12 months post-injury, 27% with moTBI and 32% with sTBI had an improvement, whereas 6% with moTBI and 6% with sTBI had a deterioration in GOSE score. Younger age and higher GCS score were associated with improved GOSE score. Improvement was least frequent for patients with a GOSE score of 3 at 6 months. In patients with a stable GOSE score of 3, an improvement in DRS score was observed in 22 (46%) patients. In conclusion, two thirds and one third of patients with mo/sTBI, respectively, had a good recovery. Importantly, change, mostly improvement, in GOSE score between 6 and 12 months was frequent and argues against the use of 6 months outcome as a time end-point in research. The GOSE does, however, not seem to be sensitive to actual change in function in the lower categories and a combination of outcome measures may be needed to describe the consequences after TBI.