Publications by authors named "Toril Skandsen"

58 Publications

One-Year Prospective Study of Plasma Biomarkers From CNS in Patients With Mild Traumatic Brain Injury.

Front Neurol 2021 21;12:643743. Epub 2021 Apr 21.

Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

To investigate the longitudinal evolution of three blood biomarkers: neurofilament light (NFL), glial fibrillary acidic protein (GFAP) and tau, in out-patients and hospitalized patients with mild traumatic brain injury (mTBI) compared to controls, along with their associations-in patients-with clinical injury characteristics and demographic variables, and ability to discriminate patients with mTBI from controls. A longitudinal observation study including 207 patients with mTBI, 84 age and sex-matched community controls (CCs) and 52 trauma controls (TCs). Blood samples were collected at 5 timepoints: acute (<24 h), 72 h (24-72 h post-injury), 2 weeks, 3 and 12 months. Injury-related, clinical and demographic variables were obtained at inclusion and brain MRI within 72 h. Plasma GFAP and tau were most elevated acutely and NFL at 2 weeks and 3 months. The group of patients with mTBI and concurrent other somatic injuries (mTBI+) had the highest elevation in all biomarkers across time points, and were more likely to be victims of traffic accidents and violence. All biomarkers were positively associated with traumatic intracranial findings on MRI obtained within 72 h. Glial fibrillary acidic protein and NFL levels were associated with Glasgow Coma Scale (GCS) score and presence of other somatic injuries. Acute GFAP concentrations showed the highest discriminability between patients and controls with an Area Under the Curve (AUC) of 0.92. Acute tau and 2-week NFL concentrations showed moderate discriminability (AUC = 0.70 and AUC = 0.75, respectively). Tau showed high discriminability between mTBI+ and TCs (AUC = 0.80). The association of plasma NFL with traumatic intracranial MRI findings, together with its later peak, could reflect ongoing secondary injury or repair mechanisms, allowing for a protracted diagnostic time window. Patients experiencing both mTBI and other injuries appear to be a subgroup with greater neural injury, differing from both the mTBI without other injuries and from both control groups. Acute GFAP concentrations showed the highest discriminability between patients and controls, were highly associated with intracranial traumatic injury, and showed the largest elevations compared to controls at the acute timepoint, suggesting it to be the most clinically useful plasma biomarker of primary CNS injury in mTBI.
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http://dx.doi.org/10.3389/fneur.2021.643743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097004PMC
April 2021

Acute Diffusion Tensor and Kurtosis Imaging and Outcome following Mild Traumatic Brain Injury.

J Neurotrauma 2021 May 10. Epub 2021 May 10.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

In this prospective cohort study, we investigated associations between acute diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) metrics and persistent post-concussion symptoms (PPCS) 3 months after mild traumatic brain injury (mTBI). Adult patients with mTBI ( = 176) and community controls ( = 78) underwent 3 Tesla magnetic resonance imaging (MRI) within 72 h post-injury, estimation of cognitive reserve at 2 weeks, and PPCS assessment at 3 months. Eight DTI and DKI metrics were examined with Tract-Based Spatial Statistics. Analyses were performed in the total sample in uncomplicated mTBI only (i.e., without lesions on clinical MRI), and with cognitive reserve both controlled for and not. Patients with PPCS ( = 35) had lower fractional anisotropy (in 2.7% of all voxels) and kurtosis fractional anisotropy (in 6.9% of all voxels), and higher radial diffusivity (in 0.3% of all voxels), than patients without PPCS ( = 141). In uncomplicated mTBI, only fractional anisotropy was significantly lower in patients with PPCS. Compared with controls, patients with PPCS had widespread deviations in all diffusion metrics. When including cognitive reserve as a covariate, no significant differences in diffusion metrics between patients with and without PPCS were present, but patients with PPCS still had significantly higher mean, radial, and axial diffusivity than controls. In conclusion, patients who developed PPCS had poorer white matter microstructural integrity acutely after the injury, compared with patients who recovered and healthy controls. Differences became less pronounced when cognitive reserve was controlled for, suggesting that pre-existing individual differences in axonal integrity accounted for some of the observed differences.
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http://dx.doi.org/10.1089/neu.2021.0074DOI Listing
May 2021

Letter to the editor: Grading of traumatic axonal injury on clinical MRI and functional outcome.

Acta Neurochir (Wien) 2021 05 25;163(5):1443-1444. Epub 2021 Feb 25.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

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http://dx.doi.org/10.1007/s00701-021-04759-6DOI Listing
May 2021

Examining Test-Retest Reliability and Reliable Change for Cognition Endpoints for the CENTER-TBI Neuropsychological Test Battery.

Front Neurol 2020 20;11:541533. Epub 2020 Oct 20.

Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States.

Seven candidate cognition composite scores have been developed and evaluated as part of a research program designed to validate a cognition endpoint for traumatic brain injury (TBI) research and clinical trials, but these composites have yet to be examined longitudinally. This study examined test-retest reliability and methods for determining reliable change for these seven candidate composite scores, using the neuropsychological test battery from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Participants (18-59 years-old) with mild TBI ( = 124), orthopedic trauma without head injury ( = 67), and healthy community controls ( = 63) from the Trondheim MTBI follow-up study completed the CENTER-TBI neuropsychological test battery at 2 weeks and 3 months after injury. The battery included both traditional paper-and-pencil tests and computerized 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 in total on each assessment): 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. The OTBM was calculated by averaging scores for all tests. The other composite scores were deficit-based scores, assigning different weights to low scores. All composites revealed better cognitive performance at the 3-month assessment compared to the 2-week assessment and the magnitude of improvement was similar across groups. Differences, in terms of effect sizes, were largest on the OTBMs. In the combined composites, the test-retest correlation was highest for the OTBM (Spearman's = 0.87, in the community control group) and lowest for the number of scores ≤5th percentile ( = 0.41). The high test-retest reliability of the OTBM appears to favor its use in TBI research; however, future studies are needed to examine these candidate composite scores in participants with more severe TBIs and cognitive deficits and the association of the composites with functional outcomes.
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http://dx.doi.org/10.3389/fneur.2020.541533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606629PMC
October 2020

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

Arch Phys Med Rehabil 2021 Jun 27;102(6):1102-1112. Epub 2020 Oct 27.

Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts; Spaulding Rehabilitation Hospital and Spaulding Research Institute, Charlestown, Massachusetts; Home Base, A Red Sox Foundation and Massachusetts General Hospital Program, Charlestown, Massachusetts.

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.
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http://dx.doi.org/10.1016/j.apmr.2020.10.106DOI Listing
June 2021

Traumatic axonal injury on clinical MRI: association with the Glasgow Coma Scale score at scene of injury or at admission and prolonged posttraumatic amnesia.

J Neurosurg 2020 Oct 23:1-12. Epub 2020 Oct 23.

Departments of1Neuromedicine and Movement Science and.

Objective: The aim in this study was to investigate if MRI findings of traumatic axonal injury (TAI) after traumatic brain injury (TBI) are related to the admission Glasgow Coma Scale (GCS) score and prolonged duration of posttraumatic amnesia (PTA).

Methods: A total of 490 patients with mild to severe TBI underwent brain MRI within 6 weeks of injury (mild TBI: median 2 days; moderate to severe TBI: median 8 days). The location of TAI lesions and measures of total TAI lesion burden (number and volume of lesions on FLAIR and diffusion-weighted imaging and number of lesions on T2*-weighted gradient echo or susceptibility-weighted imaging) were quantified in a blinded manner for clinical information. The volume of contusions on FLAIR was likewise recorded. Associations between GCS score and the location and burden of TAI lesions were examined with multiple linear regression, adjusted for age, Marshall CT score (which includes compression of basal cisterns, midline shift, and mass lesions), and alcohol intoxication. The predictive value of TAI lesion location and burden for duration of PTA > 28 days was analyzed with multiple logistic regression, adjusted for age and Marshall CT score. Complete-case analyses of patients with TAI were used for the regression analyses of GCS scores (n = 268) and PTA (n = 252).

Results: TAI lesions were observed in 58% of patients: in 7% of mild, 69% of moderate, and 93% of severe TBI cases. The TAI lesion location associated with the lowest GCS scores were bilateral lesions in the brainstem (mean difference in GCS score -2.5), followed by lesions bilaterally in the thalamus, unilaterally in the brainstem, and lesions in the splenium. The volume of TAI on FLAIR was the measure of total lesion burden most strongly associated with the GCS score. Bilateral TAI lesions in the thalamus had the largest predictive value for PTA > 28 days (OR 16.2, 95% CI 3.9-87.4). Of the measures of total TAI lesion burden, the FLAIR volume of TAI predicted PTA > 28 days the best.

Conclusions: Bilateral TAI lesions in the brainstem and thalamus, as well as the total volume of TAI lesions on FLAIR, had the strongest association with the GCS score and prolonged PTA. The current study proposes a first step toward a modified classification of TAI, with grades ranked according to their relation to these two measures of clinical TBI severity.
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http://dx.doi.org/10.3171/2020.6.JNS20112DOI Listing
October 2020

Examining the Subacute Effects of Mild Traumatic Brain Injury Using a Traditional and Computerized Neuropsychological Test Battery.

J Neurotrauma 2021 01 30;38(1):74-85. Epub 2020 Oct 30.

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Faculty of Social and Educational Sciences, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

This study investigates subacute cognitive effects of mild traumatic brain injury (MTBI) in the Trondheim Mild TBI Study, as measured, in part, by the neuropsychological test battery of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) program, including computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and traditional paper-and-pencil tests. We investigated whether cognitive function was associated with injury severity: intracranial traumatic lesions on neuroimaging, witnessed loss of consciousness (LOC), or post-traumatic amnesia (PTA) >1 h. Further, we explored which of the tests in the CENTER-TBI battery might be associated with the largest subacute effects of MTBI (i.e., at 2 weeks post-injury). We recruited 177 patients with MTBI (16-59 years of age) from a regional trauma center and an outpatient clinic,79 trauma control participants, and 81 community control participants. The MTBI group differed from community controls only on one traditional test of processing speed (coding;  = 0.009, Cliff's delta [Δ] = 0.20). Patients with intracranial abnormalities performed worse than those without on a traditional test (phonemic verbal fluency;  = 0.043, Δ = 0.27), and patients with LOC performed differently on the Attention Switching Task from the CANTAB ( = 0.020, Δ = -0.20). Patients with PTA >1 h performed worse than those with <1 h on 10 measures, from traditional tests and the CANTAB (Δ = 0.33-0.20), likely attributable, at least in part, to pre-existing differences in intellectual functioning between groups. In general, those with MTBI had good neuropsychological outcome 2 weeks after injury and no particular CENTER-TBI computerized or traditional tests seemed to be more sensitive to subtle cognitive deficits.
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http://dx.doi.org/10.1089/neu.2019.6922DOI Listing
January 2021

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

Front Neurol 2020 17;11:670. Epub 2020 Jul 17.

Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States.

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). Participants with mild traumatic brain injury (MTBI; = 140), orthopedic trauma ( = 72), and healthy community controls ( = 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. 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 the paper-and-pencil composites, the CANTAB composites, and the combined composites and lower the paper-and-pencil composites and the CANTAB composites. 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.
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http://dx.doi.org/10.3389/fneur.2020.00670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379151PMC
July 2020

Treatment of posttraumatic olfactory dysfunction with corticosteroids and olfactory training.

Acta Otolaryngol 2020 Sep 3;140(9):761-767. Epub 2020 Jun 3.

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences (MH), Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Few have investigated long-term effect of treatment of posttraumatic olfactory dysfunction (OD). To explore if sequential treatment with corticosteroids and olfactory training (OT) improved smell in patients with OD after moderate and severe traumatic brain injury (TBI). Twenty-two patients with persistent OD, mean 62 months after trauma, completed an open uncontrolled intervention study of treatment for 10 d with oral corticosteroids and thereafter for 3 months with OT twice daily. Olfaction was assessed by Sniffin' Sticks. They were tested at four-time points, with the last assessment 12 months after baseline measurements. Mean age at trauma was 45 (SD 14) years. Mean threshold, discrimination and identification (TDI) score at baseline was 14.4 (SD 7.3) and increased to mean 20.8 (SD 7.4) after 1 year (minimum -3.0; maximum 19.5, value <.001). Analysed separately, each TDI component increased significantly after 1 year. Half of the patients (11/22) experienced a clinically significant improvement of ≥6.0 TDI points. Improvement was not associated with any sociodemographic or trauma-related characteristics or with olfactory function at baseline. Treatment with corticosteroids and OT was promising in persistent OD after TBI and should be further studied.
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http://dx.doi.org/10.1080/00016489.2020.1767301DOI Listing
September 2020

The Prevalence and Stability of Sleep-Wake Disturbance and Fatigue throughout the First Year after Mild Traumatic Brain Injury.

J Neurotrauma 2020 12 8;37(23):2528-2541. Epub 2020 Jul 8.

Department of Psychology, Norwegian University of Science and Technology, Trondheim, Norway.

In this prospective, longitudinal study, we aimed to determine the prevalence and stability of sleep-wake disturbance (SWD) and fatigue in a large representative sample of patients (Trondheim mild traumatic brain injury [mTBI] follow-up study). We included 378 patients with mTBI (age 16-60), 82 matched trauma controls with orthopedic injuries, and 83 matched community controls. Increased sleep need, poor sleep quality, excessive daytime sleepiness, and fatigue were assessed at 2 weeks, 3 months, and 12 months after injury. Mixed logistic regression models were used to evaluate clinically relevant group differences longitudinally. Prevalence of increased sleep need, poor sleep quality, and fatigue was significantly higher in patients with mTBI than in both trauma controls and community controls at all time points. More patients with mTBI reported problems with excessive daytime sleepiness compared to trauma controls, but not community controls, at all time points. Patients with complicated mTBI (intracranial findings on computed tomography or magnetic resonance imaging) had more fatigue problems compared to those with uncomplicated mTBI, at all three time points. In patients with mTBI who experienced SWDs and fatigue 2 weeks after injury, around half had problems at 3 months and approximately one third at 12 months. Interestingly, we observed limited overlap between the different symptom measures; a large number of patients reported one specific problem with SWD or fatigue rather than several problems. In conclusion, our results provide strong evidence that mTBI contributes significantly to the development and maintenance of SWDs and fatigue.
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http://dx.doi.org/10.1089/neu.2019.6898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698981PMC
December 2020

Systemic Inflammation Persists the First Year after Mild Traumatic Brain Injury: Results from the Prospective Trondheim Mild Traumatic Brain Injury Study.

J Neurotrauma 2020 10 3;37(19):2120-2130. Epub 2020 Jun 3.

Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.

Innate immune activation has been attributed a key role in traumatic brain injury (TBI) and successive morbidity. In mild TBI (mTBI), however, the extent and persistence of innate immune activation are unknown. We determined plasma cytokine level changes over 12 months after an mTBI in hospitalized and non-hospitalized patients compared with community controls; and examined their associations to injury-related and demographic variables at admission. Prospectively, 207 patients presenting to the emergency department (ED) or general practitioner with clinically confirmed mTBI and 82 matched community controls were included. Plasma samples were obtained at admission, after 2 weeks, 3 months, and 12 months. Cytokine levels were analysed with a 27-plex beads-based immunoassay. Brain magnetic resonance imaging (MRI) was performed on all participants. Twelve cytokines were reliably detected. Plasma levels of interferon gamma (IFN-γ), interleukin 8 (IL-8), eotaxin, macrophage inflammatory protein-1-beta (MIP-1β), monocyte chemoattractant protein 1 (MCP-1), IL-17A, IL-9, tumor necrosis factor (TNF), and basic fibroblast growth factor (FGF-basic) were significantly increased at all time-points in patients compared with controls, whereas IFN-γ-inducing protein 10 (IP-10), platelet-derived growth factor (PDGF), and IL-1ra were not. IL-17A and FGF-basic showed significant increases in patients from admission to follow-up at 3 months, and remained increased at 12 months compared with admission. Interestingly, MRI findings were negatively associated with four cytokines: eotaxin, MIP-1β, IL-9, and IP-10, whereas age was positively associated with nine cytokines: IL-8, eotaxin, MIP-1β, MCP-1, IL-17A, IL-9, TNF, FGF-basic, and IL-1ra. TNF was also increased in those with presence of other injuries. In conclusion, mTBI activated the innate immune system consistently and this is the first study to show that several inflammatory cytokines remain increased for up to 1 year post-injury.
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http://dx.doi.org/10.1089/neu.2019.6963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502683PMC
October 2020

Change in self-reported cognitive symptoms after mild traumatic brain injury is associated with changes in emotional and somatic symptoms and not changes in cognitive performance.

Neuropsychology 2020 Jul 9;34(5):560-568. Epub 2020 Apr 9.

Department of Physical Medicine and Rehabilitation.

Objective: To investigate (a) whether self-reported cognitive symptoms after mild traumatic brain injury (MTBI) are associated with cognitive test performances, and (b) whether improvement in self-reported symptoms from 2 weeks to 3 months after MTBI is associated with improvement in cognitive test performances.

Method: Patients with MTBI ( = 135), aged 16-59, who initially presented to the emergency department, completed the Rivermead Post Concussion Symptoms Questionnaire (RPQ), the Brief Symptom Inventory 18, and cognitive tests (i.e., Controlled Oral Word Association, Coding, Rey Auditory Verbal Learning, and Trail Making test) at 2 weeks and 3 months after MTBI. Using Spearman's rank correlations (ρ), associations were examined between self-report measures and cognitive test performances at each time point and between change scores (i.e., 3-month score minus 2-week score) on each outcome.

Results: At 3 months, 27% reported cognitive symptoms to some extent. At both assessments, greater severity of RPQ cognitive symptoms was very weakly associated with worse cognitive test performances (2-week ρ range = -0.19 to -0.01; 3-month ρ range = -0.20 to -0.10). RPQ cognitive symptoms were, however, strongly related to greater somatic and emotional symptoms. Change in self-reported cognitive symptoms from 2 weeks to 3 months was not associated with change in cognitive test performance. In contrast, change in self-reported cognitive symptoms was strongly associated with change in emotional (ρ = 0.58) and somatic symptoms (ρ = 0.57).

Conclusions: These findings indicate that improvements in subjective cognitive symptoms after MTBI co-occur with improvements on other subjective metrics, but are not related to improvements in objectively measured cognitive functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000632DOI Listing
July 2020

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

Appl Neuropsychol Adult 2020 Feb 21:1-9. Epub 2020 Feb 21.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.

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 : .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 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.
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http://dx.doi.org/10.1080/23279095.2020.1722126DOI Listing
February 2020

Association of cause of injury and traumatic axonal injury: a clinical MRI study of moderate and severe traumatic brain injury.

J Neurosurg 2019 Oct 11:1-9. Epub 2019 Oct 11.

1Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim.

Objective: The authors investigated the association between the cause of injury and the occurrence and grade of traumatic axonal injury (TAI) on clinical MRI in patients with moderate or severe traumatic brain injury (TBI).

Methods: Data for a total of 396 consecutive patients, aged 7-70 years, with moderate or severe TBI admitted to a level 1 trauma center were prospectively registered. Data were included for analysis from the 219 patients who had MRI performed within 35 days (median 8, IQR 4-17 days) and for whom cause of injury was known. Cause of injury was registered as road traffic accident (RTA) or fall (both with respective subcategories), alpine skiing or snowboarding accident, or violence. The MRI protocol consisted of T2*-weighted gradient echo, FLAIR, and diffusion-weighted imaging scans. TAI lesions were evaluated in a blinded manner and categorized into 3 grades, hemispheric/cerebellar white matter (grade 1), corpus callosum (grade 2), and brainstem (grade 3). The absence of TAI was analyzed as grade 0. Contusions and mass lesions on CT were also registered.

Results: Cause of injury did not differ between included and nonincluded patients. TAI was found in 83% of patients in the included group after RTAs and 62% after falls (p < 0.001). Observed TAI grades differed between the subcategories of both RTAs (p = 0.004) and falls (p = 0.006). Pedestrians in RTAs, car drivers/passengers in RTAs, and alpine skiers had the highest prevalence of TAI (89%-100%) and the highest TAI grades (70%-82% TAI grades 2-3). TAI was found in 76% of patients after falls from > own height (45% TAI grade 2-3), 63% after falls down the stairs (26% TAI grade 2-3), and 31% after falls from ≤ own height (12% TAI grade 2-3). Moreover, 53% of patients with TAI after RTAs and 68% with TAI after falls had cortical contusions or mass lesions on CT.

Conclusions: This prospective study of moderate and severe TBI is to the authors' knowledge the first clinical MRI study to demonstrate both the high prevalence and grade of TAI after most of the different types of RTAs, alpine skiing accidents, and falls from a height. Importantly, TAI was also common following more low-energy trauma such as falls down the stairs or from own height. Physicians managing TBI patients in the acute phase should be aware of the possibility of TAI no matter the cause of injury and also when the CT scan shows cortical contusions or mass lesions.
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http://dx.doi.org/10.3171/2019.6.JNS191040DOI Listing
October 2019

Cognitive Reserve Moderates Cognitive Outcome After Mild Traumatic Brain Injury.

Arch Phys Med Rehabil 2020 01 25;101(1):72-80. Epub 2019 Sep 25.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Neurosurgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

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.
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http://dx.doi.org/10.1016/j.apmr.2019.08.477DOI Listing
January 2020

Patients with Mild Traumatic Brain Injury Recruited from Both Hospital and Primary Care Settings: A Controlled Longitudinal Magnetic Resonance Imaging Study.

J Neurotrauma 2019 11 31;36(22):3172-3182. Epub 2019 Jul 31.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.

With an emphasis on traumatic axonal injury (TAI), frequency and evolution of traumatic intracranial lesions on 3T clinical magnetic resonance imaging (MRI) were assessed in a combined hospital and community-based study of patients with mild traumatic brain injury (mTBI). The findings were related to post-concussion symptoms (PCS) at 3 and 12 months. Prospectively, 194 patients (16-60 years of age) were recruited from the emergency departments at a level 1 trauma center and a municipal outpatient clinic into the Trondheim mTBI follow-up study. MRI was acquired within 72 h ( = 194) and at 3 ( = 165) and 12 months ( = 152) in patients and community controls ( = 78). The protocol included T2, diffusion weighted imaging, fluid attenuated inversion recovery (FLAIR), and susceptibility weighted imaging (SWI). PCS was assessed with British Columbia Post Concussion Symptom Inventory in patients and controls. Traumatic lesions were present in 12% on very early MRI, and in 5% when computed tomography (CT) was negative. TAI was found in 6% and persisted for 12 months on SWI, whereas TAI lesions on FLAIR disappeared or became less conspicuous on follow-up. PCS occurred in 33% of patients with lesions on MRI and in 19% in patients without lesions at 3 months ( = 0.12) and in 21% with lesions and 14% without lesions at 12 months ( = 0.49). Very early MRI depicted cases of TAI in patients with mTBI with microbleeds persisting for 12 months. Patients with traumatic lesions may have a more protracted recovery, but the study was underpowered to detect significant differences for PCS because of the low frequency of trauma-related MRI lesions.
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http://dx.doi.org/10.1089/neu.2018.6360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818486PMC
November 2019

Incidence of Mild Traumatic Brain Injury: A Prospective Hospital, Emergency Room and General Practitioner-Based Study.

Front Neurol 2019 18;10:638. Epub 2019 Jun 18.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

There are no recent estimates of incidence rates of mild traumatic brain injury (MTBI) from Norway. Moreover, reported incidence rates rarely comprise cases of MTBI evaluated in the primary care setting. In this study, we utilized existing data collected as part of the recruitment to a large, follow-up study of patients with MTBI. We estimated the incidence rate of MTBI, including patients who visited outpatient clinics, in the age group 16-59 years in a Norwegian region. During 81 weeks in 2014 and 2015, all persons aged 16-59 years, presenting with possible MTBI to the emergency department (ED) at St. Olavs Hospital, Trondheim University Hospital or to the general practitioner (GP)-run Trondheim municipal outpatient ED, were evaluated for a diagnosis of MTBI. Patients were identified by computerized tomography (CT) referrals and patient lists. Patients referred to acute CT from their primary GP with suspicion of MTBI were also recorded. This approach identified 732 patients with MTBI. Age- and sex-specific incidence rates of MTBI were calculated using population figures from the regional catchment area. Overall incidence of MTBI in people between 16 and 59 years was 302 per 100,000 person-years (95% confidence interval 281-324). The incidence rate was highest in the age group 16-20 years, where rates were 835 per 100,000 person-years in males and 726 in females. The overall incidence rate of MTBI was lower than expected from existing estimates. Like other reports, the incidence was highest in the late teens.
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http://dx.doi.org/10.3389/fneur.2019.00638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591366PMC
June 2019

Change in Headache Suffering and Predictors of Headache after Mild Traumatic Brain Injury: A Population-Based, Controlled, Longitudinal Study with Twelve-Month Follow-Up.

J Neurotrauma 2019 12 2;36(23):3244-3252. Epub 2019 Aug 2.

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

Headache attributed to traumatic injury to the head (HAIH) is claimed to be the most common sequela following mild traumatic brain injury (MTBI), but epidemiological evidence is scarce. We explored whether patients with MTBI had an increase in headache suffering following injury compared with controls. We also studied predictors of headache. The Trondheim MTBI follow-up study is a population-based, controlled, longitudinal study. We recruited patients exposed to MTBI and controls with minor orthopedic injuries from a trauma center and a municipal outpatient clinic, and community controls from the surrounding population. Information on headache was collected through questionnaires at baseline, and 3 and 12 months post-injury. We used a generalized linear mixed model to investigate the development of headache over time in the three groups, and logistic regression to identify predictors of headache. We included 378 patients exposed to MTBI, 82 trauma controls, and 83 community controls. The MTBI-group had a larger increase in odds of headache from baseline to the first 3 months post-injury than the controls, but not from baseline to 3-12 months post-injury. Predictors for acute HAIH were female sex and pathological imaging findings on computed tomography (CT) or magnetic resonance imaging (MRI). Predictors for persistent HAIH were prior MTBI, being injured under the influence of alcohol, and acute HAIH. Patients who experience HAIH during the first 3 months post-injury have a good chance to improve before 12 months post-injury. Female sex, imaging findings on CT or MRI, prior MTBI, and being injured under the influence of alcohol may predict exacerbation of headache.
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http://dx.doi.org/10.1089/neu.2018.6328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857461PMC
December 2019

Incidence and mortality of moderate and severe traumatic brain injury in children: A ten year population-based cohort study in Norway.

Eur J Paediatr Neurol 2019 May 4;23(3):500-506. Epub 2019 Mar 4.

Clinic of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway. Electronic address:

Objective: In this study we wanted to estimate population-based rates of incidence and mortality of moderate and severe traumatic brain injury (TBI) in children in one specific region in Norway.

Methods: In the region there are seven acute care hospitals (ACHs) in addition to a Level 1 trauma centre. Of 702 869 inhabitants (2014), 145 395 were children aged 0-16 years. Data were collected during ten years (2004-2014). All children aged 0-16 years with moderate (Glasgow Coma Scale [GCS] score 9-13) or severe (GCS score ≤ 8) TBI admitted to the Level 1 trauma centre were prospectively included. Children treated outside the Level 1 trauma centre were retrospectively included from the ACHs. Children who died from TBI prehospitally were included from the National Cause of Death Registry. Poisson regression was used to estimate incidence rate ratios (with a 95% confidence interval) comparing age, sex, and time periods.

Results: A total of 71 children with moderate or severe TBI were identified. Crude incidence rates were 2·4 (95% CI 1·7-3·3) for moderate and 2·5 (95% CI 1·8-3·4) for severe TBI per 100 000 person-years (py). Mortality rate from TBI was 1·2 (95% CI 0·7-1·9) per 100 000 py, and 88% were prehospital deaths.

Conclusion: The incidence rates and mortality of moderate and severe TBI were low compared to international reports. Most likely explained by successful national prevention of TBI.
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http://dx.doi.org/10.1016/j.ejpn.2019.01.009DOI Listing
May 2019

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

J Neurosci Res 2019 05 24;97(5):568-581. Epub 2019 Jan 24.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

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.
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http://dx.doi.org/10.1002/jnr.24383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590310PMC
May 2019

Time of Injury and Relation to Alcohol Intoxication in Moderate-to-Severe Traumatic Brain Injury: A Decade-Long Prospective Study.

World Neurosurg 2019 Feb 30;122:e684-e689. Epub 2018 Oct 30.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Neurosurgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Background: Knowledge about the causes and time of injury for traumatic brain injury (TBI) is important for the development of efficient prevention policies. We aimed to study time of injury and relation to alcohol intoxication for moderate-to-severe TBI in a level 1 trauma center in Norway.

Methods: From October 2004 to September 2014, 493 consecutive patients (≥16 years) with moderate (Glasgow Coma Scale [GCS] score 9-13) and severe TBI (GCS score 3-8) were prospectively included in the Trondheim TBI Study (222 patients with moderate and 270 patients with severe TBI).

Results: Mean age was 47 years (standard deviation 21 years). Positive blood alcohol concentration (BAC) was found in 29%, and median BAC was 41.5 mmol/L (interquartile range 28.7-54.3), equal to 1.91‰. Admissions were more frequent on Saturdays (relative risk [RR] 2.67, 95% confidence interval [CI] 1.87-3.80) and Sundays (RR 2.10, 95% CI 1.45-3.03) compared with Mondays, and positive BAC was more common on weekends than weekdays (43% vs. 16%). Furthermore, admissions were more frequent in June (RR 2.26, 95% CI 1.44-3.55), July (RR 2.07, 95% CI 1.31-3.28), and December (RR 2.07, 95% CI 1.31-3.28) compared with January. The number of patients with positive BAC was greatest in December (RR 5.75, 95% CI 1.99-16.63), and 70% of these were caused by falls.

Conclusions: Our findings demonstrate that moderate-to-severe TBI admissions display a clear weekly and seasonal variation and that alcohol is an important modifiable risk factor for moderate-to-severe TBI.
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http://dx.doi.org/10.1016/j.wneu.2018.10.122DOI Listing
February 2019

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

Brain Inj 2018 9;32(8):1021-1027. Epub 2018 May 9.

a Department of Otorhinolaryngology , St. Olavs University Hospital , Trondheim , Norway.

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.
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http://dx.doi.org/10.1080/02699052.2018.1469043DOI Listing
July 2019

The epidemiology of mild traumatic brain injury: the Trondheim MTBI follow-up study.

Scand J Trauma Resusc Emerg Med 2018 Apr 27;26(1):34. Epub 2018 Apr 27.

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

Background: Mild traumatic brain injury (MTBI) is a frequent medical condition, and some patients report long-lasting problems after MTBI. In order to prevent MTBI, knowledge of the epidemiology is important and potential bias in studies should be explored. Aims of this study were to describe the epidemiological characteristics of MTBI in a Norwegian area and to evaluate the representativeness of patients successfully enrolled in the Trondheim MTBI follow-up study.

Methods: During 81 weeks in 2014 and 2015, all persons aged 16-60 years, presenting with possible MTBI to the emergency department (ED) at St. Olavs Hospital, Trondheim University Hospital or to Trondheim municipal outpatient ED, were evaluated for participation in the follow-up study. Patients were identified by CT referrals and patient lists. Patients who were excluded or missed for enrolment in the follow-up study were recorded.

Results: We identified 732 patients with MTBI. Median age was 28 years, and fall was the most common cause of injury. Fifty-three percent of injuries occurred during the weekend. Only 29% of MTBI patients were hospitalised. Study specific exclusion criteria were present in 23%. We enrolled 379 in the Trondheim MTBI follow-up study. In this cohort, Glasgow Coma Scale score was 15 at presentation in 73%; 45% of patients were injured under the influence of alcohol. Patients missed for inclusion were significantly more often outpatients, females, injured during the weekend, and suffering violent injuries, but differences between enrolled and not enrolled patients were small.

Conclusion: Two thirds of all patients with MTBI in the 16-60 age group were treated without hospital admission, patients were often young, and half of the patients presented during the weekend. Fall was the most common cause of injury, and patients were commonly injured under the influence of alcohol, which needs to be addressed when considering strategies for prevention. The Trondheim MTBI follow-up study comprised patients who were highly representative for the underlying epidemiology of MTBI.
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http://dx.doi.org/10.1186/s13049-018-0495-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921265PMC
April 2018

Return to work after severe traumatic brain injury: a national study with a one-year follow-up of neurocognitive and behavioural outcomes.

Neuropsychol Rehabil 2020 Mar 18;30(2):281-297. Epub 2018 Apr 18.

Institute of Health and Society, Research Centre for Habilitation and Rehabilitation Models and Services (CHARM), Faculty of Medicine, University of Oslo, Oslo, Norway.

The objectives were to investigate the frequency of return-to-work (RTW) one year after severe traumatic brain injury (sTBI: Glasgow Coma Scale, GCS 3-8) and to identify which demographic and injury-related characteristics and neurocognitive factors are associated with RTW. This study is part of a prospective national study on sTBI conducted in all four Norwegian Trauma Referral Centres, including patients aged >15 years over a period of three years (= 378). For the purpose of this study, only pre-employed individuals of working age (16 to 67 years) were investigated for RTW (= 143), and of these, 104 participants underwent neuropsychological testing. Measures of acute injury severity, neuropsychological composite scores (Memory, Processing Speed, Executive Functions) at the one-year follow-up, and the Behaviour Rating Inventory of Executive Functions (patient- and relative reports) were explored as predictors of RTW. The frequency of RTW was 54.5%. Multivariate logistic regression analyses identified younger age, shorter length of stay in intensive care, better Processing Speed scores, and lower levels of metacognitive difficulties as rated by relatives as significant predictors of RTW. Findings support the importance of neuropsychological measures in predicting long-term RTW and highlight the need to address neurocognitive and behavioural difficulties to improve RTW after sTBI.
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http://dx.doi.org/10.1080/09602011.2018.1462719DOI Listing
March 2020

Moderate Traumatic Brain Injury: Clinical Characteristics and a Prognostic Model of 12-Month Outcome.

World Neurosurg 2018 Jun 31;114:e1199-e1210. Epub 2018 Mar 31.

Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, The Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

Background: Patients with moderate traumatic brain injury (TBI) often are studied together with patients with severe TBI, even though the expected outcome of the former is better. Therefore, we aimed to describe patient characteristics and 12-month outcomes, and to develop a prognostic model based on admission data, specifically for patients with moderate TBI.

Methods: Patients with Glasgow Coma Scale scores of 9-13 and age ≥16 years were prospectively enrolled in 2 level I trauma centers in Europe. Glasgow Outcome Scale Extended (GOSE) score was assessed at 12 months. A prognostic model predicting moderate disability or worse (GOSE score ≤6), as opposed to a good recovery, was fitted by penalized regression. Model performance was evaluated by area under the curve of the receiver operating characteristics curves.

Results: Of the 395 enrolled patients, 81% had intracranial lesions on head computed tomography, and 71% were admitted to an intensive care unit. At 12 months, 44% were moderately disabled or worse (GOSE score ≤6), whereas 8% were severely disabled and 6% died (GOSE score ≤4). Older age, lower Glasgow Coma Scale score, no day-of-injury alcohol intoxication, presence of a subdural hematoma, occurrence of hypoxia and/or hypotension, and preinjury disability were significant predictors of GOSE score ≤6 (area under the curve = 0.80).

Conclusions: Patients with moderate TBI exhibit characteristics of significant brain injury. Although few patients died or experienced severe disability, 44% did not experience good recovery, indicating that follow-up is needed. The model is a first step in development of prognostic models for moderate TBI that are valid across centers.
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http://dx.doi.org/10.1016/j.wneu.2018.03.176DOI Listing
June 2018

Patients with Moderate and Severe Traumatic Brain Injury: Impact of Preinjury Platelet Inhibitor or Warfarin Treatment.

World Neurosurg 2018 Jun 7;114:e209-e217. Epub 2018 Mar 7.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Medical Imaging, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway. Electronic address:

Objective: We aimed to examine the effect of preinjury antithrombotic medication on clinical and radiologic neuroworsening in traumatic brain injury (TBI) and study the effect on outcome.

Methods: A total of 184 consecutive patients ≥50 years old with moderate and severe TBI admitted to a level 1 trauma center were included. Neuroworsening was assessed clinically by using the Glasgow Coma Scale (GCS) score and radiologically by using the Rotterdam CT score on repeated time points. Functional outcome was assessed with the Glasgow Outcome Scale Extended 6 months after injury.

Results: The platelet inhibitor group (mean age, 77.3 years; n = 43) and the warfarin group (mean age, 73.2 years; n = 20) were significantly older than the nonuser group (mean age, 63.7 years; n = 121; P ≤ 0.001). In the platelet inhibitor group 74% and in the warfarin group, 85% were injured by falls. Platelet inhibitors were not significantly associated with clinical or radiologic neuroworsening (P = 0.37-1.00), whereas warfarin increased the frequency of worsening in GCS score (P = 0.001-0.028) and Rotterdam CT score (P = 0.004). In-hospital mortality was higher in the platelet inhibitor group (28%; P = 0.030) and the warfarin group (50%; P < 0.001) compared with the nonuser group (13%). Platelet inhibitors did not predict mortality or worse outcome after adjustment for age, preinjury disability, GCS score, and Rotterdam CT score, whereas warfarin predicted both mortality and worse outcome.

Conclusions: In this study of patients with moderate and severe TBI, preinjury platelet inhibitors did not cause neuroworsening or predict higher mortality or worse outcome. In contrast, preinjury warfarin caused neuroworsening and was an independent risk factor for mortality and worse outcome at 6 months. Hence, fall prevention and liberal use of computed tomography examinations is important in this patient group.
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http://dx.doi.org/10.1016/j.wneu.2018.02.167DOI Listing
June 2018

The Influence of Traumatic Axonal Injury in Thalamus and Brainstem on Level of Consciousness at Scene or Admission: A Clinical Magnetic Resonance Imaging Study.

J Neurotrauma 2018 Apr 9;35(7):975-984. Epub 2018 Feb 9.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

The aim of this study was to investigate how traumatic axonal injury (TAI) lesions in the thalamus, basal ganglia, and brainstem on clinical brain magnetic resonance imaging (MRI) are associated with level of consciousness in the acute phase in patients with moderate to severe traumatic brain injury (TBI). There were 158 patients with moderate to severe TBI (7-70 years) with early 1.5T MRI (median 7 days, range 0-35) without mass lesion included prospectively. Glasgow Coma Scale (GCS) scores were registered before intubation or at admission. The TAI lesions were identified in T2*gradient echo, fluid attenuated inversion recovery, and diffusion weighted imaging scans. In addition to registering TAI lesions in hemispheric white matter and the corpus callosum, TAI lesions in the thalamus, basal ganglia, and brainstem were classified as uni- or bilateral. Twenty percent of patients had TAI lesions in the thalamus (7% bilateral), 18% in basal ganglia (2% bilateral), and 29% in the brainstem (9% bilateral). One of 26 bilateral lesions in the thalamus or brainstem was found on computed tomography. The GCS scores were lower in patients with bilateral lesions in the thalamus (median four) and brainstem (median five) than in those with corresponding unilateral lesions (median six and eight,  = 0.002 and 0.022). The TAI locations most associated with low GCS scores in univariable ordinal regression analyses were bilateral TAI lesions in the thalamus (odds ratio [OR] 35.8; confidence interval [CI: 10.5-121.8],  < 0.001), followed by bilateral lesions in basal ganglia (OR 13.1 [CI: 2.0-88.2],  = 0.008) and bilateral lesions in the brainstem (OR 11.4 [CI: 4.0-32.2],  < 0.001). This Trondheim TBI study showed that patients with bilateral TAI lesions in the thalamus, basal ganglia, or brainstem had particularly low consciousness at admission. We suggest these bilateral lesions should be evaluated further as possible biomarkers in a new TAI-MRI classification as a worst grade, because they could explain low consciousness in patients without mass lesions.
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http://dx.doi.org/10.1089/neu.2017.5252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865618PMC
April 2018

Moderate traumatic brain injury, acute phase course and deviations in physiological variables: an observational study.

Scand J Trauma Resusc Emerg Med 2016 May 23;24:77. Epub 2016 May 23.

Department of Neurosurgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Background: Patients with moderate traumatic brain injury (TBI) are a heterogeneous group with great variability in clinical course. Guidelines for monitoring and level of care in the acute phase are lacking. The main aim of this observational study was to describe injury severity and the acute phase course during the first three days post-injury in a cohort of patients with moderate TBI. Deviations from defined parameters in selected physiological variables were also studied, based on guidelines for severe TBI during the same period.

Methods: During a 5-year period (2004-2009), 119 patients ≥16 years (median age 47 years, range 16-92) with moderate TBI according to the Head Injury Severity Scale were admitted to a Norwegian level 1 trauma centre. Injury-related and acute phase data were collected prospectively. Deviations in six physiological variables were collected retrospectively.

Results: Eighty-six percent of the patients had intracranial pathology on CT scan and 61 % had extracranial injuries. Eighty-four percent of all patients were admitted to intensive care units (ICUs) the first day, and 51 % stayed in ICUs ≥3 days. Patients staying in ICUs ≥3 days had lower median Glasgow Coma Scale score; 12 (range 9-15) versus 13 (range 9-15, P = 0.003) and more often extracranial injuries (77 % versus 42 %, P = 0.001) than patients staying in ICU 0-2 days. Most patients staying in ICUs ≥3 days had at least one episode of hypotension (53 %), hypoxia (57 %), hyperthermia (59 %), anaemia (56 %) and hyperglycaemia (65 %), and the proportion of anaemia related to number of measurements was high (33 %).

Conclusion: Most of the moderate TBI patients stayed in an ICU the first day, and half of them stayed in ICUs ≥3 days due to not only intracranial, but also extracranial injuries. Deviations in physiological variables were often seen in this latter group of patients. Lack of guidelines for patients with moderate TBI may leave these deviations uncorrected. We propose that in future research of moderate TBI, patients might be differentiated with regard to their need for monitoring and level of care the first few days post-injury. This could contribute to improvement of acute phase management.
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http://dx.doi.org/10.1186/s13049-016-0269-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878035PMC
May 2016

Rehabilitation pathways and functional independence one year after severe traumatic brain injury.

Eur J Phys Rehabil Med 2016 Oct 6;52(5):650-661. Epub 2016 Apr 6.

Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway -

Background: After severe traumatic brain injury (TBI) it is recommended that patients in need of rehabilitation be transferred directly from acute care to specialized rehabilitation. However, recent European cohort studies found a variety of care pathways and delays in admission to rehabilitation after severe TBI.

Aim: To study the pathways within rehabilitation services in a Norwegian national cohort with severe TBI and the association to functional independence 12 months post-injury.

Design: Observational prospective multicenter study.

Setting: Regional trauma centers.

Population: A total of 163 adults, age 16-85 years, with severe TBI.

Methods: The main variables were transfer between acute care and rehabilitation, type of rehabilitation services and functional independence.

Results: 75% of the patients had specialized TBI rehabilitation, 11% non-specialized and 14% no in-patient rehabilitation. In total, 48% were transferred directly to specialized rehabilitation from acute units in regional trauma centers. There were no differences in injury severity between patients transferred directly and non-directly, but the direct-transfer patients were younger. At 12 months post-injury, 71% were functionally independent and 90% lived in their home. Younger age, fewer days of ventilation and shorter post-traumatic amnesia were associated with independence. Among patients treated with specialized rehabilitation, direct transfer to rehabilitation was associated with functional independence (OR=4.3, P<0.01).

Conclusions: A direct clinical pathway including specialized rehabilitation in dedicated units was associated with functional independence.

Clinical Rehabilitation Impact: Direct pathways from acute care to sub-acute specialized rehabilitation might prove beneficial to functional status.
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October 2016

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

J Neurosci Res 2016 07 6;94(7):623-35. Epub 2016 Mar 6.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

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.
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http://dx.doi.org/10.1002/jnr.23728DOI Listing
July 2016
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