Antti Brander

Who Gets Recruited in Mild Traumatic Brain Injury Research

Selection bias, common in traumatic brain injury research, limits the clinical usefulness and generalizability of study findings. The purpose of this study was to examine the effect of different inclusion and exclusion criteria on patient enrollment, and the implications for generalizability, in a mild traumatic brain injury (MTBI) study. The study was conducted at the emergency department (ED) of Tampere University Hospital. Our aim was to study outcome from MTBI in patients who do not have pre-existing conditions or other confounding factors. For this, all consecutive patients with acute head trauma (n=1344) were screened. The study design included three inclusion criteria and nine exclusion criteria. The World Health Organization Collaborating Center for Neurotrauma Task Force criteria for MTBI were used. Of all patients screened, 934 (69.5%) fulfilled the MTBI criteria. For those fulfilling the MTBI criteria, various inclusion and exclusion criteria were applied in order to yield those eligible for the outcome study. Applying these criteria excluded 95.1% of MTBI patients, leaving only 46 patients in the final sample. The final sample and the excluded patients with MTBI significantly differed in age, mechanism of injury, and injury severity characteristics. Many studies recruit fundamentally biased samples that are not generalizable to the population of persons who sustain an MTBI. Studying carefully selected samples is often necessary to address specific research questions, but such studies have serious limitations in terms of translating research findings into clinical practice.

Acute mild traumatic brain injury is not associated with white matter change on diffusion tensor imaging

This study was designed to (i) evaluate the influence of age on diffusion tensor imaging measures of white matter assessed using tract-based spatial statistics; (ii) determine if mild traumatic brain injury is associated with microstructural changes in white matter, in the acute phase following injury, in a large homogenous sample that was carefully screened for pre-injury medical, psychiatric, or neurological problems; and (iii) examine if injury severity is related to white matter changes. Participants were 75 patients with acute mild traumatic brain injury (age = 37.2 ± 12.0 years, 45 males and 30 females) and 40 controls (age = 40.6 ± 12.2 yrs, 20 males and 20 females). Age effects were analysed by comparing control subgroups aged 31-40, 41-50, and 51-60 years against a group of 18-30-year-old control subjects. Widespread statistically significant areas of abnormal diffusion tensor measures were observed in older groups. Patients and controls were compared using age and gender as covariates and in age- and gender-matched subgroups. Subgroups of patients with more severe injuries were compared to age-and gender-matched controls. No significant differences were detected in patient-control or severity analyses (all P-value > 0.01). In this large, carefully screened sample, acute mild traumatic brain injury was not associated with diffusion tensor imaging abnormalities detectable with tract-based spatial statistics.

Diffusion tensor imaging of the brain in a healthy adult population: Normative values and measurement reproducibility at 3 T and 1.5 T

Background: Diffusion tensor imaging (DTI) is an increasingly used method for investigation of brain white matter integrity in both research and clinical applications. Familiarity with normal variation of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and measurement reproducibility is essential when DTI measurements are interpreted in clinical patients. Purpose: To establish normal values for FA and ADC in a healthy adult population at 1.5 T and 3 T MRI based on region of interest (ROI) analysis, and to study the inter- and intra-observer reproducibility of the measurements. Material and Methods: Forty healthy volunteers (26 women, 14 men, mean age 38.3, SD 11.6 years) underwent conventional MRI and DTI of the brain, 30 with 3 T and 10 with 1.5 T clinical scanners. ROI-based measurements for FA and ADC values were performed in five different anatomic locations of each hemisphere and in three locations within the corpus callosum. Mean values for FA and ADC for each region were calculated. Inter-observer variation of ROI measurements was evaluated by comparing the results of the two observers, intra-observer variation by repeated measurement of 10 subjects by both observers. Results: The FA values varied considerably between different regions. The highest values were found in the genu and splenium of the corpus callosum and the lowest in the corona radiata, respectively. In general, ADC values showed less variation; the highest values were found in the body of the corpus callosum and the lowest in the corona radiata. The reproducibility of both inter- and intra-observer measurements also varied regionally. The highest agreement was found for the corpus callosum and the lowest for the corona radiata and centrum semiovale. Conclusion: In a normal adult population FA and ADC values of the brain white matter show regional variation. The repeatability of the ROI measurements also varies regionally. This regional variability must be acknowledged when these measurements are interpreted in clinical patients.

Repeatability and variation of region-of-interest methods using quantitative diffusion tensor MR imaging of the brain

BackgroundDiffusion tensor imaging (DTI) is increasingly used in various diseases as a clinical tool for assessing the integrity of the brain’s white matter. Reduced fractional anisotropy (FA) and an increased apparent diffusion coefficient (ADC) are nonspecific findings in most pathological processes affecting the brain’s parenchyma. At present, there is no gold standard for validating diffusion measures, which are dependent on the scanning protocols, methods of the softwares and observers. Therefore, the normal variation and repeatability effects on commonly-derived measures should be carefully examined.MethodsThirty healthy volunteers (mean age 37.8 years, SD 11.4) underwent DTI of the brain with 3T MRI. Region-of-interest (ROI) -based measurements were calculated at eleven anatomical locations in the pyramidal tracts, corpus callosum and frontobasal area. Two ROI-based methods, the circular method (CM) and the freehand method (FM), were compared. Both methods were also compared by performing measurements on a DTI phantom. The intra- and inter-observer variability (coefficient of variation, or CV%) and repeatability (intra-class correlation coefficient, or ICC) were assessed for FA and ADC values obtained using both ROI methods.ResultsThe mean FA values for all of the regions were 0.663 with the CM and 0.621 with the FM. For both methods, the FA was highest in the splenium of the corpus callosum. The mean ADC value was 0.727 ×10-3 mm2/s with the CM and 0.747 ×10-3 mm2/s with the FM, and both methods found the ADC to be lowest in the corona radiata. The CV percentages of the derived measures were < 13% with the CM and < 10% with the FM. In most of the regions, the ICCs were excellent or moderate for both methods. With the CM, the highest ICC for FA was in the posterior limb of the internal capsule (0.90), and with the FM, it was in the corona radiata (0.86). For ADC, the highest ICC was found in the genu of the corpus callosum (0.93) with the CM and in the uncinate fasciculus (0.92) with FM.ConclusionsWith both ROI-based methods variability was low and repeatability was moderate. The circular method gave higher repeatability, but variation was slightly lower using the freehand method. The circular method can be recommended for the posterior limb of the internal capsule and splenium of the corpus callosum, and the freehand method for the corona radiata.

Sport Concussion Assessment Tool 2 in a civilian trauma sample with mild traumatic brain injury

The aim of the study was to evaluate the validity of the Sport Concussion Assessment Tool-Second Edition (SCAT2) in patients with acute mild traumatic brain injuries (mTBIs) in a civilian trauma setting. In addition, the SCAT2 was compared to the Military Acute Concussion Evaluation (MACE). All the participants of the study were prospectively recruited from the emergency department of Tampere University Hospital (Tampere, Finland). Patients (n=49) between the ages of 18 and 60 years, with no premorbid medical or psychiatric conditions, who met the World Health Organization criteria for mTBI, were enrolled. Trauma controls (n=33) were recruited using similar study criteria. The main measures of the study consisted of SCAT2, MACE, and mTBI severity markers, including neuroimaging (computed tomography and conventional magnetic resonance imaging [MRI]), and 1-month clinical outcomes (postconcussion syndrome diagnosis and return to work status). The scoreable components of the SCAT2 performed variably across five dimensions of validity (diagnostic, criterion, divergent, predictive, and responsiveness). The Standardized Assessment of Concussion component reasonably discriminated mTBI patients from controls, was associated with MRI lesions, improved over time, and predicted return to work. Symptom scores differentiated patients with mTBIs from controls, and elevated initial symptom scores in patients with mTBI were associated with a greater risk of persistent postconcussion symptoms. The SCAT2 was superior to the MACE. The SCAT2 appears useful for detecting acute mTBI-related symptoms and cognitive impairment, refining prognosis, and monitoring recovery.

Assessing the State of Chronic Spinal Cord Injury Using Diffusion Tensor Imaging

The aim of this study was to quantify the association between diffusion tensor imaging (DTI) parameters of the cervical spinal cord and neurological disability in patients with chronic traumatic spinal cord injury (SCI). A cervical spinal cord 3T magnetic resonance imaging (MRI) with DTI sequences was performed on 28 patients with chronic traumatic SCI and 40 healthy control subjects. DTI metrics, including fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD), were calculated within the normal-appearing spinal cord area at levels C2 or C3. Clinical assessment of the patients was performed according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the motor subscale of the Functional Independence Measure (FIM). The FA values of the patients with SCI were significantly lower than those of healthy control subjects (p<0.000001). In contrast, the ADC and RD values of these patients were significantly higher than those of control subjects (ADC p<0.0001, RD p<0.00001). In patients with SCI, the FA values were positively correlated with the motor (pr=0.56, p<0.01) and sensory (pr=0.66, p<0.001) scores of ISNCSCI and with the motor subscale of FIM (pr=0.51, p<0.01). DTI revealed spinal cord pathology, which was undetectable using conventional MRI. DTI changes in regions that were remote from the site of primary injury were most likely the result of secondary degeneration of white matter tracts. Decreased FA values were correlated with poorer motor and sensory function, as well as a lack of independence in daily living. DTI is a promising quantitative and objective tool that may be used in the clinical assessment of patients with SCI.

Diffusion tensor imaging of the cervical spinal cord in healthy adult population: normative values and measurement reproducibility at 3T MRI

Background Compared to diffusion tensor imaging (DTI) of the brain, there is a paucity of reports addressing the applicability of DTI in the evaluation of the spinal cord. Most normative data of cervical spinal cord DTI consist of relatively small and arbitrarily collected populations. Comprehensive normative data are necessary for clinical decision-making. Purpose To establish normal values for cervical spinal cord DTI metrics with region of interest (ROI)- and fiber tractography (FT)-based measurements and to assess the reproducibility of both measurement methods. Material and Methods Forty healthy adults underwent cervical spinal cord 3T MRI. Sagittal and axial conventional T2 sequences and DTI in the axial plane were performed. Whole cord fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were determined at different cervical levels from C2 to C7 using the ROI method. DTI metrics (FA, axial, and radial diffusivities based on eigenvalues λ1, λ2, and λ3, and ADC) of the lateral and posterior funicles were measured at C3 level. FA and ADC of the whole cord and the lateral and posterior funicles were also measured using quantitative tractography. Intra- and inter-observer variation of the measurement methods were assessed. Results Whole cord FA values decreased and ADC values increased in the rostral to caudal direction from C2 to C7. Between the individual white matter funicles no statistically significant difference for FA or ADC values was found. Both axial diffusivity and radial diffusivity of both lateral funicles differed significantly from those of the posterior funicle. Neither gender nor age correlated with any of the DTI metrics. Intra-observer variation of the measurements for whole cord FA and ADC showed almost perfect agreement with both ROI and tractography-based measurements. There was more variation in measurements of individual columns. Inter-observer agreement varied from moderate to strong for whole cord FA and ADC. Conclusion Both ROI- and FT-based measurements are applicable methods yielding reproducible results for cervical spinal cord DTI metrics. Normative values for both measurement methods are presented.

Acute Assessment of Brain Injuries in Ground-Level Falls

Objective:The purpose of this study was to characterize traumatic brain injuries (TBI) sustained in ground-level falls (GLFs). The focus was on factors associated with acute computed tomographic (CT) findings. Methods:The sample included 575 subjects examined and treated at the Tampere University Hospital emergency department (ED). Retrospective data collection consisted of subject- and injury-related data and clinical information from the emergency department. All CT scans were analyzed and systematically coded. Results:Ground-level falls were the mechanism of injury in 48.3% (n = 278) of the subjects. In the GLF group, independent risk factors for acute traumatic CT findings were long-term alcohol abuse, older age, being found on the ground, and left temporoparietal and occipital location of direct head impact. There were no significant differences in the incidence of any intracranial traumatic lesion type between those with GLFs and other causes of TBI. None of the classic clinical TBI severity markers studied were associated with acute traumatic CT findings in patients with GLFs. Conclusions:Older age and long-term alcohol abuse increase the likelihood of acute intracranial CT abnormalities. The pattern of intracranial traumatic CT findings does not differ from other causes of TBI. Clinical signs and indices of TBI severity did not predict traumatic CT findings.

Resilience is associated with fatigue after mild traumatic brain injury.

Objective:To examine resilience as a predictor of change in self-reported fatigue after mild traumatic brain injury (MTBI). Participants:A consecutive series of 67 patients with MTBI and 34 orthopedic controls. Design: Prospective longitudinal study. Main Measures:Resilience Scale, Beck Depression Inventory–Second Edition, and Pain subscale from Ruff Neurobehavioral Inventory 1 month after injury and Barrow Neurological Institute Fatigue Scale 1 and 6 months after injury. Results:Insomnia, pain, and depressive symptoms were significantly correlated with fatigue, but even when these variables were controlled for, resilience significantly predicted the change in fatigue from 1 to 6 months after MTBI. In patients with MTBI, the correlation between resilience and fatigue strengthened during follow-up. In controls, significant associations between resilience and fatigue were not found. Conclusion:Resilience is a significant predictor of decrease in self-reported fatigue following MTBI. Resilience seems to be a relevant factor to consider in the management of fatigue after MTBI along with the previously established associated factors (insomnia, pain, and depressive symptoms).

Clinical correlates of retrograde amnesia in mild traumatic brain injury

Abstract Primary objective: The purpose of this study was to examine the clinical significance of retrograde amnesia (RA) in patients with acute mild traumatic brain injuries (MTBI). Methods and procedures: An emergency department sample of patients (n = 75), aged 18–60 years, with no pre-morbid medical or psychiatric conditions, who met the WHO criteria for MTBI were enrolled in this prospective, descriptive, follow-up study. This study examined the presence and duration of RA in relation to socio-demographics, MTBI severity markers including neuroimaging (CT, MRI) and clinical outcomes (Rivermead post-concussion symptoms questionnaire, post-concussion syndrome (PCS) diagnosis and return to work (RTW) status) at 2 weeks, 1 month and 6 months post-injury. Main outcomes and results: GCS scores and duration of post-traumatic amnesia (PTA) were related to RA. Those with GCS scores of 14 vs. 15 were more likely to have RA (χ2(1) = 13.70, p < 0.0001) and a longer duration (Mann-Whitney U = 56.0, p < 0.0001, d = 1.15) of RA. The duration of RA and PTA correlated positively (Spearman ρ(75) = 0.42, p < 0.0001) and those with RA had longer durations of PTA (Mann-Whitney U = 228.5, p = 0.001, d = 1.21). During the follow-up, the presence and duration of RA were not significantly associated with PCS diagnosis or time to RTW. Conclusions: In this study, the presence and duration of RA was not associated with outcome.