Recovery from Mild Traumatic Brain Injury in Previously Healthy Adults.

This prospective longitudinal study reports recovery from mild traumatic brain injury (MTBI) across multiple domains in a carefully selected consecutive sample of 74 previously healthy adults. The patients with MTBI and 40 orthopedic controls (i.e., ankle injuries) completed assessments at 1, 6, and 12 months after injury. Outcome measures included cognition, post-concussion symptoms, depression, traumatic stress, quality of life, satisfaction with life, resilience, and return to work. Patients with MTBI reported more post-concussion symptoms and fatigue than the controls at the beginning of recovery, but by 6 months after injury, did not differ as a group from nonhead injury trauma controls on cognition, fatigue, or mental health, and by 12 months, their level of post-concussion symptoms and quality of life was similar to that of controls. Almost all (96%) patients with MTBI returned to work/normal activities (RTW) within the follow-up of 1 year. A subgroup of those with MTBIs and controls reported mild post-concussion-like symptoms at 1 year. A large percentage of the subgroup who had persistent symptoms had a modifiable psychological risk factor at 1 month (i.e., depression, traumatic stress, and/or low resilience), and at 6 months, they had greater post-concussion symptoms, fatigue, insomnia, traumatic stress, and depression, and worse quality of life. All of the control subjects who had mild post-concussion-like symptoms at 12 months also had a mental health problem (i.e., depression, traumatic stress, or both). This illustrates the importance of providing evidence-supported treatment and rehabilitation services early in the recovery period.

Clinical correlates of retrograde amnesia in mild traumatic brain injury.

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 (χ(2)(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.

Resilience Is Associated with Outcome from Mild Traumatic Brain Injury.

Resilient individuals manifest adaptive behavior and are better able to recover from adversity. The association between resilience and outcome from mild traumatic brain injury (mTBI) is examined, and the reliability and validity of the Resilience Scale and its short form in mTBI research is evaluated. Patients with mTBI (n=74) and orthopedic controls (n=39) completed the Resilience Scale at one, six, and 12 months after injury. Additionally, self-reported post-concussion symptoms, fatigue, insomnia, pain, post-traumatic stress, and depression, as well as quality of life, were evaluated. The internal consistency of the Resilience Scale and the short form ranged from 0.91 to 0.93 for the mTBI group and from 0.86 to 0.95 for controls. The test-retest reliability ranged from 0.70 to 0.82. Patients with mTBI and moderate-to-high resilience reported significantly fewer post-concussion symptoms, less fatigue, insomnia, traumatic stress, and depressive symptoms, and better quality of life, than the patients with low resilience. No association between resilience and time to return to work was found. Resilience was associated with self-reported outcome from mTBI, and based on this preliminary study, can be reliably evaluated with Resilience Scale and its short form in those with mTBIs.

A prospective biopsychosocial study of the persistent post-concussion symptoms following mild traumatic brain injury.

This study examined multiple biopsychosocial factors relating to post-concussion symptom (PCS) reporting in patients with mild traumatic brain injuries (mTBI), including structural (computed tomography and magnetic resonance imaging [MRI]) and microstructural neuroimaging (diffusion tensor imaging [DTI]). Patients with mTBIs completed several questionnaires and cognitive testing at approximately one month (n=126) and one year (n=103) post-injury. At approximately three weeks post-injury, DTI was undertaken using a Siemens 3T scanner in a subgroup (n=71). Measures of fractional anisotropy were calculated for 16 regions of interest (ROIs) and measures of apparent diffusion coefficient were calculated for 10 ROIs. Patients were compared with healthy control subjects. Using International Classification of Diseases, Tenth Revision (ICD-10) PCS criteria and mild or greater symptom reporting, 59% of the mTBI sample met criteria at one month and 38% met criteria at one year. However, 31% of the healthy control sample also met criteria for the syndrome-illustrating a high false-positive rate. Significant predictors of ICD-10 PCS at one month were pre-injury mental health problems and the presence of extra-cranial bodily injuries. Being symptomatic at one month was a significant predictor of being symptomatic at one year, and depression was significantly related to PCS at both one month and one year. Intracranial abnormalities visible on MRI were present in 12.1% of this sample, and multifocal areas of unusual white matter as measured by DTI were present in 50.7% (compared with 12.4% of controls). Structural MRI abnormalities and microstructural white matter findings were not significantly associated with greater post-concussion symptom reporting. The personal experience and reporting of post-concussion symptoms is likely individualized, representing the cumulative effect of multiple variables, such as genetics, mental health history, current life stress, medical problems, chronic pain, depression, personality factors, and other psychosocial and environmental factors. The extent to which damage to the structure of the brain contributes to the persistence of post-concussion symptoms remains unclear.

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).

Structural integrity of medial temporal lobes of patients with acute mild traumatic brain injury.

Post-traumatic amnesia (PTA) is an acute characteristic of traumatic brain injury (TBI) and the duration of PTA is commonly used to estimate the severity of brain injury. In the context of mild traumatic brain injury (MTBI), PTA is an essential part of the routine clinical assessment. Macroscopic lesions in temporal lobes, especially hippocampal regions, are thought to be connected to memory loss. However, conventional neuroimaging has failed to reveal neuropathological correlates of PTA in MTBI. Texture analysis (TA) is an image analysis technique that quantifies the minor MRI signal changes among image pixels and, therefore, the variations in intensity patterns within the image. The objective of this work was to apply the TA technique to MR images of MTBI patients and control subjects, and to assess the microstructural damage in medial temporal lobes of patients with MTBI with definite PTA. TA was performed for fluid-attenuated inversion recovery (FLAIR) images of 50 MTBI patients and 50 age- and gender-matched controls in the regions of the amygdala, hippocampus, and thalamus. It was hypothesized that 1) there would be statistically significant differences in TA parameters between patients with MTBIs and controls, and 2) the duration of PTA would be related to TA parameters in patients with MTBI. No significant textural differences were observed between patients and controls in the regions of interest (p>0.01). No textural features were observed to correlate with the duration of PTA. Subgroup analyses were conducted on patients with PTA of>1 h, (n=33) and compared the four TA parameters to the age- and gender-matched controls (n=33). The findings were similar. This study did not reveal significant textural changes in medial temporal structures that could be related to the duration of PTA.

Return to work following mild traumatic brain injury.

OBJECTIVE: To examine factors relating to return to work (RTW) following mild traumatic brain injury (mTBI). PARTICIPANTS: One hundred and nine patients (Age: M = 37.4 years, SD = 13.2; 52.3% women) who sustained an mTBI. DESIGN: Inception cohort design with questionnaires and neuropsychological testing completed approximately 3 to 4 weeks postinjury. SETTING: Emergency Department of Tampere University Hospital, Finland. MAIN OUTCOME MEASURES: Self-report (postconcussion symptoms, depression, fatigue, and general health) and neurocognitive measures (attention and memory). RESULTS: The cumulative RTW rates were as follows: 1 week = 46.8%, 2 weeks = 59.6%, 3 weeks = 67.0%, 4 weeks = 70.6%, 2 months = 91.7%, and 1 year = 97.2%. Four variables were significant predictors of the number of days to RTW: age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue ratings (all P < .001). The largest amount of variance accounted for by these variables in the prediction of RTW was at 30 days following injury (P < .001, R = 0.504). Participants who returned to work fewer than 30 days after injury (n = 82, 75.2%) versus more than 30 days (n = 27, 24.8%) did not differ on demographic or neuropsychological variables. CONCLUSIONS: The vast majority of this cohort returned to work within 2 months. Predictors of slower RTW included age, multiple bodily injuries, intracranial abnormality at the day of injury, and fatigue.

Biopsychosocial outcome after uncomplicated mild traumatic brain injury.

The purpose of this study was to examine the biopsychosocial outcome from uncomplicated mild traumatic brain injury (MTBI) within the first 3 weeks post injury. Participants were 48 prospectively enrolled patients from the Emergency Department of Tampere University Hospital, Finland, who sustained an uncomplicated MTBI. At 3 weeks post injury, diffusion tensor imaging (DTI) of the whole brain was undertaken using a Siemens 3T scanner. Measures of fractional anisotropy (FA) were calculated for 16 regions of interest (ROIs) and measures of apparent diffusion coefficient (ADC) were calculated for 10 ROIs. Twenty-four healthy control participants also completed DTI of the whole brain for comparison. Participants were administered a brief battery of self-report (e.g., postconcussion symptoms, depression, and fatigue) and neurocognitive measures (e.g., verbal learning and memory). There were no significant differences between the uncomplicated MTBI and healthy control group on any measures of learning and memory. Compared to the control group, the uncomplicated MTBI group reported a greater number of postconcussion symptoms and fatigue, but not depression. When considering all DTI ROIs simultaneously, the MTBI group had a significantly larger number of low DTI measures (FA values) compared to the healthy controls. MTBI patients with multifocal white matter changes did not show evidence of worse symptoms, cognitive impairment, or slower return to work compared to MTBI patients with broadly normal white matter.

Outcome from Complicated versus Uncomplicated Mild Traumatic Brain Injury.

Objective. To compare acute outcome following complicated versus uncomplicated mild traumatic brain injury (MTBI) using neurocognitive and self-report measures. Method. Participants were 47 patients who presented to the emergency department of Tampere University Hospital, Finland. All completed MRI scanning, self-report measures, and neurocognitive testing at 3-4 weeks after injury. Participants were classified into the complicated MTBI or uncomplicated MTBI group based on the presence/absence of intracranial abnormality on day-of-injury CT scan or 3-4 week MRI scan. Results. There was a large statistically significant difference in time to return to work between groups. The patients with uncomplicated MTBIs had a median of 6.0 days (IQR = 0.75-14.75, range = 0-77) off work compared to a median of 36 days (IQR = 13.5-53, range = 3-315) for the complicated group. There were no significant differences between groups for any of the neurocognitive or self-report measures. There were no differences in the proportion of patients who (a) met criteria for ICD-10 postconcussional disorder or (b) had multiple low scores on the neurocognitive measures. Conclusion. Patients with complicated MTBIs took considerably longer to return to work. They did not perform more poorly on neurocognitive measures or report more symptoms, at 3-4 weeks after injury compared to patients with uncomplicated MTBIs.

Reliability, validity and clinical usefulness of the BNI fatigue scale in mild traumatic brain injury.

OBJECTIVES: The purpose of this study was to examine the reliability, validity and clinical usefulness of the Barrow Neurological Institute Fatigue Scale (BNI-FS) in patients with mild traumatic brain injuries (MTBI). METHODS AND PROCEDURE: Participants were 125 patients enrolled from the Emergency Department (ED) of Tampere University Hospital, Finland who had sustained an MTBI. The average number of days from injury to the interview and questionnaires was 24.1 (SD = 5.4, Range = 8-38). The patients were compared to a healthy control sample. Patients completed the Barrow Neurological Institute Fatigue Scale, Fatigue Impact Scale (FIS), Beck Depression Inventory-Second Edition (BDI-II), Rivermead Post-concussion Symptom Questionnaire (RPSQ) and the health assessment measure EuroQol five Dimension (EQ-5D) Visual Analogue Scale (VAS). RESULTS: The MTBI group had significantly greater total scores on the BNI-FS than the control group (p < 0.005, Cohen's d = 0.40). The internal consistency reliability for the BNI-FS, as measured by Cronbach's alpha, was 0.96 for the MTBI group and 0.87 for the control group. The 10 items were submitted to an exploratory principal components factor analysis with varimax rotation in the MTBI group. A one-factor solution, accounting for 73.3% of the total variance, appropriately summarized the data. The correlation between the BNI-FS and other measures was rs = 0.68 (p < 0.001) for the BDI-II, rs = 0.68 (p < 0.001) for the RPSQ, rs = -0.39 (p < 0.001) for the EQ-5D VAS and rs = 0.84 (p < 0.001) for the FIS. Fatigue ratings correlated positively with number of days post-injury before returning to work (rs = 0.27, p < 0.006). CONCLUSION: The BNI-FS is a relatively new, brief and highly reliable measure of fatigue.

To exclude or not to exclude: white matter hyperintensities in diffusion tensor imaging research.

OBJECTIVE: A practical methodological issue for diffusion tensor imaging (DTI) researchers is determining what to do about incidental findings, such as white matter hyperintensities (WMHI). The purpose of this study was to compare healthy control subjects with or without WMHIs on whole brain DTI. METHOD: Participants were 30 subjects (age = 37.7, SD = 11.3, Range = 18-60; 70% female) who had no known developmental, general medical, neurological or psychiatric condition that could have had an adverse affect on brain morphology. RESULTS: MRI (3 Tesla) revealed, at minimum, a WMHI in eight subjects (26.7%). Fractional anisotropy (FA) was calculated for 19 regions of interest (ROI). Frequency distributions of FA scores for the 19 ROIs were calculated. The 10th percentile for each ROI was selected as a cut-off score. Having four or more low FA scores occurred in 16.7%. More subjects with incidental findings met criterion for low FA scores (37.5%), compared to 9.1% of subjects with no findings. When subjects with minor WMHIs were retained and only those with multiple incidental findings were excluded, 8.3% of the retained subjects met criterion for low FA scores compared to 50.0% of the excluded subjects. CONCLUSIONS: The decision to include or exclude subjects who have incidental findings can influence the results of a study.

Mild traumatic brain injury: tissue texture analysis correlated to neuropsychological and DTI findings.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate whether texture analysis (TA) can detect subtle changes in cerebral tissue caused by mild traumatic brain injury (MTBI) and to determine whether these changes correlate with neuropsychological and diffusion tensor imaging (DTI) findings. MATERIALS AND METHODS: Forty-two patients with MTBIs were imaged using 1.5T magnetic resonance imaging within 3 weeks after head injury. TA was performed for the regions corresponding to the mesencephalon, centrum semiovale, and corpus callosum. Using DTI, the fractional anisotropic and apparent diffusion coefficient values for the same regions were evaluated. The same analyses were performed on a group of 10 healthy volunteers. Patients also underwent a battery of neurocognitive tests within 6 weeks after injury. RESULTS: TA revealed textural differences between the right and left hemispheres in patients with MTBIs, whereas differences were minimal in healthy controls. A significant correlation was found between scores on memory tests and texture parameters (sum of squares, sum entropy, inverse difference moment, and sum average) in patients in the area of the mesencephalon and the genu of the corpus callosum. Significant correlations were also found between texture parameters for the left mesencephalon and both fractional anisotropic and apparent diffusion coefficient values. CONCLUSIONS: The data suggest that heterogeneous texture and abnormal DTI patterns in the area of the mesencephalon may be linked with verbal memory deficits among patients with MTBIs. Therefore, TA combined with DTI in patients with MTBIs may increase the ability to detect early and subtle neuropathologic changes.

Texture analysis of MR images of patients with mild traumatic brain injury.

BACKGROUND: Our objective was to study the effect of trauma on texture features in cerebral tissue in mild traumatic brain injury (MTBI). Our hypothesis was that a mild trauma may cause microstructural changes, which are not necessarily perceptible by visual inspection but could be detected with texture analysis (TA). METHODS: We imaged 42 MTBI patients by using 1.5 T MRI within three weeks of onset of trauma. TA was performed on the area of mesencephalon, cerebral white matter at the levels of mesencephalon, corona radiata and centrum semiovale and in different segments of corpus callosum (CC) which have been found to be sensitive to damage. The same procedure was carried out on a control group of ten healthy volunteers. Patients' TA data was compared with the TA results of the control group comparing the amount of statistically significantly differing TA parameters between the left and right sides of the cerebral tissue and comparing the most discriminative parameters. RESULTS: There were statistically significant differences especially in several co-occurrence and run-length matrix based parameters between left and right side in the area of mesencephalon, in cerebral white matter at the level of corona radiata and in the segments of CC in patients. Considerably less difference was observed in the healthy controls. CONCLUSIONS: TA revealed significant changes in texture parameters of cerebral tissue between hemispheres and CC segments in TBI patients. TA may serve as a novel additional tool for detecting the conventionally invisible changes in cerebral tissue in MTBI and help the clinicians to make an early diagnosis.

Persistent symptoms in mild to moderate traumatic brain injury associated with executive dysfunction.

In order to improve detection of subtle cognitive dysfunction and to shed light on the etiology of persistent symptoms after mild-to-moderate traumatic brain injury (TBI), we employed an experimental executive reaction time (RT) test, standardized neuropsychological tests, and diffusion tensor imaging (DTI). The Executive RT-Test, an Executive Composite Score from standardized neuropsychological tests, and DTI-indices in the midbrain differentiated between patients with persistent symptoms from those fully recovered after mild-to-moderate TBI. We suggest that persistent symptoms in mild-to-moderate TBI may reflect disrupted fronto-striatal network involved in executive functioning, and the Executive RT-Test provides an objective and novel method to detect it.

Insidious cognitive decline in CADASIL.

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) causes repeated ischemic attacks leading to subcortical vascular dementia. The aim of this study was to characterize cognitive function in subjects with a C475T (R133C) mutation in the Notch3 gene, leading to CADASIL. METHODS: Prestroke (n=13) and poststroke (n=13) mutation carriers and mutation carriers with dementia (n=8) were compared with healthy noncarriers from the same families using a comprehensive set of neuropsychological tests. RESULTS: Changes in working memory and executive function were observed in the very early phase of the disease before transient ischemic attack (TIA) or stroke. Later, in the poststroke phase, the cognitive impairment concerned also mental speed and visuospatial ability. Finally, the subjects with dementia had multiple cognitive deficits, which engaged even verbal functions, verbal episodic memory, and motor speed. The 2 mutation carrier groups without dementia and the controls could be reliably distinguished using 3 tests that assessed working memory/attention, executive function, and mental speed. Episodic memory was relatively well-preserved late in the disease. CONCLUSIONS: A deterioration of working memory and executive function was already observed in the prestroke phase, which means that cognitive decline may start insidiously before the first onset of symptomatic ischemic episodes.