Recognition memory test: validity in diffuse traumatic brain injury.

Cerebral and extracerebral vulnerability to hypoxic insults after diffuse traumatic brain injury in rats

Diffuse cerebral swelling after severe traumatic brain injury (TBI) develops more commonly in children than adults; however, models of diffuse brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a recently described closed head injury model for adult rats. A total of 105 Sprague-Dawley immature rats (17 days old; average weight 38.5 +/- 5.46 g) were subjected to head impact using variable weights (0 g (sham), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neurological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period after severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurological recovery was complete in the sham-injured animals (11 rats) by 4.1 +/- 0.23 minutes (mean +/- standard error of the mean), but was delayed in both moderately injured (MI) (75 g/2 m; 11 rats) (14.97 +/- 3.99 minutes) and SI (20.57 +/- 1.31 minutes (p < 0.05)) rats. In the first 24 hours, the sham-injured animals were more active than the injured ones as reflected by a greater net weight gain: 2.9 +/- 1.0 g, 1.2 +/- 1.6 g, and -0.6 +/- 2.1 g in sham-injured, MI, and SI animals, respectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 +/- 0.7 minutes and 1.27 +/- 0.53 minutes in MI and SI groups, respectively), which either resolved or deteriorated to death. Intubation and assisted ventilation in animals with SI for 9.57 +/- 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonintubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Other injuries included neuronal death in the deep nuclei, bilateral disruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventriculomegaly. Following a diffuse TBI in immature rats, SI produced a mortality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maintaining the height of the weight drop but varying the weights. Weight loss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilatory support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.

Returning to driving following a traumatic brain injury (TBI) is often a key rehabilitation goal, as the ability to drive enables return to independence and many previous life roles. The ‘gold standard’ assessment of driving after TBI is considered to be the on-road assessment, usually conducted by a specialised occupational therapy driver assessor (OTDA). However there have been few studies investigating the patient characteristics and pre-injury and injury related factors associated with passing or failing the on-road OT driver assessment after TBI. In addition, little is known about the processes and goals of driver rehabilitation provided to those who fail the initial on-road assessment. There has also been limited research into the post-assessment driving behaviour and safety of individuals returning to driving after driver rehabilitation. <br> Accordingly, the main aims of the PhD program of research were to a) examine which patient characteristics and pre-injury and injury-related factors were associated with the outcome of initial on-road driver assessment, b) describe the range of goals, processes, timing and outcomes, including the use of restricted licensing and resources, associated with providing on-road training to those who failed an initial OT driver assessment and c) examine and compare the characteristics and self-reported pre- and post-injury driver safety and patterns of driving behaviour of those drivers who returned to driving after one on-road assessment with those who received on-road training and subsequent reassessments. <br> In Study 1, the results of all on-road driver assessments completed by patients with a TBI (n = 207), in a rehabilitation setting, over an 8-year period were reviewed retrospectively. Two outcome groups were identified: a ‘pass’ group who resumed driving after passing the initial on-road assessment and a <i>‘rehabilitation’</i> group who failed and required on-road training in the form of driving lessons. <br> <b>Key-findings</b>; Post traumatic amnesia (PTA) duration proved to be more strongly associated with driver assessment outcome than Glasgow coma scale (GCS) score. Participants, who were male, had shorter PTA duration, faster reaction time and no physical or visual impairment and were at least 3 months post-injury were more likely to pass the initial on-road assessment. These variables correctly classified 87.6% of the <i>pass</i> group and 71.2% of the <i>rehabilitation</i> group. On-road training, followed by subsequent on-road re-assessments were associated with a high probability of return to driving after TBI. <br> <b>Recommendations</b>; Factors to consider when determining whether to refer for a practical driver assessment include; ensuring that the client is at least 3 months post-injury, evidence of moderate to severe TBI measured by PTA, slowed choice reaction times and presence of physical or visual impairment that may impact on driver capacity. On–road training is an important driver rehabilitation intervention and should be offered to drivers with TBI who fail the initial on-road assessment. <br> From a sample of 340 participants, Study 2 examined the goals, outcomes, timing, use of restricted licenses and number of on-road training lessons and OT driver reassessments provided to the 94 participants who failed the initial on-road assessment. <br> <b>Key-findings</b>; The use of goal directed driving lessons to facilitate compensation for cognitive, physical or visual impairment, improve confidence or enhance previously learned driving skills and restricted licensing were found to be associated with return to driving following moderate/severe TBI. An average of seven driving lessons (range 1 – 35) and 2.5 OT driver reassessments (range 1-6), were provided to participants, resulting in 93% (n=87) of cases resuming driving and 7 (7%) failing to meet licensing standards. An open license was recommended for 42 (45%) cases and 45 (48%) resumed driving with a restricted license. The mean time for referral for driving assessment varied significantly between the pass (7.62 months) and <i>rehabilitation</i> groups (13.31 months). <br> <b>Recommendation</b>; Investment in on-road training lessons addressing individual goals, followed by reassessment and use of restricted licenses, can achieve successful return to driving following TBI. Although delaying driving by at least 3 months appears to be appropriate, a much longer time frame is often required, particularly with severe TBI. <br> Finally, Study 3 examined self-report responses of 106 participants regarding post-injury changes in driving behaviour and number of pre- and post-injury crashes. <br> <b>Key findings</b>: No significant differences were found in pre- and post-injury crash rates or in crash rates between the <i>pass</i> (n= 74) and <i>rehabilitation</i> (n= 32) groups. Many drivers reported changes to their driving behaviour: Compared to pre-injury, 36.8% of drivers reported limiting driving time, 40.6% drove more slowly and 41.5% reported greater difficulty with navigating. The <i>rehabilitation</i> group (with greater injury severity) was significantly more likely to drive less frequently, shorter distances and avoid driving with passengers, in busy traffic, at night and on freeways than the pass group. <br> <b>Recommendation</b>: As most of the study participants resumed driving and were safe to do so in the longer term, the importance of offering driver assessment and rehabilitation following moderate to severe TBI has been emphasized. <br> This PhD program of research, has also highlighted the complexity of the decision-making process required by rehabilitation clinicians in determining fitness to drive after TBI. Factors that were found to contribute to this situation included the wide variation in optimum timing for resuming driving and the range of variables that may impact on the outcome of the on-road assessment, such as injury severity, physical/visual issues, driver confidence, ability to compensate for cognitive issues and driver experience. The findings and recommendations of this PhD program may contribute to development of improved referral criteria and guidelines for resuming driving after TBI.

The study tested the ability of the Warrington Recognition Memory Test (1984) to discriminate between patients with left and right temporal lobe lesions. Forty-seven patients who had undergone unilateral temporal lobectomy (TL) (23 right- and 24 left-sided operations) were tested on the two components of the test, recognition memory for words (RMW) and recognition memory for faces (RMF). The results show that the right TL group were significantly worse than the left TL group on RMF. Conversely, the left TL group were significantly worse on the RMW test, confirming earlier results relating to material-specific deficits in long-term memory following TL. The RMF test was relatively sensitive and specific in detecting significant impairments associated with right TL, but the RMW proved much less sensitive to the effects of left TL. RMW and RMF discrepancy scores were found not to discriminate well between the two groups of patients.

Background and ObjectivesThe objective of this work was to examine the association between deployment-related traumatic brain injury (TBI) severity, frequency, and other injury characteristics with headache outcomes in veterans evaluated at a Veterans Administration (VA) polytrauma support clinic.MethodsWe conducted a retrospective chart review of 594 comprehensive TBI evaluations between 2011 and 2021. Diagnostic criteria were based on the Department of Defense/VA Consensus-Based Classification of Closed TBI. Adjusted odds ratios (AORs) and 95% CIs were estimated for headache prevalence (logistic), headache severity (ordinal), and prevalence of migraine-like features (logistic) with multiple regression analysis. Regression models were adjusted for age, sex, race/ethnicity, time since injury, and mental health diagnoses.ResultsTBI severity groups were classified as sub concussive exposure (n = 189) and mild (n = 377), moderate (n = 28), and severe TBI (n = 0). Increased headache severity was reported in veterans with mild TBI (AOR 1.72 [95% CI 1.15, 2.57]) and moderate TBI (AOR 3.89 [1.64, 9.15]) compared to those with subconcussive exposure. A history of multiple mild TBIs was associated with more severe headache (AOR 2.47 [1.34, 4.59]) and migraine-like features (AOR 5.95 [2.55, 13.77]). No differences were observed between blast and nonblast injuries; however, greater headache severity was reported in veterans with both primary and tertiary blast effects (AOR 2.56 [1.47, 4.49]). Alteration of consciousness (AOC) and posttraumatic amnesia (PTA) >30 minutes were associated with more severe headache (AOR 3.37 [1.26, 9.17] and 5.40 [2.21, 13.42], respectively). The length of time between the onset of last TBI and the TBI evaluation was associated with headache severity (AOR 1.09 [1.02, 1.17]) and prevalence of migraine-like features (AOR 1.27 [1.15, 1.40]). Last, helmet use was associated with less severe headache (AOR 0.42 [0.23, 0.75]) and lower odds of migraine-like features (AOR 0.45 [0.21, 0.98]).DiscussionOur data support the notion of a dose-response relationship between TBI severity and headache outcomes. A history of multiple mild TBIs and longer duration of AOC and PTA are unique risk factors for poor headache outcomes in veterans. Furthermore, this study sheds light on the poor headache outcomes associated with subconcussive exposure. Past TBI characteristics should be considered when developing headache management plans for veterans.

Objective Traumatic brain injury (TBI) proves to be an obstacle for Bangladeshi patients due to the lack of facilities and specialist doctors in regional sections of the country. This study aimed to record different attributes of Bangladeshi TBI patients over a year i.e., their injury characteristics, treatments received and understand their impacts on the severity of TBI. Method This cross-sectional study was carried out among 280 TBI patients treated in a tertiary care hospital in Dhaka. The physicians determined TBI's severity and prognosis as per the Glasgow Coma Scale (GCS) and Glasgow Outcome Score (GOS) respectively. Results Most TBI patients were male (76.1%) and aged between 18 and 50 years (52.2%), as in previous studies in South Asian countries. However, the prevalence of TBI due to road traffic accidents (RTAs) was much higher (67.9%) than in the earlier studies in South Asia. Additionally, more patients suffered from severe TBI (29.3%) and moderate TBI (35.7%), and a higher percentage of patients went through surgery (56.8%) compared to previous studies. A significant association of demographic (residence) and clinical characteristics (consciousness after injury, CT scan findings and treatment type) with the severity of TBI was found in bivariate analysis. It also revealed the significant dependence of clinical characteristics (TBI etiology, post-injury consciousness, treatment type and TBI severity) on TBI prognosis. Multivariate analysis showed that patients who were unconscious after TBI and with evident brain injury observed in CT scans have a substantially higher risk of having moderate or severe TBI than mild TBI. Moreover, patients with TBI due to RTAs or falls, evident brain injury in CT scans, post-surgical seizure, and moderate or severe TBI have a significantly higher risk of getting a more unfavorable TBI prognosis than moderate disability. Conclusions In this study, RTAs were found to be the major cause of TBI. Additionally, some variables were identified as possible determinants of TBI severity and prognosis among Bangladeshi patients. The correlation of these variables with TBI should be further studied with the hopes that steps will be taken to reduce TBI incidents and improve its management to reduce the overall burden.

The sensitivity of the Warrington Recognition Memory for Faces (RMF) to reliably localize temporal lobe dysfunction in surgical epilepsy candidates is not as strong as that of the Recognition Memory for Words (RMW). Previous research has indicated that its diagnostic utility is improved in patients with lower IQs. Data from 114 patients with unilateral hippocampal sclerosis was retrospectively examined to explore the accuracy of both subtests in patients with IQs within the low average/borderline impaired and intellectual disability ranges. In our group, the RMF did not discriminate between right and left hippocampal sclerosis, whilst the RMW did. However, many patients functioning within the intellectual disability range are unable to complete the RMW. There is a need to develop neuropsychological protocols appropriate for this group.

Traumatic brain injury (TBI) is associated with persistent impairments in multiple domains, including cognitive and neuropsychiatric function. Previous literature has suggested that the risk of such impairments may differ as a function of the initial severity of injury, with moderate-severe TBI (msTBI) associated with more severe cognitive dysfunction and mild TBI (mTBI) associated with a higher risk of developing an anxiety disorder. Despite this, relatively few pre-clinical studies have investigated the time course of behavioral change after different severities of injury. The current study compared the temporal profile of functional deficits incorporating locomotion, cognition, and anxiety up to 12 months post-injury after an mTBI, repeated mild TBI (rmTBI), and single msTBI in an experimental model of diffuse TBI. Injury appeared to alter the effect of aging on locomotor activity, with both msTBI and rmTBI rats showing a decrease in locomotion at 12 months relative to their earlier performance on the task, an effect not observed in shams or after a single mTBI. Further, mTBI seemed to be associated with decreased anxiety over time, as measured by increased time spent in the open arm of the elevated plus maze from 3 to 12 months post-injury. No significant findings were observed on spatial memory or volumetric magnetic resonance imaging. Future studies will need to use a more comprehensive behavioral battery, capable of capturing subtle alterations in function, and longer time points, following rats into old age, in order to more fully assess the evolution of persistent behavioral deficits in key domains after different severities of TBI, as well as their accompanying neuroimaging changes. Given the prevalence and significance of such deficits post-TBI for a person's quality of life, as well as the elevated risk of neurodegenerative disease post-injury, such investigations may play a critical role in identifying optimal windows of therapeutic intervention post-injury.

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) can negatively affect quality of life and social functioning. This study examined the relationship between PTSD and social participation in a cohort of veterans and service members (V/SM). Participants included 242 adults enrolled in the Veterans Affairs Traumatic Brain Injury Model Systems (VA TBIMS) multicenter study. Social participation was measured with the Participation Assessment with Recombined Tools-Objective. PTSD symptoms were assessed with the PTSD Checklist-Civilian Version at admission, and TBI severity was determined with the Glasgow Coma Scale. Neither TBI severity nor PTSD were associated with lower social participation at 1-year post-TBI. Marital status was the only significant predictor of social participation within this sample of V/SM with primarily moderate to severe TBI. Married V/SM with TBI reported more social participation which could lead to better rehabilitation outcomes. Unmarried V/SM may need more assistance with engagement in social activities, which can be a rehabilitation treatment target.

Adult, male, Sprague-Dawley rats were anesthetized, intubated, and mechanically ventilated with 1.5-2.0% isoflurane in oxygen (30%) and air. Rats were prepared for fluid percussion traumatic brain injury (TBI), laser Doppler flowmetry, and measurement of brain tissue nitric oxide (NO) levels using an ISO-NO electrode system. After preparation, isoflurane was reduced to 1.5%, and the rats were randomly assigned to receive sham (n = 6), moderate (1.9 atm, n = 6), or severe (2.8 atm, n = 6) parasagittal fluid percussion TBI. CBF and brain tissue NO levels were measured for 4 h, and then isoflurane levels were increased to 4.0% and the rats were decapitated and the brains were removed. Total RNA was isolated from rat brains and cytokine expression was determined. Laser Doppler flow velocity remained constant in the sham-injured rats but decreased significantly in rats subjected to moderate (p < 0.05) or severe (p < 0.05) TBI. Brain tissue NO levels remained constant in the sham-injured rats but decreased significantly (p < 0.01) after moderate TBI. Severe TBI produced slight, insignificant reductions in NO levels. Cytokine expression was very low in the shaminjured rats. TBI-induced expression of mRNAs for interleukin-1 alpha (IL-1alpha), IL-1beta, IL-6, and tumor necrosis factor-alpha (TNFa). IL-1alpha and IL-1beta mRNA expression increased significantly (p < 0.05 vs. sham-injury) after severe TBI and IL-6 and TNFa mRNA expression increased significant (p < 0.05 vs. sham-injury) after both moderate and severe TBI. Other cytokine mRNA expression was unchanged after TBI.

Executive function after severe childhood traumatic brain injury – Age-at-injury vulnerability periods: The TGE prospective longitudinal study

Proper evaluation of ski helmet designs and safety standards should rely on head impact conditions involved in skiing and snowboarding head injuries. To study these impacts, main crash scenarios involving head injuries are numerically replicated. Multibody models of skiers and snowboarders were developed to investigate five common crash scenarios involved in traumatic brain injury: forward and sideways skiing falls, snowboarding backward falls, collisions between users and collisions with obstacles. For each scenario, the influence of crash conditions on head impact (location, speed, linear and rotational accelerations) and risk of injury are evaluated. Crash conditions were initial velocity, user height, position and approach angle, slope steepness, obstacles, and snow stiffness. One thousand one hundred forty-nine crashes were simulated and three significant levels of impact conditions were discriminated over the investigated crash scenarios: 1) the smallest normal-to-slope impact velocities (6 km·h; 22 km·h) and peak linear accelerations (42g; 75g) were obtained during forward and sideways skiing falls; 2) snowboarding backward falls and collisions between users were associated with high normal-to-surface impact velocities (26 km·h; 32 km·h) and head accelerations (80g; 149g) above one published threshold for mild traumatic brain injury but below the pass/fail criteria of helmet standard tests; 3) collisions with obstacles were associated with high normal-to-surface impact velocities (19 km·h; 35 km·h) and the highest head accelerations (626g; 1885g). Current impact conditions of helmet standard evaluations consistently replicate collisions with obstacles, but need to be revised to better reflect other significant crash scenarios leading to traumatic brain injury.

Objective To investigate the effect of temperature sensitive umbilical cord mesenchymal stem cells (tsUCMSCs) transplantation under mild hypothermia environment on cognitive function of rats after severe traumatic brain injury (TBI).Methods Thirty-six male SD rats weighing (300 ± 20)g were subjected to severe TBI by fluid percussion device (2.5 atm) and managed with tsUCMSCs combined with mild hypothermia.Rats were divided into three groups:sham operation group,TBI group,and TBI + tsUCMSCs + mild hypothermia group (TBI + intervention group) according the random number table,with 12 rats per group.Latency to the platform and the time in targeted quadrant were recorded to evaluate the learning and memory with Morris water maze.Population spike (PS) and excitatory postsynaptic potential (EPSP) of long-term potential (LTP) were examined to evaluate synaptic plasticity of hippocampus.Phosphorylated Tau at Thr231 and phosphorylated GSK3 at Ser9 were detected by Western blot.Results Latency to the platform [(15.9 ±3.2) s vs (8.08 ±2.69) s,P＜0.01]was prolonged and time in targeted quadrant [(14.4 ± 3.0) s vs (36.3 ± 5.7) s,P ＜ 0.01] was shortened in TBI group at day 28 compared with sham operation group.Whereas,latency to the platform [(10.7 ± 2.8) s,at Ser9 were detected by Western blot.Results Latency to the platform [(15.9 ± 3.2) s vs (8.08 ± 2.69) s,P ＜ 0.01] was prolonged and time in targeted quadrant [(14.4 ± 3.0) svs (36.3 ± 5.7) s,P ＜0.01] was shortened in TBI group at day 28 compared with sham operation group.Whereas,latency to the platform [(10.7 ± 2.8) s,P ＜ 0.01] and time in targeted quadrant [(29.4 ± 4.4) s,P ＜ 0.05 |were reversed in TBI + intervention group.PS and EPSP of LTP were elevated in TBI group,but the elevation was suppressed in TBI + intervention group.Meanwhile,Tau hyperphosphorylation (0.80 ± 1.00vs 1.24 ±0.13,P＜0.05) and GSK3 deactivation (3.01 ±0.41 vs 1.27 ±0.22,P ＜0.01) were significantly reversed in TBI + intervention group compared with TBI group.Conclusion Combination of tsUCMSCs and mild hypothermia therapy can improve the TBI-induced cognitive deficit. Key words: Craniocerebral trauma; Stem cells ; Cognition ; Mild hypothermia

The Centers for Disease Control and Prevention estimates that approximately 1.4 million US individuals sustain traumatic brain injuries (TBIs) per year. Previous reports suggest an association between TBI and chronic pain syndromes (eg, headache) thought to be more common in patients with mild TBI and in those who have sustained brain injury from violent rather than unintentional trauma. Comorbid psychiatric disorders such as posttraumatic stress disorder (PTSD) may also mediate chronic pain symptoms. To determine the prevalence of chronic pain as an underdiagnosed consequence of TBI and to review the interaction between chronic pain and severity of TBI as well as the characteristics of pain after TBI among civilians and combatants. The Ovid/MEDLINE database was searched for articles published between 1951 and February 2008 using any combination of the terms brain injury, pain, headache, blast injury, and combat (combat disorders, war, military medicine, wounds and injuries, military personnel, veterans). The PubMed and MD Consult databases were searched in a similar fashion. The Cochrane Collaboration, National Institutes of Health Clinical Trials Database, Meta-Register of Current Controlled Trials, and CRISP databases were searched using the keyword brain injury. All articles in peer-reviewed journals reporting original data on pain syndromes in adult patients with TBI with regard to pain prevalence, pain category, risk factors, pathogenesis, and clinical course were selected, and manual searches were performed of their reference lists. The data were pooled and prevalence rates calculated. Twenty-three studies (15 cross-sectional, 5 prospective, and 3 retrospective) including 4206 patients were identified. Twelve studies assessed headache pain in 1670 patients. Of these, 966 complained of chronic headache, yielding a prevalence of 57.8% (95% confidence interval [CI], 55.5%-60.2%). Among civilians, the prevalence of chronic pain was greater in patients with mild TBI (75.3% [95% CI, 72.7%-77.9%]) compared with moderate or severe TBI (32.1% [95% CI, 29.3%-34.9%]). Twenty studies including 3289 civilian patients with TBI yielded a chronic pain prevalence of 51.5% (95% CI, 49.8%-53.2%). Three studies assessed TBI among 917 veterans and yielded a pain prevalence of 43.1% (95% CI, 39.9%-46.3%). PTSD may mediate chronic pain, but brain injury appears to have an independent correlation with chronic pain. Chronic pain is a common complication of TBI. It is independent of psychologic disorders such as PTSD and depression and is common even among patients with apparently minor injuries to the brain.

Traumatic Brain Injury (TBI) is a major problem in military and civilian medicine. Yet, there are no simple non-invasive diagnostics for TBI. Our goal is to develop and clinically validate blood-based biomarker assays for the diagnosis, prognosis and management of mild, moderate and severe TBI patients. These assays will ultimately be suitable for deployment to far-forward combat environments. Using a proteomic and systems biology approach, we identified over 20 candidate biomarkers for TBI and developed robust ELISAs for at least 6 candidate biomarkers, including Ubiquitin C-terminal hydrolase- L1 (UCH-L1), Glial Fibrillary Acidic Protein (GFAP) and a 145 kDa breakdown products of &#945;II-spectrin (SBDP 145) generated by calpain proteolysis. In a multi-center feasibility study (Biomarker Assessment For Neurotrauma Diagnosis And Improved Triage System (BANDITS), we analyzed CSF and blood samples from 101 adult patients with severe TBI [Glasgow Coma Scale (GCS) &le; 8] at 6 sites and analyzed 27 mild TBI patients and 5 moderate TBI patients [GCS 9-15] from 2 sites in a pilot study. We identified that serum levels of UCH-L1, GFAP and SBDP145 have strong diagnostic and prognostic properties for severe TBI over controls. Similarly initial post-TBI serum levels (&lt; 6 h) of UCH-L1 and GFAP have diagnostic characteristics for moderate and mild TBI. We are now furthering assay production, refining assay platforms (both benchtop and point-ofcare/ handheld) and planning a pivotal clinical study to seek FDA approval of these TBI diagnostic assays.