Outcomes of traumatic brain injury in Hong Kong: Validation with the TRISS,CRASH, and IMPACT models

We aimed to test prognostic models (the Trauma Injury Severity Score, International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury, and Corticosteroid Randomisation After Significant Head Injury models) for 14-day mortality, 6-month mortality, and 6-month unfavorable outcome in a cohort of trauma patients with traumatic brain injury (TBI) in Hong Kong. We analyzed 661 patients with significant TBI treated in a regional trauma centre in Hong Kong over a 3-year period. The discriminatory power of the models was assessed as the area under the receiver operating characteristic curve. One-sample t-tests were used to compare actual outcomes in the cohort against predicted outcomes. All three prognostic models were shown to have good discriminatory power and no significant systemic over-estimation or under-estimation. In conclusion, all three predictive models are applicable to eligible TBI patients in Hong Kong. These predictive models can be utilized to audit TBI management outcomes for trauma service development in the future.     

The prognostic factors related to traumatic brain stem injury

Objective

This study was conducted to assess the clinical significance of traumatic brain stem injury (TBSI) reflected on Glasgow Coma Score (GCS) and Glasgow Outcome Score (GOS) by various clinical variables.

Methods

A total of 136 TBSI patients were selected out of 2695 head-injured patients. All initial computerized tomography and/or magnetic resonance imaging studies were retrospectively analyzed according to demographic- and injury variables which result in GCS and GOS.

Results

In univariate analysis, mode of injury showed a significant effect on combined injury (p<0.001), as were the cases with skull fracture on radiologic finding (p<0.000). The GCS showed a various correlation with radiologic finding (p<0.000), mode of injury (p<0.002), but less favorably with impact site (p<0.052), age (p<0.054) and skull fracture (p<0.057), in order of statistical significances. However, only GOS showed a definite correlation to radiologic finding (p<0.000). In multivariate analysis, the individual variables to enhance an unfavorable effect on GCS were radiologic finding [odds ratio (OR) 7.327, 95% confidence interval (CI)], mode of injury (OR; 4.499, 95% CI) and age (OR; 3.141, 95% CI). Those which influence an unfavorable effect on GOS were radiologic finding (OR; 25.420, 95% CI) and age (OR; 2.674, 95% CI).

Conclusion

In evaluation of TBSI on outcome, the variables such as radiological finding, mode of injury, and age were revealed as three important ones to have an unfavorable effect on early stage outcome expressed as GCS. However, mode of injury was shown not to have an unfavorable effect on late stage outcome as GOS. Among all unfavorable variables, radiological finding was confirmed as the only powerful prognostic variable both on GCS and GOS.     

The significant impact of Coronavirus disease 2019 (COVID-19) on in-hospital mortality of elderly patients with moderate to severe traumatic brain injury: A retrospective observational study

Background Traumatic brain injury (TBI) is one of the main causes of death and disability among the elderly patient population. This study aimed to assess the predictors of in-hospital mortality of elderly patients with moderate to severe TBI who presented during the Coronavirus disease 2019 (COVID-19) pandemic.MethodsIn this retrospective analytical study, all elderly patients with moderate to severe TBI who were referred to our center between March 2nd, 2020 to August 1st, 2020 were investigated and compared against the TBI patients receiving treatment during the same time period within the year 2019. Patients were followed until discharge from the hospital or death. The demographic, clinical, radiological, and laboratory test data were evaluated. Data were analyzed using SPSS-21 software.FindingsIn this study, 359 elderly patients were evaluated (n = 162, Post-COVID-19). Fifty-four patients of the cohort had COVID-19 disease with a mortality rate was 33.3%. The patients with COVID-19 were 5.45 times more likely to expire before discharge (P < 0.001) than the TBI patients who were not COVID-19 positive. Other variables such as hypotension (OR, 4.57P < 0.001), hyperglycemia (OR, 2.39, P = 0.002), and use of anticoagulant drugs (OR, 2.41P = 0.001) were also associated with in-hospital death. According to the binary logistic regression analysis Age (OR, 1.72; 95% CI: 1.26–2.18; P = 0.033), Coronavirus infection (OR, 2.21; 95% CI: 1.83–2.92; P = 0.011) and Glasgow Coma Scale (GCS) (OR, 3.11; 95% CI: 2.12–4.53; P < 0.001) were independent risk factors correlated with increased risk of in-hospital mortality of elderly patients with moderate to severe TBI.ConclusionOur results showed that Coronavirus infection could increase the risk of in-hospital mortality of elderly patients with moderate to severe TBI significantly.     

颅脑外伤合并视神经损伤的临床研究

目的探讨颅脑外伤合并视神经损伤的病因、诊疗方案及影响预后的相关因素分析。方法回顾性分析我院124例颅脑外伤合并视神经损伤的临床病例资料,总结其诊治方法并通过单因素分析(χ2)观察影响预后相关因素。结果124例患者经治疗后总有效率为70.31%。手术治疗有效率为60%,药物治疗有效率为71.56%。意识障碍、视神经管骨折与预后无相关性(P0.05)。光感、治疗时间及VEP波形与视力恢复情况明显相关(P0.05)。结论视神经损伤治疗疗效较差,但早期诊断和治疗后仍能取得良好效果,目前仍以药物治疗为主,对有手术指证的应早期行手术治疗,以提高患者生存质量。     

MR imaging in the detection of diffuse axonal injury with mild traumatic brain injury

Abstract

Purpose: To evaluate the occurrence and distribution of mild traumatic brain injury (MTBI) caused by diffuse axonal injury (DAI) using magnetic resonance (MR) imaging and to attempt to correlate MR findings with post-concussion symptoms (PCS).

Patients and methods: Forty MTBI patients (mean age: 32.5 years) with normal cranial computed tomography (CT) findings were examined with standard MR protocol including T₁-weighted, T₂-weighted, fluid attenuated inversion recovery (FLAIR), gradient echo (GRE) and diffusion-weighted (DW) sequences. MR imaging was performed within 24 hours of injury. The lesions were classified as DAI based on their location and morphologic appearance.

Results: In MR imaging of five (12.5%) of the patients, the lesions compatible with DAI were observed. Four patients (10%) had the foci of low signal intensity compatible with hemorrhagic shear injury on the GRE sequence, and five (12.5%) patients had high signal intensity on FLAIR and DW sequence.

Conclusion: MR imaging can be helpful in revealing DAI lesions in patients with normal CT scan findings after MTBI. FLAIR, GRE and DW sequences are superior to conventional spin-echo images in detecting DAI lesions.     

Experimental models of traumatic axonal injury

Traumatic brain injury (TBI) is one of the leading causes of death in people under 45 years of age worldwide. Such injury is characterized by a wide spectrum of mechanisms of injury and pathologies. Traumatic axonal injury (TAI), originally described as diffuse axonal injury, is one of the most common pathological features of TBI and is thought to be responsible for the long-lasting neurological impairments following TBI. Since the late 1980s a series of in vivo and in vitro experimental models of TAI have been developed to better understand the complex mechanisms of axonal injury and to define the relationship between mechanical forces and the structural and functional changes of injured axons. These models are designed to mimic as closely as possible the clinical condition of human TAI and have greatly improved our understanding of different aspects of TAI. The present review summarizes the most widely used experimental models of TAI. Focusing in particular on in vivo models, this survey aims to provide a broad overview of current knowledge and controversies in the development and use of the experimental models of TAI.     

Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury

Traumatic axonal injury (TAI) is thought to be a major contributor to cognitive dysfunction following traumatic brain injury (TBI), however TAI is difficult to diagnose or characterize non-invasively. Diffusion tensor imaging (DTI) has shown promise in detecting TAI, but direct comparison to histologically-confirmed axonal injury has not been performed. In the current study, mice were imaged with DTI, subjected to a moderate cortical controlled impact injury, and re-imaged 4-6 h and 24 h post-injury. Axonal injury was detected by amyloid beta precursor protein (APP) and neurofilament immunohistochemistry in pericontusional white matter tracts. The severity of axonal injury was quantified using stereological methods from APP stained histological sections. Two DTI parameters - axial diffusivity and relative anisotropy - were significantly reduced in the injured, pericontusional corpus callosum and external capsule, while no significant changes were seen with conventional MRI in these regions. The contusion was easily detectable on all MRI sequences. Significant correlations were found between changes in relative anisotropy and the density of APP stained axons across mice and across subregions spanning the spatial gradient of injury. The predictive value of DTI was tested using a region with DTI changes (hippocampal commissure) and a region without DTI changes (anterior commissure). Consistent with DTI predictions, there was histological detection of axonal injury in the hippocampal commissure and none in the anterior commissure. These results demonstrate that DTI is able to detect axonal injury, and support the hypothesis that DTI may be more sensitive than conventional imaging methods for this purpose.     

Prevalence and vascular risk factors of basal ganglia calcifications in patients at risk for cerebrovascular disease

Background and purposeRisk factors for and meaning of basal ganglia calcifications outside Fahr syndrome are poorly understood. We aimed to assess the prevalence of basal ganglia calcifications and the association with vascular risk factors.Materials and methods1133 patients suspected of acute ischemic stroke from the Dutch acute stroke (DUST) study who underwent thin-slice unenhanced brain CT were analyzed. Basal ganglia calcifications were scored bilaterally as absent, mild (dot), moderate (multiple dots or single artery) and severe (confluent). Uni- and multivariable logistic regression analysis was used to determine possible risk factors (age, gender, history of stroke, smoking, hypertension, diabetes mellitus, hyperlipidemia, body mass index (BMI), renal function and family history of cardiovascular disease under 60 years) for presence of basal ganglia calcifications and ordinal regression analysis for severity of basal ganglia calcifications.ResultsMean age was 67.4 years (SD: 13.8), 56.8% were male. 337 (29.7%) patients had basal ganglia calcifications, of which 196 (58%) were mild, 103 (31%) moderate, 38 (11%) severe. In multivariable logistic regression analysis, age (OR: 1.02, 95% CI 1.01–1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.91–0.98, p 0.01) were significantly associated with the presence of basal ganglia calcifications. Ordinal regression analysis gave comparable results. Age (OR: 1.02, 95% CI 1.01–1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.92–0.99, P 0.01) were significantly associated with severity of basal ganglia calcifications.ConclusionsIn this study with patients suspected of acute ischemic stroke, basal ganglia calcifications were common and significantly associated with older age and lower BMI.     

COMT Val158Met polymorphism is associated with post-traumatic stress disorder and functional outcome following mild traumatic brain injury

Mild traumatic brain injury (mTBI) results in variable clinical trajectories and outcomes. The source of variability remains unclear, but may involve genetic variations, such as single nucleotide polymorphisms (SNPs). A SNP in catechol-o-methyltransferase (COMT) is suggested to influence development of post-traumatic stress disorder (PTSD), but its role in TBI remains unclear. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val¹⁵⁸Met polymorphism is associated with PTSD and global functional outcome as measured by the PTSD Checklist – Civilian Version and Glasgow Outcome Scale Extended (GOSE), respectively. Results in 93 predominately Caucasian subjects with mTBI show that the COMT Met¹⁵⁸ allele is associated with lower incidence of PTSD (univariate odds ratio (OR) of 0.25, 95% CI [0.09–0.69]) and higher GOSE scores (univariate OR 2.87, 95% CI [1.20–6.86]) 6-months following injury. The COMT Val¹⁵⁸Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10–0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11–0.97]). PTSD emerged as a strong predictor of poorer outcome on GOSE (multivariable OR 0.09, 95% CI [0.03–0.26]), which persists after controlling for age, GCS, and race. When accounting for PTSD in multivariable analysis, the association of COMT genotype and GOSE did not remain significant (multivariable OR 1.73, 95% CI [0.69–4.35]). Whether COMT genotype indirectly influences global functional outcome through PTSD remains to be determined and larger studies in more diverse populations are needed to confirm these findings.     

Individuals with pain need more sleep in the early stage of mild traumatic brain injury

ObjectiveHypersomnia is frequently reported after mild traumatic brain injury (mTBI), but its cause(s) remain elusive. This study examined sleep/wake activity after mTBI and its association with pain, a comorbidity often associated with insomnia.MethodsActigraphy recording was performed for 7 ± 2 consecutive days in 56 individuals at one month post-mTBI (64% male; 38 ± 12 years), 24 individuals at one year post-mTBI (58% male; 44 ± 11years), and in 20 controls (50% male; 37 ± 12 years). Pain intensity and its effect on quality of life was assessed with a visual analogue scale and the Short Form Health Survey (SF-36) bodily pain subscale.ResultsOverall, few differences in sleep/wake patterns were found between mTBI patients and controls. However, higher percentages of mTBI individuals with moderate-to-severe pain were found to require more than eight hours of sleep per day (37% vs11%; p = 0.04) and to be frequent nappers (defined as those who took three or more naps per week) (42% vs 22%; p = 0.04) compared to those with mild or no pain at one month postinjury. Correcting for age and depression, The SF-36 score was found to be a significant predictor of sleep duration exceeding eight hours per day at one month (odds ratio = 0.95; 95% confidence interval = 0.92–0.99; p = 0.01), but not at one year post-mTBI. Pain and increased sleep need (in terms of hours per day or napping frequency) were found to co-exist in as much as 29% of mTBI patients at one month postinjury.ConclusionPain could be associated with more pronounced sleep need in about one-third of mTBI patients during early recovery. Unalleviated pain, found in more than 60% of mTBI patients, should therefore be looked for in all mTBI patients reporting new onset of sleep disorder, not only in those with insomnia.     

Cerebellar atrophy after severe traumatic head injury in children

Object: The purpose of this study was to describe late neuropathological MRI findings in pediatric severe head injury and to explore the relationship between these lesions and cognitive sequelae. Methods: Thirteen infants with severe head trauma (Glasgow 6) were included in this investigation. Clinical examination, a battery of tests designed to assess neurophysiological status, and MRI investigations of the brain were obtained in periods ranging between 8 and 20 months after the accident. Hemosiderin deposits, encephalomalacia, and cerebellar atrophy were the most frequent traumatic sequelae. The lesions were located in frontal lobes, the basal ganglia, and the cerebellum. Six patients had cerebellar atrophy associated with frontal or temporal postraumatic lesions. Cerebellar clinical dysfunction was observed in only 3 of these patients. Performance on tests evaluating frontal lobe functions was depressed in 5 of them. Conclusions: Late MRI after severe head trauma in our pediatric population showed unexpected cerebellar atrophy. Its correlation with prefrontal dysfunction is difficult to confirm because of its association with other parenchymal post-traumatic lesions. Further research involving a larger sample of patients with brain injury of varying severity is in progress, to investigate whether cerebellar atrophy could be a consequence of severe head trauma. Received: 25 May 2000 Revised: 4 July 2000     

S100B and Neuron-Specific Enolase as mortality predictors in patients with severe traumatic brain injury

Objective: To determine temporal profile and prognostic ability of S100B protein and neuron-specific enolase (NSE) for prediction of short/long-term mortality in patients suffering from severe traumatic brain injury (sTBI).

Methods: Ninety-nine patients with sTBI were included in the study. Blood samples were drawn on admission and on subsequent 24, 48, 72, and 96 h.

Results: 15.2% of patients died in NeuroCritical Care Unit, and 19.2% died within 6 months of the accident. S100B concentrations were significantly higher in patients who died compared to survivors. NSE levels were different between groups just at 48 h. In the survival group, S100B levels decreased from 1st to 5th sample (p < 0.001); NSE just from 1st to 3rd (p < 0.001) and then stabilized. Values of S100B and NSE in non-survival patients did not significantly vary over the four days post sTBI. ROC-analysis showed that all S100B samples were useful tools for predicting mortality, the best the 72 h sample (AUC 0.848 for discharge mortality, 0.855 for six-month mortality). NSE ROC-analysis indicated that just the 48-h sample predicted mortality (AUC 0.733 for discharge mortality, 0.720 for six-month mortality).

Conclusion: S100B protein showed higher prognostic capacity than NSE to predict short/long-term mortality in sTBI patients.     

Cardiac-cerebral-renal associations in pediatric traumatic brain injury: Preliminary findings

ObjectiveThe clinical epidemiology of organ outcomes in pediatric traumatic brain injury (TBI) has not been examined. We describe associated markers of cerebral, cardiac and renal injury after pediatric TBI.DesignProspective observational study.PatientsChildren 0–18 years who were hospitalized with TBI.MeasurementsMeasures of myocardial (at least one elevated plasma troponin [cTnI] ≥ 0.4 ng/ml) and multiorgan (hemodynamic variables, cerebral perfusion, and renal) function were examined within the first ten days of hospital admission and within 24 h of each other.Main ResultsData from 28 children who were 11[IQR 10.3] years, male (64.3%), with isolated TBI (67.9%), injury severity score (ISS) 25[10], and admission Glasgow coma score (GCS) 11[9] were examined. Overall, 50% (14 children) had elevated cTnI, including those with isolated TBI (57.9%; 11/19), polytrauma (33.3%; 3/9), mild TBI (57.1% 8/14), and severe TBI (42.9%; 6/11). Elevated cTnI occurred within the first six days of admission and across all age groups, in both sexes, and regardless of TBI lesion type, GCS, and ISS. Age-adjusted admission tachycardia was associated with cTnI elevation (AUC 0.82; p < 0.001). Reduced urine output occurred more commonly in patients with isolated TBI (27.3% elevated cTnI vs. 0% normal cTnI).ConclusionsMyocardial injury commonly occurs during the first six days after pediatric TBI irrespective of injury severity, age, sex, TBI lesion type, or polytrauma. Age-adjusted tachycardia may be a clinical indicator of myocardial injury, and elevated troponin may be associated with cardio-cerebro-renal dysfunction.     

Brain lesion correlates of fatigue in individuals with traumatic brain injury

ABSTRACT

The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N?=?53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N?=?36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants’ decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants’ error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.     

Head injury at early ages is associated with risk of Parkinson's disease

IntroductionThe literature on the effect of head injuries on the risk of PD is inconclusive. Some researchers have hypothesized that studies that have seen an effect are simply capturing injury related to pre-clinical PD. However in animal models brain inflammation, which can be initiated by head trauma, has been shown to produce PD-like effects. Furthermore, animal studies have found that early life inflammation in particular is of relevance for PD pathology.MethodsWe conducted an unmatched case–control study of 379 neurologist confirmed PD patients and 230 controls from the greater Boston, Massachusetts area with questionnaire data on history of head injury and other covariates. We used multivariable logistic regression to estimate adjusted odds ratios (OR) and their corresponding 95% confidence intervals (CI) for PD.ResultsWhen we excluded injuries that occurred less than 10 years prior to the diagnosis of PD (in order to avoid reverse causation), we found an increased risk of PD associated with a head injury that resulted in a loss of consciousness, but it did not reach statistical significance (OR = 1.57; 95% CI = 0.89–2.80). We found a significant (p = 0.04) effect of age at first head injury. For every 5 year earlier age at first head injury with loss of consciousness the OR for PD was 1.37 (95% CI: 1.01–1.86).ConclusionOur results suggest that head injury in early life increases the risk of PD.     

Demographics and clinical characteristics of acute traumatic brain injury patients in the different Neuroimaging Radiological Interpretation System (NIRIS) categories

PurposeTo characterize the demographics, clinical and imaging findings, and outcomes of traumatic brain injury (TBI) patients in each of NeuroImaging Radiological Interpretation System (NIRIS) categories.Material and methodsWe considered all consecutive patients transported to Stanford Hospital's emergency department by ambulance or helicopter between November 2015 and April 2017. We retained adult patients (> 18 years old) for whom a trauma alert was triggered and who underwent a non-contrast head computer tomography (CT) because of suspected TBI. We reviewed the non-contrast CT scans in these patients for the NIH TBI common data elements (CDEs). We recorded, then assessed differences in terms of demographics, clinical characteristics, imaging CDEs, and outcomes in patients from the different NIRIS categories.ResultsIn all, 1152 patients were included in this study. Patients with NIRIS 0 imaging findings were significantly younger than patients in other NIRIS categories (P < 0.001). Motor vehicle accidents and falls from height were the most common mechanisms of injury across NIRIS categories. GCS scores decreased with increasing NIRIS category imaging findings and were significantly lower in patients with NIRIS 4 imaging findings (P < 0.001). Significant differences in NIRIS categories were observed for all imaging CDEs (P < 0.001), in agreement with the definition of the different NIRIS categories. Mortality increased progressively with increasing NIRIS severity.ConclusionsTBI patients in different NIRIS categories have different clinical characteristics, hospital courses and outcomes. This natural history assessment of patients from different NIRIS categories could thus serve as a reference standard for future TBI clinical trials.     

Quantitative pupillometry in patients with traumatic brain injury and loss of consciousness: A prospective pilot study

ObjectiveLoss of consciousness (LOC) is a hallmark feature in Traumatic Brain Injury (TBI), and a strong predictor of outcomes after TBI. The aim of this study was to describe associations between quantitative infrared pupillometry values and LOC, intracranial hypertension, and functional outcomes in patients with TBI.MethodsWe conducted a prospective study of patients evaluated at a Level 1 trauma center between November 2019 and February 2020. Pupillometry values including the Neurological Pupil Index (NPi), constriction velocity (CV), and dilation velocity (DV) were obtained.ResultsThirty-six consecutive TBI patients were enrolled. The median (range) age was 48 (range 21–86) years. The mean Glasgow Coma Scale score on arrival was 11.8 (SD = 4.0). DV trichotomized as low (<0.5 mm/s), moderate (0.5–1.0 mm/s), or high (>1.0 mm/s) was significantly associated with LOC (P = .02), and the need for emergent intervention (P < .01). No significant association was observed between LOC and NPi (P = .16); nor between LOC and CV (P = .07).ConclusionsOur data suggests that DV, as a discrete variable, is associated with LOC in TBI. Further investigation of the relationship between discrete pupillometric variables and NPi may be valuable to understand the clinical significance of the pupillary light reflex findings in acute TBI.     

Hourly neurologic assessments for traumatic brain injury in the ICU

Abstract

Objectives: Hourly neurologic assessments for traumatic brain injury (TBI) in the critical care setting are common practice but prolonged use may actually be harming patients through sleep deprivation. We reviewed practice patterns at our institution in order to gain insight into the role of frequent neurological assessments.

Methods: A 6-month retrospective review was performed for patients who were admitted to an intensive care unit (ICU) with the diagnosis of TBI. Electronic medical records were reviewed based on billing codes. Variables collected included but were not limited to patient demographics, frequency of nursing neurologic evaluations, Glasgow coma scale (GCS), length of stay (LOS), and disposition.

Results: A total of 124 patients were identified, 71% male with the average age of 52 years (range 19–96). Traumatic brain injury was classified as severe in 44, moderate in 18, and mild in 62 patients. A total of 89 (71·8%) patients underwent hourly nursing assessments for an average of 2·82 days. The median LOS for all patients was 7 days (range 0–109). There were 18 patients who remained on hourly neurological assessments for greater than 4 days and had a greater LOS (23 days vs 9 days, P = 0·001). Only two patients required surgery after 48 hours, both for chronic subdural hematomas.

Discussion: Hourly neurologic checks are necessary in the acute period for patients with potentially expansible intracranial hemorrhages or malignant cerebral edema, but prolonged use may be harmful. Patients with a low probability of requiring neurosurgical intervention may benefit from reducing the total duration of hourly assessments.     

Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury

A prospective, multicenter, randomized trial did not demonstrate improved outcomes in severe traumatic brain injured patients treated with mild hypothermia [Clifton, G.L., Miller, E.R., Choi, S.C., Levin, H.S., McCauley, S., Smith, K.R., Jr., Muizelaar, J.P., Wagner, F.C., Jr., Marion, D.W., Luerssen, T.G., Chesnut, R.M., Schwartz, M., 2001. Lack of effect of induction of hypothermia after acute brain injury. N. Engl. J. Med. 344, 556-563.]. However, the mean time to target temperature was over 8 h and patient inclusion was based on Glasgow Coma Scale score so brain pathology was likely diverse. There remains significant interest in the benefits of hypothermia after traumatic brain injury (TBI) and, in particular, traumatic axonal injury (TAI), which is believed to significantly contribute to morbidity and mortality of TBI patients. The long-term beneficial effect of mild hypothermia on TAI has not been established. To address this issue, we developed an in vivo rat optic nerve stretch model of TAI. Adult male Sprague-Dawley rats underwent unilateral optic nerve stretch at 6, 7 or 8 mm piston displacement. The increased number of axonal swellings and bulbs immunopositive for non-phosphorylated neurofilament (SMI-32) seen four days after injury was statistically significant after 8 mm displacement. Ultrastructural analysis 2 weeks after 8 mm displacement revealed a 45.0% decrease (p < 0.0001) in myelinated axonal density in the optic nerve core. There was loss of axons regardless of axon size. Immediate post-injury hypothermia (32 °C) for 3 h reduced axonal degeneration in the core (p = 0.027). There was no differential protection based on axon size. These results support further clinical investigation of temporally optimized therapeutic hypothermia after traumatic brain injury.     

Failure to detect an association between self-reported traumatic brain injury and Alzheimer's disease neuropathology and dementia

IntroductionRecent research with neuropathologic or biomarker evidence of Alzheimer's disease (AD) casts doubt on traumatic brain injury (TBI) as a risk factor for AD. We leveraged the National Alzheimer's Coordinating Center to examine the association between self-reported TBI with loss of consciousness and AD neuropathologic changes, and with baseline and longitudinal clinical status.MethodsThe sample included 4761 autopsy participants (453 with remote TBI with loss of consciousness; 2822 with AD neuropathologic changes) from National Alzheimer's Coordinating Center.ResultsSelf-reported TBI did not predict AD neuropathologic changes (P > .10). Reported TBI was not associated with baseline or change in dementia severity or cognitive function in participants with or without autopsy-confirmed AD.DiscussionSelf-reported TBI with loss of consciousness may not be an independent risk factor for clinical or pathological AD. Research that evaluates number and severity of TBIs is needed to clarify the neuropathological links between TBI and dementia documented in other large clinical databases.