358 The relationship between serum biomarkers of traumatic brain injury (TBI) and magnetic resonance imaging (MRI) in patients discharged from the emergency department (ED) with a normal acute CT

Aims/Objectives/BackgroundCT remains the neuroimaging of choice in patients with TBI, however the relative lack of sensitivity as compared to MRI for certain traumatic lesion types, including diffuse axonal injury (DAI), could lead to missing important intracranial findings.1 Serum biomarkers may allow screening of ED patients, highlighting those who will benefit from MRI and offer a pathway for further imaging in mild TBI patients.Methods/DesignPatients discharged from ED with a panel of 6 biomarkers (GFAP, NFL, NSE, S100B, t-tau and UCH-L1), acute CT < 24 hrs of injury and acute MRI, were extracted from the CENTER-TBI core dataset.2 Mann Whitney U test to compare median biomarker levels in relation to +ve or –ve MRI. Unadjusted Area Under ROC (AUC) calculated for detection of MRI abnormality.Results/Conclusions80 patients met inclusion criteria, 45 (56%) male, median age 36.5 yr [IQR 24.5–51.3], median GCS 15 [IQR 15–15]. 17/80 (21.25%) had MRI abnormalities. 1 intraventricular haemorrhage, 2 traumatic subarachnoid haemorrhages, 3 intraparenchymal haemorrhages and 13 DAI. Of the biomarkers (median): GFAP (0.28 vs 1.88 ng/ml, p = 0.002), NSE (13.08 vs 15.19 ng/ml, p= 0.013), S100B (0.06 vs 0.12 µg/L, p=0.002), t-tau (0.82 vs 1.58 pg/ml, p=0.002), UCH-L1 (22.33 vs 57.68 pg/ml p<0.001) were significantly raised in patients with MRI abnormality. Serum NFL concentration was not significant (5.80 vs 8.18 pg/ml, p=0.096). AUC [95% CI] for detection of MRI abnormality: GFAP (0.75 [0.61–0.89]), NFL (0.63 [0.48–0.79]), NSE (0.70 [0.55–0.85]), S100B (0.75 [0.61–0.90]), tau (0.75 [0.61–0.89]), UCH-L1 (0.82 [0.69–0.95])The results demonstrate potential utility in several acute serum biomarkers for screening of patients with a negative CT. Fair discrimination for detection of MRI pathology in this cohort was demonstrated by GFAP, NSE, S100B, total tau and UCH-L1. Further prospective analysis is required to assess the utility for biomarkers to determine MRI requirement in an ED population.ReferencesMetting Z, Rödiger LA, De Keyser J, et al. Structural and functional neuroimaging in mild-to-moderate head injury. Lancet Neurol 2007;6:699–710. doi:10.1016/S1474-4422(07)70191-6Maas AIR, Menon DK, Steyerberg EW, et al. Collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI): A prospective longitudinal observational study. Neurosurgery 2015;76:67–80. doi:10.1227/NEU.0000000000000575

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361 The relationship between intracranial MRI abnormalities and post-concussive symptoms in ED patients with a normal CT: as demonstrated on the Rivermead Post Concussion Symptom Questionnaire (RPQ)

Emergency Medicine Journal ◽

10.1136/emj-2020-rcemabstracts.35 ◽

2020 ◽

Vol 37 (12) ◽

pp. 842.2-842

Author(s):

Daniel Whitehouse ◽

Sophie Richter ◽

Stefan Winzeck ◽

Evgenios N Kornaropoulos ◽

Tilak Das ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Diffuse Axonal Injury ◽

Quantitative Mri ◽

List Type ◽

Mri Findings ◽

Number Of Patients ◽

Significant Difference ◽

Prospective Longitudinal

Aims/Objectives/BackgroundMild traumatic brain injury (TBI) is common presentation to the ED. Mild, however, is a misnomer with 10–40% of patients suffering from post-concussion symptoms for months to years following injury.1 2Patients often re-present to primary care or ED with these symptoms, and the role of repeat imaging in this cohort remains uncertain. Aims: assess TBI patients discharged from the ED with no acute intracranial findings on CT head scan, who subsequently had a research-driven MRI and documented 3-month RPQ, to determine the association between ongoing post-concussion symptoms and MRI pathology.Methods/Design91 patients in the CENTER-TBI dataset met the inclusion criteria.3 Mann-Whitney U test used to compare 3-month RPQ and MRI findings. Numbers and percentages of patients with RPQ >35 and >19 presented owing to a score of 35 predicting moderate to severe activity limitation,4 and 19 representing mean RPQ in patients with diagnosed post-concussion syndrome (PCS).2Results/Conclusions15/91 CT-ve (16.5%) patients had abnormalities on acute MRI (2 intraparenchymal haemorrhages, 13 Diffuse Axonal Injury (DAI)). No significant difference between median 3 month RPQ between MRI -ve (2.00 [IQR 0.00 – 14.00] and MRI +ve (0.00 [IQR 0.00 – 8.50]) patients (p=0.51, Mann-Whitney U test). Of patients with a RPQ >35, only 1/8 (12.5%) had a +ve MRI. Of patients with a RPQ >19 2/14 (14.3%) had +ve MRI, both DAI.No difference was found between RPQ scores of MRI positive and negative patients, suggesting no significant relationship between ongoing symptomology following mild TBI and gross MRI findings in patients with a negative acute CT. This study is limited by a small number of patients with positive neuroimaging and a lack of quantitative MRI data. Further prospective research is required to assessing a larger patient cohort and more sensitive imaging modalities to examine the utility of repeat neuroimaging in patients with ongoing concussive symptoms.ReferencesPolinder S, Cnossen MC, Real RGL, et al. A multidimensional approach to post-concussion symptoms in mild traumatic brain injury. Front. Neurol 2018;9:1113. doi:10.3389/fneur.2018.01113Ingebrigtsen T, Waterloo K, Marup-Jensen S, et al. Quantification of post-concussion symptoms 3 months after minor head injury in 100 consecutive patients. J Neurol 1998;245:609–12. doi:10.1007/s004150050254Maas AIR, Menon DK, Steyerberg EW, et al. Collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI): A prospective longitudinal observational study. Neurosurgery 2015;76:67–80. doi:10.1227/NEU.0000000000000575De Guise E, Bélanger S, Tinawi S, et al. Usefulness of the rivermead postconcussion symptoms questionnaire and the trail-making test for outcome prediction in patients with mild traumatic brain injury. Appl Neuropsychol 2016;23:213–22. doi:10.1080/23279095.2015.1038747

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Monitoring of brain interstitial total tau and beta amyloid proteins by microdialysis in patients with traumatic brain injury

Journal of Neurosurgery ◽

10.3171/2008.9.jns08584 ◽

2009 ◽

Vol 110 (6) ◽

pp. 1227-1237 ◽

Cited By ~ 77

Author(s):

Niklas Marklund ◽

Kaj Blennow ◽

Henrik Zetterberg ◽

Elisabeth Ronne-Engström ◽

Per Enblad ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Axonal Injury ◽

Diffuse Axonal Injury ◽

Enzyme Linked Immunosorbent Assay ◽

Focal Lesion ◽

Intracerebral Microdialysis ◽

Metabolic Markers ◽

Total Tau ◽

T Tau

Object Damage to axons contributes to postinjury disabilities and is commonly observed following traumatic brain injury (TBI). Traumatic brain injury is an important environmental risk factor for the development of Alzheimer disease (AD). In the present feasibility study, the aim was to use intracerebral microdialysis catheters with a high molecular cutoff membrane (100 kD) to harvest interstitial total tau (T-tau) and amyloid beta 1–42 (Aβ42) proteins, which are important biomarkers for axonal injury and for AD, following moderate-to-severe TBI. Methods Eight patients (5 men and 3 women) were included in the study; 5 of the patients had a focal/mixed TBI and 3 had a diffuse axonal injury (DAI). Following the bedside analysis of the routinely measured energy metabolic markers (that is, glucose, lactate/pyruvate ratio, glycerol, and glutamate), the remaining dialysate was pooled and two 12-hour samples per day were used to analyze T-tau and Aβ42 by enzyme-linked immunosorbent assay from Day 1 up to 8 days postinjury. Results The results show high levels of interstitial T-tau and Aβ42 postinjury. Patients with a predominantly focal lesion had higher interstitial T-tau levels than in the DAI group from Days 1 to 3 postinjury (p < 0.05). In contrast, patients with DAI had consistently higher Aβ42 levels when compared with patients with focal injury. Conclusions These results suggest that monitoring of interstitial T-tau and Aβ42 by using microdialysis may be an important tool when evaluating the presence and role of axonal injury following TBI.

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Age, Sex and Cerebral Microbleed Effects On White Matter Degradation After Traumatic Brain Injury

Innovation in Aging ◽

10.1093/geroni/igaa057.3272 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 886-887

Author(s):

Andrei Irimia ◽

Ammar Dharani ◽

Van Ngo ◽

David Robles ◽

Kenneth Rostowsky

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Diffusion Tensor ◽

Diffuse Axonal Injury ◽

Principal Component ◽

Older Age ◽

Analysis Of Covariance ◽

Future Research ◽

Cerebral Microbleed

Abstract Mild traumatic brain injury (mTBI) affects white matter (WM) integrity and accelerates neurodegeneration. This study assesses the effects of age, sex, and cerebral microbleed (CMB) load as predictors of WM integrity in 70 subjects aged 18-77 imaged acutely and ~6 months after mTBI using diffusion tensor imaging (DTI). Two-tensor unscented Kalman tractography was used to segment and cluster 73 WM structures and to map changes in their mean fractional anisotropy (FA), a surrogate measure of WM integrity. Dimensionality reduction of mean FA feature vectors was implemented using principal component (PC) analysis, and two prominent PCs were used as responses in a multivariate analysis of covariance. Acutely and chronically, older age was significantly associated with lower FA (F2,65 = 8.7, p < .001, η2 = 0.2; F2,65 = 12.3, p < .001, η2 = 0.3, respectively), notably in the corpus callosum and in dorsolateral temporal structures, confirming older adults’ WM vulnerability to mTBI. Chronically, sex was associated with mean FA (F2,65 = 5.0, p = 0.01, η2 = 0.1), indicating males’ greater susceptibility to WM degradation. Acutely, a significant association was observed between CMB load and mean FA (F2,65 = 5.1, p = 0.009, η2 = 0.1), suggesting that CMBs reflect the acute severity of diffuse axonal injury. Together, these findings indicate that older age, male sex, and CMB load are risk factors for WM degeneration. Future research should examine how sex- and age-mediated WM degradation lead to cognitive decline and connectome degeneration after mTBI.

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Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury

Journal of Neurosurgery Pediatrics ◽

10.3171/2015.10.peds15554 ◽

2016 ◽

Vol 17 (6) ◽

pp. 739-755 ◽

Cited By ~ 21

Author(s):

Shenandoah Robinson ◽

Jesse L. Winer ◽

Justin Berkner ◽

Lindsay A. S. Chan ◽

Jesse L. Denson ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Diffusion Tensor ◽

Elevated Serum ◽

Serum Biomarkers ◽

Receptor Expression ◽

Acute Injury ◽

Chronic Injury ◽

Western Blots ◽

Targeted Interventions

OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1–4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13–28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst–like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNFα p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13–16 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16–23 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13–P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats. CONCLUSIONS Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial–compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement.

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#3104 Is dipsogenic diabetes insipidus the same condition as psychogenic polydipsia?

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-bnpa.27 ◽

2021 ◽

Vol 92 (8) ◽

pp. A11.2-A11

Author(s):

Ewelina de Leon ◽

Graeme Yorston

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Head Injury ◽

Literature Review ◽

Diabetes Insipidus ◽

Endocrine Disruption ◽

Psychiatric Disease ◽

List Type ◽

Psychogenic Polydipsia

Objectives/AimsTraumatic brain injury is a common cause of permanent or long-term disability,1 and up to 80% of people with moderate to severe brain injury have some degree of pituitary insufficiency. Endocrine disruption has been documented in medical literature since the 1940s,2-4 where central diabetes insipidus has been described as a common transient complication which causes polydipsia (insatiable thirst). However, polydipsia can be caused by other conditions. It is classified into dipsogenic, in a syndrome of disordered thirst-regulating mechanism in patients without psychiatric disease called dipsogenic diabetes insipidus, psychogenic, as a compulsive water drinking in patients with psychiatric conditions referred to as psychogenic polydipsia or psychogenic diabetes insipidus and iatrogenic where large quantities of water are consumed for health benefits. All of which are referred to as primary polydipsia if these conditions cannot be distinguished. Dipsogenic diabetes insipidus and psychogenic polydipsia can be easily mixed up, misdiagnosed or even unrecognised, mainly because their pathophysiology is still unclear. Are these conditions different, or is there anything that can relate them to each other? With this literature review, we are aiming to find the link between subsets of polydipsia after brain trauma, to compare proposed differential diagnosis and their functionality in clinical settings.MethodA literature review was conducted following a search of MEDLINE, CINAHL Plus, APA PsycArticles, APA PsycBooks, APA PsycInfo databases from 1858 onwards.ResultsWe will present our findings from the literature review.ConclusionPolydipsia is a common clinical problem and requires careful evaluation and management to prevent long term neurological sequelae, and there are no evidence-based treatment guidelines.References National Institute of Health and Care Excellence (NICE). (2019). Head Injury. CG176. Retrieved from: https://www.nice.org.uk/guidance/cg176 Escamilla RF, Lisser H. Simmonds disease: A clinical study with revie of the literature; Differentiation from anorexia nervosa by statistical analysis of 595 cases, 101 of which were provided pathologically. The Journal of Clinical Endocrinology & Metabolism 1942;2(2):6596. Porter RJ, Miller RA. Diabetes insipidus following closed head injury. Journal of Neurology, Neurosurgery, and Psychiatry 1946;11:528562. Webb NE, Little B, Loupee-Wilson S, Power EM. Traumatic brain injury and neuro-endocrine disruption: medical and psychosocial rehabilitation. NeuroRehabilitation (Reading, Mass.) 2014;34(4):625636.

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Traumatic Brain Injury Caused by Motor Vehicle Collision and Alcoholism in Piauí

Arquivos Brasileiros de Neurocirurgia Brazilian Neurosurgery ◽

10.1055/s-0036-1583935 ◽

2016 ◽

Vol 37 (03) ◽

pp. 174-181

Author(s):

Benjamim Vale ◽

Juçara Castro ◽

Marx Araújo ◽

Herb Morais ◽

Lívio Macêdo

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Motor Vehicle ◽

Care Service ◽

Diffuse Axonal Injury ◽

Total Sample ◽

Motor Vehicle Collision ◽

Alcoholic Beverages ◽

Trauma Patients ◽

Vehicle Collision

Objectives To determine the relationship between alcohol consumption and the incidence of traumatic brain injury (TBI) with diffuse axonal injury (DAI), determining these indices, checking acquired comorbidities and characterizing the patients by gender, age and race/color, as well as describing the characteristics of the motor vehicle collision (vehicle, period of the day, day of the week and site) in people admitted to an emergency hospital in the city of Teresina, in the state of Piauí, Brazil. Methods We have analyzed the data contained in the medical records of patients admitted with a history of motor vehicle collision and severe TBI in intensive care units, based on the forms provided by the Mobile Emergency Care Service (SAMU, in the Portuguese acronym) in the period between February 28 and November 28, 2013. Results In the period covered by the present study, 200 individuals were analyzed, and 54 (27%) had consumed alcohol; of these 11 had DAI. Of the total sample, 17% (34) presented DAI, however, with unknown data regarding the consumption of alcoholic beverages. Conclusion Considering the data, we observed that the profile of the head trauma patients are brown men, mostly (53.5%) aged between 15 and 30 years. The collisions occurred mostly on weekends and at night (55%), and 89.5% of the crashes involved motorcycles.

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Clinical application of magnetic resonance in acute traumatic brain injury

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2008000100013 ◽

2008 ◽

Vol 66 (1) ◽

pp. 53-58 ◽

Cited By ~ 12

Author(s):

Dionei F. Morais ◽

Antonio R. Spotti ◽

Waldir A. Tognola ◽

Felipe F.P. Gaia ◽

Almir F. Andrade

Keyword(s):

Traumatic Brain Injury ◽

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Magnetic Resonance ◽

Subdural Hematoma ◽

Diffuse Axonal Injury ◽

Correlation Method ◽

Acute Subdural Hematoma ◽

Acute Traumatic Brain Injury ◽

Magnetic Resonance Imaging Mri

PURPOSE: To evaluate the clinical applications of magnetic resonance imaging (MRI) in patients with acute traumatic brain injury (TBI): to identify the type, quantity, severity; and improvement clinical-radiological correlation. METHOD: Assessment of 55 patients who were imaged using CT and MRI, 34 (61.8%) males and 21 (38.2%) females, with acute (0 to 5 days) and closed TBI. RESULTS: Statistical significant differences (McNemar test): ocurred fractures were detected by CT in 29.1% and by MRI in 3.6% of the patients; subdural hematoma by CT in 10.9% and MRI in 36.4 %; diffuse axonal injury (DAI) by CT in 1.8% and MRI in 50.9%; cortical contusions by CT in 9.1% and MRI in 41.8%; subarachnoid hemorrhage by CT in 18.2% and MRI in 41.8%. CONCLUSION: MRI was superior to the CT in the identification of DAI, subarachnoid hemorrhage, cortical contusions, and acute subdural hematoma; however it was inferior in diagnosing fractures. The detection of DAI was associated with the severity of acute TBI.

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The Use of a Cellular Strain Injury Criterion and Diffusion Tensor Imaging in a Computational Model of Traumatic Brain Injury

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19562 ◽

2010 ◽

Author(s):

Rika M. Wright ◽

K. T. Ramesh

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mechanical Loading ◽

Computational Models ◽

Diffusion Tensor ◽

Diffuse Axonal Injury ◽

Element Model ◽

Cellular Level ◽

Cellular Injury ◽

Injury Mechanisms

With the increase in the number of soldiers sustaining traumatic brain injury from military incidents and the recent attention on sports related traumatic brain injury, there has been a focused effort to develop preventative and treatment methods for traumatic brain injury (TBI). Traumatic brain injury is caused by mechanical loading to the head, such as from impacts, sudden accelerations, or blast loading, and the pathology can range from focal damage in the brain to widespread diffuse injury [1]. In this study, we investigate the injury mechanisms of diffuse axonal injury (DAI), which accounts for the second largest percentage of deaths due to brain trauma [2]. DAI is caused by sudden inertial loads to the head, and it is characterized by damage to neural axons. Despite the extensive research on DAI, the coupling between the mechanical loading to the head and the damage at the cellular level is still poorly understood. Unlike previous computational models that use macroscopic stress and strain measures to determine injury, a cellular injury criterion is used in this work as numerous studies have shown that cellular strain can be related to the functional damage of neurons. The effectiveness of using this cellular injury criterion to predict damage in a finite element model of DAI is investigated.

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