Early management of severe traumatic brain injury Rosenfeld, Jeffrey V, Prof; Maas, Andrew I, Prof; Bragge, Peter, PhD ...
The Lancet (British edition),
09/2012, Letnik:
380, Številka:
9847
Journal Article
Recenzirano
Severe traumatic brain injury remains a major health-care problem worldwide. Although major progress has been made in understanding of the pathophysiology of this injury, this has not yet led to ...substantial improvements in outcome. In this report, we address present knowledge and its limitations, research innovations, and clinical implications. Improved outcomes for patients with severe traumatic brain injury could result from progress in pharmacological and other treatments, neural repair and regeneration, optimisation of surgical indications and techniques, and combination and individually targeted treatments. Expanded classification of traumatic brain injury and innovations in research design will underpin these advances. We are optimistic that further gains in outcome for patients with severe traumatic brain injury will be achieved in the next decade.
Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker ...will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury TRACK-TBI). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve AUC 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended GOS-E threshold used). Our results support a role for multiple biomarker measurements in TBI research. ( ClinicalTrials.gov Identifier NCT01565551).
Traumatic brain injury (TBI) is among the leading causes of death and disability worldwide, with enormous negative social and economic impacts. The heterogeneity of TBI combined with the lack of ...precise outcome measures have been central to the discouraging results from clinical trials. Current approaches to the characterization of disease severity and outcome have not changed in more than three decades. This prospective multicenter observational pilot study aimed to validate the feasibility of implementing the TBI Common Data Elements (TBI-CDEs). A total of 650 subjects who underwent computed tomography (CT) scans in the emergency department within 24 h of injury were enrolled at three level I trauma centers and one rehabilitation center. The TBI-CDE components collected included: 1) demographic, social and clinical data; 2) biospecimens from blood drawn for genetic and proteomic biomarker analyses; 3) neuroimaging studies at 2 weeks using 3T magnetic resonance imaging (MRI); and 4) outcome assessments at 3 and 6 months. We describe how the infrastructure was established for building data repositories for clinical data, plasma biomarkers, genetics, neuroimaging, and multidimensional outcome measures to create a high quality and accessible information commons for TBI research. Risk factors for poor follow-up, TBI-CDE limitations, and implementation strategies are described. Having demonstrated the feasibility of implementing the TBI-CDEs through successful recruitment and multidimensional data collection, we aim to expand to additional study sites. Furthermore, interested researchers will be provided early access to the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data set for collaborative opportunities to more precisely characterize TBI and improve the design of future clinical treatment trials. (ClinicalTrials.gov Identifier NCT01565551.).
•Transient focal ischemia and reperfusion injury was produced by 1-h MCA occlusion followed by 23-h reperfusion.•Infarct volume and brain edema were greatly reduced in AQP4-deficient mice.•The ...neuroprotective effect of AQP4 deletion suggests the therapeutic utility of AQP4 inhibition in stroke.
Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood–brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-h transient MCAO produced by intraluminal suture blockade followed by 23h of reperfusion. In nine AQP4+/+ and nine AQP4−/− mice, infarct volume was significantly reduced by an average of 39±4% at 24h in AQP4−/− mice, cerebral hemispheric edema was reduced by 23±3%, and Evans Blue extravasation was reduced by 31±2% (mean±SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4−/− mice. The reduced infarct volume in AQP4−/− mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke.
The plural of an anecdote is not evidence, yet anecdotal international reports are accumulating from ear, nose, and throat (ENT) surgeons and other health-care workers on the front lines that ...anosmia, with or without dysgeusia, are symptoms frequently associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To further complicate matters, immediate self-recognition of olfactory dysfunction is typically only present in the most severe cases, or it is only self-identified after a prolonged latency period.1,2 A scarcity of acute-phase advanced neuroimaging studies, difficulties in obtaining histopathological tissue specimens, and an absence of viral cultures of infected olfactory neuroepithelium compound the difficulties in studying this phenomenon. ...in the context of normal trans-nasal airflow of odorant molecules (ie, no oedema in the nasal vault or olfactory cleft), and in the absence of intranasal disease (eg, infectious rhinosinusitis, allergic or vasomotor rhinitis, or polyposis), until now patients with sensorineural viral anosmia have been seldom seen in general otolaryngology practice—on the order of approximately one to two new-onset patients each year. ...up until the coronavirus disease 2019 (COVID-19) pandemic, the low prevalence of sensorineural viral anosmia in society as a whole has made clinical research challenging.
Blood-derived biomarkers for brain and spinal cord diseases are urgently needed. The introduction of highly sensitive immunoassays led to a rapid increase in the number of potential blood-derived ...biomarkers for diagnosis and monitoring of neurological disorders. In 2018, the FDA authorized a blood test for clinical use in the evaluation of mild traumatic brain injury (TBI). The test measures levels of the astrocytic intermediate filament glial fibrillary acidic protein (GFAP) and neuroaxonal marker ubiquitin carboxy-terminal hydrolase L1. In TBI, blood GFAP levels are correlated with clinical severity and extent of intracranial pathology. Evidence also indicates that blood GFAP levels hold the potential to reflect, and might enable prediction of, worsening of disability in individuals with progressive multiple sclerosis. A growing body of evidence suggests that blood GFAP levels can be used to detect even subtle injury to the CNS. Most importantly, the successful completion of the ongoing validation of point-of-care platforms for blood GFAP might ameliorate the decision algorithms for acute neurological diseases, such as TBI and stroke, with important economic implications. In this Review, we provide a systematic overview of the evidence regarding the utility of blood GFAP as a biomarker in neurological diseases. We propose a model for GFAP concentration dynamics in different conditions and discuss the limitations that hamper the widespread use of GFAP in the clinical setting. In our opinion, the clinical use of blood GFAP measurements has the potential to contribute to accelerated diagnosis and improved prognostication, and represents an important step forward in the era of precision medicine.
Objective
To determine the clinical relevance, if any, of traumatic intracranial findings on early head computed tomography (CT) and brain magnetic resonance imaging (MRI) to 3‐month outcome in mild ...traumatic brain injury (MTBI).
Methods
One hundred thirty‐five MTBI patients evaluated for acute head injury in emergency departments of 3 LEVEL I trauma centers were enrolled prospectively. In addition to admission head CT, early brain MRI was performed 12 ± 3.9 days after injury. Univariate and multivariate logistic regression were used to assess for demographic, clinical, socioeconomic, CT, and MRI features that were predictive of Extended Glasgow Outcome Scale (GOS‐E) at 3 months postinjury.
Results
Twenty‐seven percent of MTBI patients with normal admission head CT had abnormal early brain MRI. CT evidence of subarachnoid hemorrhage was associated with a multivariate odds ratio of 3.5 (p = 0.01) for poorer 3‐month outcome, after adjusting for demographic, clinical, and socioeconomic factors. One or more brain contusions on MRI, and ≥4 foci of hemorrhagic axonal injury on MRI, were each independently associated with poorer 3‐month outcome, with multivariate odds ratios of 4.5 (p = 0.01) and 3.2 (p = 0.03), respectively, after adjusting for head CT findings and demographic, clinical, and socioeconomic factors.
Interpretation
In this prospective multicenter observational study, the clinical relevance of abnormal findings on early brain imaging after MTBI is demonstrated. The addition of early CT and MRI markers to a prognostic model based on previously known demographic, clinical, and socioeconomic predictors resulted in a >2‐fold increase in the explained variance in 3‐month GOS‐E. ANN NEUROL 2013;73:224–235
Seizures are important neurological complications after traumatic brain injury (TBI) and are reported for up to 50% of patients with TBI. Despite several studies, no drug strategy has been able to ...alter the biological events leading to epileptogenesis. The glial water channel, aquaporin-4 (AQP4), was shown to facilitate cytotoxic cell swelling in ischemia and glial scar formation after stab wound injury. In this study, we examined post-traumatic seizure susceptibility of AQP4-deficient mice (AQP4
) after injection of pentylenetetrazole (PTZ) 1 month after controlled cortical impact (CCI) and compared them to wild-type sham injury controls. After PTZ injection, AQP4
mice demonstrated dramatically shortened seizure latency (120 ± 40 vs. 300 ± 70 sec;
< 0.001) and increased seizure severity (grade 7.5 ± 0.4 vs. 5.8 ± 0.4;
< 0.001) compared to their wild-type counterparts. Morphometric analysis demonstrated a significant 2-fold reduction in astrocytosis, with a concomitant increase in microgliosis in injured AQP4-null mice compared to their injured wild-type counterparts (44 ± 2 vs. 24 ± 3 cells per high power field cells/hpf, respectively;
< 0.0001). Minocycline, an inhibitor of microglia, reversed the post-TBI epilepsy phenotype of AQP4-null mice. After minocycline treatment, AQP4
mice demonstrated similar latency of seizures evoked by PTZ (723 ± 35 vs. 696 ± 38 sec;
> 0.05) and severity of seizures evoked by PTZ (grade 4.0 ± 0.5 vs. 3.81 ± 0.30;
> 0.05) compared to wild-type counterparts. Immunohistochemical analysis demonstrated decreased immunostaining of microglia to levels comparable to wild-type (12 ± 2 vs. 11 ± 4 cells/hpf, respectively;
> 0.05). Taken together, these results suggest a protective role of AQP4 in post-traumatic seizure susceptibility by promoting astrogliosis, formation of a glial scar, and preventing microgliosis.
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