Poor outcome in frail elderly patient after severe TBI

OBJECTIVE: To investigate the influence of frailty in elderly with severe TBI on mortality and functional outcome.METHOD: 126 patients with TBI aged 60 years or older and with a presenting Glasgow Coma Scale score of 8 or lower were retrospectively included. To investigate frailty, we used the CSHA Clinical Frailty Scale. The primary outcome measures were mortality, and the secondary outcome measures were Glasgow Outcome Scale Extended (GOSE) at discharge and GOSE at 6 months after trauma.RESULTS: High frailty was a significant predictor for mortality (OR 2.38, p 0.047), if adjusted for the injury severity scale. High frailty was also a significant predictor for poor functional outcome after 6 months (OR 4.35, p 0.03). After 6 months, the GOSE of the low frailty group was significantly higher than in the high frailty group (p 0.019). Also, the improvement of the GOSE was significant in the low frailty group (p 0.007), while in the high frailty group there was no significant improvement of the GOSE (p 0.546) after 6 months.CONCLUSION: Frailty has a significant impact on outcome in elderly with severe TBI. There is a higher mortality in the frail elderly and there is less recovery after TBI.</p

Risk of Intracranial Complications in Minor Head Injury:The Role of Loss of Consciousness and Post-Traumatic Amnesia in a Multi-Center Observational Study

Various guidelines for minor head injury focus on patients with a Glasgow Coma Scale (GCS) score of 13-15 and loss of consciousness (LOC) or post-traumatic amnesia (PTA), while clinical management for patients without LOC or PTA is often unclear. We aimed to investigate the effect of presence and absence of LOC or PTA on intracranial complications in minor head injury. A prospective multi-center cohort study of all patients with blunt head injury and GCS score of 15 was conducted at six Dutch centers between 2015 and 2017. Five centers used the national guideline and one center used a local guideline-both based on the CT in Head Injury Patients (CHIP) prediction model-to identify patients in need of a computed tomography (CT) scan. We studied the presence of traumatic findings and neurosurgical interventions in patients with and without LOC or PTA. In addition, we assessed the association of LOC and PTA with traumatic findings with logistic regression analysis and the additional predictive value of LOC and PTA compared with other risk factors in the CHIP model. Of 3914 patients, 2249 (58%) experienced neither LOC nor PTA and in 305 (8%) LOC and PTA was unknown. Traumatic findings were present in 153 of 1360 patients (11%) with LOC or PTA and in 67 of 2249 patients (3%) without LOC and PTA. Five patients without LOC and PTA had potential neurosurgical lesions and one patient underwent a neurosurgical intervention. LOC and PTA were strongly associated with traumatic findings on CT, with adjusted odds ratios of 2.9 (95% confidence interval [CI] 2.2-3.8) and 3.5 (95% CI 2.7-4.6), respectively. To conclude, patients who had minor head injury with neither LOC nor PTA are at risk of intracranial complications. Clinical guidelines should include clinical management for patients without LOC and PTA, and they should include LOC and PTA as separate risk factors rather than as diagnostic selection criteria

Update of the CHIP (CT in Head Injury Patients) decision rule for patients with minor head injury based on a multicenter consecutive case series

OBJECTIVE: To update the existing CHIP (CT in Head Injury Patients) decision rule for detection of (intra)cranial findings in adult patients following minor head injury (MHI).METHODS: The study is a prospective multicenter cohort study in the Netherlands. Consecutive MHI patients of 16 years and older were included. Primary outcome was any (intra)cranial traumatic finding on computed tomography (CT). Secondary outcomes were any potential neurosurgical lesion and neurosurgical intervention. The CHIP model was validated and subsequently updated and revised. Diagnostic performance was assessed by calculating the c-statistic.RESULTS: Among 4557 included patients 3742 received a CT (82%). In 383 patients (8.4%) a traumatic finding was present on CT. A potential neurosurgical lesion was found in 73 patients (1.6%) with 26 (0.6%) patients that actually had neurosurgery or died as a result of traumatic brain injury. The original CHIP underestimated the risk of traumatic (intra)cranial findings in low-predicted-risk groups, while in high-predicted-risk groups the risk was overestimated. The c-statistic of the original CHIP model was 0.72 (95% CI 0.69-0.74) and it would have missed two potential neurosurgical lesions and one patient that underwent neurosurgery. The updated model performed similar to the original model regarding traumatic (intra)cranial findings (c-statistic 0.77 95% CI 0.74-0.79, after crossvalidation c-statistic 0.73). The updated CHIP had the same CT rate as the original CHIP (75%) and a similar sensitivity (92 versus 93%) and specificity (both 27%) for any traumatic (intra)cranial finding. However, the updated CHIP would not have missed any (potential) neurosurgical lesions and had a higher sensitivity for (potential) neurosurgical lesions or death as a result of traumatic brain injury (100% versus 96%).CONCLUSIONS: Use of the updated CHIP decision rule is a good alternative to current decision rules for patients with MHI. In contrast to the original CHIP the update identified all patients with (potential) neurosurgical lesions without increasing CT rate.</p

A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches

Non-steroidal anti-inflammatory drugs (NSAIDs) that act as cyclo-oxygenase (COX) inhibitors are commonly used in the treatment of a range of headache disorders, although their mechanism of action is unclear. Indomethacin is of particular interest given its very special effect in some primary headaches. Here the in vivo technique of intravital microscopy in rats has been utilised as a model of trigeminovascular nociception to study the potential mechanism of action of indomethacin. Dural vascular changes were produced using electrical (neurogenic) dural vasodilation (NDV), calcitonin gene-related peptide (CGRP) induced dural vasodilation and nitric oxide (NO) induced dural vasodilation using NO donors. In each of these settings the effect of intravenously administered indomethacin (5 mg kg−1), naproxen (30 mg kg−1) and ibuprofen (30 mg kg−1) was tested. All of the tested drugs significantly inhibited NDV (between 30 and 52%). Whilst none of them was able to inhibit CGRP-induced dural vasodilation, only indomethacin reduced NO induced dural vasodilation (35 ± 7%, 10 min post administration). We conclude NSAIDs inhibit release of CGRP after NDV without an effect on CGRP directly. Further we describe a differentiating effect of indomethacin inhibiting nitric oxide induced dural vasodilation that is potentially relevant to understanding its unique action in disorders such as paroxysmal hemicrania and hemicrania continua

Antidromic vasodilatation and the migraine mechanism

Despite the fact that an unprecedented series of new discoveries in neurochemistry, neuroimaging, genetics and clinical pharmacology accumulated over the last 20 years has significantly increased our current knowledge, the underlying mechanism of the migraine headache remains elusive. The present review article addresses, from early evidence that emerged at the end of the nineteenth century, the role of ‘antidromic vasodilatation’ as part of the more general phenomenon, currently defined as neurogenic inflammation, in the unique type of pain reported by patients suffering from migraine headaches. The present paper describes distinctive orthodromic and antidromic properties of a subset of somatosensory neurons, the vascular- and neurobiology of peptides contained in these neurons, and the clinical–pharmacological data obtained in recent investigations using provocation tests in experimental animals and human beings. Altogether, previous and recent data underscore that antidromic vasodilatation, originating from the activation of peptidergic somatosensory neurons, cannot yet be discarded as a major contributing mechanism of the throbbing head pain and hyperalgesia of migraine

Brain death and postmortem organ donation: Report of a questionnaire from the CENTER-TBI study

Background: We aimed to investigate the extent of the agreement on practices around brain death and postmortem organ donation. Methods: Investigators from 67 Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study centers completed several questionnaires (response rate: 99%). Results: Regarding practices around brain death, we found agreement on the clinical evaluation (prerequisites and neurological assessment) for brain death determination (BDD) in 100% of the centers. However, ancillary tests were required for BDD in 64% of the centers. BDD for nondonor patients was deemed mandatory in 18% of the centers before withdrawing life-sustaining measures (LSM). Also, practices around postmortem organ donation varied. Organ donation after circulatory arrest was forbidden in 45% of the centers. When withdrawal of LSM was contemplated, in 67% of centers the patients with a ventricular drain in situ had this removed, either sometimes or all of the time. Conclusions: This study showed both agreement and some regional differences regarding practices around brain death and postmortem organ donation. We hope our results help quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation

How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study

Background The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. Methods We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75-224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). Conclusion We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.Peer reviewe