Risk factors of recurrence in chronic subdural hematoma and a proposed extended classification of internal architecture as a predictor of recurrence.

Chronic subdural hematomas (cSDHs) constitute one of the most prevalent intracranial disease entities requiring surgical treatment. Although mostly taking a benign course, recurrence after treatment is common and associated with additional morbidity and costs. Aim of this study was to develop hematoma-specific characteristics associated with risk of recurrence. All consecutive patients treated for cSDH in a single university hospital between 2015 and 2019 were retrospectively considered for inclusion. Size, volume, and midline shift were noted alongside relevant patient-specific factors. We applied an extended morphological classification system based on internal architecture in CT imaging consisting of eight hematoma subtypes. A logistic regression model was used to assess the classification's performance on predicting hematoma recurrence. Recurrence was observed in 122 (32.0%) of 381 included patients. Apart from postoperative depressed brain volume (OR 1.005; 95% CI 1.000 to 1.010; p = 0.048), neither demographic nor factors related to patient comorbidity affected recurrence. The extended hematoma classification was identified as a significant predictor of recurrence (OR 1.518; 95% CI 1.275 to 1.808; p < 0.001). The highest recurrence rates were observed in hematomas of the homogenous (isodense: 41.4%; hypodense: 45.0%) and sedimented (50.0%) types. Our results support that internal architecture subtypes might represent stages in the natural history of chronic subdural hematoma. Detection and treatment at a later stage of spontaneous repair can result in a reduced risk of recurrence. Based on their high risk of recurrence, we advocate follow-up after treatment of sedimented and homogenous hematomas.

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride.

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs-nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)-might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.

Seizure after surgical treatment of chronic subdural hematoma-Associated factors and effect on outcome.

Introduction: Chronic subdural hematoma (cSDH) is becoming more prevalent due to population aging and the increasing use of antithrombotic drugs. Postoperative seizure in cSDH have a negative effect on outcome, and there currently no consensus regarding prophylactic anti-epileptic drug (AED) treatment. The objective of this study was to evaluate predisposing and triggering factors associated with postoperative epileptic seizure in patients with cSDH. Methods: All patients, who were surgically treated for cSDH in a single tertiary care center between 2015 and 2019, were considered for inclusion. Relevant patient- and hematoma-specific characteristics were retrospectively extracted from hospital records. Paroxysmal events categorized by the treating physician as suspected postoperative seizures were noted. The clinical outcome was extracted from the last available follow-up visit and classified according to the Glasgow outcome scale (GOS). Results: Of the included 349 patients, 54 (15.5%) developed suspected postoperative epileptic complications in the form of early seizure (≤ 7 days) in 11 patients (3.2%) and late seizure (>7 days) in 43 patients (12.3%). In the logistic regression analysis, solely depressed brain volume (supratentorial volume (ml) not filled with re-expanded brain) was independently associated with postoperative seizure (odds ratio [OR] 1.006, 95% CI: 1.001-1.011; p = 0.034). The occurrence of postoperative seizure (OR 6.210, 95% CI: 2.704-14.258; p < 0.001) and preoperative Markwalder grading (OR 2.919, 95% CI: 1.538-5.543; p = 0.001) were independently associated with unfavorable (GOS1-3) outcome. Conclusion: Larger postoperative depressed brain volume was the only factor independently associated with suspected postoperative seizure, and it could help identify a subgroup of patients with higher susceptibility to epileptic events. Based on our data, no formal recommendation can be made regarding the prophylactic use of anti-epileptic drugs. Nevertheless, the relative safety of new generation AEDs and the detrimental effect of postoperative seizure on outcome may justify its use in a selected patient population.

A Retrospective Analysis of Randomized Controlled Trials on Traumatic Brain Injury: Evaluation of CONSORT Item Adherence.

Traumatic brain injury (TBI) contributes to death and disability, resulting in an enormous individual and socio-economic challenges. Despite huge efforts, there are still controversies on treatment strategies and early outcome estimation. We evaluate current randomized controlled trials (RCTs) on TBI according to their fulfillment of the CONSORT (Consolidated Statement of Reporting Trials) statement's criteria as a marker of transparency and the quality of study planning and realization. A PubMed search for RCTs on TBI (January 2014-December 2019) was carried out. After screening of the abstracts (n = 1.926), the suitable full text manuscripts (n = 72) were assessed for the fulfillment of the CONSORT criteria. The mean ratio of consort statement fulfillment was 59% (±13%), 31% of the included studies (n = 22) complied with less than 50% of the CONSORT criteria. Citation frequency was moderately related to ratio of CONSORT item fulfillment (r = 0.4877; p < 0.0001) and citation frequency per year (r = 0.5249; p < 0.0001). The ratio of CONSORT criteria fulfillment was associated with the impact factor of the publishing journal (r = 0.6428; p < 0.0001). Essential data for study interpretation, such as sample size determination (item 7a), participant flow (item 13a) as well as losses and exclusions (item 13b), were only reported in 53%, 60% and 63%, respectively. Reporting and methodological aspects in RCTs on TBI still may be improved. Thus, the interpretation of study results may be hampered due to methodological weaknesses.

Argon treatment after experimental subarachnoid hemorrhage: evaluation of microglial activation and neuronal survival as a subanalysis of a randomized controlled animal trial.

Hereinafter, we evaluate argon's neuroprotective and immunomodulatory properties after experimental subarachnoid hemorrhage (SAH) examining various localizations (hippocampal and cortical regions) with respect to neuronal damage and microglial activation 6, 24 and 72 hours after SAH. One hour after SAH (endovascular perforation rat model) or sham surgery, a mixture of gas containing 50% argon (argon group) or 50% nitrogen (control group) was applied for 1 hour. At 6 hours after SAH, argon reduced neuronal damage in the hippocampal regions in the argon group compared to the control group (P < 0.034). Hippocampal microglial activation did not differ between the treatment groups over time. The basal cortical regions did not show a different lesion pattern, but microglial activation was significantly reduced in the argon group 72 hours after SAH (P = 0.034 vs. control group). Whereas callosal microglial activation was significantly reduced at 24 hours in the argon-treated group (P = 0.018). Argon treatment ameliorated only early hippocampal neuronal damage after SAH. Inhibition of microglial activation was seen in some areas later on. Thus, argon may influence the microglial inflammatory response and neuronal survival after SAH; however, due to low sample sizes the interpretation of our results is limited. The study protocol was approved by the Government Agency for Animal Use and Protection (Protocol number: TVA 10416G1; initially approved by the "Landesamt für Natur, Umwelt und Verbraucherschutz NRW," Recklinghausen, Germany, on April 28, 2009).

A 6-Step Approach to Gain Higher Quality Results From Organotypic Hippocampal Brain Slices in a Traumatic Brain Injury Model.

Introduction: Organotypic Hippocampal Brain Slices (OHBS) provide an advantageous alternative to in vivo models to scrutinize Traumatic Brain Injury (TBI). We followed a well-established TBI protocol, but noticed that several factors may influence the results in such a setup. Here, we describe a structured approach to generate more comparable results and discuss why specific eligibility criteria should be applied. Methods: We defined necessary checkpoints and developed inclusion and exclusion criteria that take the observed variation in such a model into consideration. Objective measures include the identification and exclusion of pre-damaged slices and outliers. Six steps were outlined in this study. Results: A six-step approach to enhance comparability is proposed and summarized in a flowchart. We applied the suggested measures to data derived from our TBI-experiments examining the impact of three different interventions in 1459 OHBS. Our exemplary results show that through equal requirements set for all slices more precise findings are ensured. Conclusion: Results in a TBI experiment on OHBS should be analyzed critically as inhomogeneities may occur. In order to ensure more precise findings, a structured approach of comparing the results should be followed. Further research is recommended to confirm and further develop this framework.

Argon attenuates the emergence of secondary injury after traumatic brain injury within a 2-hour incubation period compared to desflurane: an in vitro study.

Despite years of research, treatment of traumatic brain injury (TBI) remains challenging. Considerable data exists that some volatile anesthetics might be neuroprotective. However, several studies have also revealed a rather neurotoxic profile of anesthetics. In this study, we investigated the effects of argon 50%, desflurane 6% and their combination in an in vitro TBI model with incubation times similar to narcotic time slots in a daily clinical routine. Organotypic hippocampal brain slices of 5- to 7-day-old mice were cultivated for 14 days before TBI was performed. Slices were eventually incubated for 2 hours in an atmosphere containing no anesthetic gas, argon 50% or desflurane 6% or both. Trauma intensity was evaluated via fluorescent imagery. Our results show that neither argon 50% nor desflurane 6% nor their combination could significantly reduce the trauma intensity in comparison to the standard atmosphere. However, in comparison to desflurane 6%, argon 50% displayed a rather neuroprotective profile within the first 2 hours after a focal mechanical trauma (P = 0.015). A 2-hour incubation in an atmosphere containing both gases, argon 50% and desflurane 6%, did not result in significant effects in comparison to the argon 50% group or the desflurane 6% group. Our findings demonstrate that within a 2-hour incubation time neither argon nor desflurane could affect propidium iodide-detectable cell death in an in vitro TBI model in comparison to the standard atmosphere, although cell death was less with argon 50% than with desflurane 6%. The results show that within this short time period processes concerning the development of secondary injury are already taking place and may be manipulated by argon.

Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled Animal Trial.

OBJECTIVE: The neuroprotective properties of the noble gas xenon have already been demonstrated using a variety of injury models. Here, we examine for the first time xenon's possible effect in attenuating early brain injury (EBI) and its influence on posthemorrhagic microglial neuroinflammation in an in vivo rat model of subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats (n = 22) were randomly assigned to receive either Sham surgery (n = 9; divided into two groups) or SAH induction via endovascular perforation (n = 13, divided into two groups). Of those randomized for SAH, 7 animals were postoperatively ventilated with 50 vol% oxygen/50 vol% xenon for 1 h and 6 received 50 vol% oxygen/50 vol% nitrogen (control). The animals were sacrificed 24 h after SAH. Of each animal, a cerebral coronal section (-3.60 mm from bregma) was selected for assessment of histological damage 24 h after SAH. A 5-point neurohistopathological severity score was applied to assess neuronal cell damage in H&E and NeuN stained sections in a total of four predefined anatomical regions of interest. Microglial activation was evaluated by a software-assisted cell count of Iba-1 stained slices in three cortical regions of interest. RESULTS: A diffuse cellular damage was apparent in all regions of the ipsilateral hippocampus 24 h after SAH. Xenon-treated animals presented with a milder damage after SAH. This effect was found to be particularly pronounced in the medial regions of the hippocampus, CA3 (p = 0.040), and dentate gyrus (DG p = 0.040). However, for the CA1 and CA2 regions, there were no statistical differences in neuronal damage according to our histological scoring. A cell count of activated microglia was lower in the cortex of xenon-treated animals. This difference was especially apparent in the left piriform cortex (p = 0.017). CONCLUSION: In animals treated with 50 vol% xenon (for 1 h) after SAH, a less pronounced neuronal damage was observed for the ipsilateral hippocampal regions CA3 and DG, when compared to the control group. In xenon-treated animals, a lower microglial cell count was observed suggesting an immunomodulatory effect generated by xenon. As for now, these results cannot be generalized as only some hippocampal regions are affected. Future studies should assess the time and localization dependency of xenon's beneficial properties after SAH.