ObjectComplement activation has been suggested to play a role in the development of secondary injuries following traumatic brain injury (TBI). The present study was initiated in order to analyze complement activation in relation to the primary brain injury and to secondary insults, frequently occurring following TBI.MethodsTwenty patients suffering from severe TBI (Glasgow coma score ≤8) were included in the study. The “membrane attack complex,” C5b9, which is the cytolytic end product of the complement system was analyzed in cerebrospinal fluid (CSF). The degree of brain tissue damage was assessed using the release of S100B and neuron-specific enolase (NSE) to the CSF and blood. The blood–brain barrier was assessed using the CSF/serum quotient of albumin (QA).ResultsFollowing impact, initial peaks (0–48 h) of C5b9, S100B, and NSE with a concomitant loss of integrity of the blood–brain barrier were observed. Secondary insults at the intensive care unit were monitored. Severe secondary insults were paralleled by a more pronounced complement activation (C5b9 in CSF) as well as increased levels of S100B (measured in CSF), but not with NSE.ConclusionThis human study indicates that complement activation in the brain is triggered not only by the impact of trauma per se but also by the amount of secondary insults that frequently occur at the scene of accident as well as during treatment in the neurointensive care unit. Complement activation and in particular the end product C5b9 may in turn contribute to additional secondary brain injuries by its membrane destructive properties.
Lumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10−12) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH.
This paper illustrates the feasibility and utility of combining cranial anatomy and brain function on the same 3D-printed model, as evidenced by a neurosurgical planning case study of a 29-year-old female patient with a low-grade frontal-lobe glioma. We herein report the rapid prototyping methodology utilized in conjunction with surgical navigation to prepare and plan a complex neurosurgery. The method introduced here combines CT and MRI images with DTI tractography, while using various image segmentation protocols to 3D model the skull base, tumor, and five eloquent fiber tracts. This 3D model is rapid-prototyped and coregistered with patient images and a reported surgical navigation system, establishing a clear link between the printed model and surgical navigation. This methodology highlights the potential for advanced neurosurgical preparation, which can begin before the patient enters the operation theatre. Moreover, the work presented here demonstrates the workflow developed at the National University Hospital of Iceland, Landspitali, focusing on the processes of anatomy segmentation, fiber tract extrapolation, MRI/CT registration, and 3D printing. Furthermore, we present a qualitative and quantitative assessment for fiber tract generation in a case study where these processes are applied in the preparation of brain tumor resection surgery.
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