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The Role of Neuroimaging in the Determination of Brain Death.

ABSTRACT: Brain death determination (BDD) is primarily a clinical diagnosis, where death is defined as the permanent loss of brainstem function. In scenarios where clinical examinations are inaccurate, ancillary imaging tests are required. The choice of ancillary imaging test is variable, but the common denominator for all of them is to establish a lack of cerebral blood flow. The purpose of this study was to compare the diagnostic accuracy and interrater reliability of different ancillary imaging tests used for BDD.Archival data were retrospectively analyzed for all patients who underwent any ancillary imaging test for BDD at our institution. The results of ancillary imaging tests were compared with, the reference standard, the clinical checklist for declaration of brain death. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different ancillary imaging tests for BDD were performed. Interobserver agreement between two observers was measured using kappa statistics for each of the imaging modalities.A total of 74 patients underwent 41 computer tomography perfusion (CTP), 54 CT angiogram, 15 radionuclide scans, 1 cerebral angiogram, 3 magnetic resonance imaging, and 71 nonenhanced CT (NECT) head for BDD. All ancillary tests (except NECT head) showed 100% specificity and PPV. CTP had the highest sensitivity and NPV. All ancillary imaging tests demonstrated very high interrater reliability.The uses of ancillary imaging tests for BDD are increasing. Within this study's limitations, CTP followed by radionuclide scan were found to be the most accurate and reliable ancillary imaging test for BDD.

SUBMITTER: MacDonald D

PROVIDER: S-EPMC6055878 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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The Role of Neuroimaging in the Determination of Brain Death.

MacDonald Derek D Stewart-Perrin Brandie B Shankar Jai Jai Shiva JJS

Journal of neuroimaging : official journal of the American Society of Neuroimaging 20180511 4

<h4>Background and purpose</h4>Brain death determination (BDD) is primarily a clinical diagnosis, where death is defined as the permanent loss of brainstem function. In scenarios where clinical examinations are inaccurate, ancillary imaging tests are required. The choice of ancillary imaging test is variable, but the common denominator for all of them is to establish a lack of cerebral blood flow. The purpose of this study was to compare the diagnostic accuracy and interrater reliability of diff ...[more]

PMID: 29749664

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Project description:Genetic variants in the human leukocyte antigen and killer cell immunoglobulin-like receptor regions have been associated with many brain-related diseases, but how they shape brain structure and function remains unclear. To identify the genetic variants in HLA and KIR genes associated with human brain phenotypes, we performed a genetic association study of ∼30 000 European unrelated individuals using brain MRI phenotypes generated by the UK Biobank (UKB). We identified 15 HLA alleles in HLA class I and class II genes significantly associated with at least one brain MRI-based phenotypes (P < 5 × 10-8). These associations converged on several main haplotypes within the HLA. In particular, the human leukocyte antigen alleles within an ancestral haplotype 8.1 were associated with multiple MRI measures, including grey matter volume, cortical thickness (TH) and diffusion MRI (dMRI) metrics. These alleles have been strongly associated with schizophrenia. Additionally, associations were identified between HLA-DRB1*04∼DQA1*03:01∼DQB1*03:02 and isotropic volume fraction of diffusion MRI in multiple white matter tracts. This haplotype has been reported to be associated with Parkinson's disease. These findings suggest shared genetic associations between brain MRI biomarkers and brain-related diseases. Additionally, we identified 169 associations between the complement component 4 (C4) gene and imaging phenotypes. We found that C4 gene copy number was associated with cortical TH and dMRI metrics. No KIR gene copy numbers were associated with image-derived phenotypes at genome-wide threshold. To address the multiple testing burden in the phenome-wide association study, we performed a multi-trait association analysis using trait-based association test that uses extended Simes procedure and identified MRI image-specific associations. This study contributes to insight into how critical immune genes affect brain-related traits as well as the development of neurological and neuropsychiatric disorders.

Project description:BackgroundBrain stem cardiovascular regulatory dysfunction during brain death is underpinned by an upregulation of nitric oxide synthase II (NOS II) in rostral ventrolateral medulla (RVLM), the origin of a life-and-death signal detected from blood pressure of comatose patients that disappears before brain death ensues. Furthermore, the ubiquitin-proteasome system (UPS) may be involved in the synthesis and degradation of NOS II. We assessed the hypothesis that the UPS participates in brain stem cardiovascular regulation during brain death by engaging in both synthesis and degradation of NOS II in RVLM.Methodology/principal findingsIn a clinically relevant experimental model of brain death using Sprague-Dawley rats, pretreatment by microinjection into the bilateral RVLM of proteasome inhibitors (lactacystin or proteasome inhibitor II) antagonized the hypotension and reduction in the life-and-death signal elicited by intravenous administration of Escherichia coli lipopolysaccharide (LPS). On the other hand, pretreatment with an inhibitor of ubiquitin-recycling (ubiquitin aldehyde) or ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1) potentiated the elicited hypotension and blunted the prevalence of the life-and-death signal. Real-time polymerase chain reaction, Western blot, electrophoresis mobility shift assay, chromatin immunoprecipitation and co-immunoprecipitation experiments further showed that the proteasome inhibitors antagonized the augmented nuclear presence of NF-?B or binding between NF-?B and nos II promoter and blunted the reduced cytosolic presence of phosphorylated I?B. The already impeded NOS II protein expression by proteasome inhibitor II was further reduced after gene-knockdown of NF-?B in RVLM. In animals pretreated with UCH-L1 inhibitor and died before significant increase in nos II mRNA occurred, NOS II protein expression in RVLM was considerably elevated.Conclusions/significanceWe conclude that UPS participates in the defunct and maintained brain stem cardiovascular regulation during experimental brain death by engaging in both synthesis and degradation of NOS II at RVLM. Our results provide information on new therapeutic initiatives against this fatal eventuality.

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The Role of Neuroimaging in the Determination of Brain Death.

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The Role of Neuroimaging in the Determination of Brain Death.

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