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Lansdell Theresa A. Fisher Courtney Simmonds Kent Reeves Mat J. Woo Daniel Dorrance Anne M. Demel Stacie L. 《Neurogenetics》2019,20(2):83-89
neurogenetics - Intracranial aneurysms (IA) are weakened outpouchings of the arterial wall in the cerebrovasculature. Rupture of an IA often leads to devastating consequences. The early... 相似文献
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J. Fisher L. Krisa D.M. Middleton B.E. Leiby J.S. Harrop L.M. Shah E.D. Schwartz A. Doshi S.H. Faro F.B. Mohamed A.E. Flanders 《AJNR. American journal of neuroradiology》2021,42(4):787
BACKGROUND AND PURPOSE:The National Institute of Neurological Disorders and Stroke common data elements initiative was created to provide a consistent method for recording and reporting observations related to neurologic diseases in clinical trials. The purpose of this study is to validate the subset of common data elements related to MR imaging evaluation of acute spinal cord injury.MATERIALS AND METHODS:Thirty-five cervical and thoracic MR imaging studies of patients with acute spinal cord injury were evaluated independently in 2 rounds by 5 expert reviewers. Intra- and interrater agreement were calculated for 17 distinct MR imaging observations related to spinal cord injury. These included ordinal, categoric, and continuous measures related to the length and location of spinal cord hemorrhage and edema as well as spinal canal and cord measurements. Level of agreement was calculated using the interclass correlation coefficient and kappa.RESULTS:The ordinal common data elements spinal cord injury elements for lesion center and rostral or caudal extent of edema or hemorrhage demonstrated agreement ranging from interclass correlation coefficient 0.68 to 0.99. Reproducibility ranged from 0.95 to 1.00. Moderate agreement was observed for absolute length of hemorrhage and edema (0.54 to 0.60) with good reproducibility (0.78 to 0.83). Agreement for the Brain and Spinal Injury Center score showed the lowest interrater agreement with an overall kappa of 0.27 (0.20, 0.34). For 7 of the 8 variables related to spinal cord injury, agreement improved between the first and second evaluation. Continuous diameter measures of the spinal cord and spinal canal using interclass correlation coefficient varied substantially (0.23 to 0.83).CONCLUSIONS:Agreement was more consistent for the ordinal measures of spinal cord injury than continuous measures. Good to excellent agreement on length and location of spinal cord hemorrhage and edema can be achieved with ordinal measures alone.In 2006, the National Institute of Neurological Disorders and Stroke (NINDS) began a process to develop common data elements (CDEs) to provide a standardized method for the collection of clinical data related to neurologic diseases.1-3 Recognizing that there is a lack of clear and consistent terminology for spine disorders, particularly spinal cord injury (SCI), in 2014, the NINDS convened a workgroup comprising expert stakeholders for the development of SCI CDE instruments that included clinical care assessments and imaging.3-8 This new set of SCI CDE instruments aimed to increase the efficiency and value of clinical research studies and treatment, increase data quality, facilitate data sharing, and help educate new clinical investigators.3 Investigators are expected to incorporate the CDE modules in grant applications and National Institutes of Health–funded research.The MR imaging SCI CDE subset was created to be a comprehensive and standardized terminology for describing MR imaging findings in patients with SCI. This collection consists of a case report form (CRF) containing 35 discrete measures and responses divided into 4 main categories: general imaging characteristics, spinal injury features, canal and cord measurements, and chronic SCI features. The responses are of 3 types: Boolean, categoric, and an ordinal range representing specific anatomic locations. These measures were chosen to represent both objective and subjective assessment derived from routine clinical MR images. The workgroup codified these features using existing CDEs that have proved value in the published literature, and when ones did not exist, the workgroup developed the feature and the response parameters.As with the development of any CRF used for a clinical trial or research, the goal is to provide an instrument that provides useful data representations that are reproducible across trained observers and institutions, require minimal cognitive effort, minimize ambiguity, and are both accurate and precise. Reproducibility of the observations through rigorous testing by multiple observers is a needed step to validate the instrument before clinical or research use. However, the evaluation process may not entirely reproduce the clinical environment in which it is meant to be used such that datasets and observers are overly prepared or optimized. Therefore, the goal of this study is to determine the inter- and intrarater reliability of the NINDS MR imaging CDEs when assessed by MR imaging experts with familiarity with SCI. We hypothesize that there will be good to excellent agreement (kappa >0.4) among the expert raters after limited training. 相似文献
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John M. Ringman Yuchuan Qiao Alexander Garbin Beth E. Fisher Brent Fogel Kecia Watari Knoell 《Neurocase》2020,26(5):299-304
ABSTRACT We report a patient with autism-like deficits in emotional connectedness, executive dysfunction, and ataxia beginning at age 39. He had compound heterozygous variants in SPG7 (A510V and 1552+1 G>T substitutions), mutation of which is classically associated with spastic paraparesis. Diffusion MRI demonstrated abnormalities in the cerebellar outflow tracts. Transcranial magnetic stimulation showed a prolonged cortical silent period representing exaggerated cortical inhibition, as previously described with pure cerebellar degeneration. The acquired cerebellar cognitive affective syndrome in association with specific anatomic and neurophysiological abnormalities in the cerebellum expand the spectrum of SPG7-related neurodegeneration and support a role for cerebellar output in socio-emotional behavior. 相似文献
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Regulator of G protein signaling (RGS) proteins are gatekeepers regulating the cellular responses induced by G protein-coupled receptor (GPCR)-mediated activation of heterotrimeric G proteins. Specifically, RGS proteins determine the magnitude and duration of GPCR signaling by acting as a GTPase-activating protein for Gα subunits, an activity facilitated by their semiconserved RGS domain. The R7 subfamily of RGS proteins is distinguished by two unique domains, DEP/DHEX and GGL, which mediate membrane targeting and stability of these proteins. RGS6, a member of the R7 subfamily, has been shown to specifically modulate Gαi/o protein activity which is critically important in the central nervous system (CNS) for neuronal responses to a wide array of neurotransmitters. As such, RGS6 has been implicated in several CNS pathologies associated with altered neurotransmission, including the following: alcoholism, anxiety/depression, and Parkinson’s disease. In addition, unlike other members of the R7 subfamily, RGS6 has been shown to regulate G protein-independent signaling mechanisms which appear to promote both apoptotic and growth-suppressive pathways that are important in its tumor suppressor function in breast and possibly other tissues. Further highlighting the importance of RGS6 as a target in cancer, RGS6 mediates the chemotherapeutic actions of doxorubicin and blocks reticular activating system (Ras)-induced cellular transformation by promoting degradation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) to prevent its silencing of pro-apoptotic and tumor suppressor genes. Together, these findings demonstrate the critical role of RGS6 in regulating both G protein-dependent CNS pathology and G protein-independent cancer pathology implicating RGS6 as a novel therapeutic target. 相似文献
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