Development of a core measurement set for research in degenerative cervical myelopathy: a study protocol (AO Spine RECODE-DCM CMS)

Introduction
Progress in degenerative cervical myelopathy (DCM) is hindered by inconsistent measurement and reporting. This impedes data aggregation and outcome comparison across studies. This limitation can be reversed by developing a core measurement set (CMS) for DCM research. Previously, the AO Spine Research Objectives and Common Data Elements for DCM (AO Spine RECODE-DCM) defined ‘what’ should be measured in DCM: the next step of this initiative is to determine ‘how’ to measure these features. This protocol outlines the steps necessary for the development of a CMS for DCM research and audit.

Methods and analysis
The CMS will be developed in accordance with the guidance developed by the Core Outcome Measures in Effectiveness Trials and the Consensus-based Standards for the selection of health Measurement Instruments. The process involves five phases. In phase 1, the steering committee agreed on the constructs to be measured by sourcing consensus definitions from patients, professionals and the literature. In phases 2 and 3, systematic reviews were conducted to identify tools for each construct and aggregate their evidence. Constructs with and without tools were identified, and scoping reviews were conducted for constructs without tools. Evidence on measurement properties, as well as on timing of assessments, are currently being aggregated. These will be presented in phase 4: a consensus meeting where a multi-disciplinary panel of experts will select the instruments that will form the CMS. Following selection, guidance on the implementation of the CMS will be developed and disseminated (phase 5). A preliminary CMS review scheduled at 4 years from release.

Ethics and dissemination
Ethical approval was obtained from the University of Cambridge (HBREC2019.14). Dissemination strategies will include peer-reviewed scientific publications; conference presentations; podcasts; the identification of AO Spine RECODE-DCM ambassadors; and engagement with relevant journals, funders and the DCM community.

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Giugno 2022

Abstract TP238: Optogenetic Stimulation Of Cortico-thalamic Circuits Promotes Oligodendrogenesis In The Degenerative Thalamus After Stroke

Stroke, Volume 53, Issue Suppl_1, Page ATP238-ATP238, February 1, 2022. Introduction:Loss of neuronal activity after stroke can impact many activity-dependent processes including oligodendrocyte maturation and myelination. The cortico-thalamic circuit is particularly disrupted after cortical stroke, resulting in secondary axonal degeneration in the thalamus. This secondary thalamic injury is associated with worsened functional outcomes. Increasing neuronal activity by optogenetic stimulation promotes oligodendrogenesis and myelination in normal conditions. In this study, we use optogenetic stimulation to selectively re-activate the cortico-thalamic circuit after stroke and examine its effects on oligodendrocytes in the degenerative thalamus.Methods:C57BL6 male mice (6-8 weeks old) were injected AAV1-CaMKIIa-hChR2 virus in the ipsilesional somatosensory cortex and implanted an optic fiber in the ipsilesional thalamus. After six weeks, the left middle cerebral artery was permanently occluded to generate infarct in iS1. Stimulated mice were given daily optogenetic stimulations between Post-stroke Day (PD) 4 to 14. Brain sections were immunostained to detect primary cortical injury and secondary thalamic injury (NeuN), and neuroinflammation (CD68) and oligodendrogenesis (Olig2 and CC1) in the thalamus.Results:ChR2 is specifically expressed in the somatosensory cortico-thalamic tract. Neuronal loss and robust neuroinflammation were observed in iTH after stroke, but there was no significant difference between non-stimulated and stimulated mice. However, stimulated mice exhibited 5.5 times increase in the numbers of mature oligodendrocytes (Olig2+CC1+, p=0.02, n=5/group), and 5.4 times increase in the numbers of oligodendrocyte progenitor cells (Olig2+, p=0.03) in the degenerative thalamus.Conclusion:Our data demonstrate that selective re-activation of the cortical-thalamic circuits promoted oligodendrogenesis in the secondary degenerative thalamus after stroke. As the secondary thalamic injury allows an extended treatment window, targeting secondary injury is a promising approach to improve stroke recovery. Current studies are testing the effects of cortico-thalamic circuit stimulation in myelination in the degenerative thalamus and functional outcome after stroke.

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Febbraio 2022