Neurology and neurorehabilitation
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Research outputs from the Neurology department at the RD&E.
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Item Adenylyl Cyclase in Ocular Health and Disease: A Comprehensive Review(MDPI, 2024-06-01) Thompson, P.; Vilkelyte, V.; Woronkowicz, M.; Tavakoli, M.; Skopinski, P.; Roberts, H.Adenylyl cyclases (ACs) are a group of enzymes that convert adenosine-5'-triphosphate (ATP) to cyclic adenosine 3',5' monophosphate (cAMP), a vital and ubiquitous signalling molecule in cellular responses to hormones and neurotransmitters. There are nine transmembrane (tmAC) forms, which have been widely studied; however, the tenth, soluble AC (sAC) is less extensively characterised. The eye is one of the most metabolically active sites in the body, where sAC has been found in abundance, making it a target for novel therapeutics and biomarking. In the cornea, AC plays a role in endothelial cell function, which is vital in maintaining stromal dehydration, and therefore, clarity. In the retina, AC has been implicated in axon cell growth and survival. As these cells are irreversibly damaged in glaucoma and injury, this molecule may provide focus for future therapies. Another potential area for glaucoma management is the source of aqueous humour production, the ciliary body, where AC has also been identified. Furthering the understanding of lacrimal gland function is vital in managing dry eye disease, a common and debilitating condition. sAC has been linked to tear production and could serve as a therapeutic target. Overall, ACs are an exciting area of study in ocular health, offering multiple avenues for future medical therapies and diagnostics. This review paper explores the diverse roles of ACs in the eye and their potential as targets for innovative treatments.Item Not all knees are the same(British Editorial Society of Bone and Joint Journal, 2024-06-01) MacDessi, S. J.; van de Graaf, V. A.; Wood, J. A.; Griffiths-Jones, W.; Bellemans, J.; Chen, D. B.The aim of mechanical alignment in total knee arthroplasty is to align all knees into a fixed neutral position, even though not all knees are the same. As a result, mechanical alignment often alters a patient's constitutional alignment and joint line obliquity, resulting in soft-tissue imbalance. This annotation provides an overview of how the Coronal Plane Alignment of the Knee (CPAK) classification can be used to predict imbalance with mechanical alignment, and then offers practical guidance for bone balancing, minimizing the need for soft-tissue releases.Item Acute monocular visual loss: time to call the stroke team?(BMJ, 2024-05-01) Day, J.; Monla-Haidar, H.; Raman, V.; Weatherby, S.A man in his 90s presented with acute monocular loss of vision; the emergency department triage alerted the stroke team. He underwent urgent parallel assessments by the stroke and ophthalmology teams and was diagnosed with central retinal artery occlusion. The ultimate decision was made to manage him conservatively, rather than with intravenous thrombolysis, and his visual function has remained poor. We discuss the current evidence for using intravenous thrombolysis in people with central retinal artery occlusion and use this case to exemplify the practical issues that must be overcome if ongoing randomised clinical trials of central retinal artery occlusion confirm a definite benefit from using intravenous thrombolysis.Item Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study(Wiley, 2024-05-01) Tait, L.; Staniaszek, L. E.; Galizia, E.; Martin-Lopez, D.; Walker, M. C.; Azeez, A. A. A.; Meiklejohn, K.; Allen, D.; Price, C.; Georgiou, S.; Bagary, M.; Khalsa, S.; Manfredonia, F.; Tittensor, P.; Lawthom, C.; Howes, B. B.; Shankar, R.; Terry, J. R.; Woldman, W.OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.Item Implementing a strategic plan for research(Mark Allen Group, 2024-06-01) Shepherd, M.; Quinn, H.Effective integration of research within healthcare organisations is recognised to improve outcomes. A research strategy within a hospital Trust in South West England was revised, following the launch of a national Chief Nursing Officer (CNO) strategy that promotes research engagement and activity. The aim was to develop, implement and evaluate this revised strategic plan for research. High-level engagement within the organisation was established and previous initiatives evaluated. A 6-year plan with 2-year targets was defined and evaluated at year end. The four pillars of the CNO strategy were central to the revised strategy, underpinned by digital innovation. Evaluation of the earlier strategy indicated excellent engagement with the Chief Nurse Research Fellow initiative and the Clinical Academic Network. The 'Embedding Research In Care' (ERIC) unit was reconfigured to an ERIC model, which aided question generation and project development. Year one objectives were achieved within the revised plan. Implementing a research strategy within an organisation requires a cultural shift and a long-term vision is required with measurable objectives. The team demonstrated significant progress through high-level leadership, mentoring and cross-professional collaboration.