Medicine (Western Health) - Research Publications
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ItemCarotid artery stenosis and inflammatory biomarkers: the role of inflammation-induced immunological responses affecting the vascular systems(AME PUBLISHING COMPANY, 2020-10)The death, disability and economic cost of stroke are enormous. Indeed, among the 16 million people worldwide who suffer a stroke' annually, nearly six million die, and another five million are left permanently disabled making prevention of stroke one of the most important priorities in healthcare. Currently carotid artery stenosis (CS) or narrowing of the common carotid artery (CCA) or internal carotid artery (ICA) due to atherosclerotic plaque, accounts for 20-30% of all ischemic strokes. Atherosclerosis is now regarded as a chronic inflammatory disease in response to vascular compromise especially from hypertension. This has long been known to lead to inflammation and atherosclerotic plaque formation in the blood vessels. This mini-review aims to highlight the role of inflammation and neuro-immunological processes in carotid artery disease. Various cellular elements of inflammation and advanced imaging techniques have been identified as potential markers of plaque progression. Therapies related to decreasing and modulating immune-responsive inflammation in the carotid vessels have been shown to translate into decreased occurrence of acute neurologic events and improvement of clinical outcomes.
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ItemHighlighting the Role of Universally Available and Innate Immune Cell Counts in Acute Ischemic Stroke: A Scoping Review(MDPI, 2021-04)Stroke is one of the leading causes of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of acute ischemic stroke (AIS), during the index event and the repair process. Research on neurovascular inflammation has created a renewed interest in the use of easily available biomarkers reflective of innate and adaptive immunological changes with potential diagnostic, prognostic, and therapeutic implications particularly in AIS. The current scoping review aimed to assess the significance the neutrophil to lymphocyte (NLR) in AIS and its related complications and explore their association with post-stroke recovery trajectory. The Arksey and O’Malley methodological framework was employed to review the published papers on the neutrophil–lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000–2020 were included in this scoping review. Fifty-three published papers were reviewed. This review’s key finding is that a canonical inflammatory response occurs in the hyperacute, acute, subacute, and chronic stages of stroke. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes) are associated with poorer outcomes during the acute interventions as well as the recovery trajectory. This scoping review’s findings highlights the utility of a systems biology-based approach in stroke care.
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ItemCase Report: Posterior Reversible Leukoencephalopathy Syndrome (PRES) as a Biologically Predictable Neurological Association in Severe COVID-19. First Reported Case From Australia and Review of Internationally Published Cases(FRONTIERS MEDIA SA, 2021-01-27)Reports of different types of neurological manifestations of COVID-19 are rapidly increasing, including changes of posterior reversible leukoencephalopathy syndrome (PRES). Here we describe the first reported case of COVID-19 and PRES in Australia diagnosed on basis of MRI brain imaging and confirmed clinically by presence of confusion, delirium, headaches, also associated with hypertension and blood pressure variability and stable long-term kidney problems. He made full recovery as his blood pressure was controlled and clinical status was supported with appropriate supportive therapy. Although traditionally a rare condition, PRES is likely to be more common among patients with COVID-19 pathobiology there is Renin downregulation of ACE2 receptors, involvement of Renin-Angiotensin-Aldosterone system, endotheliitis, cytokine storm, and hyper-immune response. Thus we advocate clinical suspicion and early brain imaging with MRI brain among vulnerable patients with known co-morbidities, and diagnosed with COVID-19 given that hypertension and blood pressure variability are often exacerbated by acute SARS-CoV-2 immune reactions. Such acute hypertensive encephalopathy was able to be reversed with timely supportive therapy ensuring re-hydration and re-establishment of blood pressure control.
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ItemCOVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception-A Systematic Review(FRONTIERS MEDIA SA, 2021-01-28)Clinical reports of neurological manifestations associated with severe coronavirus disease 2019 (COVID-19), such as acute ischemic stroke (AIS), encephalopathy, seizures, headaches, acute necrotizing encephalitis, cerebral microbleeds, posterior reversible leukoencephalopathy syndrome, hemophagocytic lymphohistiocytosis, peripheral neuropathy, cranial nerve palsies, transverse myelitis, and demyelinating disorders, are increasing rapidly. However, there are comparatively few studies investigating the potential impact of immunological responses secondary to hypoxia, oxidative stress, and excessive platelet-induced aggregation on the brain. This scoping review has focused on the pathophysiological mechanisms associated with peripheral and consequential neural (central) inflammation leading to COVID-19-related ischemic strokes. It also highlights the common biological processes shared between AIS and COVID-19 infection and the importance of the recognition that severe respiratory dysfunction and neurological impairments associated with COVID and chronic inflammation [post-COVID-19 neurological syndrome (PCNS)] may significantly impact recovery and ability to benefit from neurorehabilitation. This study provides a comprehensive review of the pathobiology of COVID-19 and ischemic stroke. It also affirms that the immunological contribution to the pathophysiology of COVID-19 is predictive of the neurological sequelae particularly ischemic stroke, which makes it the expectation rather than the exception. This work is of fundamental significance to the neurorehabilitation community given the increasing number of COVID-related ischemic strokes, the current limited knowledge regarding the risk of reinfection, and recent reports of a PCNS. It further highlights the need for global collaboration and research into new pathobiology-based neurorehabilitation treatment strategies and more integrated evidence-based care.
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ItemAcute Ischemic Stroke in SARS-CoV, MERS-CoV, SARS-CoV-2: Neurorehabilitation Implications of Inflammation Induced Immunological Responses Affecting Vascular Systems(FRONTIERS MEDIA SA, 2020-12-22)Coronaviruses (CoVs) are enveloped RNA viruses and have been shown to cause mild to severe respiratory infections in humans, with some severe cases inducing neurological manifestations. The lethality and Neurological effects of the Severe Acute Respiratory Syndrome (SARS-CoV), Middle-East Respiratory Syndrome (MERS-CoV), and recently the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) have been well documented though currently there is little literature regarding long term effects and the implications for neurorehabilitation. SARS-CoV-2 and MERS-CoV have been linked to the infection associated inflammatory cytokine storms and induced hypercoagulopathic states that affect the entire vascular system including that of the brain. This mini-review provides an overview of the commonalities among studies published on all three types of the coronavirus related to acute ischemic stroke (AIS). The aim was to elucidate the physiological mechanisms underpinning COVID-2 and to reflect the similarities with the chronic inflammation induced symptoms of AIS that are likely to prove a further challenge for neurorehabilitation clinicians post COVID. In terms of increased incidence of COVID and AIS, it is likely that in depth knowledge of increased thrombotic risk in this population will require appropriate anticoagulation treatment, and other therapeutic interventions as well as neurorehabilitation interventions. Lastly the risk of spreading the virus requires further balancing of the provision of neurorehabiliatation services useful to the patient.
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ItemAcute Ischemic Stroke in COVID-19: A Case-Based Systematic Review(FRONTIERS MEDIA SA, 2020-09-25)Corona virus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) is recognized as a global pandemic by WHO 2020 with 5,934 936 infections, 367,166 deaths and affecting over 200 countries as of 30th May 2020. Acute Ischemic Stroke (AIS) in brain is also emerging as an important neurovascular/neurological complication of COVID-19, associated with extreme immune responses leading to dysregulated coagulation system and generalized thrombo-embolic status and increased risk of AIS especially among usually less vulnerable younger adults in this cohort. Thus, in early June 2020, we aimed to review the clinical data on all published cases of COVID-19 and concomitant AIS, with a view to understanding the pertinent clinical, laboratory and imaging features. The neutrophil-lymphocyte ratio (NLR) at time of hospital admission for COVID infection correlates positively with the duration of time before onset of clinical features of AIS. Higher NLR, C-Reactive protein, serum ferritin, D-dimer and fibrinogen levels are associated with poor prognosis of AIS in COVID-19 with 75% of patients dying or being severely disabled at present. Currently it is too early to comment on the long-term outcomes for survivors.
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ItemFirst Australian Case of Good Recovery of a COVID-19 Patient With Severe Neurological Symptoms Post Prolonged Hospitalization(CUREUS INC, 2020-09-10)A case of a 75-year-old man with COVID-19, severe neurological symptoms (acute stroke-like symptoms and signs and full recovery after a prolonged hospital stay), and intracranial hypertension is discussed with an in-depth review of his clinical features, biochemistry, haematology, highlighting the relationship between changes in neutrophil-lymphocyte ratio, C-reactive protein level, D-dimer level, and the clinical onset of acute ischemic stroke-like symptoms in the setting of COVID-19 and major neurological manifestations. This is the first such case reported in Australia to date. This case also illustrates the recovery of a patient with COVID-19 complicated with severe neurological symptoms (acute ischemic stroke-like symptoms) during the prolonged intensive care unit stay (at day 26) followed by slow neurorehabilitation and normal recovery from both respiratory and neurological involvement. The onset of acute stroke-like symptoms appears to be closely associated with changes of neutrophil-lymphocyte ratio and in C-reactive protein, and D-dimer levels.