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Editorial: Stress, mood, and fatigue: Tackling "invisible" obstacles in stroke rehabilitation and recovery

Gyawali P, Wong D, Hordacre B, Ong LK, English C

Front Neurol, 2022;13:1121667.
PMID: 36733449 DOI: 10.3389/fneur.2022.1121667
Fulltext Role of Purinergic Signalling in Endothelial Dysfunction and Thrombo-Inflammation in Ischaemic Stroke and Cerebral Small Vessel Disease

Lee NT, Ong LK, Gyawali P, Nassir CMNCM, Mustapha M, Nandurkar HH, et al.

Biomolecules, 2021 07 06;11(7).
PMID: 34356618 DOI: 10.3390/biom11070994

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood-brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.
Fulltext Exploring the relationship between fatigue and circulating levels of the pro-inflammatory biomarkers interleukin-6 and C-reactive protein in the chronic stage of stroke recovery: A cross-sectional study

Gyawali P, Hinwood M, Chow WZ, Kluge M, Ong LK, Nilsson M, et al.

Brain Behav Immun Health, 2020 Dec;9:100157.
PMID: 34589899 DOI: 10.1016/j.bbih.2020.100157

Background: The precise mechanisms underlying the aetiology of post-stroke fatigue remain poorly understood. Inflammation has been associated with clinically significant fatigue across a number of neurological disorders; however, at present there is a lack of evidence regarding the association of fatigue and inflammation in the chronic phase of stroke recovery.
Aims: The aim of this study was to examine fatigue in a cohort of stroke survivors in the chronic phase of stroke, compared with matched controls, and to explore associations between the pro-inflammatory cytokine interleukin-6, high-sensitivity C-reactive Protein and fatigue.
Methods: We performed an exploratory cross-sectional study of 70 people in the chronic phase of stroke recovery, and 70 age matched controls. Fatigue was assessed using the Fatigue Assessment Scale. Interleukin-6 was measured in serum using a commercially available enzyme immunoassay kit. Both outcome measures were assessed contemporaneously.
Results: Clinically significant fatigue, defined as a score ≥24 on the Fatigue Assessment Scale, was reported by 60% of stroke survivors, and 15.7% of controls. The odds of experiencing clinically significant fatigue was 8.04 times higher among stroke survivors compared to control participants (odds ratio 8.045; 95% CI: 3.608, 17.939; P
Fulltext Opposing Associations of Stress and Resilience With Functional Outcomes in Stroke Survivors in the Chronic Phase of Stroke: A Cross-Sectional Study

Gyawali P, Chow WZ, Hinwood M, Kluge M, English C, Ong LK, et al.

Front Neurol, 2020;11:230.
PMID: 32390923 DOI: 10.3389/fneur.2020.00230

Stroke survivors report significant levels of psychological distress post stroke. To date, most studies conducted have focused on the relationship between psychological stress and functional outcomes in the acute phase of stroke. However, no studies had considered the role of stress over the chronic phase, where stress may continue to exert negative effects on cognitive and psychological processes. Further, the role of potentially modulatory variables, such as psychological resilience, on stroke outcomes has been understudied. The purpose of this study was to consider the relationships between stress and resilience with functional outcomes in long-term survivors of stroke. People (N = 70) who had experienced a stroke between 5 months and 28 years ago were included in the cross-sectional study, along with age-matched controls (N = 70). We measured stress using both the Perceived Stress Scale and biological markers, and resilience using both the Brief Resilience Scale and the Connor-Davidson Resilience Scale. Stroke outcomes were assessed using the Stroke Impact Scale. We found that, compared with age-matched controls, stroke survivors reported greater levels of perceived stress, and lower levels of resilience. In stroke survivors, both perceived stress and resilience were independently associated with stroke outcomes in linear regression models. In particular, these relationships were observed for cognitive outcomes including mood, memory, and communication. The association between stress and stroke outcome did not differ across time post stroke. Given that resilience is a modifiable psychological construct, future research may consider whether strategies directed at enhancing resilience may improve recovery from stroke. Australia and New Zealand Clinical Trials Registry: ACTRN12617000736347.
Fulltext Similar cognitive deficits in mice and humans in the chronic phase post-stroke identified using the touchscreen-based paired-associate learning task

Chow WZ, Ong LK, Kluge MG, Gyawali P, Walker FR, Nilsson M

Sci Rep, 2020 Nov 11;10(1):19545.
PMID: 33177588 DOI: 10.1038/s41598-020-76560-x

For many chronic stroke survivors, persisting cognitive dysfunction leads to significantly reduced quality of life. Translation of promising therapeutic strategies aimed at improving cognitive function is hampered by existing, disparate cognitive assessments in animals and humans. In this study, we assessed post-stroke cognitive function using a comparable touchscreen-based paired-associate learning task in a cross-sectional population of chronic stroke survivors (≥ 5 months post-stroke, n = 70), age-matched controls (n = 70), and in mice generated from a C57BL/6 mouse photothrombotic stroke model (at six months post-stroke). Cognitive performance of stroke survivors was analysed using linear regression adjusting for age, gender, diabetes, systolic blood pressure and waist circumference. Stroke survivors made significantly fewer correct choices across all tasks compared with controls. Similar cognitive impairment was observed in the mice post-stroke with fewer correct choices compared to shams. These results highlight the feasibility and potential value of analogous modelling of clinically meaningful cognitive impairments in chronic stroke survivors and in mice in chronic phase after stroke. Implementation of validated, parallel cross-species test platforms for cognitive assessment offer the potential of delivering a more useful framework for evaluating therapies aimed at improving long-term cognitive function post-stroke.
Fulltext The Urological Association of Asia clinical guideline for urinary stone disease

Taguchi K, Cho SY, Ng AC, Usawachintachit M, Tan YK, Deng YL, et al.

Int J Urol, 2019 07;26(7):688-709.
PMID: 31016804 DOI: 10.1111/iju.13957

The Urological Association of Asia, consisting of 25 member associations and one affiliated member since its foundation in 1990, has planned to develop Asian guidelines for all urological fields. The field of stone diseases is the third of its guideline projects. Because of the different climates, and social, economic and ethnic environments, the clinical practice for urinary stone diseases widely varies among the Asian countries. The committee members of the Urological Association of Asia on the clinical guidelines for urinary stone disease carried out a surveillance study to better understand the diversity of the treatment strategy among different regions and subsequent systematic literature review through PubMed and MEDLINE database between 1966 and 2017. Levels of evidence and grades of recommendation for each management were decided according to the relevant strategy. Each clinical question and answer were thoroughly reviewed and discussed by all committee members and their colleagues, with suggestions from expert representatives of the American Urological Association and European Association of Urology. However, we focused on the pragmatic care of patients and our own evidence throughout Asia, which included recent surgical trends, such as miniaturized percutaneous nephrolithotomy and endoscopic combined intrarenal surgery. This guideline covers all fields of stone diseases, from etiology to recurrence prevention. Here, we present a short summary of the first version of the guideline - consisting 43 clinical questions - and overview its key practical issues.