Circulating Biomarkers in Long-Term Stroke Prognosis: A Scoping Review Focusing on the South African Setting

Abstract

Cerebrovascular disease, including both ischaemic and haemorrhagic strokes, remains one of the highest causes of global morbidity and mortality. Developing nations, such as South Africa (SA), are affected disproportionately. Early identification of stroke patients at risk of poor clinical prognosis may result in improved outcomes. In addition to conventional neuroimaging, the role of predictive biomarkers has been shown to be important. Little data exist on their applicability within SA. This scoping review aimed to evaluate the currently available data pertaining to blood biomarkers that aid in the long-term prognostication of patients following stroke and its potential application in the South African setting. This scoping review followed a 6-stage process to identify and critically review currently available literature pertaining to prognostic biomarkers in stroke. An initial 1191 articles were identified and, following rigorous review, 41 articles were included for the purposes of the scoping review. A number of potential biomarkers were identified and grouped according to the function or origin of the marker. Although most biomarkers showed great prognostic potential, the cost and availability will likely limit their application within SA. The burden of stroke is increasing worldwide and appears to be affecting developing countries disproportionately. Access to neuroradiological services is not readily available in all settings and the addition of biomarkers to assist in the long-term prognostication of patients following a stroke can be of great clinical value. The cost and availability of many of the reviewed biomarkers will likely hinder their use in the South African setting.

Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs)

“…The top two pathways identified were metabolic processes/pathways and coagulation and complement pathways, which are relevant to hemorrhagic events. Coagulation signaling is linked to hemorrhagic stroke risk and outcomes [35][36][37][38][39], leading to proposals for coagulation-targeted therapies and circulating prognostic biomarkers [36,40]. Similarly, the complement cascade has also been associated with hemorrhagic stroke.…”

Blood prognostic biomarker signatures for hemorrhagic cerebral cavernous malformations (CCMs)

“…The top two pathways identified were metabolic processes/pathways and coagulation and complement pathways, which are relevant to hemorrhagic events. Coagulation signaling is linked to hemorrhagic stroke risk and outcomes [61][62][63][64][65] , leading to proposals for coagulation-targeted therapies and circulating prognostic biomarkers 62,66 . Similarly, the complement cascade has also been associated with hemorrhagic stroke.…”

The burden of suspected strokes in uMgungundlovu – Can biomarkers aid prognostication?

“…The cost of potential biomarkers and their applicability within the South African context has been reported in a recently published scoping review (Jansen Van Vuuren et al 2022 ). The cost of some of the currently available biomarkers may limit its immediate implementation.…”

“…More than 58 biomarkers used in the various stages of diagnosis, management, monitoring and prognostication of strokes have been identified (Dolmans et al 2019 ; Donkel et al 2019 ; Jickling & Sharp 2015 ; Martin & Price 2018 ; Misra et al 2017 , 2020 ; Whiteley et al 2008 ). The use of biomarkers to assist in prognostication following a stroke has been discussed in a recently published scoping review (Jansen Van Vuuren et al 2022 ). Many of the available biomarkers are not readily available in SA either because of prohibitive cost or the requirement of specialised equipment to perform the laboratory investigations.…”