Does Current Research Evidence Indicate the Need to Conduct Serum Investigation(s) for Ischaemic Lesions in Acute...

Ischaemic injury occurring in association with acute intracerebral haemorrhage (ICH) is increasingly recognised, most commonly as remote diffusion-weighted imaging (DWI) lesions. However, the mechanisms, timing, and clinical significance of these lesions remain incompletely defined. This narrative review evaluates whether current evidence supports serum biomarker testing as part of the acute work-up for ischaemic lesions after ICH.

We distinguish diagnostic utility (identifying or predicting lesions) from prognostic utility (predicting outcomes). Candidate biomarkers are narratively appraised by assessing: (i) evidence linking circulating levels to magnetic resonance imaging (MRI)-defined remote DWI lesions, (ii) mechanistic alignment with post-ICH microvascular injury, and (iii) limitations of the available clinical evidence. Across astrocytic and neuronal injury markers (glial fibrillary acidic protein, S100 calcium-binding protein B [S100B], neurofilament light chain [NfL]) and systemic inflammatory indices (C-reactive protein [CRP], neutrophil-lymphocyte ratio [NLR]), the prevailing signal reflects global injury burden or the differentiation between haemorrhagic and ischaemic stroke subtypes rather than lesion-specific detection. Lactate dehydrogenase (LDH) has demonstrated direct association with remote lesions in a retrospective ICH cohort but lacks brain specificity and is vulnerable to extracranial confounding. Prognostic biomarkers (inflammatory, oxidative, and haemostasis-related) predict general ICH outcomes but are yet to be validated for risk stratification specifically in patients with secondary DWI lesions.

Overall, no single serum biomarker currently justifies routine clinical testing to detect or guide management of remote DWI lesions after ICH. Future work should prioritise temporally resolved, multi-marker panels validated against serial MRI-defined lesion phenotypes to characterise the ischaemic phenotype and support precision haemodynamic and anti-inflammatory strategies.