Diffusion-weighted imaging (DWI) has been increasingly utilized in the emergent evaluation of acute ischemic stroke (AIS) patients. DWI enhances sensitivity and specificity and enables the use of delayed reperfusion treatments in selected cases. However, DWI is not devoid of limitations. DWI-negative AIS is not uncommon in clinical practice and is reported in up to 1 of 4 AIS patients. We reviewed the relevant literature and searched the PubMed and Google Scholar databases for studies reporting on DWI-negative AIS prevalence during the 2021-2025 time period. Additionally, we included cases from our practice to highlight key points. DWI-negative AIS prevalence was 16% in one meta-analysis and ranged from 6.9% to 23.2% in identified studies that met our inclusion criteria. The biological, pathophysiological, technical, epidemiological and clinical factors that contribute to DWI-negative stroke are presented in detail. Overall, the application of diffusion imaging modalities for stroke is not bereft of blind spots despite enhanced sensitivity. Over-reliance on advanced neuroimaging and unfamiliarity with its limitations predispose DWI to errors in AIS assessment. Awareness of the predisposing factors, treatment effect, and prognosis guides appropriate decision-making, promoting good outcomes. Prospective appropriately designed trials should address the lingering questions identified, such as the association between time of imaging and DWI negativity.
Nikolakakis et al. (Wed,) studied this question.