Heterogeneity and risk assessment in minor ischemic stroke

Minor ischemic stroke is often defined by a low National Institutes of Health Stroke Scale (NIHSS) score, yet patients with similar scores may have very different vascular lesions, tissue injury, and stroke mechanisms. This narrative review examines four domains that modify prognosis and management: symptom relevance, vascular and hemodynamic status, tissue status, and etiologic subtype. Adverse trajectories differ in timing. Early neurological deterioration (END) or infarct growth usually occurs within hours to days, recurrent ischemia clusters over days to weeks, and incomplete recovery may persist for months. A low NIHSS score may occur despite a disabling posterior-circulation or eloquent deficit, large- or medium-vessel occlusion, poor collateral flow, hypoperfusion, branch atheromatous disease, or an active embolic source. These outcomes are distinct from the mechanisms that drive them; high-risk minor stroke is not limited to large-vessel occlusion. PRISMS did not demonstrate benefit of alteplase over aspirin in selected patients with minor nondisabling stroke, ARAMIS found dual antiplatelet therapy noninferior to alteplase in a similarly selected population, and TEMPO-2 did not support routine tenecteplase in minor stroke selected by intracranial occlusion or focal perfusion abnormality. At ESOC 2026, MILD-MT investigators reported a higher proportion of patients achieving 90-day mRS 0-1 with endovascular therapy (EVT) plus best medical management than with best medical management alone in a selected group with anterior-circulation LVO, NIHSS <6, and favorable perfusion imaging. These findings are not directly comparable with TEMPO-2 because the intervention, imaging selection, reperfusion mechanism, time window, and outcome context differed. Short-course dual antiplatelet therapy remains supported for eligible non-cardioembolic minor stroke, while longer-term prevention should be tailored to the identified etiologic subtype. The modified Rankin Scale may miss residual deficits after minor stroke; measures such as the Canadian Outcome Scale for Minor Stroke (COSMOS) may capture performance, participation, and personally meaningful activities more sensitively. The four-domain framework is intended to organize clinical assessment, not to serve as a validated prediction score or treatment algorithm.