Early neurological deterioration in acute lacunar ischaemic stroke: systematic review of incidence, mechanisms, and prospects for treatment.

ABSTRACT

BACKGROUND: Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischaemic strokes. In acute lacunar ischaemic stroke, despite often mild initial symptoms, early neurological deterioration (END) occurs in approximately 15-20% of patients and is associated with poor functional outcome, yet its mechanisms are not well understood. AIMS: In this review we systematically evaluated data on (1) definitions and incidence of END; (2) mechanisms of small vessel occlusion; (3) predictors and mechanisms of END; and (4) prospects for the prevention or treatment of patients with END. SUMMARY OF REVIEW We identified 67 reports (including 13407 participants) describing the incidence of END in acute lacunar ischaemic stroke. The specified timescale for END varied from <24h to 3 weeks. The rate of END ranged between 2.3% and 47.5 with a pooled incidence of 23.54% (95% CI 21.02-26.05%) but heterogeneity was high (I2=90.29%). The rates of END defined by NIHSS decreases of ≥1, ≥2, ≥3, and 4 points were 24.17 (21.19-27.16)%; 22.98 (20.48-25.30)%; 23.33 (16.23-30.42)%; and 10.79 (2.09-23.13)%, respectively, with lowest heterogeneity and greatest precision for a cut-off of ≥2 points. Of the 20/67 studies (30%) reporting associations of END with clinical outcome, 19/20 (95%) reported worse outcomes (usually measured using the modified Rankin score at 90 days or at hospital discharge) in patients with END. In a meta-regression analysis female sex, hypertension, diabetes, and smoking, were associated with END. CONCLUSIONS: Early neurological deterioration occurs in over 20% of patients with acute lacunar ischaemic stroke and might provide a novel target for clinical trials. A definition of an NIHSS ≥2 decrease is most used and provides the best between-study homogeneity. END is consistently associated with poor functional outcome. Further research is needed to better identify patients at risk of END, to understand the underlying mechanisms and to carry out new trials to test potential interventions.