Early neurological deterioration in acute lacunar ischemic stroke: Systematic review of incidence, mechanisms, and prospects for treatment

Abstract

Background: Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischemic strokes. In acute lacunar ischemic 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 13,407 participants) describing the incidence of END in acute lacunar ischemic stroke. The specified timescale for END varied from <24 h to 3 weeks. The rate of END ranged between 2.3% and 47.5% with a pooled incidence of 23.54% (95% confidence interval (CI) = 21.02-26.05) but heterogeneity was high (I² = 90.29%). The rates of END defined by National Institutes of Health Stroke Scale (NIHSS) decreases of ⩾1, ⩾2, ⩾3, and 4 points were as follows: 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 cutoff 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: END occurs in more than 20% of patients with acute lacunar ischemic 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.

Keywords: Acute stroke therapy; antithrombotic; cerebral perfusion; lacunar stroke; small vessel disease; stroke.

Figure 1.

PRISMA flow diagram of included studies.

Figure 2.

Forest plots showing the incidence of early neurological deterioration in acute lacunar ischemic stroke. (a) All studies, and (b) studies grouped by the NIHSS threshold for deterioration.

Figure 3.

Arterial branch and intrinsic pathology associated with small vessel occlusion: (a) atherosclerotic plaque obstructing a perforating branch artery; (b) “junctional atheroma” extending from the parent vessel into the perforating branch artery; (c) microatheroma obstructing the orifice of the perforating branch artery; and (d) arteriolosclerosis affecting the distal perforating artery branch. The gray areas indicate infarction; branch atheromatous disease (BAD; a to c) typically causes a larger and more proximal area of infarction than occlusion due to arteriolosclerosis.

Figure 4.

CT perfusion (CTP) in acute lacunar ischemic stroke. A 45-year-old male presented with slurred speech, confusion, and right hemiataxia. Acute ischemia was not identified on the non-contrast CT (NCCT, a) but CTP revealed an area of increased Tmax in the left paramedian thalamus (b, red arrow) that corresponded to diffusion restriction on diffusion-weighted imaging (DWI, c). A 60-year-old male presenting with dysarthria and left-sided facial weakness. An acute infarct was not identified on the NCCT (d), but the CTP cerebral blood flow was lowered in the left internal capsule (e, red arrow), which corresponded to an acute infarct shown on DWI (f). A 70-year-old patient presented with right-sided weakness and dysphagia. NCCT showed a subtle ill-defined region of low attenuation that was indistinguishable from chronic small vessel disease (g). However, CTP showed an area of increased mean transit time in the left hemipons (h, red arrow), which corresponded to an acute infarct on DWI (i).