Risk factors and clinical significance of post-stroke incident ischemic lesions

Abstract

Introduction: While incident ischemic lesions (IILs) are not unusual on follow-up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown.

Methods: In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months.

Results: At 6 months, 78 patients (15.5%) had IILs, mostly diffusion-weighted imaging-positive (72%) and clinically covert (91%). Older age and small vessel disease (SVD) lesions were baseline risk factors for IILs. IILs were associated with worse cognitive (beta for global cognition: -0.31, 95% confidence interval [CI]: -0.48 to -0.14) and functional outcomes (beta for modified Rankin scale [mRS]: 0.36, 95% CI: 0.14 to 0.58), and higher recurrent stroke risk (hazard ratio: 3.81, 95% CI: 1.35 to 10.69). IILs partially explained the relationship between SVD and poor cognition.

Discussion: IILs are common and are associated with worse cognitive and functional outcomes and stroke recurrence risk. Assessing IILs following stroke might aid prognostication.

Highlights: Incident ischemic lesions (IILs) were assessed with registered baseline and 6-month magnetic resonance imaging (MRI) scans in a stroke cohort. IILs 6 months after stroke are present in one-sixth of patients and are mostly clinically silent. Small vessel disease burden is the main baseline risk factor for IILs. IILs are associated with cognitive and functional impairment and stroke recurrence. Assessing IILs by follow-up MRI aids long-term prognostication for stroke patients.

Keywords: cerebral small vessel disease; cognitive impairment; functional outcome; incident ischemic lesions; recurrent stroke; stroke.

FIGURE 1

Characteristics of IILs at 6 months after stroke. (A) Examples of IILs on brain MRI scans at 6 months. Left: 77‐year‐old patient with incident DWI+/FLAIR+ cortical infarct; right: 59‐year‐old patient with incident DWI−/FLAIR+ small subcortical infarct. For more details see Methods and Figure S1 in Supplement. (B) Distribution of IIL counts among participants who had IILs (N = 78). (C) Boxplot of volume of IILs and index stroke in participants with IILs. (D) Number of participants with different MRI signals of IILs. (E) Number of participants with and without symptoms corresponding to IILs. (F) Number of IILs with different types of IILs stratified by index stroke. Fisher's exact tests were applied to compare categorical differences across all six groups and between any pair of groups. The results showed a significant difference across all six groups; CES had a higher proportion of CI‐IILs than LAS, SAO, and Hemorr. Strokes, with all p‐values being <.05. SSI refers to a lesion up to 20 mm in diameter on the axial plane in the territory of penetrating arteries, following STRIVE criteria. LSI refers to a lesion located in the subcortex with an axial diameter above 20 mm. CI refers to a lesion located in the cortex of any size. (G) Number of IILs in locations compared to the vascular territories of the index stroke. N represents the number of participants; n represents the number of IILs. CES, cardioembolic stroke; CI: cortical infarct; DWI, diffusion‐weighted imaging; FLAIR, fluid‐attenuated inversion recovery; Hemorr., hemorrhagic stroke; IIL, incident ischemic lesion; LAS, large artery stroke; LSI, large subcortical infarct; MRI, magnetic resonance imaging; SAO, small artery occlusion; SSI, small subcortical infarct; TOAST, Trial of Org 10172 in Acute Stroke Treatment.

FIGURE 2

Study profile. MRI, magnetic resonance imaging.

FIGURE 3

Associations between IILs at 6 months and cognitive and functional outcomes, as well as recurrent stroke over 36 months after the index stroke. (A) Median and interquartile range of z‐scores of global cognitive performance at 6, 12, and 36 months stratified by IIL status. (B) Distributions of mRS score at 6, 12, and 36 months stratified by IIL status. (C) Associations of presence of IILs with cognitive and functional scores across 36 months using linear GEEs. The models in C adjusted for age, sex, NIHSS score, educational years, and cognitive impairment (MoCA<26 or MMSE<24 if MoCA is not available) at baseline. p‐values were corrected for multiple comparisons with the FDR method. (D) Cumulative incidence curve of recurrent stroke stratified by presence and absence of IILs based on the competing‐risk model. Hazard ratios associated with the presence of IILs for recurrent stroke between 6 and 36 months after the index stroke were calculated using competing‐risk regression models (cause‐specific and subdistribution hazard models) incorporating the competing risk of non‐stroke death. The two models adjusted for age, sex, and NIHSS score at baseline and recurrent clinical stroke between baseline and 6 months. BI, Barthel index; CI, confidence interval; csHR, cause‐specific hazard ratio; FDR, false discovery rate; IILs, incident ischemic lesions; GEE, generalized estimating equation; IADL, instrumental activities of daily living; MMSE, Mini‐Mental State Examination; MoCA, Montreal Cognitive Assessment; mRS, modified Rankin scale; NIHSS, National Institutes of Health Stroke Scale; sdHR, subdistribution hazard ratio.*mRS assesses functional outcome, with a score ranging from 0 (no symptoms) to 5 (serious functional impairment)