Association of Leukoaraiosis with Stroke Recurrence within 5 Years after Initial Stroke

Background: Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA₂DS₂VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. Methods: In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA₂DS₂VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. Results: White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA₂DS₂VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed improved C-statistics: the recalibrated CHA₂DS₂VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). Conclusions: An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA₂DS₂VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence.

Section: Discussionsupporting

confidence: 91%

White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction

Andersen¹,

Larsen

Gorst‐Rasmussen³

et al. 2016

“…Furthermore, venous congestion is implicated in the pathogenesis of LA as well as increased platelet activation and hypercoagulability, which could lead to occlusion of the microcirculation, further impending microvascular patency [24][25][26]. It has been shown that severe LA contributes to cognitive dysfunction after stroke, interfering with rehabilitation efforts [27,28].…”

Section: Discussionmentioning

confidence: 99%

Severe Leukoaraiosis Is Associated with Poor Outcome after Successful Recanalization of M1 Middle Cerebral Artery Occlusion Strokes

Mutzenbach

Müller-Thies-Broussalis

Killer‐Oberpfalzer

et al. 2020

Background: Severe leukoaraiosis (LA) is an established risk factor for poor outcome after mechanical thrombectomy (MT) for large vessel occlusion stroke. There is uncertainty whether this association also applies to successfully recanalized patients with M1 segment middle cerebral artery (MCA) occlusions. Methods: A retrospective single-centre study of patients with successful reperfusion (thrombolysis in cerebral infarction, TICI 2b or 3) after MT for an M1 MCA occlusion was performed over a 7-year period. LA score (LAS) was assessed using the age-related white matter change scale on pre-interventional brain imaging. Results: A total of 209 patients (median age 75.0 years) were included. LAS was assessed on pre-interventional imaging by computed tomography in 177 (84.7%) patients and magnetic resonance imaging in 32 (15.3%) patients. The median LAS was 1 (IQR 0-8), and severe LA consisted of the top 25 percentile, ranging from 9 to 24. Multivariable analysis demonstrated an association of severe LA (OR 0.32, 95% CI 0.12-0.88, p = 0.023), higher NIHSS on admission (OR 0.89, 95% CI 0.84-0.94, p < 0.001), advanced age (OR 0.97, 95% CI 0.95-1.00, p = 0.039), good leptomeningeal collaterals (OR 3.65, 95% CI 1.46-8.15, p = 0.001), and TICI 3 score (OR 3.26, 95% CI 10.52-7.01) with good clinical outcome after 3 months as measured with the modified Rankin scale. Conclusion: Severe LA is associated with poor clinical outcome at 3 months in acute stroke patients undergoing MT due to emergent M1 MCA occlusion.

“…Previous studies have documented that an increasing burden of white matter hyperintensities is associated with an increased risk of stroke recurrence [25][26][27] . Since lacunes and white matter hyperintensities may be considered part of the same pathologic process, we are not surprised that increasing burdens of both these entities carry higher risk of stroke recurrence.…”

Section: Discussionmentioning

confidence: 99%

Multiple Silent Lacunes Are Associated with Recurrent Ischemic Stroke

Andersen¹,

Skjøth²,

Yavarian³

et al. 2016

Background: Silent lacunes are a common finding on brain imaging in ischemic stroke patients, but the prognostic significance of these lesions is uncertain. We aimed at investigating the association of silent lacunes and the risk of ischemic stroke recurrence, death, and cardiovascular events in a cohort of patients with incident ischemic stroke and no atrial fibrillation (AF). Methods: We included 786 patients (mean age 59.5 (SD 14.0); 42.9% females) in a registry-based, observational cohort study on patients with first-ever ischemic stroke. On brain MRI we assessed the number of silent lacunes as none, single, or multiple and we calculated stratified incidence rates of the outcomes. Cox proportional hazard ratios (HRs) adjusted for age, gender, congestive heart failure, hypertension, diabetes, and vascular disease were calculated with no silent lacunes as reference. In additional analyses, we further adjusted for white matter hyperintensities. Patients were followed up until death or recurrence of ischemic stroke. Results: In 81 (10.3%) patients, a single silent lacune was present, and in 87 (11.1%) patients, multiple silent lacunes were present. Patients with at least one silent lacune were older (mean age 66.1 vs. 57.7, p < 0.001) and were more often hypertensive (60.1 vs. 43.4%, p < 0.001) compared to patients with no silent lacunes. During a median follow-up time of 2.9 (interquartile range 3.1) years, we observed 53 recurrent ischemic strokes, 76 deaths, and 96 cardiovascular events. Incidence rates per 100 person-years of ischemic stroke recurrence were 1.6, 2.5, and 5.0 for none, single, and multiple silent lacunes respectively. Corresponding incidence rates were 2.6, 2.4, and 4.4 for death, and 3.4, 4.0, and 6.6 for cardiovascular events respectively. Adjusted HRs of ischemic stroke recurrence were 1.53 (0.67-3.49) and 2.52 (1.25-5.09) for a single and multiple silent lacunes, respectively. Further adjustment for white matter hyperintensities maintained positive association although not significant. Corresponding adjusted HRs were 0.56 (0.25-1.25) and 0.65 (0.33-1.25) for death and 1.16 (0.61-2.22) and 1.51 (0.86-2.66) for cardiovascular events. Conclusions: In this large cohort of patients with incident ischemic stroke and no AF, an increasing number of silent lacunes was associated with increasing incidence rates of ischemic stroke recurrence. In the adjusted Cox proportional hazard analyses, the presence of multiple silent lacunes was significantly associated with an increased risk of ischemic stroke recurrence. The risk of death or cardiovascular events was not significantly influenced by the presence of silent lacunes.