Background: Approximately one in four stroke patients suffer from recurrent vascular events, underlying the necessity to improve secondary stroke prevention strategies. Immune mechanisms are causally associated with coronary atherosclerosis. However, stroke is a heterogeneous disease and the relative contribution of inflammation across stroke mechanisms is not well understood. The optimal design of future randomized control trials (RCTs) of anti-inflammatory therapies to prevent recurrence after stroke must be informed by a clear understanding of the prognostic role of inflammation according to stroke subtype and individual patient factors.
Aim: In this narrative review, we discuss (1) inflammatory pathways in the etiology of ischemic stroke subtypes; (2) the evidence on inflammatory markers and vascular recurrence after stroke; and (3) review RCT evidence of anti-inflammatory agents for vascular prevention.
Summary of review: Experimental work, genetic epidemiological data, and plaque-imaging studies all implicate inflammation in atherosclerotic stroke. However, emerging evidence also suggests that inflammatory mechanisms are also important in other stroke mechanisms. Advanced neuroimaging techniques support the role of neuroinflammation in blood-brain barrier dysfunction in cerebral small vessel disease (cSVD). Systemic inflammatory processes also promote atrial cardiopathy, incident and recurrent atrial fibrillation (AF). Although several inflammatory markers have been associated with recurrence after stroke, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are presently the most promising markers to identify patients at increased vascular risk. Several RCTs have shown that anti-inflammatory therapies reduce vascular risk, including stroke, in coronary artery disease (CAD). Some, but not all of these trials, selected patients on the basis of elevated hsCRP. Although unproven after stroke, targeting inflammation to reduce recurrence is a compelling strategy and several RCTs are ongoing.
Conclusion: Evidence points toward the importance of inflammation across multiple stroke etiologies and potential benefit of anti-inflammatory targets in secondary stroke prevention. Taking the heterogeneous stroke etiologies into account, the use of serum biomarkers could be useful to identify patients with residual inflammatory risk and perform biomarker-led patient selection for future RCTs.
Background and purpose: Cervical artery dissection (CAD) involving the carotid or vertebral arteries is an important cause of stroke in younger patients. The purpose of this systematic review is to assess the risk of recurrent CAD.
Methods: A systematic review and meta-analysis was conducted on studies in which patients experienced radiographically confirmed dissections involving an extracranial segment of the carotid or vertebral artery and in whom CAD recurrence rates were reported.
Results: Data were extracted from 29 eligible studies (n = 5898 patients). Analysis of outcomes was performed by pooling incidence rates with random effects models weighting by inverse of variance. The incidence of recurrent CAD was 4% overall (95% confidence interval (CI) = 3-7%), 2% at 1 month (95% CI = 1-5%), and 7% at 1 year in studies with sufficient follow-up (95% CI = 4-13%). The incidence of recurrence associated with ischemic events was 2% (95% CI = 1-3%).
Conclusions: We found low rates of recurrent CAD and even lower rates of recurrence associated with ischemia. Further patient-level data and clinical subgroup analyses would improve the ability to provide patient-level risk stratification.
Background and objectives: Cerebral microinfarcts (CMIs) are the most common type of brain ischemia; however, they are extremely rare in the general population. CMIs can be detected by magnetic resonance diffusion-weighted imaging (MRI-DWI) only for a very short period of approximately 2 weeks after their formation and are associated with an increased stroke risk and cognitive impairment. We aimed to examine CMI detection rate in patients with lung cancer (LC), which is strongly associated with ischemic stroke risk relative to other cancer types.
Methods: We used the Clalit Health Services record (representing more than 5 million patients) to identify adults with LC and breast, pancreatic, or colon cancer (non-lung cancer, NLC) who underwent brain magnetic resonance diffusion (MRI) scan within 5 years following cancer diagnosis. All brain MRI scans were reviewed, and CMIs were documented, as well as cardiovascular risk factors.
Results: Our cohort contained a total of 2056 MRI scans of LC patients and 1598 of NLC patients. A total of 143 CMI were found in 73/2056 (3.5%) MRI scans of LC group compared to a total of 29 CMI in 22/1598 (1.4%) MRI scans of NLC (p < 0.01). Cancer type (e.g. LC vs NLC) was the only associated factor with CMI incidence on multivariate analysis. After calculating accumulated risk, we found an incidence of 2.5 CMI per year in LC patients and 0.5 in NLC.
Discussion: CMIs are common findings in cancer patients, especially in LC patients and therefore might serve as a marker for occult brain ischemia, cognitive decline, and cancer-related stroke (CRS) risk.
Background: In stroke patients with insulin resistance (IR), post-stroke cognitive impairment (PSCI) is associated with higher risk of recurrent stroke, but the effect of pioglitazone on that risk has not been explored. The goal of this study was to compare the secondary stroke prevention effect of pioglitazone against placebo in patients with versus without PSCI.
Methods: We studied patients enrolled in the Insulin Resistance Intervention after Stroke (IRIS) trial with a post-stroke modified Mini-Mental State Examination (3MS) cognitive assessment (mean time of assessment: 79 days post-stroke). We considered a baseline score of ⩽ 88 on the 3MS to indicate global PSCI, and domain-specific summary scores in the lowest quartile to indicate attention, language, memory, orientation, and visuospatial impairments.
Results: In n = 3338 patients with IR, the effect of pioglitazone versus placebo on secondary stroke significantly differed by initial post-stroke global (interaction p = 0.0127) and memory impairment status (interaction p = 0.0003). Hazard ratios (HRs) were time-dependent such that, among those with either global or memory impairment, pioglitazone has an increasingly stronger protective effect at later timepoints. There was no statistically significant effect of pioglitazone among those without either global or memory impairment. The effect of pioglitazone versus placebo on myocardial infarction (MI) also significantly differed by global impairment status (interaction p = 0.030). Pioglitazone was protective among those with global impairment (HR = 0.23 [95% CI: 0.08, 0.71]) but not among those without (HR = 0.88 [95% CI: 0.59, 1.31]).
Conclusion: These data indicate that pioglitazone treatment may be more effective at reducing risk of recurrent stroke and MI in stroke patients with PSCI. Simple cognitive testing 2-3 months post-stroke may identify patients for whom treatment would be most beneficial.
Background: There is growing evidence suggesting efficacy of endovascular therapy for M2 occlusions of the middle cerebral artery. More than one recanalization attempt is often required to achieve successful reperfusion in M2 occlusions, associated with general concerns about the safety of multiple maneuvers in these medium vessel occlusions.
Aim: The aim of this study was to investigate the association between the number of recanalization attempts and functional outcomes in M2 occlusions in comparison with large vessel occlusions (LVO).
Methods: Retrospective multicenter cohort study of patients who underwent endovascular therapy for primary M2 occlusions. Patients were enrolled in the German Stroke Registry at 1 of 25 comprehensive stroke centers between 2015 and 2021. The study cohort was subdivided into patients with unsuccessful reperfusion (mTICI 0-2a) and successful reperfusion (mTICI 2b-3) at first, second, third, fourth, or ⩾fifth recanalization attempt. Primary outcome was 90-day functional independence defined as modified Rankin Scale score of 0-2. Safety outcome was the occurrence of symptomatic intracranial hemorrhage. Internal carotid artery or M1 occlusions were defined as LVO and served as comparison group.
Results: A total of 1078 patients with M2 occlusion were included. Successful reperfusion was observed in 87.1% and 90-day functional independence in 51.9%. The rate of functional independence decreased gradually with increasing number of recanalization attempts (p < 0.001). In both M2 occlusions and LVO, successful reperfusion within three attempts was associated with greater odds of functional independence, while success at ⩾fourth attempt was not. Patients with ⩾4 attempts exhibited higher rates of symptomatic intracranial hemorrhage in M2 occlusions (6.5% vs 2.7%, p = 0.02) and LVO (7.2% vs 3.5%, p < 0.001).
Conclusion: This study suggests a clinical benefit of successful reperfusion within three recanalization attempts in endovascular therapy for M2 occlusions, which was similar in LVO. Our findings reduce concerns about the risk-benefit ratio of multiple attempts in M2 medium vessel occlusions.
Data access statement: The data that support the findings of this study are available on reasonable request after approval of the German Stroke Registry (GSR) steering committee.
Clinical trial registration information: ClinicalTrials.gov Identifier: NCT03356392.
Background: Several published systematic reviews have drawn conflicting conclusions on the effect of abnormal body weight (i.e. being underweight, overweight or obese) on outcomes following stroke. The 'obesity paradox' seen in several diseases (wherein obesity, often associated with mortality and morbidity, appears to be protective and improve outcomes) may be evident after stroke, but inconsistent results of existing reviews, and the issue of being underweight, are worth investigating further.
Aims: To better understand the impact of body weight on prognosis after stroke, we aimed to answer the following research question: What is the effect of abnormal body weight (underweight, overweight, or obesity) on mortality and functional recovery in adults after stroke?
Summary of review: We conducted an umbrella review to synthesize existing evidence on the effects of abnormal body weight on stroke outcomes. We searched Cumulated Index to Nursing and Allied Health Literature (CINAHL) Complete, COCHRANE Database of Systematic Reviews, PubMed, Medline, PEDro, and EMBASE Classic + EMBASE, from inception until 28 February 2023. Seven systematic reviews (1,136,929 participants) from 184 primary studies (counting duplicates) were included. While the risk of mortality increases with being underweight (body mass index (BMI) < 18.5 kg/m2), excess body weight (being overweight (BMI = 25-29.9 kg/m2) or obese (BMI > 30 kg/m2)) is associated with reduced mortality. The impact of abnormal body weight on functional recovery is less clear; data from studies of being underweight are associated with poor functional outcomes while those from studies of excess body weight are inconclusive.
Conclusion: Abnormal body weight effects post-stroke outcomes and should be considered in clinical decision-making, prognostic research, and clinical trials of rehabilitation interventions. The "obesity paradox" is evident after stroke, and excess body weight is associated with reduced mortality compared to normal body weight. It is recommended that body weight is routinely recorded for stroke patients, and further research, including well-designed cohort studies with reliable weight data, is needed to further investigate the impact of body weight and distribution on post-stroke outcomes.