Gadolinium Enhancement in Intracranial Atherosclerotic Plaque and Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Gadolinium enhancement on high-resolution magnetic resonance imaging (MRI) has been proposed as a marker of inflammation and instability in intracranial atherosclerotic plaque. We performed a systematic review and meta-analysis to summarize the association between intracranial atherosclerotic plaque enhancement and acute ischemic stroke. METHODS AND RESULTS: We searched the medical literature to identify studies of patients undergoing intracranial vessel wall MRI for evaluation of intracranial atherosclerotic plaque. We recorded study data and assessed study quality, with disagreements in data extraction resolved by a third reader. A random-effects odds ratio was used to assess whether, in any given patient, cerebral infarction was more likely in the vascular territory supplied by an artery with MRI-detected plaque enhancement as compared to territory supplied by an artery without enhancement. We calculated between-study heterogeneity using the Cochrane Q test and publication bias using the Begg-Mazumdar test. Eight articles published between 2011 and 2015 met inclusion criteria. These studies provided information about plaque enhancement characteristics from 295 arteries in 330 patients. We found a significant positive relationship between MRI enhancement and cerebral infarction in the same vascular territory, with a random effects odds ratio of 10.8 (95% CI 4.1-28.1, P<0.001). No significant heterogeneity (Q=11.08, P=0.14) or publication bias (P=0.80) was present. CONCLUSIONS: Intracranial plaque enhancement on high-resolution vessel wall MRI is strongly associated with ischemic stroke. Evaluation for plaque enhancement on MRI may be a useful test to improve diagnostic yield in patients with ischemic strokes of undetermined etiology.National Institutes of Health/National Institute of Neurological Disorders and Stroke (Grant ID: K23NS082367), National Institutes of Health/ National Center for Advancing Translational Sciences (Grant ID: KL2TR000458)This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/JAHA.116.00381

Factors impacting D-dimer levels in patients with acute ischemic cerebrovascular events.

BACKGROUND AND OBJECTIVES A better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). METHODS Data on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed. RESULTS In total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381-1468] versus 442 µg/L [interquartile range 244-800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [β] 0.728; 95% confidence interval [CI] 0.324-1.121). This was followed by an immediate decrease (β -13.022; 95% CI -20.401 to -5.643) and then by a second, late increase after 35 h (β 11.750; 95% CI 4.71-18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients. CONCLUSION The time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker

Transient ischemic attacks in patients with active and occult cancer.

BACKGROUND AND AIM Paraneoplastic coagulopathy can present as stroke and is associated with specific biomarker changes. Identifying paraneoplastic coagulopathy can help guide secondary prevention in stroke patients, and early cancer detection might improve outcomes. However, unlike ischemic stroke, it remains unclear whether paraneoplastic coagulopathy is associated with transient ischemic attacks (TIA). This study assessed the presence of cancer-related biomarkers in TIA patients and evaluated long-term mortality rates in patients with and without active cancer. METHODS Active cancer was retrospectively identified in consecutive TIA patients treated at a comprehensive stroke center between 2015 and 2019. An association between the presence of cancer and cancer-related biomarkers was assessed using multivariable logistic regression. Long-term mortality after TIA was analyzed using multivariable Cox regression. RESULTS Among 1436 TIA patients, 72 had active cancer (5%), of which 17 were occult (1.2%). Cancer-related TIA was associated with male gender (adjusted odds ratio [aOR] 2.29, 95% CI 1.12-4.68), history of smoking (aOR 2.77, 95% CI 1.34-5.7), elevated D-dimer (aOR 1.77, 95% CI 1.26-2.49), lactate dehydrogenase (aOR 1.003, 95% CI 1.00-1.005), lower leukocyte count (aOR 1.20, 95% CI 1.04-1.38), and lower hemoglobin (aOR 1.02, 95% CI 1.00-1.04). Long-term mortality was associated with both active cancer (adjusted hazard ratios [aHR] 2.47, 95% CI 1.58-3.88) and occult cancer (aHR 3.08, 95% CI 1.30-7.32). CONCLUSION Cancer-related TIA is not uncommon. Biomarkers known to be associated with cancer-related stroke also seem to be present in TIA patients. Early identification would enable targeted treatment strategies and could improve outcomes in this patient population

Absence of susceptibility vessel sign and hyperdense vessel sign in patients with cancer-related stroke

Background and aimIdentification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients.MethodsSVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression.ResultsOf the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45–6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73–13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54–2.11).ConclusionThe absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care

Potential Misdiagnoses of Bell's Palsy in the Emergency Department

Study objectiveWe evaluate the incidence of potentially incorrect emergency department (ED) diagnoses of Bell's palsy and identify factors associated with identification of a serious alternative diagnosis on follow-up.MethodsWe performed a retrospective cohort study from California's Office of Statewide Health Planning and Development for 2005 to 2011. Subjects were adult patients discharged from the ED with a diagnosis of Bell's palsy. Information related to demographics, imaging use, and comorbidities was collected. Our outcome was one of the following diagnoses made within 90 days of the index ED visit: stroke, intracranial hemorrhage, subarachnoid hemorrhage, brain tumor, central nervous system infection, Guillain-Barré syndrome, Lyme disease, otitis media/mastoiditis, or herpes zoster. We report hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with misdiagnosis.ResultsA total of 43,979 patients were discharged with a diagnosis of Bell's palsy. Median age was 45 years. On 90-day follow-up, 356 patients (0.8%) received an alternative diagnosis, and 39.9% were made within 7 days. Factors associated with the receiving alternative diagnosis included increasing age (HR 1.11, 95% CI 1.01 to 1.21, every 10 years), black race (HR&nbsp;1.68; 95% CI 1.13 to 2.48), diabetes (HR 1.46; 95% CI 1.10 to 1.95), and computed tomography or magnetic resonance imaging use (HR 1.43; 95% CI 1.10 to 1.85). Private insurance was negatively associated with an alternative diagnosis (HR 0.65; 95% CI 0.46 to 0.93). Stroke, herpes zoster, Guillain-Barré, and otitis media accounted for 85.4% of all alternative diagnoses.ConclusionEmergency providers have a very low rate of misdiagnosing Bell's palsy. The association between imaging use and misdiagnosis is likely confounded by patient acuity. Increasing age and diabetes are modest risk factors for misdiagnosis

Predicting Future Brain Tissue Loss From White Matter Connectivity Disruption in Ischemic Stroke

Background and purposeThe Network Modification (NeMo) Tool uses a library of brain connectivity maps from normal subjects to quantify the amount of structural connectivity loss caused by focal brain lesions. We hypothesized that the Network Modification Tool could predict remote brain tissue loss caused by poststroke loss of connectivity.MethodsBaseline and follow-up MRIs (10.7±7.5 months apart) from 26 patients with acute ischemic stroke (age, 74.6±14.1 years, initial National Institutes of Health Stroke Scale, 3.1±3.1) were collected. Lesion masks derived from diffusion-weighted images were superimposed on the Network Modification Tool's connectivity maps, and regional structural connectivity losses were estimated via the Change in Connectivity (ChaCo) score (ie, the percentage of tracks connecting to a given region that pass through the lesion mask). ChaCo scores were correlated with subsequent atrophy.ResultsStroke lesions' size and location varied, but they were more frequent in the left hemisphere. ChaCo scores, generally higher in regions near stroke lesions, reflected this lateralization and heterogeneity. ChaCo scores were highest in the postcentral and precentral gyri, insula, middle cingulate, thalami, putamen, caudate nuclei, and pallidum. Moderate, significant partial correlations were found between baseline ChaCo scores and measures of subsequent tissue loss (r=0.43, P=4.6×10(-9); r=0.61, P=1.4×10(-18)), correcting for the time between scans.ConclusionsChaCo scores varied, but the most affected regions included those with sensorimotor, perception, learning, and memory functions. Correlations between baseline ChaCo and subsequent tissue loss suggest that the Network Modification Tool could be used to identify regions most susceptible to remote degeneration from acute infarcts

Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for Treatment.

Ischemic stroke is an important cause of morbidity and mortality in cancer patients. The underlying mechanisms linking cancer and stroke are not completely understood. Long-standing and more recent evidence suggests that cancer-associated prothrombotic states, along with treatment-related vascular toxicity, such as with chemotherapy and immunotherapy, contribute to an increased risk of ischemic stroke in cancer patients. Novel biomarkers, including coagulation, platelet and endothelial markers, cell-free DNA, and extracellular vesicles are being investigated for their potential to improve risk stratification and patient selection for clinical trials and to help guide personalized antithrombotic strategies. Treatment of cancer-related stroke poses unique challenges, including the need to balance the risk of recurrent stroke and other thromboembolic events with that of bleeding associated with antithrombotic therapy. In addition, how and when to restart cancer treatment after stroke remains unclear. In this review, we summarize current knowledge on the mechanisms underlying ischemic stroke in cancer, propose an etiological classification system unique to cancer-related stroke to help guide patient characterization, provide an overview of promising biomarkers and their clinical utility, and discuss the current state of evidence-based management strategies for cancer-related stroke. Ultimately, a personalized approach to stroke prevention and treatment is required in cancer patients, considering both the underlying cancer biology and the individual patient's risk profile

Abstract Number ‐ 20: Predictors of Outcomes for Patients with Malignancy and Acute Ischemic Stroke Undergoing Endovascular Therapy

Introduction Patients with active cancer face an increased risk for stroke. Randomized trials studying the efficacy of endovascular therapy for patients with large vessel occlusions generally excluded patients with cancer. Herein, we sought to better understand predictors of outcome for active cancer patients undergoing mechanical thrombectomy for acute ischemic stroke. Methods We conducted a retrospective cohort study of stroke thrombectomy cases performed at our institution from January 2010 to November 2021. Baseline clinical characteristics (age, gender, cancer type, use of anticoagulation, NIHSS, use of tPA, time to reperfusion) were recorded. Study outcomes were successful endovascular reperfusion (≥ TICI 2b) and poor clinical outcome, defined as inpatient death or disposition to hospice. Pearson Chi‐square test and Fisher’s exact test were used to analyze categorical variables, and Mann‐Whitney U tests were used for continuous variables. Multivariable logistic regression analyses were performed to evaluate for independent associations between baseline characteristics and study outcomes. Results Between 2010–2021, we identified 49 patients with active cancer who underwent mechanical thrombectomy for stroke. Their mean age was 63 years (SD, 12), and 43% were men. The leading cancer types were lung (33%) and colorectal (14%). Successful reperfusion was achieved in 78% (95% CI, 66–90%) of patients, and 49% (95% CI, 34–63%) ultimately had a poor clinical outcome. Multivariable analyses yielded no significant predictors for successful reperfusion, while higher NIHSS (1.03, 95% CI, 1.01‐1.06, p = 0.011) and higher cancer stage (1.19, 95% CI, 1.04‐1.34, p = 0.014) were found to be predictors for poor clinical outcome. Conclusions The link between cancer and stroke has become increasingly appreciated. As tPA is often contraindicated in cancer patients with stroke because of recent bleeding or anticoagulant use, thrombectomy may be the only intervention to preserve one’s quality of life. However, we found that despite a high successful reperfusion rate, nearly half of these patients died or were made hospice during the index hospitalization. Future studies should investigate the reasons for poor clinical outcomes in these patients and whether different antithrombotic, blood pressure, or anti‐neoplastic strategies after thrombectomy could improve outcomes