Characteristics of cryptogenic stroke in cancer patients

Abstract

ObjectiveTo clarify the characteristics of cryptogenic stroke in patients with active cancer.MethodsPatients with or without cancer diagnosed with acute ischemic stroke between January 2006 and February 2015 were extracted from a prospectively collected stroke database of Osaka University Hospital. Patients were categorized according to the presence of active cancer and known stroke mechanisms.ResultsAmong 1191 patients with acute ischemic stroke, 145 (12%) had active cancer. Patients with active cancer were diagnosed more often with cryptogenic stroke than were patients without cancer (47% vs. 12%, P < 0.001). Compared with cryptogenic stroke patients without cancer, cryptogenic stroke patients with active cancer had fewer atherosclerotic risk factors, lower nutrition status, higher plasma D‐dimer levels, and multiple vascular lesions. In a multivariate logistic analysis, plasma D‐dimer level (odds ratio [OR] per 1 standard deviation increase: 6.30; 95% confidence interval [CI]: 2.94–15.69; P < 0.001), and the presence of multiple vascular lesions (OR: 6.40; 95% CI: 2.35–18.35; P < 0.001) were independent predictors of active cancer. When comparing active cancer patients who had known stroke mechanisms with those who had cryptogenic stroke, high plasma D‐dimer levels, multiple vascular lesions, and receiving chemotherapy and/or radiation therapy were associated with cryptogenic stroke etiology.InterpretationIn cryptogenic stroke, patients with active cancer has a unique pathology characterized by high plasma D‐dimer levels and multiple vascular lesions. The hypercoagulable state and malnutrition due to cancer and its treatments potentially influence the development of cryptogenic stroke in cancer patients.

When to Screen Ischaemic Stroke Patients for Cancer

“…Similar findings with regard to blood coagulation factors and aetiology have also been shown [6, 8, 13, 27, 28], but as of yet, there is no score in place predicting active cancer in stroke patients. Based on our findings we constructed a predictive score for clinical use in order to detect ischaemic stroke patients with concomitant active cancer.…”

“…The proportion of stroke patients with active or occult cancer is debated and study findings reveal a value ranging from <2 to 13% [12, 27-29]. However, with increasing age of populations and thereby higher incidence of both stroke and cancer, uncovering cancer-associated strokes is becoming increasingly important.…”

Plasma D‐dimer levels and ischaemic lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke

“…Furthermore, high plasma D-dimer levels and lesions in multiple vascular regions in patients with cryptogenic stroke independently predicted the presence of occult cancer. These findings suggest that the clinical features reported in cancer patients with cryptogenic stroke [9][10][11] appear to be useful for the identification of occult cancer in these patients. Similarly, these results confirm our hypothesis that plasma D-dimer levels and lesions in multiple vascular regions are useful to predict the presence of occult cancer as an Data are presented as median (interquartile range) or percentage (number).…”

Ischemic stroke in cancer patients: A review of an underappreciated pathology

“…30, 31 These cancer-related cryptogenic strokes tend to be associated with high D-dimer levels, infarctions in multiple vascular territories, and metastatic disease. 32, 54, 55 One common theory is that many cryptogenic strokes in cancer patients are from cardioembolic manifestations of cancer-mediated hypercoagulability, specifically nonbacterial thrombotic endocarditis, which comprises sterile, platelet-fibrin vegetations on cardiac valves. 31 Supporting this hypothesis is an older, highly-cited autopsy study of 256 cancer patients with cerebrovascular disease, which reported that nonbacterial thrombotic endocarditis was the leading cause of symptomatic ischemic stroke in this population.…”