Clues to Occult Cancer in Patients with Ischemic Stroke

Abstract

BackgroundWe hypothesized that hidden malignancy could be detected in patients with cryptogenic stroke without active cancer when they showed the distinctive characteristics of cancer-related stroke.Methods and FindingsAmong 2,562 consecutive patients with acute ischemic stroke, patients with cryptogenic stroke were analyzed and categorized into two groups according to the presence of active cancer: cryptogenic stroke with active cancer (cancer-related stroke, CA-stroke) group and without active cancer (CR-stroke) group. Patients with active lung cancer without stroke were also recruited for comparison purposes (CA-control). Clinical factors, lesion patterns on diffusion-weighted MRI (DWI), and laboratory findings were analyzed among groups. A total of 348 patients with cryptogenic stroke were enrolled in this study. Among them, 71 (20.4%) patients had active cancer at the time of stroke. The D-dimer levels were significantly higher in patients with CA-stroke than those with CR-stroke or CA-control (both p<0.001). Regarding lesion patterns, patients with CA-stroke mostly had multiple lesions in multiple vascular territories, while more than 80% of patients with CR-stroke had single/multiple lesions in a single vascular territory (P<0.001). D-dimer levels (OR 1.11 per 1 µg/mL increase; 95% CI 1.06–1.15; P<0.001) and DWI lesion patterns (OR 7.13; 95% CI 3.42–14.87; P<0.001) were independently associated with CA-stroke. Workup for hidden malignancy was performed during hospitalization in 10 patients who showed elevated D-dimer levels and multiple infarcts involving multiple vascular territories but had no known cancer, and it revealed hidden malignancies in all the patients.ConclusionPatients with CA-stroke have distinctive D-dimer levels and lesion patterns. These characteristics can serve as clues to occult cancer in patients with cryptogenic stroke.

Evaluation of Cryptogenic Stroke With Advanced Diagnostic Techniques

“…In a recent analysis of patients with cryptogenic stroke, patients with active cancer were present (71 of 348 patients; 20%) and had distinctive D-dimer levels (a marker of coagulopathy, >20× higher than those without cancer) and infarct patterns (multiple lesions in multiple vascular territories). 60 Interestingly, in this study, among 10 patients who showed such characteristics but no known cancer, workup for hidden malignancy reveled occult cancer in all patients (Figure 4). Therefore, patients who present with characteristic symptoms and infarct patterns, and no other apparent explanation for their index stroke, D-dimer level and screening for hidden malignancy (serological or radiological tests) should be considered.…”

Small-animal PET demonstrates brain metabolic change after using bevacizumab in a rat model of cerebral ischemic injury

“…Clinical presentation of CVD in cancer patients is common: 14.6% of such patients have pathologic evidence of CVD, and 7.4% show clinical symptoms [5] . Although current therapeutic strategies improve the survival rate and extend the lifetime of cancer patients, increased risk of ischemic stroke is frequently observed in the same individuals [6] . Therefore, exploring the therapeutic strategies for recent ischemic stroke in cancer patients is a serious challenge.…”

Association between thrombophilia and ischemic stroke: when is work-up for hypercoagulable state indicated?

“…Another study by Kim et al found a 20.4% of patients with cryptogenic stroke had active cancer at the time of stroke. The common sites were lung, lymphoma, hepatobiliary and gastrointestinal [17,18]. Clues to OM in these patients include high D-dimer levels (odd ratio 1.11 per 1 µg/mL increase) and multiple ischemic lesions in multiple vascular territories as shown by two retrospective studies [17].…”

“…The common sites were lung, lymphoma, hepatobiliary and gastrointestinal [17,18]. Clues to OM in these patients include high D-dimer levels (odd ratio 1.11 per 1 µg/mL increase) and multiple ischemic lesions in multiple vascular territories as shown by two retrospective studies [17]. Therefore, patients with acute ischemic stroke should be encouraged to undergo age appropriate screening for cancer.…”

“…Family or personal history of clotting events (specially venous) at a young age or in unusual locations with no clear explanation for stroke and elevated D-dimer, there should be low threshold for appropriate work-up [17,19]. In patients who have a family history of specific cancer type, screening for the respective cancer can be considered.…”