Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms

Abstract

Systemic cancer and ischemic stroke are common conditions and two of the most frequent causes of death among the elderly. The association between cancer and stroke has been reported worldwide. Stroke causes severe disability for cancer patients, while cancer increases the risk of stroke. Moreover, cancer-related stroke is expected to increase due to advances in cancer treatment and an aging population worldwide. Because cancer and stroke share risk factors (such as smoking and obesity) and treatment of cancer can increase the risk of stroke (e.g., accelerated atherosclerosis after radiation therapy), cancer may accelerate conventional stroke mechanisms (i.e., atherosclerosis, small vessel disease, and cardiac thrombus). In addition, active cancer and chemotherapy may enhance thrombin generation causing stroke related to coagulopathy. Patients with stroke due to cancer-related coagulopathy showed the characteristics findings of etiologic work ups, D-dimer levels, and infarct patterns. In this review, we summarized the frequency of cancer-related stroke among patients with ischemic stroke, mechanisms of stroke with in cancer patients, and evaluation and treatment of cancer-related stroke. We discussed the possibility of cancer-related stroke as a stroke subtype, and presented the most recent discoveries in the pathomechanisms and treatment of stroke due to cancer-related coagulopathy.

Keywords: Cancer; Coagulopathy; Neoplasms; Stroke; Subtype; Thrombosis.

Figure 1.

Stroke subtypes, including cancer-related stroke. NBTE, non-bacterial thrombotic endocarditis; DVT, deep vein thrombosis; PE, paradoxical embolism; CVT, cerebral venous thrombosis.

Figure 2.

Overview of some of the pathways involved in the pathogenesis of cancer-related coagulopathy in stroke patients. Dashed lines represent the possible mechanisms involved in venous thrombosis, but have not been reported in cancer-related stroke. EV, extracellular vesicle; NET, neutrophil extracellular trap; RBC, red blood cell; PFO, patent foramen ovale.

Figure 3.

Hidden cancer and stroke caused by cancer-related coagulopathy. A 49-year-old woman presented with recurrent left arm weakness and sensory changes. Vascular study and transthoracic echocardiogram were negative. Microembolic signals were detected during transcranial Doppler monitoring. TCD shunt test showed right-to-left shunt and leg duplex revealed occlusion of right leg veins. Serum D-dimer level was elevated to 6.23 μg/mL (normal <0.5 μg/mL) and CA-125 level was 489.6 U/mL (normal range up to 35 U/mL). Abdominopelvic magnetic resonance image (MRI) showed a 6 cm right ovarian cancer and a 2.2 cm endometrial cancer, both at stage 1a with no metastasis. D-dimer level was lower after anticoagulation with enoxaparin. The patient experienced recurrent stroke with elevation of D-dimer levels during the period of discontinuation for tumor resection. After surgery, anticoagulation therapy was restarted and she remained stable without stroke recurrence. Anticoagulation therapy was discontinued after 6 months of surgery, and D-dimer levels remained in the normal range. DWI, diffusion-weighed image; LMWH, low-molecular weight heparin; TCD MES, transcranial duplex microembolic signal.