The etiology of ischemic stroke is complicated and various. But in clinical work, malignant tumor is often neglected as the cause of ischemic stroke. In the present study, there were 11(73.33%) cases of lung cancer, including 7 cases of lung adenocarcinoma. It could be seen that Trousseau's syndrome with MAIS was more common in lung cancer, which might be related to the high incidence of lung cancer in Chinese population. In addition, adenocarcinoma had a higher proportion of Trousseau's syndrome with MAIS in lung cancer. This is because the sialic acid moieties of mucin from adenocarcinoma can cause a direct nonenzymatic activation of factor X. On the side, carcinoma mucins interact with the selectin adhesion molecule, namely L-selectin, which is expressed on leukocytes, and P-selectin, which is expressed on platelets and endothelial cells. It is more likely to cause ischemic stroke . It is worth noting that in our study, 6 patients had an ischemic stroke first, and then found a tumor lesion. So, ischemic stroke might be the first manifestation of an undiagnosed cancer .
The most common mechanism in patients with Trousseau’s syndrome is hypercoagulable state. Its potential mechanisms include hypercoagulability induced by cancer procoagulant, tissue factor, mucin secreted by carcinomas, hypoxia, and the MET oncogene, which upregulates plasminogen activator inhibitor-1 (PAI-1) and cyclooxygenase-2 (COX-2) associated with coagulopathy . In clinical practice, most patients are assessed for hypercoagulability by monitoring their D-dimer levels. Previous studies showed that plasma D-dimer levels were significantly elevated in patients with cancer-associated ischemic stroke compared to those suffering from non-cancer-associated ischemic stroke . Therefore, most scholars believe that Trousseau syndrome is related to increased plasma D-dimer, and if there is no timely diagnosis and treatment, the plasma D-dimer will show persistent increase and recurrent cerebral infarction. Moreover, one research had shown that serial D-dimer levels of 10 patients who died within 90 days were significantly higher than those of the 11 patients who survived up to 90 days . This suggests that serial D-dimer determinations may be a good biomarker and a useful prognostic indicator for Trousseau syndrome patients. In our study, all the 15 patients showed different degrees of increase of D-dimer. The mean D-dimer level was 12.39 µg/ml, significantly elevated than normal. So we found D-dimer is an important diagnostic biomarker of Trousseau's syndrome, and confirmed with the previous studies. The other mechanism of Trousseau’s syndrome is nonbacterial thrombotic endocarditis (NBTE), which is characterized by nonbacterial vegetation without valvular destruction . But NBTE is diagnosed infrequently before death but prevalence can increase up to 32% in postmortem series .None of the 15 patients in this study underwent transesophageal echocardiography, so the presence of NBTE could not be completely excluded.
In our study, various tumor markers had increased to varying degrees. Especially for CYFRA-211, all the 15 patients of which is higher than normal. We considered that this might be associated with a higher proportion of lung cancer. Therefore, patients with increased CYFRA-211 in multiple acute ischemic strokes should pay special attention to the possibility of lung cancer. According to previous reports, the serum tumor markers CA19-9 and CA125 were found to be markedly elevated, which may also had been involved in the formation of thromboembolism . Another study had suggested that CA125 and CA15-3 expression were associated with the incidence of thromboembolism in cancer patients, and the significantly increased of CA125 was associated with the recurrence of ischemic strokes in patients with metastatic cancer [11, 12]. Most patients in our study showed an increase in NSE, CA125, CA153, and CA199. In the meantime, we found AFP was normal in all patients. This is related to the fact that it is a specific indicator of liver cancer. In conclusion, patients with Trousseau’s syndrome may have elevated levels of tumor markers, which may also be associated with thromboembolic formation.
We found that the clinical manifestations of patients were hemiplegia, (or) dysarthria and dizziness. The average score of NIHSS was 2.13. So the symptoms and signs of focal neurological deficits in patients with Trousseau’s syndrome may be similar with traditional ischemic strokes, but not serious. Four(26.7%) of our patients had Peripheral venous thrombosis, including subclavian venous thrombosis(n = 2), deep left leg venous thrombosis(n = 2), Bilateral calf muscle vein thrombosis(n = 2). Thus patients with Trousseau's syndrome with MAIS may have vein thrombosis at the same time, which is consistent with other literature reports . This suggests that patients in this category should be alert to the possibility of peripheral venous thrombosis, and perform peripheral vascular examination as soon as possible.
Imaging results in this study revealed that all patients had multiple infarction lesions in DWI, usually with no significant stenosis of the brain arteries on MRA (Fig. 2).Most of the infarct lesions had a characteristic appearance, being nonenhancing, nonring-appearing clusters or single areas of restricted diffusion of 0.5–2 cm with a peripheral location or larger vascular territories, uncommonly in a watershed distribution, and with absence of diffuse cortical ribbon or deep gray nuclei involvement . In our study, there were 13 patients with bilateral anterior and posterior circulation, 1 patient with unilateral anterior circulation plus posterior circulation, and 1 patient with bilateral anterior circulation. These results suggest that the anterior and posterior circulation is the most compelling MR imaging feature of Trousseau's syndrome with MAIS. In particular, DWI presented a higher proportion of bilateral anterior and bilateral posterior circulation. Some studies sought to highlight the “Three Territory Sign” (TTS) (bilateral anterior and posterior circulation acute ischemic diffusion-weighted imaging [DWI] lesions), as a radiographic marker of stroke due to malignancy [14, 15]. Therefore, it is necessary to pay attention to the screening of the unknown neoplasia in patients with similar imaging characteristics.
The major approach for treating Trousseau's syndrome is to eliminate the causative tumor . For Trousseau's syndrome with MAIS early anticoagulant therapy is more important. At the present time, direct oral anticoagulants have not been recommended for such patients . Thirteen of the fifteen patients in the present study were given anticoagulation with low molecular heparin, and most of which were improved after treatment and 4 patients were not. So low molecular heparin maybe effectively in a short-term for Trousseau's syndrome with MAIS.