Cancer-associated Stroke Research Articles

Correlation of enlarged perivascular spaces in basal ganglion and cancer-associated stroke: a case–control study in China

IntroductionThe incidence of cancer-associated ischaemic stroke (IS) is increasingly prevalent. This study aimed to assess the levels of enlarged perivascular spaces in basal ganglion (BG-EPVS) in cancer-associated patients who had...

Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke

Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke. To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke. Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024. Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined. The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage. Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%]). Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin. ClinicalTrials.gov Identifier: NCT03192215.

Cancer-Associated Stroke: Thrombosis Mechanism, Diagnosis, Outcome, and Therapeutic Strategies.

Cancer can induce hypercoagulability, which may lead to stroke. This occurs when tumor cells activate platelets as part of their growth and metastasis. Tumor cells activate platelets by generating thrombin and expressing tissue factor, resulting in tumor cell-induced platelet aggregation. Histopathological studies of thrombi obtained during endovascular thrombectomy in patients with acute stroke and active cancer have shown a high proportion of platelets and thrombin. This underscores the crucial roles of platelets and thrombin in cancer-associated thrombosis. Cancer-associated stroke typically occurs in patients with active cancer and is characterized by distinctive features. These features include multiple infarctions across multiple vascular territories, markedly elevated blood D-dimer levels, and metastasis. The presence of cardiac vegetations on echocardiography is a robust indicator of cancer-associated stroke. Suspicion of cancer-associated stroke during endovascular thrombectomy arises when white thrombi are detected, particularly in patients with active cancer. Cancer-associated stroke is almost certain when histopathological examination of thrombi shows a very high platelet and a very low erythrocyte composition. Patients with cancer-associated stroke have high risks of mortality and recurrent stroke. However, limited data are available on the optimal treatment regimen for stroke prevention in these patients. Thrombosis mechanism in cancer is well understood, and distinct therapeutic targets involving thrombin and platelets have been identified. Therefore, direct thrombin inhibitors and/or antiplatelet agents may effectively prevent stroke recurrence. Additionally, this strategy has potential benefits in cancer treatment as accumulating evidence suggests that aspirin use reduces cancer progression, metastasis, and cancer-related mortality. However, clinical trials are necessary to assess the efficacy of this strategy involving the use of direct thrombin inhibitors and/or antiplatelet therapies.

Cancer-associated ischemic stroke: current knowledge and future directions

Because cancer is a strong prothrombotic, there is an increased risk of thromboembolism, which includes ischemic stroke, especially in the first six to twelve months following a cancer diagnosis. The risk of ischemic stroke differs according to the location and stage of cancer. Given that the risk increases prior to a cancer diagnosis, stroke may be the initial sign of occult cancer. Although data on the risk, treatment, and outcomes of cancer-associated stroke are more limited than those on cancer-associated venous thromboembolism, the condition is still recognized as a thrombotic complication of cancer. Up to 10% of ischemic stroke patients also have a concurrent cancer diagnosis, and these patients seem to have higher short-term mortality and morbidity rates. With more people expected to survive longer after cancer treatment and an increasing number of cancer survivors, the burden of stroke among cancer patients is predicted to rise. This narrative review aims to provide an overview of the pathophysiologic mechanisms, treatment options, and epidemiology of ischemic stroke, including cancer screening for those who have cryptogenic (unexplained) stroke.

Clinical features and prognostic factors of patients with cancer-associated stroke.

Cerebrovascular diseases in cancer patients significantly aggravate their condition and prognosis; therefore, prompt and accurate diagnosis and treatment are important. The purpose of this study was to investigate patient demographics, laboratory data, brain magnetic resonance imaging (MRI) findings, and prognosis among patients with stroke and cancer, especially cancer-associated ischemic stroke (CAIS). We performed a retrospective, single-center study. We enrolled consecutive patients who had acute stroke and were admitted to our hospital between January 2011 and December 2021. We collected general demographic characteristics, cancer histopathological type, laboratory data, brain MRI findings, and prognosis data. Among 2040 patients with acute stroke, a total of 160 patients (7.8%) had active cancer. The types of strokes were cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack in 124, 25, 5, and 6 patients, respectively. Among the patients with ischemic stroke, there were 69 cases of CAIS. Pancreas and adenocarcinoma were the most frequent types of primary tumor and histopathology. Patients with adenocarcinoma and those with cerebral infarctions in both bilateral anterior and posterior cerebral circulation areas showed higher D-dimer levels. Pancreatic cancer and high plasma D-dimer levels were associated with poor survival rate. CAIS was seen more frequently in patients with pancreatic cancer and adenocarcinoma. Pancreatic cancer and high plasma D-dimer levels were potential factors of poor prognosis in patients with CAIS.

Von Willebrand Factor Antigen Levels Predict Poor Outcomes in Patients With Stroke and Cancer: Findings From the Multicenter, Prospective, Observational SCAN Study.

Patients with acute ischemic stroke and active cancer have more severe neurological symptoms, elevated risks of stroke recurrence, and death compared with the general population. We examined whether von Willebrand factor (vWF) antigen levels at stroke onset were associated with the poor outcomes of patients with stroke and cancer. Using data from 90 patients with acute ischemic stroke and active cancer who were registered in the SCAN (Ischemic Stroke in Patients With Cancer and Neoplasia) study, a prospective multicenter, observational study in Japan, we divided patients into 2 groups according to their median vWF antigen levels (high, n=46; or low, n=44). The high-vWF group had a significantly higher initial National Institutes of Health Stroke Scale score (median, 7 [interquartile range, 3-11.25] versus 3 [interquartile range, 1-8.5]; P<0.05) and a significantly higher incidence of cryptogenic stroke (32 [70%] versus 16 [36%]; P<0.01) and venous thromboembolism (7 [15%] versus 0 [0%]; P<0.01), as well as multiple lesions (28 [62%] versus 12 [27%]; P<0.001), than the low-vWF group. We observed no significant difference in the rate of stroke recurrence within 1 year between the groups. However, increased vWF levels were an independent predictor of death within 1 year of stroke onset, after adjusting for potential confounders (odds ratio, 6.77 [95% CI, 1.49-30.78]; P<0.05). Elevated vWF antigen levels were associated with adverse outcomes in patients with cancer-associated stroke and may represent a useful biomarker to guide future therapeutic interventions.

NEUROLOGIC COMPLICATION IN LUNG ADENOCARCINOMA EFGR MUTATION WITH A CONSOLIDATION-TO-TUMOR-RATIO (CTR) &gt;75%

Lung adenocarcinoma (LAC) accounts for a large proportion of lung cancer subtypes and causes various neurologic complications. This calls for extensive use of CT scans for detecting lung cancer which contains ground glass opacity (GGO). A Consolidation-to-tumor-ratio (CTR) &gt;75% has a worse prognosis in LAC. A male 50-years-old came with paraplegia, complaining suddenly that his legs could not be moved. The patient performed a spine MRI with the result indicating a spinal metastatic process. Furthermore, the Chest X-ray only showed consolidation in the right paracardial area but the chest CT confirmed as lung mass followed by histopathology examination result of LAC with EFGR mutation. After three months, the patient also had multiple cerebral infarcts. We reported one case of LAC EFGR mutation with a CTR of 83%. higher CTR has more invasive adenocarcinomas and also correlated with immunosuppressive conditions compared with a low CTR. The patient was diagnosed lately after a complication of spinal compression. The other neurological complication is multiple cerebral infarcts. The pathogenesis of cancer-associated stroke has not been fully clarified. The pathophysiological mechanisms of these cerebrovascular complications are multifactorial. Other biological markers may also be of interest, including high levels of C-reactive protein (CRP), high levels of fibrinogen, decreased hemoglobin, and hypoalbuminemia. Retrospective studies on acute stroke detected significantly higher levels of fibrinogen and CRP in patients with cryptogenic stroke and occult malignancy. LAC with a CTR &gt;75% is more invasive due to neurologic complications such as spinal metastases and stroke infarction. Keywords: Lung adenocarcinoma, CTR, Stroke, Metastase

ISCHEMIC STROKE AND HEMOSTASIS DISORDERS IN ONCOLOGICAL PROCESS: A LITERATURE REVIEW

Malignant neoplasms are associated with an increased risk of developing acute cerebrovascular accidents. This article provides a review of the literature on hemostatic disorders during oncological processes in patients with ischemic stroke. Cancer-associated stroke can develop for several reasons, including direct effects of the tumor, as well as indirectly through the development of blood coagulation disorders, concomitant infectious diseases, or complications of antitumor therapy. One of the most common pathogenetic mechanisms is cancer-associated coagulopathy. Trousseau syndrome is a variant of paraneoplastic syndrome, characterized by a state of hypercoagulability with the development of thrombosis that precedes the diagnosis of a malignant neoplasm or develops simultaneously with it. Cerebral ischemia in Trousseau’s syndrome is characterized by a multifocal pattern of lesions according to neuroimaging data. To date, there are no clear diagnostic criteria for cancer-associated stroke, which is often one of the first clinical manifestations of the oncological process. According to various studies, laboratory markers of hypercoagulability can serve as predictors of previously undiagnosed malignancy in patients with cryptogenic ischemic stroke. Currently, more and more attempts are being made to develop diagnostic scales based on clinical and neuroimaging characteristics of stroke to identify hidden oncological processes. Another important aspect of the issue remains the lack of evidence-based recommendations for the treatment of ischemic stroke associated with cancer. Given the prevalence of stroke in cancer patients, potentially poor functional prognosss, higher rates of post-stroke mortality and high relapse rates, further research into this issue is required.

Occurrence and Outcomes of Acute Cerebrovascular Events in Patients with Non-Hodgkin Lymphoma

Background Stroke or Cerebrovascular Accident (CVA) is one of the leading causes of mortality in the world whether it be ischemic or hemorrhagic 1,2. There has been an association of increased incidence of stroke in patients with cancer due to multiple factors 3. Regarding hematologic malignancies, there have been studies to assess the risk of developing stroke in patients with Hodgkin lymphoma (HL), however the information on non-Hodgkin lymphoma (NHL) is limited and not well understood4. We conducted a retrospective case-control study to assess the incidence, risks, and complications and length of stay of patients with current or prior history of NHL who developed an ischemic stroke. Methods This case-control study identified 29,632 patients older than 18 years, with or without CVA and with or without active or history of Non-Hodgkin Lymphoma (NHL) who were admitted to diverse private hospitals between 2018-2022. The patients were divided into two groups, one with current or prior NHL (n=10,699) and a control group of patients (n=18,933) with similar characteristics. Patients with active hemorrhagic stroke, pregnancy, malignancies other than NHL, prior hemorrhagic or ischemic stroke, infective endocarditis, atrial fibrillation, and acute coronary syndrome on admission were excluded. We compared patient's characteristics and the risk of developing a stroke based on the presence or absence of NHL as well as the factors that increased hospital mortality. Length of stay was evaluated as a secondary outcome. Bivariate statistical analysis was used to calculate the odds ratios using RStudio 4.2.2 and JMP Pro 16.0 for all data analysis. Results Of the group with NHL 46.39 % (n=4958) were female, and 53.61% (n=5729) were male, 42% were current or former smokers (n=4497), 27.49% (n=2941) had diabetes, 44.68% (n=4780) had hypertension; 3.34% (357) of them passed away. Of the control group 57.51 % (n=10876) were female, and 42.49% (n=8036) were male, 35% were current or former smokers (n=6763), 16.43% (n=3111) had diabetes, 28.89% (n=5469) had hypertension; 0.47% (n=88) of them passed away. The mean length of stay of patients with stroke was 7.99 days in the NHL group, and 5.99 days in the control group. Regarding the admissions due to stroke, there were 214 patients in the group with NHL, and in the control group where there were 113. Patients with NHL are more likely to have a CVA compared to the control group (OR 2.39 p&amp;lt;0.0001 CI 1.47~3.85) Patients who have NHL are more likely to die (OR=6.08 p&amp;lt;0.001) CI 4.77~7.74) compared to patients without NHL from all causes. Conclusion Patients with Non-Hodgkin lymphoma have an increased risk of developing a stroke compared to patients with similar characteristics but without NHL (or other malignancies). It was also noted that patients had an increased length of stay. Other variables and characteristics of patients that were identified to be more likely to have a CVA and statistically significant for this sample are already well-known risk factors for CVA including diabetes, hypertension, and cardiovascular disease. However, this study aimed to isolate those variables to identify the risk for stroke in this unique population. Our study limitation is the broad spectrum of NHL and possible confounders between the different variants of NHL. More studies are needed to investigate this. References Navi B, Reiner A, Kamel H, et al. Risk of Arterial Thromboembolism in Patients with Cancer. J Am Coll Cardiol. 2017 Aug, 70 (8) 926-938.Turner, M., Murchie, P., Derby, S. et al. Is stroke incidence increased in survivors of adult cancers? A systematic review and meta-analysis. J Cancer Surviv 16, 1414-1448 (2022). https://doi.org/10.1007/s11764-021-01122-7Dardiotis E, Aloizou AM, Markoula S, et al. Cancer-associated stroke: Pathophysiology, detection, and management (Review). Int J Oncol. 2019;54(3):779-796. doi:10.3892/ijo.2019.4669Wei Y, Yang Q, Qin Q, et al. Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study. Eur Neurol. 2020;83(1):41-48. doi:10.1159/000506046

Driver gene KRAS aggravates cancer-associated stroke outcomes

The incidence of cancer-associated stroke has increased with the prolonged survival times of cancer patients. Recent genetic studies have led to progress in cancer therapeutics, but relationships between oncogenic mutations and stroke remain elusive. Here, we focused on the driver gene KRAS, which is the predominant RAS isoform mutated in multiple cancer types, in cancer associated stroke study. KRASG13D/− and parental human colorectal carcinoma HCT116 cells were inoculated into mice that were then subjected to a photochemically-induced thrombosis model to establish ischemic stroke. We found that cancer inoculation exacerbated neurological deficits after stroke. Moreover, mice inoculated with KRASG13D/− cells showed worse neurological deficits after stroke compared with mice inoculated with parental cells. Stroke promoted tumor growth, and the KRASG13D/− allele enhanced this growth. Brain RNA sequencing analysis and serum ELISA showed that chemokines and cytokines mediating pro-inflammatory responses were upregulated in mice inoculated with KRASG13D/− cells compared with those inoculated with parental cells. STAT3 phosphorylation was promoted following ischemic stroke in the KRASG13D/− group compared with in the parental group, and STAT3 inhibition significantly ameliorated stroke outcomes by mitigating microglia/macrophage polarization. Finally, we compared the prognosis and mortality of colorectal cancer patients with or without stroke onset between 1 January 2007 and 31 December 2020 using a hospital-based cancer registry and found that colorectal cancer patients with stroke onset within 3 months after cancer diagnosis had a worse prognosis. Our work suggests an interplay between KRAS and ischemic stroke that may offer insight into future treatments for cancer-associated stroke.

Coagulation Factor Expression and Composition of Arterial Thrombi in Cancer-Associated Stroke.

Cancer is associated with an increased risk of stroke. Tumor cells activate platelets, induce a coagulation cascade, and generate thrombin. The composition of thrombi may reflect the mechanism of thrombosis, aiding the determination of the treatment strategy. Here, we investigated the composition and expression of coagulation factors in the thrombi of patients with cancer-associated stroke. Patients with stroke who underwent endovascular thrombectomy between September 2014 and June 2020 and whose cerebral thrombi were obtained were divided into those with cancer-associated stroke (cancer group) and propensity score-matched patients without cancer (control group), using 1:1 matching based on age and sex. Immunohistochemistry was performed of the thrombi, and the composition and expression of coagulation factors were compared between groups. Among the 320 patients who underwent endovascular thrombectomy and who had thrombi obtained, this study included 23 patients with cancer and 23 matched controls. In both groups, the median age was 65 years, and 12 patients (52.2%) were men. Platelet composition was significantly higher in the cancer group than in the control group (median [interquartile range], 51.3% [28.0%-61.4%] versus 9.5% [4.8%-14.0%]; P<0.001). Among coagulation factors, thrombin (26.2% [16.2%-52.7%] versus 4.5% [1.3%-7.2%]; P<0.001) and tissue factors (0.60% [0.34%-2.06%] versus 0.37% [0.22%-0.60%]; P=0.024) were higher and factor X was lower (1.25% [0.39%-3.60%] versus 2.33% [1.67%-4.48%]; P=0.034) in the cancer group. There was a positive correlation between thrombin and platelets in the cancer group (r=0.666; P=0.001) but not in the control group (r=-0.167; P=0.627). Cerebral thrombi in patients with cancer-associated stroke showed higher proportions of platelets, thrombin, and tissue factors, suggesting their key roles in arterial thrombosis in cancer and providing a therapeutic perspective for preventing stroke in patients with cancer-associated stroke.

Effects of cancer on stroke recurrence and mortality: A single-center retrospective cohort study.

Whether patients with stroke and cancer have specific characteristics remains controversial. In addition, research regarding the effects of individual cancer types on stroke outcomes remains scarce. This study investigated the mortality and stroke recurrence rates in patients with stroke and concomitant cancer and evaluated outcome predictors. This study retrospectively enrolled 2610 patients in the Taipei Veterans General Hospital Stroke Registry registered from January 2019 to December 2020. A total of 1868 patients were included after excluding those without acute ischemic stroke or hospitalization. The patients were then categorized into the following diagnostic groups: cancer-associated stroke (CAS), stroke and inactive cancer, and stroke without cancer. The discharge mortality rate, 1-year mortality rate, and 1-year stroke recurrence rate were compared. Multiple clinical characteristics and comorbidities-age, sex, stroke severity, coagulopathy, common vascular risk factors, and acute stroke treatment-were also assessed. A total of 302 (16.2%) patients had concomitant cancer; 39 (2.1%) patients were classified as having CAS and 263 (14.1%) as having stroke with inactive cancer. The baseline characteristics, stroke severity, and type of acute reperfusion therapy were similar among the three groups. However, the stroke recurrence and mortality rates were much higher in the patients with CAS in both short-term and long-term follow-up. The 30-day and 1-year mortality rates for the CAS, inactive cancer, and no cancer groups were 17.9%, 12.5%, and 4.7%, (p<0.001) and 51.3%, 33.8%, and 12.4%, (p<0.001) respectively. Patients with stroke and active cancer had similar stroke severity. However, the 1-year mortality and stroke recurrence rates were higher in these patients than in patients with inactive cancer or the control group.

Cerebrovascular Events During Treatment for Systemic Malignant Tumors in Patients with Moyamoya Disease

With the increasing incidence of malignancies, the importance of cancer-associated stroke is emphasized. Although moyamoya disease is a leading cause of stroke, no reports have documented cancer-associated stroke in patients with this condition. We aimed to investigate cerebrovascular events during malignancy treatments in patients with moyamoya disease. A total of 405 patients with moyamoya disease who visited our hospital between January 2000 and March 2022 were retrospectively examined. We evaluated the management of moyamoya disease, presence of the ring finger protein 213 p.Arg4810Lys variant, treatments for malignant tumors, presence of cerebrovascular events during treatment, and follow-up periods and outcomes. Among the 405 patients, 17 patients with moyamoya disease (4.2%) were diagnosed with malignancies. Among patients aged 60years and over, 7 out of 67 (10.4%) had malignancies. Of the 17 patients, 11 (64.7%) were symptomatic, and 7 (41.2%) had revascularization surgery. 9 patients were treated with oral antiplatelet drugs. There was no significant difference between the groups with and without malignancy regarding the presence of the ring finger protein 213 p.Arg4810Lys variant (80.0% vs. 62.7%, P= 0.33). All patients underwent surgical treatment, and 7 (41.2%) received chemotherapy. One death due to tumor progression was reported. No cerebrovascular event was observed during malignancy treatments and follow-up periods, which had a mean duration of 6years. In our cohort, malignancy treatments in patients with moyamoya disease were safely conducted without cerebrovascular events. However, it is advisable to avoid hypotension, dehydration, hyperventilation, and long-term discontinuation of antiplatelet drugs during the treatment of malignant tumors.

Cryptogenic stroke. Part 4: Antiphospholipid syndrome and cancer

Cryptogenic embolic stroke (embolic strokes of undetermined source, ESUS) is an intermediate diagnosis in patients with unknown etiology of stroke and implies the absence of large sources of cardioembolism and significant extra- and intracranial stenoses and probably embolic pathogenesis of cerebral infarction. In the previous parts of the article, we discussed the issues of diagnosis and secondary prevention of ESUS with underlying potential aortoaortic sources of embolism, paradoxical embolism and atrial cardiopathy. This article discusses the issues of epidemiology, pathogenesis, diagnosis and secondary prevention of ischemic stroke with underlying antiphospholipid syndrome (APS) and cancer-associated stroke (RAI). Both mechanisms of stroke are associated with hypercoagulability, often manifest as multifocal cortical brain lesions, and respond to anticoagulant therapy. While APS should be suspected primarily in young women with pathology of pregnancy, arterial and venous thrombosis, as well as livedo reticularis (racemosa), RAI does not have a specific clinical picture, but can manifest as diffuse cortical infarcts (symptom of three pools) combined with increased D-dimer level. If APS is suspected, appropriate haematological screening is required, followed by the use of the Sydney diagnostic criteria. Possible diagnosis of RAI often requires transesophageal echocardiography (ruling out non-bacterial thromboendocarditis) and oncological screening. Secondary prevention of APS consists in prescribing warfarin with the target international normalized ratio (INR) of 2.0 to 3.0. RAI is treated with anticoagulants, but the choice of a drug and dose is determined by the balance between thrombotic/thromboembolic and hemorrhagic risks.

Stroke and Disseminated Intravascular Coagulation in a Patient With Metastatic Prostate Cancer.

Cancer and stroke comprise two of the most common causes of death worldwide. Despite a significantly increased risk of stroke among patients with cancer, most stroke trials have excluded patients with malignancy. There is thus limited evidence to help guide management decisions in this complex population. We present the case of a 78-year-old man with recurrent strokes - both ischemic and hemorrhagic - in the setting of newly-identified metastatic prostate cancer. An atypical cause of cancer-associated stroke is reviewed and the management is discussed.

Cancer-Associated Stroke and Acute Endovascular Reperfusion Therapy.

Since stroke is often associated with cancer, acute stroke patients with cancer undergoing endovascular therapy (EVT) are not uncommon. Reportedly, the proportion of such cases is approximately 6%-7% of all stroke EVT cases. Ischemic stroke in patients with active cancer (cancer-associated stroke) includes not only strokes caused by cancer-related hypercoagulability but also coincident strokes due to common etiologies, strokes associated with tumor emboli, direct tumor invasion of blood vessels, and strokes associated with cancer therapy. Stroke caused by cancer-related hypercoagulability itself encompasses various entities, including paradoxical embolism, stroke due to nonbacterial thrombotic endocarditis, and in situ arterial occlusion due to disseminated intravascular coagulation or thrombotic microangiopathy. Thus, diverse mechanisms contribute to cancer-associated stroke, emphasizing the need to consider individualized treatment strategies for acute cases involving large vessel occlusion. Observational studies have shown that EVT for cancer-associated stroke results in poorer clinical outcomes, but with comparable rates of successful reperfusion and symptomatic intracranial hemorrhage when compared with stroke patients without cancer. This suggests that denying patients EVT solely on the basis of comorbid active cancer is inappropriate, and decision-making should be shared with the patients and their families, preferably through a multidisciplinary team approach. Thrombi retrieved from patients with stroke caused by cancer-related hypercoagulability have unique characteristics, being predominantly platelet rich and difficult to retrieve. Preprocedural imaging and serum biomarkers, including the hyperdense vessel sign on non-contrast CT, susceptibility vessel sign on T2* or susceptibility-weighted MRI, three-territory sign on MRI, and D-dimer levels, are valuable in evaluating the stroke subtype and thrombus features. Thrombectomy techniques, such as contact aspiration and stent retriever monotherapy, have shown varying degrees of effectiveness for stroke caused by cancer-related hypercoagulability, warranting further study. After reperfusion therapy, appropriate treatment for the prevention of stroke recurrence should be initiated, considering the specific stroke subtypes. In conclusion, cancer-associated stroke encompasses diverse subtypes, and thrombi associated with stroke caused by cancer-related hypercoagulability present various challenges for thrombectomy. Individualized treatment approaches based on underlying mechanisms are essential for improving outcomes in acute stroke patients with active cancer. Optimization of preprocedural diagnosis, EVT techniques, and secondary prevention of stroke caused by cancer-related hypercoagulability will lead to better management of these patients and enhance their quality of life.

Cancer-associated stroke: a study of prevalence and predictors among ischaemic stroke patients

The association between cancer and stroke is well documented and entails a worse prognosis for both pathologies. However, the prevalence of active and occult cancer among stroke patients is not sufficiently established, and neither are the predictors of cancer-associated stroke. Their knowledge is important for better identification and optimisation of the treatment of these patients. The aim of this retrospective study is to analyse the characteristics of ischaemic stroke in patients with and without active cancer in a sample of patients admitted to a stroke unit for two years. An overall descriptive and case-control analysis is performed to assess the differences between the two groups. In a sample of 616 patients with ischaemic stroke, a prevalence of cancer was found to be 19.2%, which was active (prior or diagnosed after the stroke) in 7.5% of them. Active cancer was associated with the finding of lesions in several vascular territories, lower haemoglobin and haematocrit values, and higher fibrinogen and C-reactive protein values, a tendency to worse functional status and higher mortality at three months. A high prevalence of systemic cancer, of any type, as well as active and occult, was found among patients with ischaemic stroke. The presence of ischaemic lesions in several vascular territories and some laboratory markers could be factors to consider in attributing the stroke to cancer or looking for an occult neoplasm in some patients.

Cancer-associated stroke in a patient with testicular cancer - case report

Introduction. Cerebral venous thrombosis is a rare cerebrovascular disease that affects about 5 in 1 million people each year and accounts for 0.5% of all strokes. There is significant overlap of many risk factors for cerebral venous thrombosis and venous thromboembolism: cancer, obesity, genetic thrombophilia, trauma, infection, and prior neurosurgery. Testicular cancer is a malignant tumor found in testicular cells and it is generally called testicular germ cell tumor. This case report puts emphasis on the importance of recognizing cerebral venous thrombosis as one of the cancer-associated symptoms that can help set the appropriate diagnosis, which, however, is not very common for this type of disease. Case report. A 58-year-old patient has been examined many times due to recurrent strokes. Lumbar puncture, computed tomography scan, magnetic resonance imaging, magnetic resonance angiography, magnetic resonance venography, immunoserology and electroencephalography have been performed. Apart from the vascular changes in the brain blood vessels, the cause of the stroke was not clear. Further?more, the patient was examined by a hematologist and an urologist. Laboratory testing showed increased levels of alpha fetoprotein and beta-human chorionic gonadotropin, however, no tumor was found in the suspected testis. Eventually, the patient underwent retroperitoneal lymph mass percutaneous core biopsy procedure and was diagnosed with non-seminoma germ cell tumor - Yolk sac tumor. Conclusion. Patients with cerebral venous thrombosis require multidisciplinary approach for the appropriate diagnosis.

Cancer-associated stroke

Background. Systemic cancer and stroke are the most common diseases and the frequent death factors in older people worldwide. The relationship between cancer and stroke is complex, since cancer leads to an increased risk of stroke through specific pathophysiological mechanisms. Purpose. Analyzing possible mechanisms of development of cancer-associated stroke, strategies of diagnosis and treatment. Materials and methods. The contributions were selected based on PubMed (https://pubmed.ncbi.nlm.nih.gov/), Clinical Key Elsevier (https://www.clinicalkey.com), Cochrane Library (https://www.cochranelibrary.com/) and GoogleScholar (https://scholar.google.com/) databases published from 2012 to 2022, dealing with cancer-associated stroke. Results and discussion. There are several underlying pathophysiological mechanisms of cancer-associated stroke, which may be directly related to cancer or caused by cancer complications. The most common ones are intravascular cancer coagulopathy, non-bacterial thrombotic endocarditis, a direct impact of the tumor on the vascular system or therapeutic and diagnostic interventions for the treatment of cancer that is chemotherapy, radiation therapy complications, as well as activation of the usual mechanisms of stroke, atherosclerosis in particular. The risk of stroke is also related to cancer aggressiveness. The characteristic features of cancer-associated stroke which is related to cancer coagulopathy are multiple lesions in various arterial areas, as well as laboratory data indicating coagulopathy in the form of increased level of D-dimer, elevated C-reactive protein, low hematocrit. Conclusions. Cancer leads to an increased risk of stroke due to specific pathophysiological mechanisms. These mechanisms are multiple and complex, but the most well-known and widespread is cancer intravascular coagulopathy, which has specific laboratory biomarkers. Numerous studies continue investigating the factors associated with coagulopathy in stroke patients, cancer characteristics, and evaluation of biological markers of stroke-causing intravascular coagulopathy, as well as monitoring the effects of anticoagulation therapy in patients with cancer-associated stroke.

Post-Treatment Plasma D-Dimer Levels Are Associated With Short-Term Outcomes in Patients With Cancer-Associated Stroke.

Background and ObjectiveHypercoagulability is associated with increased risks of ischemic stroke and subsequent mortality in patients with active cancer. This study investigated the relationships between plasma D-dimer levels after stroke treatment and short-term outcomes in patients with cancer-associated stroke.MethodsThis retrospective, observational, multicenter study analyzed consecutive patients with cancer-associated ischemic stroke. Hypercoagulability was assessed by plasma D-dimer levels before and after stroke treatment. Short-term outcomes were assessed in terms of poor outcomes (a modified Rankin Scale score >3), cumulative rates of recurrent ischemic stroke, and mortality at 30 days after admission.ResultsOf 282 patients, 135 (47.9%) showed poor outcomes. Recurrent ischemic stroke was observed in 28 patients (9.9%), and the cumulative mortality rate was 12.4%. Multivariate analysis showed that post-treatment plasma D-dimer levels ≥10 μg/ml were independently associated with both poor outcomes (adjusted odds ratio [OR], 9.61; 95% confidence interval [CI], 3.60–25.70; P < 0.001) and mortality (adjusted OR, 9.38; 95% CI, 3.32–26.44; P < 0.001). Pre-treatment plasma D-dimer levels ≥10 μg/ml were not associated with these outcomes. Patients who received heparin had higher pre-treatment plasma D-dimer levels than those treated with other anticoagulants. Heparin produced a significant reduction in D-dimer levels from pre- to post-treatment without increasing the incidence of hemorrhagic events.ConclusionA high plasma D-dimer level after stroke treatment was associated with poor short-term outcomes in patients with cancer-associated stroke. Using anticoagulants to reduce D-dimer levels may improve short-term outcomes in these patients.