Cancer and stroke: commonly encountered by clinicians, but little evidence to guide clinical approach.

The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.

Five-year readmission and mortality differ by ischemic stroke subtype.

BACKGROUND: Ischemic stroke subtype may influence the risk of readmission and mortality after ischemic stroke (IS) and transient ischemic attack (TIA) due to differences in comorbidity, risk factors, and stroke severity. We aimed to study the five-year incidence and risk of all-cause readmission, cause-specific readmission and mortality after IS or TIA by stroke subtype. METHODS: The medical records of 1453 patients admitted with IS or TIA to the stroke unit at Haukeland University Hospital, Norway, between 2007 and 2012 were reviewed for identification of unplanned readmissions within five years after discharge. Stroke etiology was classified as large-artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined etiology (SOE), multiple etiologies (ME), or cryptogenic stroke (CS). Kaplan-Meier estimates and Cox regression analyses were used to determine incidences and risk of readmission and death. RESULTS: The five-year incidence of all-cause readmission was 72.6% (74% LAA, 81% CE, 65% SVO, 55% SOE, 71% ME, and 67% CS), with infections, cardiac disease, stroke-related events and fractures as the most frequent causes. Compared to patients with other subtypes, SVO subtype had a 21% lower risk of all-cause readmission and a 48% lower risk of death, whereas CE had a 25% higher risk of all cause readmission and a 34% higher risk of death. CE subtype also had a 75% higher risk of readmission due to cardiac disease, whereas CS subtype had a 44% lower risk of readmission with cardiac disease. CONCLUSION: The five-year incidence of readmission and mortality varied among the stroke subtypes. The risk of readmission and death are especially high in patients with CE subtype, and lowest for patients with SVO subtype.

Intravenous Thrombolysis in Ischemic Stroke Patients With Active Cancer.

Introduction: It has been difficult to state specific guidelines for IV-tPA use in cancer patients. Many of the randomized tPA-trials included too few patients with cancer or excluded patients with cancer entirely. In this report, we aimed to study the use of IV-tPA in patients with active cancer and acute ischemic stroke. We also investigated if the cancer patients who received IV-tPA experienced adverse events. Methods: All patients with ischemic stroke admitted to the Stroke Unit at Haukeland University Hospital were prospectively registered in the NORSTROKE database and every patient's medical record was searched for cancer diagnoses. Results: Of 1,646 patients admitted with ischemic stroke, 82 (5.0%) patients had active cancer. The total number of patients treated with IV-tPA was 16.2%. Five patients with stroke and active cancer were treated with IV-tPA (6.1%) and none suffered adverse events. Of the patients with no history of cancer, 261 (16.7%) were treated with IV-tPA and 3.8% experienced tPA-related adverse events. Conclusions: Few patients with active cancer receive thrombolysis for acute ischemic stroke. We report five cancer patients (three known and two occult) treated with IV-tPA for ischemic stroke without tPA-related adverse events.

When to Screen Ischaemic Stroke Patients for Cancer.

BACKGROUND AND PURPOSE: Ischemic stroke can be the first manifestation of cancer and it is therefore important to ascertain which stroke patients should be considered for cancer-diagnostic investigations. We aimed to determine the frequency of active cancer in patients with acute ischemic stroke and to compare clinical findings in stroke patients with active cancer to ischemic stroke patients with no history of cancer. Finally, we aimed to develop a predictive and feasible score for clinical use to uncover underlying malignancy. METHODS: All ischemic stroke patients admitted to the stroke unit in the Department of Neurology, Haukeland University Hospital were consecutively included in the Norwegian Stroke Research Registry (NORSTROKE). Stroke etiology was determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Data on cancer diagnoses was obtained from patients' medical records and the Cancer Registry of Norway. Active cancer was defined as cancer diagnosis, metastasis of known cancer, recurrent cancer or receiving cancer treatment, all within 12 months before or after the index stroke. Based on variables independently associated with active cancer, a predictive score was developed using the area under the receiver operating characteristic (AUC-ROC) curves. Bayes' theorem was used to calculate post-test probabilities of active cancer. RESULTS: Of the 1,646 ischemic stroke patients included, 82 (5.0%) had active cancer. Increased D-dimer (OR = 1.1, 95% CI: 1.1-1.2, p = <0.001), lower Hb (OR = 0.6, 95% CI: 0.5-0.7, p = <0.001), smoking (OR = 2.2, 95% CI: 1.2-4.3, p = 0.02) and suffering a stroke of undetermined etiology (OR = 1.9, 95% CI: 1.1-3.3, p = 0.03) were factors independently associated with active cancer. These were included in the final predictive score which gave an AUC of 0.73 (95% CI: 0.65-0.81) in patients younger than 75 years of age. Assuming the prevalence of cancer to be 5%, the score shows that if a patient fulfills all 3 score points, the probability of active cancer is 53%. CONCLUSIONS: Active cancer was found in 5% of our ischemic stroke patients. We found that a clinical score comprising elevated D-dimer ≥3 mg/L, lower Hb ≤12.0 g/dL and previous or current smoking is feasible for predicting active cancer in ischemic stroke patients.

The Impact of Ischaemic Stroke Subtype on 30-day Hospital Readmissions.

BACKGROUND: Stroke aetiology may affect the risk and causes of readmission after ischaemic stroke (IS) and transient ischaemic attack (TIA) due to differences in risk factors, functional outcome, and treatment. We aimed to examine frequencies, causes, and risk of 30-day readmission by stroke subtype, determine predictors of 30-day readmission, and study the impact of 30-day readmissions on one-year mortality. METHODS: All surviving patients admitted with IS or TIA from July 2007 to December 2013 were followed by review of medical records for all unplanned readmissions within 30 days after discharge. Stroke subtype was classified as large-artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined aetiology (SOE), or stroke of undetermined aetiology (SUE). Cox regression analyses were performed to assess the risk of 30-day readmission for the stroke subtypes and identify predictors of 30-day readmission, and its impact on one-year mortality. RESULTS: Of 1874 patients, 200 (10.7%) were readmitted within 30 days [LAA 42/244 (17.2%), CE 75/605 (12.4%), SVO 12/205 (5.9%), SOE 6/32 (18.8%), SUE 65/788 (8.3%)]. The most frequent causes of readmissions were stroke-related event, infection, recurrent stroke/ TIA, and cardiac disease. After adjusting for age, sex, functional outcome, length of stay, and the risk factor burden, patients with LAA and SOE subtype had significantly higher risks of readmission for any cause, recurrent stroke or TIA, and stroke-related events. Predictors of 30-day readmission were higher age, peripheral arterial disease, enteral feeding, and LAA subtype. Thirty-day readmission was an independent predictor of one-year mortality. CONCLUSIONS: Patients with LAA or SOE have a high risk of 30-day readmission, possibly caused by an increased risk of recurrent stroke and stroke-related events. Awareness of the risk of readmission for different causes and appropriate handling according to stroke subtype may be useful for preventing some readmissions after stroke.

Cancer-Associated Stroke: The Bergen NORSTROKE Study.

BACKGROUND: Underlying malignancy can cause ischemic stroke in some patients. Mechanisms include the affection of the coagulation cascade, tumor mucin secretion, infections and nonbacterial endocarditis. The release of necrotizing factor and interleukins may cause inflammation of the endothelial lining, creating a prothrombotic surface that triggers thromboembolic events, including stroke. The aims of this study were to assess the occurrence of cancer in patients who had recently suffered an ischemic stroke and to detect possible associations between stroke and cancer subtypes. METHODS: All ischemic stroke patients registered in the Norwegian Stroke Research Registry (NORSTROKE) as part of the ongoing Bergen NORSTROKE study were included. Blood samples were obtained on admission. Stroke etiology was determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, and the severity of stroke was defined according to the National Institute of Health Stroke Scale score. Information about cancer disease after stroke was obtained from patient medical records and The Cancer Registry of Norway. RESULTS: From a total of 1,282 ischemic stroke patients with no history of cancer, 55 (4.3%) patients were diagnosed with cancer after stroke. The median time from stroke onset to cancer diagnosis was 14.0 months (interquartile range 6.2-24.5). Twenty-three (41.8%) patients were diagnosed with cancer within 1 year and 13 (23.6%) within 6 months. The most common cancer type was lung cancer (19.0%). By Cox regression analysis, cancer after stroke was associated with elevated D-dimer levels on admittance (p < 0.001), age (p = 0.01) and smoking (p = 0.04). CONCLUSIONS: Cancer-associated stroke is rare, and routine investigation for cancer seems unwarranted in acute ischemic stroke. However, in stroke patients with elevated levels of blood coagulation factors, C-reactive protein, higher age and a history of smoking, underlying malignancy should be considered. Our study suggests that an unknown stroke etiology does not predict malignancy.