Elevated CA125 is Related to Stroke Due to Cancer- Associated Hypercoagulation.

BACKGROUND: Cancer-associated hypercoagulation is one of the major pathophysiological mechanisms of stroke in cancer patients. Carcinomatous mucins are considered to play an important role in cancer-associated hypercoagulation. Therefore, carbohydrate antigen-125 (CA125), which is a typical mucin molecule and mucin-producing tumor marker, may be related to stroke due to cancer-associated hypercoagulation. AIMS: We aimed to clarify the association of CA125 with a hypercoagulable state in acute stroke patients with active cancer. METHODS: We studied 77 acute ischemic stroke patients with active cancer who had undergone CA125 measurement. The study patients were categorized into hypercoagulation or non-hypercoagulation groups. The hypercoagulation group was defined as stroke patients with a D-dimer value exceeding 3 µg/mL and multiple vascular territory infarcts. Elevation of tumor markers was defined as values more than twice the upper limit of the normal range. RESULTS: Forty-five (58%) and 32 (42%) patients were classified into hypercoagulation and non-hypercoagulation groups, respectively. The hypercoagulation group showed elevated CA125 and CEA levels, no history of hypertension, and pancreatic cancer more frequently, and higher CRP values, lower hemoglobin values, longer prothrombin time and lower platelet counts than the non-hypercoagulation group. In multivariable analysis, only elevation of CA125 was independently associated with the hypercoagulation group (adjusted odds ratio: 5.59 [95% confidence interval]: 1.33-26.41). CONCLUSIONS: CA125, a tumor marker for mucin-producing tumors, was related to stroke due to cancer- associated hypercoagulation. CA125 may be a potential biomarker for cancer-associated hypercoagulation.

Cancer-Associated Hypercoagulation Increases the Risk of Early Recurrent Stroke in Patients with Active Cancer.

BACKGROUND: This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke. METHODS: We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days. RESULTS: One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher -D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42-30.7, p = 0.015). CONCLUSIONS: Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk.

Seasonal Variations in Neurological Severity and Outcomes of Ischemic Stroke　- 5-Year Single-Center Observational Study.

BACKGROUND: Seasonal variations in the severity and outcomes of stroke remain unclarified.Methods and Results:A total of 2,965 acute ischemic stroke patients from a single-center prospective registry were studied. Among the total patients, stroke onset did not vary by season, though it varied with a peak in winter when limited to patients >75 years old (P=0.026), when limited to patients with moderate-to-severe initial neurological deficits (National Institutes of Health Stroke Scale Score ≥10, P=0.014), and when limited to those with cardioembolic stroke (n=1,031, P=0.010). In 1,934 patients with noncardioembolic stroke, stroke onset did not vary by season. After multivariable adjustment, moderate-to-severe neurological deficits were more common in winter (odds ratio 1.37, 95% confidence interval 1.10-1.72) and spring (1.27, 1.01-1.60), and death at 1 year was more common in summer than in fall (1.55, 1.03-2.36); death or dependency (modified Rankin Scale score 3-6) and death or bedridden (score of 5-6) were not differently common among the seasons. CONCLUSIONS: Overall ischemic stroke showed a fairly even distribution among the 4 seasons. Cardioembolic stroke was more common in winter. Ischemic stroke patients had more moderate-to-severe initial neurological deficits in winter and spring. Poor clinical outcomes at 1 year were generally similar among the seasons. Ischemic stroke is not necessarily a winter-dominant disease.

Slowly progressive Lemierre's syndrome with orbital pain and exophthalmos.

Lemierre's syndrome is an oropharyngeal bacterial infection characterized by rapidly progressive septic thrombophlebitis of the internal jugular vein. A lack of appropriate antibiotic therapy can be life-threatening. We describe the case of a 39-year-old man with Lemierre's syndrome who presented with long-lasting orbital pain and acute exophthalmos 6 weeks after initial infection. This report is to help clinicians consider the diagnosis of Lemierre's syndrome when encountering a patient with long-lasting orbital pain and acute exophthalmos. Neck ultrasonography is useful for detecting thrombophlebitis of the internal jugular vein in Lemierre's syndrome patients.

Incidence and predictors of ischemic stroke events during hospitalization in patients with transient ischemic attack.

BACKGROUND: The purpose of this study was to elucidate the incidence and predictors of ischemic stroke or recurrent transient ischemic attack (TIA) during acute hospitalization in patients with TIA. METHODS: We carried out a multicenter retrospective study to clarify the characteristics of in-patients with TIA. The subjects of this study were TIA patients admitted to 13 stroke hospitals within 7 days after onset between 2008 and 2009. TIA was defined as focal neurologic symptoms ascribable to a vascular etiology lasting less than 24 h. We investigated the incidence and predictors of ischemic events including ischemic stroke or recurrent TIA during hospitalization. RESULTS: A total of 464 patients with TIA (292 men, 69 ± 13 years) were registered. Of those, 400 (86.2%) were admitted within 24 h of TIA onset. The mean length of hospital stay was 13 days. During hospitalization, 8 patients had ischemic strokes and 26 had recurrent TIAs. The leading subtype of 8 ischemic strokes was small vessel disease (n = 3) followed by cardioembolism (n = 2). Multiple logistic regression analysis showed that hypertension (OR: 3.41; 95% CI: 1.23-12.3), MRI-diffusion-weighted image positivity (OR: 2.49; 95% CI: 1.15-5.25), and hemiparesis (OR: 2.30; 95% CI: 1.02-5.88) were independently associated with ischemic events during hospitalization. CONCLUSIONS: In this study, 1.7% of patients with TIA had ischemic stroke during acute hospitalization, and the most common subtype was small vessel disease. Subsequent ischemic stroke and recurrent TIA were associated with hypertension, positive DWI findings, and hemiparesis.

Absence of susceptibility vessel sign with cancer- associated hypercoagulability-related stroke.

BACKGROUND AND PURPOSE: Susceptibility vessel sign (SVS), a hypointense signal on MR T2-weighted gradient-recalled echo images, is associated with erythrocyte-predominant thrombi, which are often present in cardioembolism (CE). In contrast, cancer-associated hypercoagulability (CAH)-related stroke, which is presumably caused by fibrin-predominant thrombi, is associated with the absence of SVS. We hypothesized that the prevalence of SVS may be of help in distinguishing CAH-related stroke from CE. This study attempted to validate this hypothesis and investigated the usefulness of SVS in differentiating CAH-related stroke from CE. MATERIALS AND METHODS: We retrospectively studied both CAH-related stroke patients (CAH group) and CE patients (CE group), who had major cerebral artery occlusion on MR angiography that was performed within 6 hours of stroke onset. All patients visited our department from 2015 to 2021. CAH-related stroke was defined as 1) complication of active cancer, 2) pre-treatment D-dimer value >3 µg/mL, 3) multiple vascular territories infarctions, and 4) lack of any other specifically identified causes of stroke. We compared SVS positivity rates within each group. Multivariable logistic regression analysis was used to assess the association between the absence of SVS and CAH-related stroke. RESULTS: Of 691 patients with CAH-related stroke or CE, major cerebral artery occlusion was observed in 10 patients in the CAH group and 198 patients in the CE group. The absence of SVS was identified in 55 of 208 patients and was significantly more frequent in the CAH versus the CE group (90% versus 24%, p < 0.05). For predicting CAH-related stroke, absence of SVS demonstrated a sensitivity of 90% (95% confidence interval [95%CI] 59-99), specificity of 78% (95%CI 71-83), positive predictive value of 18 (95%CI 10- 31), negative predictive value of 99% (95%CI 96-99), and a likelihood ratio of 4.06. Multivariable logistic regression analysis revealed that the absent of SVS was independently associated with CAH-related stroke (odds ratio 43, 95% [CI] 6.8-863; p < 0.01). CONCLUSIONS: The absence of SVS was more frequent in CAH-related stroke versus that found for CE. These findings could potentially be helpful for clinical management and differentiating between CE and CAH-related stroke. ABBREVIATIONS: CAH, cancer-associated hypercoagulability; CE, cardioembolism; SVS, susceptibility vessel sign; GRE, gradient recalled echo.

D-Dimer Trends Predict Recurrent Stroke in Patients with Cancer-Related Hypercoagulability.

INTRODUCTION: In patients with cancer-associated hypercoagulability (CAH)-related stroke, D-dimer trends after anticoagulant therapy may offer a biomarker of treatment efficacy. The purpose of this study was to clarify the association between D-dimer trends and recurrent stroke after anticoagulant therapy in patients with CAH-related stroke. METHODS: We performed retrospective cohort study of consecutive patients with CAH-related stroke at two stroke centers from 2011 to 2020. The ratio of posttreatment to pretreatment D-dimer levels (post/pre ratio) was used as an indicator of D-dimer trends after anticoagulant therapy. Fine-Gray models were used to evaluate the association between post/pre ratio and recurrent stroke. RESULTS: Among 360 acute ischemic stroke patients with active cancer, 73 patients with CAH-related stroke were included in this study. Recurrent stroke occurred in 13 patients (18%) during a median follow-up time of 28 days (interquartile range, 11-65 days). Multivariate analysis revealed that high post/pre ratio was independently associated with recurrent stroke (per 0.1 increase: hazard ratio 2.20, 95% confidence interval 1.61-3.01, p = 0.012). CONCLUSION: D-dimer levels after anticoagulant therapy were associated with recurrent stroke in CAH-related stroke patients. Patients with neutral trends in high D-dimer levels after anticoagulant therapy were at high risk of recurrent stroke.

Clinical significance of fluid-attenuated inversion recovery vascular hyperintensities in transient ischemic attack.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is often identified in patients with acute ischemic stroke. The purpose of this study was to determine the clinical significance of FVH in patients with transient ischemic attack (TIA). METHODS: Consecutive inpatients with TIA who underwent MRI within 24 hours of symptom onset were studied. The frequency, relative factors, and time course of FVH were determined. RESULTS: Of the 202 patients who were enrolled (76 women, mean age, 69.0 ± 13.2 years), FVH was identified in 41 patients (20%). Multivariate analysis showed that atrial fibrillation (odds ratio, 7.14; 95% confidence interval [CI], 2.69-18.1), arterial occlusive lesion (odds ratio, 4.89; 95% CI, 3.03-12.2), and hemiparesis (odds ratio, 2.81; 95% CI, 1.17-7.48) was independently associated with FVH. Of 23 recurrence-free patients with FVH positive undergoing follow-up MRI at a median of 7 days after the onset, FVH was no longer positive in 15 patients (65%). Atrial fibrillation was more common (P=0.027) and arterial occlusive lesion was less common (P<0.001) in patients with transient FVH compared with those with persistent FVH. Within 90 days after the onset, 13 patients developed recurrent TIA or ischemic stroke. After Cox proportional hazard analysis, FVH (hazard ratio, 3.65; 95% CI, 1.09-12.7), arterial occlusive lesion (hazard ratio, 4.15; 95% CI, 1.18-17.1), and coexistence of FVH and arterial occlusive lesion (hazard ratio, 13.9; 95% CI, 3.36-71.0) were significantly associated with recurrent TIA or ischemic stroke. CONCLUSIONS: The presence of FVH early after symptom onset may help to diagnosis TIA, to identify the potential mechanisms of TIA and to predict recurrence risk after a TIA.

Long-term effectiveness of anticoagulants in oldest-old stroke survivors with atrial fibrillation.

BACKGROUND: Long-term anticoagulant therapy in oldest-old persons poses the risk of bleeding complications. The aim of this study was to evaluate the long-term benefits of anticoagulant therapy for oldest-old stroke survivors with AF. METHODS: Patients with atrial fibrillation (AF) who were 90 years of age or older and were prescribed an anticoagulant on discharge were identified from a set of data from a prospective follow-up registry of 1,484 consecutive patients admitted for ischemic stroke or transient ischemic attack over a 4-year period beginning in 2014. The outcome measures were stroke and death following discharge. RESULTS: Of the 77 identified patients with AF who were 90 years of age or older, 71 were prescribed an anticoagulant (median age 93 years, 73% women). Thirty-nine patients were given a direct oral anticoagulant (DOAC) (median age 92 years, 69% women), and 32 were given warfarin (median age 93 years, 78% women). During the follow-up period (median 466 days), 9 patients (13%) had stroke recurrence (recurrence rate: 14%/year), and 25 patients (35%) died (mortality rate: 33%/year). The type of all recurrent strokes was ischemic, and no fatal bleeding occurred. There was no difference in the incidence of recurrent strokes according to anticoagulant type (DOAC 15%/year, warfarin 13%/year, P = 0.743), but a higher proportion of patients on warfarin died (21% vs. 47%, P = 0.002). CONCLUSIONS: Given that a higher proportion of oldest-old stroke survivors with AF on anticoagulant therapy have recurrent ischemic stroke rather than hemorrhagic stroke, long-term anticoagulant therapy may be justified for secondary stroke prevention.

Effects of 24-hour blood pressure and heart rate recorded with ambulatory blood pressure monitoring on recovery from acute ischemic stroke.

BACKGROUND AND PURPOSE: This study used ambulatory blood pressure (BP) monitoring to generate BP and heart rate (HR) profiles soon after stroke onset and evaluated the association between determined values and 3-month stroke outcomes. METHODS: We analyzed 24-hour ambulatory BP monitoring records from 104 patients with acute ischemic stroke. Ambulatory BP monitoring was attached at the second and eighth hospitalization days (Days 1 and 7). Both BP and HR were characterized using baseline, mean, maximum, and minimum values and coefficient of variation during 24-hour recording periods. Outcomes at 3 months were assessed as independence according to a modified Rankin Scale score of ≤2 and poor according to the score of ≥5. RESULTS: Sixty-six (63%) patients achieved independence and 12 (11%) had poor outcomes. Mean ambulatory BP monitoring values changed from 150.5±19.5/85.7±11.3 mm Hg on Day 1 to 139.6±19.3/80.0±11.7 mm Hg on Day 7. After multivariate adjustment, mean values of systolic BP (OR, 0.63; 95% CI, 0.45-0.85), diastolic BP (0.61; 0.37-0.98), pulse pressure (0.55; 0.33-0.85), and HR (0.61; 0.37-0.98) recorded on Day 1 as well as mean HR on Day 7 (0.47; 0.23-0.87) were inversely associated with independence and mean values of systolic BP (1.92; 1.15-3.68), diastolic BP (5.28; 1.92-22.85), and HR (4.07; 1.83-11.88) on Day 1 as well as mean HR on Day 7 (4.92; 1.36-36.99) were positively associated with a poor outcome. CONCLUSIONS: All of systolic BP, diastolic BP, pulse pressure, and HR on Day 1 and HR on Day 7 assessed using ambulatory BP monitoring were associated with outcomes of patients with stroke at 3 months.

Trousseau's syndrome associated with pulmonary pleomorphic carcinoma exhibiting aggressive features: A case report.

Trousseau's syndrome is characterized as an unexpected, cancer-related thrombotic event, such as a cerebral infarction or a deep vein thrombosis/pulmonary embolism. We describe the first reported case of Trousseau's syndrome with pulmonary pleomorphic carcinoma and aggressive features. A 74 year-old man presenting with a pulmonary mass, which was identified as pleomorphic carcinoma with extensive lymph node involvement, in the left lower lobe, underwent a left lower lobectomy. Immunohistochemical analysis revealed that neoplastic cells exhibited an extensive expression of tissue factors with a mucin-producing adenocarcinoma component. Three months postoperatively, diffuse infiltration rapidly appeared in the left lung, which was identified as lymphangitic carcinomatosis via bronchoscopy. Prior to treatment for cancer recurrence, the patient presented with a left hemiplegia due to a cerebral infarction via multiple thromboses, with no evidence of atherosclerotic or cardiogenic thrombi. Elevated D-dimer and carbohydrate antigen 125 levels and the presence of a fibrin thrombus retrieved from the occluded vessel suggested Trousseau's syndrome as the etiology of the brain infarction. A hypercoagulable state associated with the aggressive recurrence of pulmonary pleomorphic carcinoma, accompanied by cancer cell production of mucin and tissue factors may be a potential mechanism for cancer-related thrombosis.

[Subacute sensory neuronopathy associated with squamous cell carcinoma of the lung: a case report].

We report a 59-year-old man who developed dysesthesia in all extremities with severe loss of deep sensation over three months. A radiating radicular pain was also noted in the extremities. The nerve conduction study barely elicited sensory nerve action potentials both in the median and in the sural nerve. An extensive search for anti-neuronal antibodies including anti-Hu and anti-CV2 antibody was negetive. The biopsy specimen of an enlarged tracheobronchial lymph node revealed squamous cell carcinoma. The subsequent chemotherapy and radiation therapy for the neoplasm improved the radicular pain and the deep sensation to a moderate extent, leading to the diagnosis of paraneoplastic subacute sensory neuropathy (SSN). In general, cases with paraneoplastic SSN are associated mostly with small cell lung cancer, and quite rarely with squamous cell lung cancer. The early detection and the treatment of the primary tumor are crucial in a patient with subacute progression of sensory-dominant neuropathy.

[Constructive disturbance and low-level perfusion in parietal areas in amyotrophic lateral sclerosis with dementia].

Although amyotrophic lateral sclerosis with dementia (ALS-D) has been characterized by symptoms of fronto-temporal dysfunction, we report two patients with ALS-D who showed constructive disturbance and low-level perfusion in the parietal areas. The first was a 69-year-old woman (Case 1) who had been diagnosed with the bulbar type of ALS. She showed fronto-temporal dementia as well as low scores and disturbance on block construction and copying; however, she showed a better score on the imitation of finger postures. The second was a 73-year-old woman (Case 2) who had been diagnosed with the leg onset type of ALS. She showed mild impairment of the frontal function as well as mild disturbance on block construction and copying, but no problem on the imitation of finger postures. Case 1 showed more severe symptoms of dementia and constructive disturbance than Case 2, whereas Case 2 showed lower levels of cerebral perfusion over more extensive areas than Case 1. Cases 1 and 2 were compatible with definite ALS according to the El Escorial Criteria, and they showed constructive disturbance with characteristics reported previously, such as both left and right hemisphere damage and constructive disturbance similar to those seen in Alzheimer's disease. In addition, they showed poorer scores on performing tasks requiring the use of objects (block construction and copying) rather than using their body (imitation of finger postures).