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.

[Recurrent cerebral embolism due to the disseminated carcinomatosis of bone marrow with early gastric cancer].

A 67-year-old woman who had undergone laparoscopic proximal gastrectomy for early gastric cancer 10 months previously was admitted to our hospital due to dysarthria. Brain MRI demonstrated acute multiple small infarcts in the right middle cerebral artery (MCA) and the right posterior inferior cerebellar artery (PICA) territory, and she was diagnosed as embolic stroke. Anticoagulant therapy did not prevent further ischemic stroke. No embolic sources were detected by MR angiography, carotid duplex sonography, transthoracic and transesophageal echocardiography, and Holter electrocardiography. We also performed upper gastrointestinal endoscopy and contrast-enhanced CT of the thoracoabdominal area, but there was no evidence of local recurrence or lymph node metastases of gastric cancer. As the ALP and D-dimer levels were gradually increasing, we performed PET/CT, which revealed fluorodeoxyglucose (FDG) uptake in the vertebra bone, and disseminated carcinomatosis of bone marrow with early gastric cancer was diagnosed after bone marrow biopsy on Day 41. After undergoing chemotherapy, she had no further stroke and died on Day 207.

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.

Blood biomarkers associated with neurological deterioration in patients with acute penetrating artery territory infarction: A multicenter prospective observational study.

Background and purpose Neurological deterioration in acute penetrating artery territory infarction is unpredictable and associated with unfavorable clinical outcomes. The aim of this prospective study was to clarify the cause of neurological worsening and predict clinical outcomes using blood biomarkers. Methods Eight Japanese stroke centers participated. Blood samples were obtained within 24 h (the first sampling) and on day 7 in hospital (the second sampling) in patients with penetrating artery territory infarction, arriving within two days of stroke onset. Symptomatic worsening was defined as a minimum increase of one point on the National Institutes of Health Stroke Scale. Poor outcome was defined as a modified Rankin Scale score of ≥3 at 90 days after ictus. Results Of the 89 patients, 25 (28%) had symptomatic worsening, and 25 (28%) had a poor outcome. Although tumor necrosis factor-alpha, high-sensitivity C-reactive protein levels were significantly increased in both groups at the second sampling, soluble lectin-like oxidized low-density lipoprotein receptor-1, CD40 ligand, and pro-adrenomedullin levels were significantly increased and ADAMTS13 activity was decreased in symptomatic worsening patients ( p < 0.05 for all). After multivariate adjustment, a low number of CD34+ cells at the first sampling was an independent predictor of poor outcome (odds ratio, 0.20; 95% confidence interval, 0.04-0.74, p = 0.011, per 1 cell/µl increase). Conclusions Blood biomarkers associated with atherosclerotic processes seem to be an indication for symptomatic worsening, and the number of CD34+ cells may help to predict three-month functional outcome in patients with penetrating artery territory infarction.

Diffuse large B-cell lymphoma presenting with central pontine myelinolysis: a case report.

INTRODUCTION: The most common cause of central pontine myelinolysis is an overly rapid correction of hyponatremia, although it can also occur in patients with any condition leading to nutritional or electrolyte stress. We report a case of diffuse large B-cell lymphoma with central pontine myelinolysis developing at the onset of disease. To the best of our knowledge, hematological malignancies presenting with central pontine myelinolysis have been rarely reported, especially in previously untreated patients, as in our case report. CASE PRESENTATION: A 78-year-old Japanese woman presented to a neighborhood clinic with persistent high fever, edema, and general weakness. Despite the absence of specific neurological findings, brain magnetic resonance imaging showed an abnormal lesion in the central pons area of her brain (hyperintense on T2-weighted and hypointense on T1-weighted sequences), compatible with central pontine myelinolysis. She was admitted to our emergency department in a state of shock one month later. The results of her blood tests showed greatly elevated C-reactive protein and lactate dehydrogenase levels. She had severe hypoalbuminemia and mild hyponatremia, and showed signs of disseminated intravascular coagulation. Mild bilateral pleural effusion, prominent subcutaneous edema, and splenomegaly were detected on her systemic computed tomography scan. Her body fluid cultures did not show signs of infection and her spinal aspiration did not show pleocytosis or abnormal cells. A diagnosis of diffuse large B-cell lymphoma was made based on the results of her bone marrow examination. As she was critically ill before the diagnosis was made, she was treated with methylprednisolone pulse therapy, followed by systemic chemotherapy (rituximab with modified THP-COP regimen, including cyclophosphamide, pirarubicin, vindesine, and prednisolone), which resulted in complete remission and recovery without any neurological defects, and resolution of her abnormal findings on magnetic resonance imaging. CONCLUSIONS: Central pontine myelinolysis is a serious condition that may result in neuropathological sequelae and mortality, and clinicians should be aware of its potential presence in patients with malignancies.

Two Japanese CADASIL families exhibiting Notch3 mutation R75P not involving cysteine residue.

Most previously reported mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) result in an odd number of cysteine residues within the epidermal growth factor (EGF)-like repeats in Notch3. We report here R75P mutation in two Japanese CADASIL families not directly involving cysteine residues located within the first EGF-like repeats. Probands in both families had repeated episodes of stroke, depression, dementia as well as T2 high-intensity lesions in the basal ganglia and periventricular white matter, but fewer white matter lesions in the temporal pole on MRI. These families provide new insights into the diagnosis and pathomechanisms of CADASIL.