A high prevalence of ES was observed in cancer patients with ischemic stroke, especially in those without CSMs. Elevated D-dimer levels were independently associated with ES, and decreased dramatically with the use of anticoagulants. ANN NEUROL 2010;68:213-219.

Background and PurposePatients with active cancer are at an increased risk for stroke. Hypercoagulability plays an important role in cancer-related stroke. We aimed to test whether 1) hypercoagulability is a predictor of survival, and 2) correction of the hypercoagulable state leads to better survival in patients with stroke and active cancer.MethodsWe recruited consecutive patients with acute ischemic stroke and active systemic cancer between January 2006 and July 2015. Hypercoagulability was assessed using plasma D-dimer levels before and after 7 days of anticoagulation treatment. The study outcomes included overall and 1-year survival. Plasma D-dimer levels before and after treatment were tested in univariate and multivariate Cox regression models. We controlled for systemic metastasis, stroke mechanism, age, stroke severity, primary cancer type, histology, and atrial fibrillation using the forward stepwise method.ResultsA total of 268 patients were included in the analysis. Patients with high (3rd–4th quartiles) pre-treatment plasma D-dimer levels showed decreased overall and 1-year survival (adjusted HR, 2.19 [95% CI, 1.46–3.31] and 2.70 [1.68–4.35], respectively). After anticoagulation treatment, post-treatment D-dimer level was significantly reduced and independently associated with poor 1-year survival (adjusted HR, 1.03 [95% CI, 1.01–1.05] per 1 μg/mL increase, P=0.015). The successful correction of hypercoagulability was a protective factor for 1-year survival (adjusted HR 0.26 [CI 0.10–0.68], P=0.006).ConclusionsHypercoagulability is associated with poor survival after stroke in patients with active cancer. Effective correction of hypercoagulability may play a protective role for survival in these patients.

BackgroundCancer and ischemic stroke are two of the most common causes of death among the elderly, and associations between them have been reported. However, the main pathomechanisms of stroke in cancer patients are not well known, and can only be established based on accurate knowledge of the characteristics of cancer-related strokes. We review herein recent studies concerning the clinical, laboratory, and radiological features of patients with cancer-related stroke.Main ContentsThis review covers the epidemiology, underlying mechanisms, and acute and preventive treatments for cancer-related stroke. First, the characteristics of stroke (clinical and radiological features) and systemic cancer (type and extent) in patients with cancer-specific stroke are discussed. Second, the role of laboratory tests in the early identification of patients with cancer-specific stroke is discussed. Specifically, serum D-dimer levels (as a marker of a hypercoagulable state) and embolic signals on transcranial Doppler (suggestive of embolic origin) may provide clues regarding changes in the levels of coagulopathy related to cancer and anticoagulation. Finally, strategies for stroke treatment in cancer patients are discussed, emphasizing the importance of preventive strategies (i.e., the use of anticoagulants) over acute revascularization therapy in cancer-related stroke.ConclusionRecent studies have revealed that the characteristics of cancer-related stroke are distinct from those of conventional stroke. Our understanding of the characteristics of cancer-related stroke is essential to the correct management of these patients. The studies presented in this review highlight the importance of a personalized approach in treating stroke patients with cancer.

Age of onset could be an important predictor of lesion location and clinical course of patients with NMOSD.

Most clinical trials have focused on the presence of perfusion-and diffusion-weighted imaging (PWI-DWI) mismatch by more than 20%, and different stroke subtypes were lumped together. We hypothesized that intracranial large artery atherosclerotic stroke (IC-LAA) would show different PWI-DWI and magnetic resonance angiography (MRA)-DWI mismatch profiles, compared with other stroke subtypes. Consecutive patients underwent pretreatment multiparametric magnetic resonance imaging for the acute middle cerebral artery infarcts within 6 h of symptom onset. We assessed the difference in the DWI-PWI mismatch ratio, severity of hypoperfusion, and MRA-DWI mismatch among the stroke subtypes. Of 86 patients, 19 (22.1%) had IC-LAA; 42 (48.8%) cardioembolic stroke, 15 (17.4%) extracranial-LAA, and 10 (11.6%) had cryptogenic embolic stroke. Although the volume of the penumbra was not different among the groups, the mismatch ratio was higher (P = 0.003) and the severity of hypoperfusion was lower in the IC-LAA group (P = 0.001). The MRA-DWI mismatch was more prevalent in the IC-LAA group than in other groups (P < 0.001). Collateral grading, assessed in 41 patients, was more likely to be intermediate/excellent in the IC-LAA group (P < 0.001). Multivariate testing revealed that a larger mismatch ratio and less severe hypoperfusion, and MRA-DWI mismatch were independently associated with IC-LAA. Our data show that patients with IC-LAA had different mismatch profiles, which were related to better collaterals, compared with other subtypes.

Background Hereditary transthyretin (ATTRv) amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We aimed to assess the efficacy and safety of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ATTRv amyloidosis with polyneuropathy. MethodsThis multi-country, multi-centre, open-label extension (OLE) trial enrolled patients at 43 sites in 19 countries as of 24 September 2018. Patients were eligible if they had completed the phase 3 APOLLO (randomised, double-blind, placebo-controlled [2:1], 18-month study) or phase 2 OLE (single-arm, 24-month study) parent studies and tolerated the study drug. Eligible patients from APOLLO (APOLLO-patisiran [received patisiran during APOLLO] and APOLLO-placebo [received placebo during APOLLO] groups) and the phase 2 OLE (phase 2 OLE patisiran group) studies enrolled in this Global OLE trial and receive patisiran 0•3 mg/kg by intravenous infusion every 3 weeks for up to 5 years. Efficacy assessments include measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress. Patients included in the current efficacy analyses are those who had completed 12-month efficacy assessments as of the data cut-off. Safety analyses included all patients who received ≥1 dose of patisiran up to the data cut-off. The Global OLE is ongoing with no new enrolment, and current findings are based on the 12-month interim analysis. The study is registered with ClinicalTrials.gov, NCT02510261.

Fatigue is a prevalent symptom and major burden in neuroimmunological diseases. In neuromyelitis optica spectrum disorder (NMOSD), a severe autoimmune central nervous system (CNS) inflammatory disease with autoantibodies reactive to aquaporin-4, there are few reports about fatigue and quality of life (QOL). We aimed to evaluate the severity of fatigue and its relationship with QOL in patients with NMOSD. We prospectively studied patients with NMOSD who were in remission and seropositive for anti-aquaporin-4 antibody, and they were divided into 2 groups based on the presence of fatigue assessed using the Functional Assessment of Chronic Illness Therapy-fatigue score. Sleep quality, depression, pain, and QOL were also evaluated. A total of 35 patients were enrolled (mean age, 46.5 ± 14.1 years; female: male = 29:6), and the median Expanded Disability Status Scale (EDSS) score was 2.0 (range, 0 to 8.0). The patients with fatigue (N = 25, 71.4%) had poorer sleep quality and more severe depression than those without fatigue (p = 0.009 and p = 0.001). Both the physical and mental QOL scores were lower in patients with fatigue than in those without fatigue (p = 0.033 and p = 0.004). Multiple linear regression analyses showed that the degree of fatigue with EDSS score and pain were independent predictors of physical aspects of QOL (B = 0.382, p = 0.001), whereas depression was the only predictor of the mental components of QOL (B = -0.845, p = <0.001). Fatigue is a common symptom and an important predictor of QOL in patients with NMOSD.

Background: In neuromyelitis optica spectrum disorder (NMOSD), brain involvement is common and cognitive dysfunction is frequently found. The study investigated alterations of white matter (WM) connectivity using graph theory and correlations with cognitive dysfunction in patients with NMOSD.Methods: We prospectively enrolled patients with NMOSD (N = 14) and age- and sex-matched healthy controls (N = 21). Structural connections between any pair of the 90 cortical and subcortical regions were established using diffusion tensor imaging and graph theory. Network-based statistics was employed to assess differences in WM connectivity between the NMOSD and healthy control groups. We further investigated the relationship between the topological network characteristics and cognitive test performances.Results: WM network analysis showed decreased total strength of brain networks and two disrupted sub-networks in patients with NMOSD. The first featured six hub nodes in the rectus, hippocampus, calcarine, cuneus, and precuneus with the left-sided predominance. The second had six hub nodes in the orbitomiddle frontal, post-central, superior parietal, superior, and middle temporal, and caudate with the right-sided predominance. Compared to healthy controls, NMOSD patients showed poor performance on tests for attention/working memory and processing speed, visuospatial processing, and executive function, which were associated with significant decreases in nodal clustering coefficient, local efficiency, and regional efficiency in the disrupted sub-networks (all p < 0.05).Conclusions: The data show the overall WM disruption and the relationship between poor cognitive function and sub-network alterations identified by the network analysis in NMOSD patients. We suggest that cognitive dysfunction is related to dysconnectivity of WM network including default mode network in NMOSD.