Jin Myoung Seok

Coagulopathy and Embolic Signal in Cancer Patients with Ischemic Stroke

It has been reported that embolic signal (ES) detected by transcranial Doppler (TCD) has clinical significance, especially in patients with recent stroke attributable to arterial or cardiac embolism. Therefore, we conducted this study to determine whether the prevalence of ES is high in ischemic stroke patients with cancer and related to hypercoagulopathy.

Ischemic Stroke and Cancer: Stroke Severely Impacts Cancer Patients, While Cancer Increases the Number of Strokes

Background Cancer 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 Contents This 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. Conclusion Recent 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.

MR mismatch profiles in patients with intracranial atherosclerotic stroke: a comprehensive approach comparing stroke subtypes

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.

Hypercoagulability and Mortality of Patients with Stroke and Active Cancer: The OASIS-CANCER Study

Background and Purpose Patients 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. Methods We 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. Results A 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). Conclusions Hypercoagulability 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.

Usefulness of phrenic latency and forced vital capacity in patients with ALS with latent respiratory dysfunction

OBJECTIVES The pulmonary function test (PFT) is a non-invasive and easily available technique to assess respiratory function in patients with amyotrophic lateral sclerosis (ALS); however, patients with dyspnea sometimes show normal PFT findings. Herein, we investigated whether phrenic nerve conduction study (NCS) and PFT are useful to evaluate respiratory function of patients with ALS with normal value ranges in the PFT. METHODS We prospectively enrolled 34 patients with definite or probable ALS, who showed FVC (%) ⩾80 of predicted and 78 healthy subjects. PFT and phrenic NCS were performed with the measurement of forced vital capacity (FVC, %), forced expiratory volumes in 1s (FEV1, %), FEV1/FCV ratio (%), and phrenic compound muscle action potential amplitude, and latency. RESULTS Compared to healthy controls, ALS patients showed delayed phrenic nerve latency and the decrease of FVC (%) (p=0.006 and p<0.0001, respectively). ROC curve analysis demonstrated that phrenic latency (AUC=0.7655) and FVC (%) (AUC=0.8239) discriminated ALS patients from healthy subjects. CONCLUSION We demonstrated that ALS patients had early respiratory dysfunction, despite normal PFT findings. SIGNIFICANCE Phrenic latency and FVC (%) can be helpful to discriminate ALS patients with latent respiratory dysfunction from healthy subjects.

Clinical presentation and ischemic zone on MRI in cancer patients with acute ischemic stroke.

Aims: This study was conducted to evaluate the clinical and MRI profiles in acute cancer strokes, and to demonstrate our experience with thrombolytic therapy in cancer stroke patients. Methods: We prospectively studied active cancer patients with acute ischemic stroke who underwent MRI within 48 h of the onset of symptoms. Patients were grouped based on the presence of conventional stroke mechanisms (CSM). Clinical characteristics and MRI profiles were evaluated. Results: A total of 70 patients were finally included in this study. Patients without CSM were more frequently presented with encephalopathy than those with CSM (29.4 vs. 2.8%, p = 0.002). The diffusion-perfusion mismatch pattern was more prevalent in patients with CSM (21 patients, 58.3%) than in patients without CSM (8 patients, 23.5%). Patients who had a higher tertiles of D-dimer level were significantly less likely to have the diffusion-perfusion mismatch pattern (p = 0.015). Among patients who presented within 6 h of the onset of stroke, revascularization therapy was performed in 4 of 16 (25%) patients with CSM, but none of the patients without CSM. Conclusion: Based on the stroke mechanisms, the optimal strategy of thrombolytic therapy should be considered differently in cancer patients with acute ischemic stroke.

Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life

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.

Increased lipoprotein(a) is associated with polyvascular disease in patients undergoing coronary artery bypass graft.

OBJECTIVE We sought to identify clinical and biochemical predictors of disease in multiple vascular territories, in patients with established coronary heart disease. METHODS A total of 470 patients (329 men, 141 female) who had undergone coronary artery bypass grafting (CABG) were enrolled in this prospective study. Polyvascular disease was defined on the presence of existing symptomatic or asymptomatic carotid artery stenosis and/or peripheral artery disease, which is present in 32.1% of patients (n=151). RESULTS Clinical and laboratory features independently associated with the presence of polyvascular disease included age ≥65 years, male sex, hypertension, former or current smoker, low BMI, and high Lp(a). Lp(a) was the only biochemical marker that had an independent association with polyvascular disease (OR=1.01 per 1mg/dl increase; 95% CI, 1.00-1.01). The fourth quartile of Lp(a) has significant associations with the risk of two or more vascular territories involvement (OR=1.866; 95% CI, 1.056-3.297), and three vascular territories involvement (OR=4.240; 95% CI, 1.405-12.798). There was a significant trend towards patients with the highest quartile of Lp(a) that has association with more advanced polyvascular disease (test for trend: p=0.008 for involvement of three vascular territories). CONCLUSION High Lp(a) was independently associated with polyvascular disease in patients who undergo CABG, which is suggestive of an indirect evidence of the pathophysiologic function of Lp(a) in polyvascular disease.

The composite autonomic symptom scale 31 is a useful screening tool for patients with Parkinsonism

Differentiation of multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinsons disease (PD) is important, but an effective tool for differentiation has not been identified. We investigated the efficacy of the composite autonomic symptom scale 31 (COMPASS 31) questionnaire as a tool for evaluating autonomic function in parkinsonism patients. In this study, we enrolled drug-naïve patients with MSA-P and PD, and administered the COMPASS-31 and an objective autonomic dysfunction test (AFT). Demographic and clinical data, including parkinsonism and autonomic dysfunction, were compared between the two groups. Additionally, we determined the optimal COMPASS 31 cut-off score to differentiate MSA-P from PD for use as a screening tool. In this study, 27 MSA-P patients and 41 PD patients were recruited. The total COMPASS 31 score was well correlated with the objective AFT results. When we compared the COMPASS 31 score between the two groups, MSA-P patients showed higher total scores and sub-scores in the orthostatic intolerance, gastrointestinal, and bladder domains compared with PD patients. Similarly, MSA-P patients had more abnormalities in expiration to inspiration ratio, Valsalva ratio and pressure recovery time than PD patients in objective AFT. With 13.25 as the cut-off score for diagnosis of MSA-P, the total COMPASS-31 score demonstrated high sensitivity (92.6%) and moderate specificity (51.2%) with an area under the curve of 0.765. Based on our results, the COMPASS 31 is an effective tool for evaluation of autonomic function in patients with parkinsonism. The COMPASS-31 could be used as a sensitive and convenient screening tool, especially for the differentiation between MSA-P and PD.

Clinical characteristics of late-onset neuromyelitis optica spectrum disorder: A multicenter retrospective study in Korea:

Background: There are currently few studies regarding late-onset neuromyelitis optica spectrum disorder (LO-NMOSD). Objective: We aimed to describe the characteristic features of patients with LO-NMOSD in Korea. Methods: Anti-aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder (NMOSD) from nine tertiary hospitals were reviewed retrospectively. The patients were divided into two groups based on age of onset: LO-NMOSD (⩾50 years of age at onset) versus early-onset neuromyelitis optica spectrum disorder (EO-NMOSD) (<50 years of age at onset). Clinical, laboratory, and magnetic resonance imaging (MRI) parameters were investigated. Results: Among a total of 147 patients (125 female; age of onset, 39.4 ± 15.2 years), 45 patients (30.6%) had an age of onset of more than 50 years. Compared to patients with EO-NMOSD, patients with LO-NMOSD had more frequent isolated spinal cord involvement at onset (64.4% vs 37.2%, p = 0.002), less frequent involvement of the optic nerve (40.0% vs 67.7%, p = 0.002), and less frequent brain MRI lesions (31.1% vs 50.0%, p = 0.034). Furthermore, there was a significant positive correlation between age of onset and Expanded Disability Status Scale (EDSS) score at last follow-up (r = 0.246, p = 0.003). Conclusion: Age of onset could be an important predictor of lesion location and clinical course of patients with NMOSD.