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1.
J Clin Neurol ; 20(1): 86-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38179636

RESUMO

BACKGROUND AND PURPOSE: Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. METHODS: This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. RESULTS: The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. CONCLUSIONS: Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.

2.
J Clin Neurol ; 17(2): 229-235, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33835743

RESUMO

BACKGROUND AND PURPOSE: Epidemiologic data suggest that cluster headache (CH) is significantly associated with cigarette smoking. The aim of this study was to determine differences in features between patients with a smoking history and those who are never-smokers, using data from a prospective multicenter registry. METHODS: Data used in this study were obtained from the Korean Cluster Headache Registry that collected data from consecutive patients diagnosed with CH. We compared clinical and demographic features between ever-smokers (current or former smokers) and never-smokers. RESULTS: This study enrolled 250 patients who were diagnosed with CH, of which 152 (60.8%) were ever-smokers and 98 (39.2%) were never-smokers. The age at CH onset was significantly lower in the never-smoker group than in the ever-smoker group [27.1±12.9 years vs. 30.6±10.9 years (mean±standard deviation), p=0.024]. Seasonal rhythmicity (58.1% vs. 44.7%, p=0.038) and triptan responsiveness (100% vs. 85.1%, p=0.001) were higher in never-smokers, while other clinical features such as pain severity, duration, attack frequency, and associated autonomic symptoms did not differ significantly between the groups. The male-to-female ratio was markedly higher in ever-smokers (29.4:1) than in never-smokers (1.7:1). CONCLUSIONS: Most of the clinical features did not differ significantly between patients with a smoking history and never-smokers. However, the age at CH onset, sex ratio, and seasonal rhythmicity were significantly associated with smoking history.

3.
J Am Heart Assoc ; 8(21): e013215, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31640456

RESUMO

Background An increased risk of acute ischemic stroke is recognized among patients with cancer. However, the mechanism behind cancer-related stroke is unclear. In this study, we determined the presence of associated venous thromboembolism and arterial thromboembolism and their clinical impact on patients with cancer-related stroke. Methods and Results Patients with embolic stroke of undetermined source with or without cancer were evaluated for venous thromboembolism (deep vein thrombosis [DVT] and/or pulmonary embolism) and arterial thromboembolism by using Doppler sonography to determine the presence of lower-extremity DVT and the microembolic signal of the symptomatic cerebral circulation, respectively. Infarct volume was determined by diffusion-weighted magnetic resonance imaging. The multivariable linear regression and Cox proportional hazard analysis were used to investigate the effect of DVT and microembolic signal on infarct volume and 1-year survival, respectively. Of 142 screened patients, 118 were included (37 with, 81 without cancer). Those with cancer had a higher prevalence of DVT or microembolic signal than did the noncancer group (62.2% versus 19.8%; P<0.001). Among patients with cancer-related stroke, DVT was associated with a greater infarct volume in magnetic resonance imaging (beta, 13.14; 95% CI, 1.62-24.66; P=0.028). Presence of DVT (hazard ratio, 16.79; 95% CI, 2.05-137.75; P=0.009) and microembolic signal (hazard ratio, 8.16; 95% CI, 1.36-48.85; P=0.022) were independent predictors of poor 1-year survival. Conclusions Patients with cancer-associated embolic stroke of undetermined source have an elevated risk of associated venous thromboembolism and arterial thromboembolism, both of which have a significant negative impact on 1-year survival. The results of this study may enhance our understanding of cancer-associated stroke and improve risk stratification of patients with this disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov/.Unique identifier: NCT02212496.


Assuntos
Neoplasias/complicações , Embolia Pulmonar/complicações , Acidente Vascular Cerebral/complicações , Trombose Venosa/complicações , Idoso , Angiografia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/mortalidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prevalência , Estudos Prospectivos , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/mortalidade , Fatores Sexuais , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/mortalidade , Análise de Sobrevida , Ultrassonografia Doppler , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/mortalidade
4.
PLoS One ; 14(8): e0221155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31449536

RESUMO

The criterion for the remission period of chronic cluster headache (CCH) was recently revised from < 1 month to < 3 months in the third edition of the International Classification of Headache Disorders (ICHD-3). However, information on the clinical features of CCH based on the ICHD-3 criteria is currently limited. The present study aimed to investigate the clinical features of CCH based on ICHD-3 using data from the Korean Cluster Headache Registry (KCHR). The KCHR is a multicentre prospective registry of patients with cluster headache (CH) from 15 hospitals. Among the 250 participants with CH, 12 and 176 participants were classified as having CCH and episodic cluster headache (ECH), respectively. Among 12 participants with CCH, 6 (50%) had remission periods of < 1 month, and the remaining 6 (50%) had a remission period of 1-3 months. Six participants had CCH from the time of onset of CH, and in the other 6 participants, CCH evolved from ECH. CCH subjects had later age of onset of CH, developed the condition after a longer interval after CH onset, and had more migraine and less nasal congestion and/or rhinorrhoea than ECH subjects. Clinical features of CCH with remission periods < 1 month were not significantly different from those of CCH with remission periods of 1-3 months, except for the total number of bouts. More current smoking and less diurnal rhythmicity were observed in participants with CCH evolved from ECH compared to those with ECH. In conclusion, the number of subjects with CCH doubled when the revised ICHD-3 criteria were used. Most of clinical characteristics of CCH did not differ when the previous and current version of ICHD was applied and compared. Some clinical features of CCH were different from those of ECH, and smoking may have a role in CH chronification.


Assuntos
Cefaleia Histamínica/fisiopatologia , Cefaleia/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Adulto , Cefaleia Histamínica/classificação , Cefaleia Histamínica/epidemiologia , Feminino , Cefaleia/classificação , Cefaleia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/classificação , Transtornos de Enxaqueca/epidemiologia
5.
Front Neurol ; 9: 205, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29740381

RESUMO

The objective of this study was to investigate the potential benefits of statin therapy initiation in acute stroke in patients with active cancer. This study was conducted in two parts. First, data from patients who are presented with stroke and active cancer were obtained from prospectively collected multicenter hospital-based stroke registries. Patients were classified into statin user and non-user groups; the statin group was further divided into low-potency and high-potency statin subgroups. The primary outcome was time to mortality. Second, we obtained data from the Korean National Health Information Service-National Sample Cohort (NHIS-NSC) database for external validation and analyzed the effect of statins on mortality, taking compliance into consideration. For the stroke registry cohort, statin use was independently associated with reduced mortality in a multivariable model [hazard ratio (HR) = 0.675, 95% confidence interval (CI) = 0.457-0.996]. There was no interaction between statin use and cancer characteristics, vascular risk factors, or laboratory findings. A dose-dependent relationship between statin use and survival was also demonstrated. Analysis of the NHIS-NSC database found a similar association between statin therapy and reduced mortality (adjusted HR = 0.64, 95% CI = 0.45-0.90) and this effect persisted even after controlling for the adherence of statin use (HR = 0.60, 95% CI = 0.41-0.89). Statin therapy could be associated with reduced mortality in patients with acute stroke and active cancer.

6.
Stroke ; 49(5): 1282-1285, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29610261

RESUMO

BACKGROUND AND PURPOSE: Coagulopathy is an important cause of stroke in cancer patients. However, underlying mechanisms and clinical factors related to coagulopathy remain unclear. We hypothesized that certain characteristics of cancer affect coagulopathy in patients with lung cancer and ischemic stroke. METHODS: Consecutive patients with active lung cancer and acute ischemic stroke were prospectively studied. Volume and pattern of acute brain infarcts and plasma levels of circulating tumor extracellular vesicles (EVs) were measured using flow cytometry. In vitro experiments investigated the pathophysiological mechanisms underlying cancer-associated coagulopathy. RESULTS: Of 114 patients, 95 (83.3%) had an adenocarcinoma cell type and 95 (83.3%) had distant metastasis. Acute brain infarct volumes were larger and circulating EV levels were higher in patients with an adenocarcinoma cell type than in those with other cell types. The presence of metastasis was not associated with infarct volume or circulating EV levels. Coagulation assays demonstrated dose-dependent shorter clotting times after treatment with EVs from adenocarcinoma cell lines than with the use of EVs from squamous cell carcinoma. These findings were confirmed by coagulation assays using circulating EVs from patients with adenocarcinoma and stroke and from those with conventional stroke mechanisms. CONCLUSIONS: Our findings indicate that cancer cell type is associated with circulating EV levels and coagulopathy in patients with lung cancer and stroke.


Assuntos
Adenocarcinoma de Pulmão/sangue , Carcinoma de Células Escamosas/sangue , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/sangue , Acidente Vascular Cerebral/sangue , Trombofilia/sangue , Células A549 , Antígeno AC133/metabolismo , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Idoso , Antígenos CD/metabolismo , Caderinas/metabolismo , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Trombofilia/complicações , Trombofilia/metabolismo
7.
Cephalalgia ; 38(2): 389-392, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28058942

RESUMO

Background Intraorbital lesions associated with symptomatic trigeminal autonomic cephalalgias (TACs) are rarely reported. We present a case of orbital metastatic leiomyosarcoma, presenting with chronic paroxysmal hemicrania-like headache. Case report A 43-year-old man presented with a severe paroxysmal headache in his left periocular and frontal area for a year. The attacks occurred 10-12 times per day, lasting 10-15 minutes with ipsilateral lacrimation and conjunctival injection. Neurological examination and brain MRI without contrast were unremarkable. Different medications were tried, without beneficial effects. A follow-up contrast-enhanced brain MRI performed one year after the baseline MRI revealed an enhancing mass in the left superior oblique muscle. Orbital metastatic leiomyosarcoma arising from the thigh was revealed. He received gamma knife surgery, which completely resolved the headache. Discussion Intraorbital lesion should be considered a possibility in patients with headache mimicking TACs. Baseline contrast-enhanced MRI is essential, and repeated MRI scans might be needed if clinically indicated.


Assuntos
Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/secundário , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/secundário , Hemicrania Paroxística/diagnóstico por imagem , Adulto , Humanos , Leiomiossarcoma/complicações , Masculino , Neoplasias Orbitárias/complicações , Hemicrania Paroxística/etiologia
8.
Eur J Vasc Endovasc Surg ; 54(5): 573-578, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28893482

RESUMO

OBJECTIVE/BACKGROUND: Despite randomised evidence, the debate continues about the preferred treatment strategy for carotid stenosis in routine clinical practice. The aim of this study was to compare early outcomes and restenosis rates after carotid endarterectomy (CEA) and carotid stenting (CAS) in unselected patients using propensity score matching (PSM). METHODS: The 30 day incidence of major adverse clinical events (MACE; defined as stroke, transient ischaemic attack, myocardial infarction, or death) and procedure related complications, as well as restenosis rates during follow-up were compared between unselected patients undergoing CEA or CAS between January 2002 and December 2015 at a single institution. PSM was used to balance the following factors between the CEA and CAS cohorts: age, sex, hypertension, diabetes, dyslipidaemia, smoking, atrial fibrillation, previous percutaneous coronary intervention or coronary artery bypass grafting, valvular heart disease, contralateral carotid occlusion, degree of carotid stenosis, and symptomatic status. Statistical comparisons of outcomes were based on logistic regression analysis and log rank test. RESULTS: Of 1184 patients (654 CEA and 530 CAS), 452 PSM pairs of CEA and CAS patients were created. The CAS group showed a relatively higher 30 day incidence of MACE (7.5% vs. 2.4%; odds ratio [OR] 3.261, 95% confidence interval [CI] 1.634-6.509; p = .001) but a lower incidence of procedure related complications (1.5% vs. 5.3%; OR 0.199, 95% CI 0.075-0.528; p = .001). During a mean follow-up of 49.1 months (range 1-180 months), restenosis rates were higher after CAS than after CEA (1.5% vs. 1.0% at 12 months and 5.4% vs. 1.2% at 24 months, respectively; p = .008). CONCLUSION: This PSM based observation reconfirmed previous trial results in both asymptomatic and symptomatic patients with carotid artery stenosis in routine clinical practice: CEA showed lower 30 day MACE and mid-term restenosis rates than CAS.


Assuntos
Angioplastia/efeitos adversos , Estenose das Carótidas/epidemiologia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Stents , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
J Korean Med Sci ; 32(3): 502-506, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28145655

RESUMO

Cluster headache (CH) is a rare underdiagnosed primary headache disorder with very severe unilateral pain and autonomic symptoms. Clinical characteristics of Korean patients with CH have not yet been reported. We analyzed the clinical features of CH patients from 11 university hospitals in Korea. Among a total of 200 patients with CH, only 1 patient had chronic CH. The average age of CH patients was 38.1 ± 8.9 years (range 19-60 years) and the average age of onset was 30.7 ± 10.3 years (range 10-57 years). The male-to-female ratio was 7:1 (2.9:1 among teen-onset and 11.7:1 among twenties-onset). Pain was very severe at 9.3 ± 1.0 on the visual analogue scale. The average duration of each attack was 100.6 ± 55.6 minutes and a bout of CH lasted 6.5 ± 4.5 weeks. Autonomic symptoms were present in 93.5% and restlessness or agitation was present in 43.5% of patients. Patients suffered 3.0 ± 3.5 (range 1-25) bouts over 7.3 ± 6.7 (range 1-30) years. Diurnal periodicity and season propensity were present in 68.5% and 44.0% of patients, respectively. There were no sex differences in associated symptoms or diurnal and seasonal periodicity. Korean CH patients had a high male-to-female ratio, relatively short bout duration, and low proportion of chronic CH, unlike CH patients in Western countries.


Assuntos
Cefaleia Histamínica/diagnóstico , Adulto , Fatores Etários , Cefaleia Histamínica/patologia , Bases de Dados Factuais , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Estações do Ano , Índice de Gravidade de Doença , Fatores Sexuais , Fumar , Inquéritos e Questionários , Adulto Jovem
10.
J Neurol ; 264(4): 724-732, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28220286

RESUMO

Hypertrophic pachymeningitis (HP) is an important neurologic complication of granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis). The aim of this study is to investigate the clinical features, radiological findings, and diagnostic pitfalls of GPA-related HP. A retrospective chart review was performed to screen patients diagnosed with GPA at Samsung Medical Center between 1997 and 2016. Neurologic manifestation, laboratory findings, neuroimaging data, and clinical course were evaluated in all patients. Characteristics of patients with HP were compared to those of patients without HP. Sixty-five patients with GPA were identified. Twenty-five of these patients had central nervous system involvement. HP (N = 9, 36%) was the second most common radiologic finding. Other neurologic findings included stroke (N = 7, 28%) and granulomatous disease (N = 10, 40%). Patients with HP had lower incidences of systemic manifestations (N = 2, 22.2% vs. N = 38, 67.9%, p = 0.013 in the lung and N = 1, 11.1% vs. N = 28, 50.0%, p = 0.030 in the kidney) than those without HP. Six patients with GPA-related HP were MPO-ANCA positive (66.7%) and two had PR3-ANCA (22.2%). Most of the patients with HP presented with headache (N = 8, 88.9%) at a rate that is similar to those of primary headache disorders (migraine, tension-type, and stabbing) and other secondary headache disorders (postural type and meningitis). Patients with HP rarely had neurologic deficits (N = 3, 37.5%). Different clinical or radiologic features may be observed in GPA-related HP. Early recognition and accurate diagnosis of GPA-related HP are needed in addition to neuroimaging findings.


Assuntos
Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico por imagem , Hipertrofia/complicações , Meningite/complicações , Adulto , Idoso , Anticorpos/sangue , Anticorpos Antinucleares/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Distribuição de Qui-Quadrado , Feminino , Humanos , Hipertrofia/diagnóstico por imagem , Masculino , Meningite/diagnóstico por imagem , Pessoa de Meia-Idade , Mieloblastina/imunologia , Neuroimagem , Exame Neurológico , Estudos Retrospectivos
11.
Headache ; 57(3): 488-493, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27943273

RESUMO

BACKGROUND: Dural enhancement is a characteristic finding in both spontaneous intracranial hypotension and hypertrophic pachymeningitis. Positional headache is the most important feature that distinguishes the two diseases. We report a patient with granulomatosis with polyangiitis (formerly Wegener's granulomatosis) who initially manifested like spontaneous intracranial hypotension. CASE PRESENTATION: We report here the case of a 63-year old man who presented with severe positional headache. The patient had typical symptoms, symmetric dural enhancement, and a recent history of nontraumatic subdural hygroma which led to the diagnosis of spontaneous intracranial hypotension, but was finally diagnosed as granulomatosis with polyangiitis-associated secondary hypertrophic pachymeningitis. Cyclophosphamide therapy was effective for the maintenance of remission. CONCLUSIONS: Hypertrophic pachymeningitis associated with granulomatosis with polyangiitis can present with positional headache and subdural hygroma, mimicking spontaneous intracranial hypotension. Granulomatosis with polyangiitis should be suspected when patients with spontaneous intracranial hypotension or hypertrophic pachymeningitis show atypical features.


Assuntos
Granulomatose com Poliangiite/complicações , Hipotensão Intracraniana/fisiopatologia , Meningite/complicações , Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/diagnóstico por imagem , Humanos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Meningite/diagnóstico por imagem , Pessoa de Meia-Idade , Tomógrafos Computadorizados
12.
J Stroke ; 19(1): 77-87, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28030894

RESUMO

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.

13.
PLoS One ; 11(7): e0159170, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27427978

RESUMO

BACKGROUND: Cancer and stroke, which are known to be associated with one another, are the most common causes of death in the elderly. However, the pathomechanisms that lead to stroke in cancer patients are not well known. Circulating extracellular vesicles (EVs) play a role in cancer-associated thrombosis and tumor progression. Therefore, we hypothesized that cancer cell-derived EVs cause cancer-related coagulopathy resulting in ischemic stroke. METHODS: Serum levels of D-dimer and EVs expressing markers for cancer cells (epithelial cell adhesion molecule [CD326]), tissue factor (TF [CD142]), endothelial cells (CD31+CD42b-), and platelets (CD62P) were measured using flow cytometry in (a) 155 patients with ischemic stroke and active cancer (116 - cancer-related, 39 - conventional stroke mechanisms), (b) 25 patients with ischemic stroke without cancer, (c) 32 cancer patients without stroke, and (d) 101 healthy subjects. RESULTS: The levels of cancer cell-derived EVs correlated with the levels of D-dimer and TF+ EVs. The levels of cancer cell-derived EVs (CD326+ and CD326+CD142+) were higher in cancer-related stroke than in other groups (P<0.05 in all the cases). Path analysis showed that cancer cell-derived EVs are related to stroke via coagulopathy as measured by D-dimer levels. Poor correlation was observed between TF+ EV and D-dimer, and path analysis demonstrated that cancer cell-derived EVs may cause cancer-related coagulopathy independent of the levels of TF+ EVs. CONCLUSIONS: Our findings suggest that cancer cell-derived EVs mediate coagulopathy resulting in ischemic stroke via TF-independent mechanisms.


Assuntos
Coagulação Intravascular Disseminada/etiologia , Vesículas Extracelulares/patologia , Neoplasias/complicações , Acidente Vascular Cerebral/etiologia , Tromboplastina/análise , Idoso , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/patologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/patologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia
14.
Int J Stroke ; 11(9): 999-1008, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27462098

RESUMO

BACKGROUND: Moyamoya disease is a unique cerebrovascular occlusive disease of unknown etiology. Ring finger protein 213 (RNF213) was identified as a susceptibility gene for Moyamoya disease in East Asian countries. However, the pathogenesis of Moyamoya disease remains unclear. METHODS: We prospectively analyzed clinical data for 139 patients with Moyamoya disease (108 bilateral Moyamoya disease, 31 unilateral Moyamoya disease), 61 patients with intracranial atherosclerotic stroke, and 68 healthy subjects. We compared the genetic (RNF213 variant) and protein biomarkers for caveolae (caveolin-1), angiogenesis (vascular endothelial growth factor (VEGF) and receptor (VEGFR2), and antagonizing cytokine (endostatin)) and endothelial dysfunction (asymmetric dimethylarginine (ADMA), and nitric oxide and its metabolites (nitrite and nitrate)) between patients with Moyamoya disease and intracranial atherosclerotic stroke. We then performed path analysis to evaluate whether a certain protein biomarker mediates the association between genes and Moyamoya disease. RESULTS: Caveolin-1 level was decreased in patients with Moyamoya disease and markedly decreased in RNF213 variant carriers. Circulating factors such as VEGF and VEGFR2 did not differ among the groups. Markers for endothelial dysfunction were significantly higher in patients with intracranial atherosclerotic stroke but normal in those with Moyamoya disease. Path analysis showed that the presence of the RNF213 variant was associated with caveolin-1 levels that could lead to Moyamoya disease. The level of combined marker of Moyamoya disease (caveolin-1) and intracranial atherosclerotic stroke (ADMA, an endothelial dysfunction marker) predicted Moyamoya disease with good sensitivity and specificity. CONCLUSION: Our results suggest that Moyamoya disease is a caveolae disorder but is not related to endothelial dysfunction or dysregulation of circulating cytokines.


Assuntos
Adenosina Trifosfatases/genética , Caveolina 1/metabolismo , Células Endoteliais/metabolismo , Doença de Moyamoya/genética , Doença de Moyamoya/metabolismo , Ubiquitina-Proteína Ligases/genética , Biomarcadores/metabolismo , Células Cultivadas , Feminino , Predisposição Genética para Doença , Variação Genética , Heterozigoto , Humanos , Arteriosclerose Intracraniana/genética , Arteriosclerose Intracraniana/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
PLoS One ; 10(6): e0130663, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26125557

RESUMO

BACKGROUND: Both Moyamoya disease (MMD) and intracranial atherosclerotic stenosis (ICAS) are more prevalent in Asians than in Westerners. We hypothesized that a substantial proportion of patients with adult-onset MMD were misclassified as having ICAS, which may in part explain the high prevalence of intracranial atherosclerotic stroke in Asians. METHOD: We analyzed 352 consecutive patients with ischemic events within the MCA distribution and relevant intracranial arterial stenosis, but no demonstrable carotid or cardiac embolism sources. Conventional angiography was performed in 249 (70.7%) patients, and the remains underwent MRA. The occurrence of the c.14429G>A (p.Arg4810Lys) variant in ring finger protein 213 (RNF213) was analyzed. This gene was recently identified as a susceptibility gene for MMD in East Asians. RESULTS: The p.Arg4810Lys variant was observed in half of patients with intracranial stenosis (176 of 352, 50.0%), in no healthy control subjects (n = 51), and in 3.2% of stroke control subjects (4 of 124 patients with other etiologies). The presence of basal collaterals, bilateral involvement on angiography, and absence of diabetes were independently associated with the presence of the RNF213 variant. Among 131 patients who met all three diagnostic criteria and were diagnosed with MMD, three-fourths (75.6%) had this variant. However, a significant proportion of patients who met two criteria (57.7%), one criterion (28.6%), or no criteria (20.0%) also had this variant. Some of them developed typical angiographic findings of MMD on follow-up angiography. CONCLUSIONS: Careful consideration of MMD is needed when diagnosing ICAS because differential therapeutic strategies are required for these diseases and due to the limitations of the current diagnostic criteria for MMD.


Assuntos
Povo Asiático/genética , Estenose das Carótidas/genética , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/genética , Adenosina Trifosfatases , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/epidemiologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Variação Genética/genética , Humanos , Masculino , Pessoa de Meia-Idade , Ubiquitina-Proteína Ligases/genética , Adulto Jovem
16.
J Oncol ; 2015: 502089, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064116

RESUMO

Background. The aim of this study was to determine which anticoagulant is superior for secondary prevention of cancer-associated stroke, using changes in D-dimer levels as a biomarker for recurrent thromboembolic events. Methods. We conducted a retrospective, single center observational study including patients with cancer-associated stroke who were treated with either enoxaparin or warfarin. Blood samples for measuring the initial and follow-up D-dimer levels were collected at admission and a median of 8 days after admission, respectively. Multiple logistic regression analysis was conducted to evaluate the factors that influenced D-dimer levels after treatment. Results. Although the initial D-dimer levels did not differ between the two groups, the follow-up levels were dramatically decreased in patients treated with enoxaparin, while they did not change with use of warfarin (3.88 µg/mL versus 17.42 µg/mL, p = 0.026). On multiple logistic regression analysis, use of warfarin (OR 12.95; p = 0.001) and the presence of systemic metastasis (OR 18.73; p = 0.017) were independently associated with elevated D-dimer levels (≥10 µg/mL) after treatment. Conclusion. In cancer-associated stroke patients, treatment with enoxaparin may be more effective than treatment with warfarin for lowering the D-dimer levels. Future prospective studies are warranted to show that enoxaparin is better than warfarin for secondary prevention in cancer-associated stroke.

17.
J Vasc Surg ; 59(3): 749-55, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24360588

RESUMO

OBJECTIVE: To determine the impact of contralateral carotid occlusion (CCO) and/or vertebral artery occlusion (VAO) on the development of early postoperative neurologic complications after carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS: A retrospective analysis was conducted using a database of patients who underwent CEA (n = 698) or CAS (n = 455) at a single institution. Excluded were 44 CEAs synchronously performed with coronary artery bypass grafting and 76 CASs performed without an embolic protective device (n = 69) or that resulted in technical failures (n = 7). All CEAs were the conventional type and performed under general anesthesia, and carotid shunts were routinely used. Patients were categorized into three groups according to patency of the contralateral carotid and vertebral arteries: Group I (no CCO or VAO); Group II (CCO with or without VAO); Group III (with VAO but no CCO). CCO or VAO were diagnosed with two or more carotid imaging studies including duplex ultrasonography, computed tomography angiography, magnetic resonance angiography, or conventional carotid angiography. Patient groups were compared with demographics, preoperative symptomatic status, and frequencies of early (<30 days) symptomatic neurologic complications (ESNCs) including transient ischemic attack and stroke. Postprocedural stroke alone was separately compared. Univariate (χ(2) or Fisher's exact test) and multivariate analysis (multiple logistic regression) were conducted to determine predictors of ESNC or postprocedural stroke. RESULTS: ESNCs and postprocedural stroke developed significantly more often with CAS compared with CEA (ESNC, 2.6% vs 8.1%; P < .001; stroke, 1.3% vs 6.8%; P < .001). In group II, the frequency of ESNCs was higher (6.8% vs 1.8%; P = .044), but the frequency of postprocedural stroke was not significantly higher (2.3% vs 0.9%; P = .405) in the CEA group. By multivariate analysis, the presenting symptom of stroke (odds ratio, 3.612; 95% confidence interval, 1.288-10.130; P = .015) and group II (odds ratio, 7.242; 95% confidence interval, 1.727-30.374; P = .007) were independent risk factors of ESNC following CEA but not CAS. When we analyzed the risk factor for postprocedural stroke alone, the presenting symptom of stroke was the only risk factor, while presence of CCO or VAO was not. CONCLUSIONS: CAS was followed by a significantly higher frequency of ESNC and postprocedural stroke compared with CEA. By subgroup analysis, CCO was a risk factor for ESNC but not for postprocedural stroke alone in patients undergoing CEA. Unilateral or bilateral VAO was not associated with a higher rate of ESNC or stroke in CEA or CAS.


Assuntos
Angioplastia/instrumentação , Estenose das Carótidas/terapia , Endarterectomia das Carótidas , Stents , Insuficiência Vertebrobasilar/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia/efeitos adversos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Distribuição de Qui-Quadrado , Endarterectomia das Carótidas/efeitos adversos , Feminino , Humanos , Ataque Isquêmico Transitório/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Insuficiência Vertebrobasilar/fisiopatologia
18.
Eur Neurol ; 68(6): 368-76, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23095856

RESUMO

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.


Assuntos
Isquemia Encefálica/patologia , Imagem de Difusão por Ressonância Magnética , Neoplasias/tratamento farmacológico , Terapia Trombolítica , Adulto , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Terapia Trombolítica/métodos
19.
PLoS One ; 7(9): e44865, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23024771

RESUMO

BACKGROUND: Leukoaraiosis and cerebral microbleeds (CMB), which represent cerebral microangiopathy, commonly coexist in patients with acute lacunar stroke. Since they may have different impacts on stroke prognosis and treatment, it is important to know the factors associated with leukoaraiosis-predominant vs. CMB-predominant microangiopathies. METHODS: We prospectively recruited 226 patients with acute lacunar infarction and divided them into four groups according to the Fazekas' score and the presence of CMB: mild, red (predominant CMB), white (predominant leukoaraiosis) and severe microangiopathy groups. For comparison, we also evaluated 50 patients with intracerebral hemorrhage (ICH). We evaluated the clinical and laboratory findings of microangiopathy subtypes in patients with acute lacunar stroke and then compared them with those of primary ICH. RESULTS: The risk factor profile was different among the groups. Patients with acute lacunar infarct but mild microangiopathy were younger, predominantly male, less hypertensive, and more frequently had smoking and heavy alcohol habits than other groups. The risk factor profile of red microangiopathy was similar to that of ICH but differed from that of white microangiopathy. The subjects in the white microangiopathy group were older and more frequently had diabetes than those in the red microangiopathy or ICH group. After adjustments for other factors, age [odds ratio (OR) 1.13; 95% confidence interval (CI) 1.08-1.18; p<0.001] and diabetes (OR 2.28; 95% CI 1.02-5.13; p = 0.045) were independently associated with white microangiopathy, and age (OR 1.05; 95% CI 1.01-1.08; p = 0.010) was independent predictor for red microangiopathy compared to mild microangiopathy. CONCLUSION: Patients with acute lacunar infarction have a different risk factor profile depending on microangiopathic findings. Our results indicate that diabetes may be an one of determinants of white (leukoaraiosis-predominant) microangiopathy, whereas smoking and alcohol habits in relatively young people may be a determinants of mild microangiopahic changes in patients with lacunar infarction.


Assuntos
Hemorragia Cerebral/complicações , Leucoaraiose/complicações , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral Lacunar/complicações , Acidente Vascular Cerebral Lacunar/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Hemorragia Cerebral/diagnóstico , Feminino , Humanos , Leucoaraiose/diagnóstico , Masculino , Pessoa de Meia-Idade , Neuroimagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco
20.
J Clin Neurol ; 7(2): 53-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21779292

RESUMO

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.

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