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1.
Brain Behav ; 13(12): e3282, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37815172

RESUMO

OBJECTIVE: The aim of this study was to investigate the utility of quantitative electroencephalography (QEEG) as a diagnostic tool for migraine and as an indicator of treatment response by comparing QEEG characteristics between migraine patients and controls, and monitoring changes in these characteristics alongside clinical symptoms in response to treatment BACKGROUND: We hypothesized that patients with migraine exhibit distinctive characteristics in QEEG measurements, which could be used as potential diagnostic biomarkers and as a tool for monitoring treatment response. METHODS: A total of 720 patients were included in the study, comprising 619 patients with migraine and 101 subjects as a control group. QEEG measurements were analyzed for absolute power across specific frequency bands: delta wave (0.5-4 Hz), theta wave (4-8 Hz), alpha wave (8-12 Hz), beta wave (12-25 Hz), and high beta wave (25-30 Hz). The absolute power was normalized against a normative dataset from NeuroGuide, with electrodes being highlighted for significance if they exceeded 1.96. Clinical symptoms were also monitored for correlation with QEEG changes. RESULTS: Our analysis showed that patients with migraine exhibited significantly higher absolute power across all frequencies, most markedly within the high beta frequency range. When considering electrodes with z-scores exceeding the threshold of 1.96 in the high beta range, a significant association with migraine diagnosis was observed (per 1 electrode increase, OR 1.06; 95% CI 1.01-1.11; p = .012). Moreover, pre- and posttreatment changes in QEEG measurements corresponded with changes in clinical symptoms. CONCLUSION: Patients with migraine have distinctive QEEG measurements, particularly regarding absolute power and the number of electrodes that surpassed the z-score threshold in high beta wave activity. These findings suggest the potential of QEEG as a diagnostic biomarker and as a tool for monitoring treatment response in migraine patients, warranting further large-scale studies for confirmation and expansion.


Assuntos
Eletroencefalografia , Transtornos de Enxaqueca , Humanos , Transtornos de Enxaqueca/diagnóstico , Biomarcadores
2.
Stroke ; 53(1): 20-28, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34583525

RESUMO

BACKGROUND AND PURPOSE: Stem cell-based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell-based therapy in patients with ischemic stroke. METHODS: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging. RESULTS: For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference. CONCLUSIONS: Stem cell-based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01716481.


Assuntos
Isquemia Encefálica/terapia , AVC Isquêmico/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Atividade Motora/fisiologia , Neuroimagem/métodos , Recuperação de Função Fisiológica/fisiologia , Administração Intravenosa , Adulto , Idoso , Isquemia Encefálica/diagnóstico por imagem , Feminino , Humanos , AVC Isquêmico/diagnóstico por imagem , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
3.
PLoS One ; 16(2): e0246817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33592008

RESUMO

In animal models of stroke, behavioral assessments could be complemented by a variety of neuroimaging studies to correlate them with recovery and better understand mechanisms of improvement after stem cell therapy. We evaluated morphological and connectivity changes after treatment with human mesenchymal stem cells (hMSCs) in a rat stroke model, through quantitative measurement of T2-weighted images and diffusion tensor imaging (DTI). Transient middle cerebral artery occlusion rats randomly received PBS (PBS-only), FBS cultured hMSCs (FBS-hMSCs), or stroke patients' serum cultured hMSCs (SS-hMSCs). Functional improvement was assessed using a modified neurological severity score (mNSS). Quantitative analyses of T2-weighted ischemic lesion and ventricular volume changes were performed. Brain microstructure/connectivity changes were evaluated in the ischemic recovery area by DTI-derived microstructural indices such as relative fractional anisotropy (rFA), relative axial diffusivity (rAD), and relative radial diffusivity (rRD), and relative fiber density (rFD) analyses. According to mNSS results, the SS-hMSCs group showed the most prominent functional improvement. Infarct lesion volume of the SS-hMSCs group was significantly decreased at 2 weeks when compared to the PBS-only groups, but there were no differences between the FBS-hMSCs and SS-hMSCs groups. Brain atrophy was significantly decreased in the SS-hMSCs group compared to the other groups. In DTI, rFA and rFD values were significantly higher and rRD value was significant lower in the SS-hMSCs group and these microstructure/connectivity changes were correlated with T2-weighted morphological changes. T2-weighted volume alterations (ischemic lesion and brain atrophy), and DTI microstructural indices and rFD changes, were well matched with the results of behavioral assessment. These quantitative MRI measurements could be potential outcome predictors of functional recovery after treatment with stem cells for stroke.


Assuntos
Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Transplante de Células-Tronco Mesenquimais , Acidente Vascular Cerebral , Animais , Modelos Animais de Doenças , Xenoenxertos , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia
4.
Neurology ; 96(7): e1012-e1023, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33472925

RESUMO

OBJECTIVE: To test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke. METHODS: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery. RESULTS: A total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range 28-83) years, and mean interval between stroke onset to randomization was 20.2 (range 5-89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious treatment-related adverse events. CONCLUSIONS: IV application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that autologous MSCs do not improve 90-day outcomes in patients with chronic stroke. CLINICALTRIALSGOV IDENTIFIER: NCT01716481.


Assuntos
AVC Isquêmico/terapia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
5.
Neurology ; 93(21): e1955-e1963, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31645472

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke. METHODS: In this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death. RESULTS: In the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25-4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32-6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups. CONCLUSION: Among patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence. CLINICALTRIALSGOV IDENTIFIER: NCT01600235. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.


Assuntos
Pressão Sanguínea , Encéfalo/irrigação sanguínea , Circulação Colateral , Hipertensão , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Edema Encefálico/epidemiologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Planejamento de Assistência ao Paciente , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
6.
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
7.
Front Neurol ; 10: 44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30761076

RESUMO

Background and Purpose: Patients undergoing carotid artery stenting (CAS) who show low responsiveness to clopidogrel may have a higher risk of peri-procedural embolic events. This study aimed to compare the effectiveness and safety of clopidogrel and ticlopidine plus Ginkgo biloba in clopidogrel-resistant patients undergoing CAS. Methods: In this multi-center, randomized, controlled trial, we used platelet reactivity test to select patients undergoing CAS who showed clopidogrel resistance, and compared treatments using clopidogrel and ticlopidine plus ginkgo. The primary outcome was the incidence of new ischemic lesion in the ipsilateral hemisphere of CAS. Detection of microembolic signal on transcranial Doppler was the secondary outcome. The clinical outcomes were also monitored. Results: This trial was discontinued after 42 patients were randomized after preplanned interim sample size re-estimation indicated an impractical sample size. The primary endpoint occurred in 12/22 patients (54.5%) in the clopidogrel group and 13/20 patients (65.0%) in the ticlopidine-ginkgo group (P = 0.610). No significant differences in the presence of microembolic signal (15.0 vs. 11.8%, P = 0.580), clinical outcomes (ischemic stroke or transient ischemic attack, 0.0 vs. 5.5%; acute myocardial infarction 0.0 vs. 0.0%; all-cause death, 4.5 vs. 0.0%), or incidence of adverse events were found in the two groups. In terms of resistance to clopidogrel, treatment with ticlopidine-ginkgo significantly increased the P2Y12 Reaction Units (difference, 0.0 [-0.3-3.0] vs. 21.0 [6.0-35.0], P < 0.001). Conclusions: In patients who showed clopidogrel resistance, ticlopidine-ginkgo treatment was safe and increased P2Y12 Reaction Units; however, compared to clopidogrel, it failed to improve surrogate and clinical endpoints in patients undergoing CAS. This multimodal biomarker-based clinical trial is feasible in neurointerventional research. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT02133989.

8.
J Stroke ; 19(1): 88-96, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28030891

RESUMO

BACKGROUND AND PURPOSE: Perfusion-diffusion mismatch has been evaluated to determine whether the presence of a target mismatch helps to identify patients who respond favorably to recanalization therapies. We compared the impact on infarct growth of collateral status and the presence of a penumbra, using magnetic resonance perfusion (MRP) techniques. METHODS: Consecutive patients who were candidates for recanalization therapy and underwent serial diffusion-weighted imaging (DWI) and MRP were enrolled. A collateral flow map derived from MRP source data was generated by automatic post-processing. The impact of a target mismatch (Tmax>6 s/apparent diffusion coefficient (ADC) volume≥1.8, ADC volume<70 mL; and Tmax>10 s for ADC volume<100 mL) on infarct growth was compared with MR-based collateral grading on day 7 DWI, using multivariate linear regression analysis. RESULTS: Among 73 patients, 55 (75%) showed a target mismatch, whereas collaterals were poor in 14 (19.2%), intermediate in 36 (49.3%), and good in 23 (31.5%) patients. After adjusting for initial severity of stroke, early recanalization (P<0.001) and the MR-based collateral grading (P=0.001), but not the presence of a target mismatch, were independently associated with infarct growth. Even in patients with a target mismatch and successful recanalization, the degree of infarct growth depended on the collateral status. Perfusion status at later Tmax time points (beyond the arterial phase) was more closely correlated with collateral status. CONCLUSIONS: Patients with good collaterals show a favorable outcome in terms of infarct growth, regardless of the presence of a target mismatch pattern. The presence of slow blood filling predicts collateral status and infarct growth.

9.
J Stroke ; 18(3): 304-311, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27733026

RESUMO

BACKGROUND AND PURPOSE: Left atrial dysfunction has been reported in patients with patent foramen ovale (PFO). Here we investigated the role of left atrial dysfunction in the development of embolic stroke in patients with PFO. METHODS: We identified consecutive patients with embolic stroke of undetermined sources except for PFO (PFO+ESUS). Healthy subjects with PFO served as controls (PFO+control). A stratified analysis by 10-year age group and an age- and sex- matching analysis were performed to compare echocardiographic markers between groups. In the PFO+ESUS group, infarct patterns of PFO-related stroke were determined (cortical vs. cortico-subcortical) and analyzed in correlation with left atrial function parameters. RESULTS: A total of 118 patients and 231 controls were included. The left atrial volume indices (LAVIs) of the PFO+ESUS patients were higher than those of the PFO+controls in age groups of 40-49, 50-59, and 60-69 years (P<0.001, P=0.003, and P=0.027, respectively), and in the age- and sex-matched analysis (P=0.001). In the PFO+ESUS patients, a higher (>28 mL/m2) LAVI was more associated with the cortical infarct pattern (P=0.043 for an acute infarction and P=0.024 for a chronic infarction, both adjusted for age and shunt amount). The degree of right-to-left shunting was not associated with infarct patterns, but with the posterior location of acute infarcts (P=0.028). CONCLUSIONS: Left atrial enlargement was associated with embolic stroke in subjects with PFO. Left atrial physiology might contribute to the development of PFO-related stroke and need to be taken into consideration for optimal prevention of PFO-related stroke.

10.
J Neurol Sci ; 369: 176-180, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27653885

RESUMO

Among embolic strokes of undetermined source, under-recognized etiology such as extra-cardiac shunt could be a potential risk factor. We sought to characterize infarction patterns on diffusion-weighted imaging (DWI) and transesophageal echocardiography (TEE) findings in extra-cardiac shunt-related stroke. We enrolled 96 consecutive patients with cryptogenic stroke who had an extra- or intra-cardiac shunt. Diagnosis of the shunt was performed using TEE with agitated saline contrast and pulmonary vein isolation. Infarction patterns on DWI and total lesion volume were analyzed. Bubble amounts through the shunt were classified via the International Consensus Criteria (ICC). Short-term prognosis, patterns and size of DWI lesions, and involved vascular territories were not significantly different between two groups. Multivariate analysis revealed that extra-cardiac shunt group has a smaller total infarct volume (odds ratio [OR]=0.427, 95% confidence interval [95% CI] 0.228-0.799, p=0.008), and significantly higher bubble grade during resting state and lower grade during the Valsalva maneuver (OR= 0.539, 95% CI 0.438-0.663, p<0.001). Stroke related to an extra-cardiac shunt presented smaller infarct volume, favorable clinical outcomes and characteristic finding on TEE with agitated saline contrast. Further study is needed to confirm whether the extra-cardiac shunt is an independent risk factor.


Assuntos
Ecocardiografia Transesofagiana , Defeitos dos Septos Cardíacos/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Manobra de Valsalva/fisiologia , Adulto , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Modelos Logísticos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas
11.
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
12.
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
13.
Eur Neurol ; 75(3-4): 178-85, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27046023

RESUMO

BACKGROUND/AIMS: To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD. METHODS: We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed. RESULTS: The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs. CONCLUSION: Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Colateral , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/genética , Doença de Moyamoya/patologia , Adolescente , Adulto , Idoso , Envelhecimento/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Adulto Jovem
14.
J Am Heart Assoc ; 5(3): e002975, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-27006118

RESUMO

BACKGROUND: From a therapeutic viewpoint, it is important to differentiate the underlying causes of embolism in patients with cryptogenic stroke, such as aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. We investigated the clinical and radiological characteristics of these 3 common causes of cryptogenic embolism to develop models for decision making in etiologic workups. METHODS AND RESULTS: A total of 321 consecutive patients with acute infarcts from cryptogenic embolism were included. Patients were divided into 3 groups-aortic arch atheroma (n=40), patent foramen ovale (n=153), and paroxysmal atrial fibrillation (n=128)-based on extensive cardiologic workups. We used a multinomial logistic regression analysis to detect the clinical and diffusion-weighted imaging factors associated with the probability of aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. Clinical and radiological features differed among the groups. The patent foramen ovale group had a healthy vascular risk factor profile and showed posterior circulation involvement compared with other groups (P<0.01). In contrast, paroxysmal atrial fibrillation-related strokes had higher initial National Institutes of Health Stroke Scale (NIHSS) scores and larger lesions than the other groups (P<0.001). The aortic arch atheroma group had clinical features similar to those of the paroxysmal atrial fibrillation group but showed small lesions scattered in multiple vascular territories (P<0.001). Multivariate regression analysis revealed that age, initial NIHSS score, lesion size (≥20 mm), multiple (≥3) lesions, and involvement of posterior circulation or multiple vascular territories differentiated the 3 groups (pseudo, R(2)=0.656). The prediction ability of this model was validated in the external validation cohort (n=117, area under the curve 0.78). CONCLUSIONS: Our data indicate that patients with cryptogenic embolic stroke show distinct clinical and radiological features depending on the underlying causes.


Assuntos
Doenças da Aorta/diagnóstico , Aterosclerose/diagnóstico , Fibrilação Atrial/diagnóstico , Procedimentos Clínicos , Técnicas de Apoio para a Decisão , Forame Oval Patente/diagnóstico , Embolia Intracraniana/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Doenças da Aorta/complicações , Doenças da Aorta/patologia , Aortografia , Aterosclerose/complicações , Aterosclerose/patologia , Fibrilação Atrial/complicações , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética , Avaliação da Deficiência , Ecocardiografia Transesofagiana , Eletrocardiografia Ambulatorial , Feminino , Forame Oval Patente/complicações , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/fisiopatologia , Modelos Logísticos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Imagem Multimodal/métodos , Análise Multivariada , Placa Aterosclerótica , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , República da Coreia , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fluxo de Trabalho
15.
J Neurol Sci ; 359(1-2): 381-8, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26671146

RESUMO

OBJECTIVE: We sought to identify the clinical outcome and predictors for ischemic stroke recurrence in adults with symptomatic moyamoya disease (MMD). METHODS: We analyzed 104 adult MMD patients with ischemic stroke or TIA registered at our institution. All patients underwent digital subtraction angiography and single photon emission computed tomography to measure disease severity and cerebral vascular reserve (CVR). A Cox regression model was used to identify predictors of recurrent ischemic stroke. RESULTS: Fifty-nine patients were non-surgically treated and 45 patients were surgically treated. In the non-surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 1.6% in the first year and 11.8% in the 5th year. Hypertension (hazard ratio [HR]=0.07, 95% confidence interval [CI] 0.01-0.99), diabetes (HR=35.16, 95% CI 2.61-474.16), presence of steno-occlusive lesion in posterior cerebral arteries (HR=17.53, 95% CI 2.02-152.43), and extended or global decreased CVR (HR=13.62, 95% CI 1.55-119.84) were independent predictors of recurrence. In the surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 24.4% in the first year and 24.4% in the 5th year. Half of the recurred patients experienced recurrent ischemic strokes postoperatively. Diabetes was the only predictor of recurrent ischemic stroke (HR=6.17, 95% CI 1.31-29.14). CONCLUSIONS: In non-surgically treated MMD, PCA stenosis and CVR were identified as predictors of ischemic stroke recurrence. Diabetes was an independent predictor of recurrent ischemic stroke in both non-surgical and surgically treated MMD groups.


Assuntos
Isquemia Encefálica/complicações , Doença de Moyamoya/complicações , Acidente Vascular Cerebral , Resultado do Tratamento , Adulto , Angiografia Digital , Isquemia Encefálica/etiologia , Revascularização Cerebral/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/cirurgia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Tomografia Computadorizada de Emissão de Fóton Único
16.
J Stroke ; 17(3): 229-37, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26437990

RESUMO

Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.

17.
Stroke ; 46(10): 2800-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26306754

RESUMO

BACKGROUND AND PURPOSE: Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. METHODS: Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. RESULTS: Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). CONCLUSIONS: Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Colateral/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Acidente Vascular Cerebral/patologia , Idoso , Área Sob a Curva , Circulação Cerebrovascular/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Curva ROC , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
18.
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
19.
J Stroke ; 17(2): 192-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26060806

RESUMO

BACKGROUND AND PURPOSE: Advantages of new oral anticoagulations may be greater in atrial fibrillation (AF) patients of poor anticoagulation control with warfarin. The SAMe-TT2R2 scoring system, based on clinical variables, was recently developed to aid in identifying these patients. In this study, we investigated the association of this clinical composite score with genetic factors related warfarin dosing and the quality of anticoagulation control. METHODS: Clinical and genetic data were collected from 380 consecutive Korean patients with AF (CHA2DS2-VASc score, 3.5±1.8) who were followed for an average of 4 years. We evaluated factors associated with time in therapeutic range (TTR, INR 2-3), including the CYP2C9 and VKORC1 genotypes and the SAMe-TT2R2 score (Sex female, Age <60 years, Medical history [>two co-morbidities], Treatment [interacting drugs, e.g., amiodarone], Tobacco use within 2 years [doubled], and Race non-white [doubled]). RESULTS: The average SAMe-TT2R2 score was 3.4±0.9, range 2-7; and 153 patients (40.2%) had SAMe-TT2R2 scores ≥4. Time in specific INR ranges varied depending on the VKORC1 genotype but not with the CYP2C9 genotype or the SAMe-TT2R2 score. TTR was higher in patients with the VKORC1 1173C>T than in VKORC1 TT (61.7±16% vs. 56.7±17.4%, P=0.031). Multivariate testing showed that VKORC1 genotype but not the SAMe-TT2R2 score was significantly associated with labile INRs. There was no correlation between the SAMe-TT2R2 scores and pharmacogenetic data. CONCLUSIONS: A genetic factor, but none of the common clinical and demographic factors, as combined in the SAMe-TT2R2 score, was associated with the quality of anticoagulation control in Korean patients with AF.

20.
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.

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